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BACKGROUND: Reactive oxygen species (ROS) trigger different morphogenic processes in filamentous fungi and have been shown to play a role in the regulation of the biosynthesis of some secondary metabolites. Some bZIP transcription factors, such as Yap1, AtfA and AtfB, mediate resistance to oxidative stress and have a role in secondary metabolism regulation. In this work we aimed to get insight into the molecular basis of this regulation in the industrially important fungus Penicillium chrysogenum through the characterization of the role played by two effectors that mediate the oxidative stress response in development and secondary metabolism. RESULTS: In P. chrysogenum, penicillin biosynthesis and conidiation are stimulated by the addition of H2O2 to the culture medium, and this effect is mediated by the bZIP transcription factors PcYap1 and PcRsmA. Silencing of expression of both proteins by RNAi resulted in similar phenotypes, characterized by increased levels of ROS in the cell, reduced conidiation, higher sensitivity of conidia to H2O2 and a decrease in penicillin production. Both PcYap1 and PcRsmA are able to sense H2O2-generated ROS in vitro and change its conformation in response to this stimulus. PcYap1 and PcRsmA positively regulate the expression of brlA, the first gene of the conidiation central regulatory pathway. PcYap1 binds in vitro to a previously identified regulatory sequence in the promoter of the penicillin gene pcbAB: TTAGTAA, and to a TTACTAA sequence in the promoter of the brlA gene, whereas PcRsmA binds to the sequences TGAGACA and TTACGTAA (CRE motif) in the promoters of the pcbAB and penDE genes, respectively. CONCLUSIONS: bZIP transcription factors PcYap1 and PcRsmA respond to the presence of H2O2-generated ROS and regulate oxidative stress response in the cell. Both proteins mediate ROS regulation of penicillin biosynthesis and conidiation by binding to specific regulatory elements in the promoters of key genes. PcYap1 is identified as the previously proposed transcription factor PTA1 (Penicillin Transcriptional Activator 1), which binds to the regulatory sequence TTAGTAA in the pcbAB gene promoter. This is the first report of a Yap1 protein directly regulating transcription of a secondary metabolism gene. A model describing the regulatory network mediated by PcYap1 and PcRsmA is proposed.
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Penicillium chrysogenum , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación Fúngica de la Expresión Génica , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo , Penicillium chrysogenum/genética , Penicillium chrysogenum/metabolismo , Metabolismo Secundario/genéticaRESUMEN
BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.
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Proteínas de Transferencia de Ésteres de Colesterol/genética , Sacarosa en la Dieta/efectos adversos , Ingestión de Alimentos/genética , Lípidos/sangre , Conducta Sedentaria , Adulto , Alelos , Indio Americano o Nativo de Alaska/genética , Antropometría , Estudios Transversales , Dieta/efectos adversos , Registros de Dieta , Dislipidemias/genética , Femenino , Genotipo , Humanos , Masculino , México/etnología , Polimorfismo Genético , Factores de RiesgoRESUMEN
BACKGROUND: In order to further identify the needed interventions for continued poverty reduction in our study area Cuatro Santos, northern Nicaragua, we aimed to elucidate what predicts poverty, measured by the Unsatisfied Basic Need index. This analysis was done by using decision tree methodology applied to the Cuatro Santos health and demographic surveillance databases. METHODS: Using variables derived from the health and demographic surveillance update 2014, transferring individual data to the household level we used the decision tree framework Conditional Inference trees to predict the outcome "poverty" defined as two to four unsatisfied basic needs using the Unsatisfied Basic Need Index. We further validated the trees by applying Conditional random forest analyses in order to assess and rank the importance of predictors about their ability to explain the variation of the outcome "poverty." The majority of the Cuatro Santos households provided information and the included variables measured housing conditions, assets, and demographic experiences since the last update (5 yrs), earlier participation in interventions and food security during the last 4