756 resultados para Aparell de Golgi
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Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early tran - script 1 (RAET1)as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies.
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La microbiota intestinal dels diabètics és diferent. L'absència i l'excés d'alguns bacteris podrien estar darrere de la malaltia, indica un estudi a 'Nature'
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Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co- ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.
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This is the first TEM examination of vitellogenesis in the cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax and a member of a little-studied trypanorhynch family, the Aporhynchidae. The synthetic activity of vitellocytes plays two important functions in the developmental biology of cestodes: (1) their shell-globules serve in eggshell formation; and (2) their accumulated reserves of glycogen and lipids represent a food source for the developing embryo. In A. menezesi, vitelline follicles consist of cells at various stages of development, from peripheral, immature cells of the gonial type to mature cells towards the centre of the follicle. These stages are: (I) immature; (II) early differentiation; (III) advanced maturation; and (IV) mature. Gradual changes involved in this process occur within each stage. Vitellogenesis involves: (1) an increase in cell volume; (2) the development of a smooth endoplasmic reticulum and an accelerated formation and accumulation of both unsaturated and saturated lipid droplets, along with their continuous enlargement and fusion; (3) the formation of individual β-glycogen particles and their accumulation in the form of glycogen islands scattered among lipid droplets in the cytoplasm of maturing and mature vitellocytes; (4) the rapid accumulation of large, moderately saturated lipid droplets accompanied by dense accumulations of β-glycogen along with proteinaceous shell-globules or shell-globule clusters in the peripheral layer during the advanced stage of maturation; (5) the development of cisternae of granular endoplasmic reticulum that produce dense, proteinaceous shell-globules; (6) the development of Golgi complexes engaged in the packaging of this material; and (7) the progressive and continuous enlargement of shell-globules into very large clusters in the peripheral layer during the advanced stage of maturation. Vitellogenesis in A. menezesi, only to some extent, resembles that previously described for four other trypanorhynchs. It differs in: (i) the reversed order of secretory activities in the differentiating vitellocytes, namely the accumulation of large lipid droplets accompanied by glycogenesis or β-glycogen formation during early differentiation (stage II), i.e. before the secretory activity, which is predominantly protein synthesis for shell-globule formation (stage III); (ii) the very heavy accumulation of large lipid droplets during the final stage of cytodifferentiation (stage IV); and (iii) the small number of β-glycogen particles present in mature vitellocytes. Ultracytochemical staining with PA-TCH-SP for glycogen proved positive for a small number of β-glycogen particles in differentiating and mature vitellocytes. Hypotheses, concerning the interrelationships of patterns of vitellogenesis, possible modes of egg formation, embryonic development and life-cycles, are commented upon.
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Hemoglobin (Hb) has been proposed to be a major pro-oxidant in raw and cooked meats. To understand the mechanisms and differentiate between the pro-oxidant and antioxidant potential of oxyhemoglobin (OxyHb) and methemoglobin (MetHb), their pro-oxidant activity, protein solubility, radical scavenging capacity, iron content and contribution of non-chelatable iron on lipid oxidation were determined as a function of thermal treatments. The ability of native OxyHb and MetHb to promote lipid oxidation was similar and higher than their corresponding OxyHb or MetHb heated at 68 and 90 degrees C but not different from those at 45 degrees C. The pro-oxidant activity of MetHb heated at 68 and 90 degrees C were similar whereas the pro-oxidant activity of OxyHb heated at 68 degrees C was higher than that heated at 90 degrees C. The decreased pro-oxidant activity of heat-denatured Hb was associated with a decrease in the solubility of heme iron while free iron showed little impact on the lipid oxidation.
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Background: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. Methods: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox"s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. Results: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. Conclusions: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically.
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SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer"s disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.
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This is the first TEM examination of vitellogenesis in the cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax and a member of a little-studied trypanorhynch family, the Aporhynchidae. The synthetic activity of vitellocytes plays two important functions in the developmental biology of cestodes: (1) their shell-globules serve in eggshell formation; and (2) their accumulated reserves of glycogen and lipids represent a food source for the developing embryo. In A. menezesi, vitelline follicles consist of cells at various stages of development, from peripheral, immature cells of the gonial type to mature cells towards the centre of the follicle. These stages are: (I) immature; (II) early differentiation; (III) advanced maturation; and (IV) mature. Gradual changes involved in this process occur within each stage. Vitellogenesis involves: (1) an increase in cell volume; (2) the development of a smooth endoplasmic reticulum and an accelerated formation and accumulation of both unsaturated and saturated lipid droplets, along with their continuous enlargement and fusion; (3) the formation of individual β-glycogen particles and their accumulation in the form of glycogen islands scattered among lipid droplets in the cytoplasm of maturing and mature vitellocytes; (4) the rapid accumulation of large, moderately saturated lipid droplets accompanied by dense accumulations of β-glycogen along with proteinaceous shell-globules or shell-globule clusters in the peripheral layer during the advanced stage of maturation; (5) the development of cisternae of granular endoplasmic reticulum that produce dense, proteinaceous shell-globules; (6) the development of Golgi complexes engaged in the packaging of this material; and (7) the progressive and continuous enlargement of shell-globules into very large clusters in the peripheral layer during the advanced stage of maturation. Vitellogenesis in A. menezesi, only to some extent, resembles that previously described for four other trypanorhynchs. It differs in: (i) the reversed order of secretory activities in the differentiating vitellocytes, namely the accumulation of large lipid droplets accompanied by glycogenesis or β-glycogen formation during early differentiation (stage II), i.e. before the secretory activity, which is predominantly protein synthesis for shell-globule formation (stage III); (ii) the very heavy accumulation of large lipid droplets during the final stage of cytodifferentiation (stage IV); and (iii) the small number of β-glycogen particles present in mature vitellocytes. Ultracytochemical staining with PA-TCH-SP for glycogen proved positive for a small number of β-glycogen particles in differentiating and mature vitellocytes. Hypotheses, concerning the interrelationships of patterns of vitellogenesis, possible modes of egg formation, embryonic development and life-cycles, are commented upon.
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Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'
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This study analyzes the capillarity and fibre-type distribution of six locomotory muscles of gulls. The morphological basis and the oxygen supply characteristics of the skeletal muscle of a species with a marked pattern of gliding flight are established, thus contributing to a better understanding of the physiology of a kind of flight with low energetic requirements. The four wing muscles studied (scapulotriceps, pectoralis, scapulohumeralis, and extensor metacarpi) exhibited higher percentages of fast oxidative glycolytic fibres (>70%) and lower percentages of slow oxidative fibres (<16%) than the muscles involved in nonflight locomotion (gastrocnemius and iliotibialis). Capillary densities ranged from 816 to 1,233 capillaries mm(-2), having the highest value in the pectoralis. In this muscle, the fast oxidative glycolytic fibres had moderate staining for succinate dehydrogenase and relatively large fibre sizes, as deduced from the low fibre densities (589-665 fibres mm(-2)). All these findings are seen as an adaptive response for gliding, when the wing is held outstretched by isometric contractions. The leg muscles studied included a considerable population of slow oxidative fibres (>14% in many regions), which suggests that they are adapted to postural activities. Regional variations in the relative distributions of fibre types in muscle gastrocnemius may reflect different functional demands placed on this muscle during terrestrial and aquatic locomotion. The predominance of oxidative fibres and capillary densities under 1,000 capillaries mm(-2) in leg muscles is probably a consequence of an adaptation for slow swimming and maintenance of the posture on land rather than for other locomotory capabilities, such as endurance or sprint activities.
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Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.
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AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively) and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively). We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase) and mitochondrial biogenesis (PGC-1α) and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.
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All plants are typically confronted to simultaneous biotic and abiotic stress throughout their life cycle. Low inorganic phosphate (Pi) is the most common nutrient deficiency limiting plant growth in natural and agricultural ecosystems while insect herbivory accounts for major losses in plant productivity and impacts on ecological and evolutionary changes in plant populations. Here we report that plants experiencing Pi deficiency induce the jasmonic acid (JA) pathway and enhance their defence against insect herbivory. The phol mutant is impaired in the translocation of Pi from roots to shoots and shows the typical symptoms associated with Pi deficiency, including high anthocyanin and poor shoot growth. These phol shoot phenotypes were significantly attenuated by blocking the JA biosynthesis or signalling pathways. Wounded phol leaves hyper-accumulated JA in comparison to wild type, leading to increased resistance against the generalist herbivore Spodoptera littoralis. Pi deficiency also triggered enhanced resistance to herbivory in wild-type Arabidopsis as well as tomato and tobacco, revealing that the link between Pi deficiency and JA-mediated herbivory resistance is conserved in a diversity of plants, including crops. We performed a phol suppressor screen to identify new components involved in the adaptation of plants to Pi deficiency. We report that the THO RNA TRANSCRIPTION AND EXPORT (THO/TREX) complex is a crucial component involved in modulating the Pi- deficiency response. Knockout mutants of at least three members of the THO/TREX complex, including TEX1, HPR1, and TH06, can suppress the phol shoot phenotype. Grafting experiments showed that loss of function of TEX1 only in the root was sufficient to suppress the reduced shoot growth phenotype of phol while maintaining low Pi contents. This indicates that TEX1 is involved in a long distance root-to-shoot signalling component of the Pi-deficiency response. We identified a small MYB-like transcription factor, RAD LIKE 3 (RL3), as a potential downstream target of the THO/TREX complex. RL3 expression is induced in phol mutants but attenuated in phol-7 texl-4 double mutants. Identical to knockout mutants of the THO/TREX complex, rl3 mutants can suppress the phol shoot phenotypes. Interestingly, RL3 is induced during Pi deficiency and is described in the literature as likely being mobile. It is therefore a promising new candidate involved in the root-to-shoot Pi-deficiency signalling response. Finally, we report that PHOl and its homologue PH01:H3 are involved in the co-regulation of Pi and zinc (Zn) homeostasis. PH01;H3 is up-regulated in response to Zn deficiency and, like PHOl, is expressed in the root vascular cylinder and localizes to the Golgi when expressed transiently in tobacco cells. The phol;h3 mutant accumulates more Pi as compared to wild-type when grown in Zn-deficient medium, but this increase is abolished in the phol phol;h3 double mutant. These results suggest that PH01;H3 restricts the PHOl-mediated root-to-shoot Pi transfer in responsé to Zn deficiency. Résumé Au cours de leur cycle de vie, toutes les plantes sont généralement confrontées à divers stress biotiques et abiotiques. La carence nutritionnelle la plus fréquente, limitant la croissance des plantes dans les écosystèmes naturels et agricoles, est la faible teneur en phosphate inorganique (Pi). Au niveau des stress biotiques, les insectes herbivores sont responsables de pertes majeures de rendement et ont un impact considérable sur les changements écologiques et évolutifs dans les populations des plantes. Au cours de ce travail, nous avons mis en évidence que les plantes en situation de carence en Pi induisent la voie de l'acide jasmonique (JA) et augmentent leur défense contre les insectes herbivores. Le mutant phol est déficient dans le transport du phosphate des racines aux feuilles et démontre les symptômes typiques associés à la carence, tels que la forte concentration en anthocyane et une faible croissance foliaire. Ces phénotypes du mutant phol sont significativement atténués lors d'un blocage de la voie de la biosynthèse ou des voies de signalisation du JA. La blessure des feuilles induit une hyper-accumulation de JA chez phol, résultant en une augmentation de la résistance contre l'herbivore généraliste Spodoptera littoralis. Outre Arabidopsis, la carence en Pi induit une résistance accrue aux insectes herbivores aussi chez la tomate et le tabac. Cette découverte révèle que le lien entre la carence en Pi et la résistance aux insectes herbivores via le JA est conservé dans différentes espèces végétales, y compris les plantes de grandes cultures. Nous avons effectué un crible du suppresseur de phol afin d'identifier de nouveaux acteurs impliqués dans l'adaptation de la plante à la carence en Pi. Nous rapportons que le complexe nommé THO RNA TRANSCRIPTION AND EXPORT (THO/TREX) est un élément crucial participant à la réponse des feuilles à la carence en Pi. Les mutations d'au moins trois des membres que composent le complexe THO/TREX, incluant TEX1, HPR1 et 77/06, peuvent supprimer le phénotype de phol. Des expériences de greffes ont montré que la perte de fonction de TEX1, seulement dans la racine, est suffisante pour supprimer le phénotype de la croissance réduite des parties aériennes observé chez le mutant phol, tout en maintenant de faibles teneurs en Pi foliaire. Ceci indique que TEX1 est impliqué dans la signalisation longue distance entre les racines et les parties aériennes. Nous avons identifié un petit facteur de transcription proche de la famille des MYB, RAD LIKE 3 (RL3), comme une cible potentielle en aval du complexe THO / TREX. L'expression du gène RL3 est induite dans le mutant phol mais atténuée dans le double mutant phol-7 texl-4. Exactement comme les plantes mutées d'un des membres du complexe THO/TREX, le mutant rl3 peut supprimer le phénotype foliaire de phol. RL3 est induit au cours d'une carence en Pi et est décrit dans la littérature comme étant potentiellement mobile. Par conséquent, il serait un nouveau candidat potentiellement impliqué dans la réponse longue distance entre les racines et les parties aériennes lors d'un déficit en Pi. Enfin, nous reportons que PHOl et son homologue PHOl: H3 sont impliqués dans la co- régulation de l'homéostasie du Pi et du zinc (Zn). PHOl; H3 est sur-exprimé en réponse au déficit en Zn et, comme PHOl, est exprimé dans les tissus vasculaires des racines et se localise dans l'appareil de Golgi lorsqu'il est exprimé de manière transitoire dans des cellules de tabac. Le mutant phol; h3 accumule plus de Pi par rapport aux plantes sauvages lorsqu'il est cultivé sur un milieu déficient en Zn, mais cette augmentation en Pi est abolie dans le double mutant phol phol; h3. Ces résultats suggèrent qu'en réponse à une carence en Zn, PHOl; H3 limite l'action de PHOl et diminue le transfert du Pi des racines aux parties aériennes.
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El projecte que es presenta a continuació és el resultat fruit de la detecció d’un problema de comunicació entre les escoles (sobretot de primària) i el pares dels alumnes que hi cursen els estudis, i la necessitat de trobar-hi una solució. Amb aquesta premissa, i tenint en compte que la tecnologia cada vegada ens ofereix més i millors eines per gestionar les nostres necessitats, es porta a terme la construcció d’un servei al núvol (Saas) capaç de cobrir aquestes necessitats i de fer-ho de la manera més senzilla i eficient possible. La plataforma Aula és un servei on tant professors com pares dels alumnes poden comunicar-se i consultar la informació referent als seus alumnes (en el cas del professors), i dels seus fills (en el cas dels pares/tutors). La solució adoptada ha de ser capaç de funcionar sobre qualsevol aparell (ordinador, tablet o mòbil) i en qualsevol lloc on hi hagi connexió a Internet. No s’ha de realitzar cap tipus d’instal·lació un cop el sistema estigui funcionant, i s’hi podran registrar tants centres com siguin necessaris, així com professionals i pares dels alumnes. També s’ha valorat el manteniment mínim del sistema i la seva escalabilitat, per poder fer front a diferents volums de dades. Així doncs, el projecte Aula es presenta com una solució per gestionar el dia a dia dels professors i alumnes, però que no pretén ser substitut de cap altre sistema de gestió que pugui tenir el centre.
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Presentamos un recien nacido varón de 48 horas de vida que ingresa por cianosis, bradicardia e hipotonia. Es fruto de la séptima gestación de una madre añosa de 41 años de edad entre cuyos antecedentes sólo resaltan tres abortos previos al embarazo actual, dos de ellos provocados.Este embarazo fue bien controlado..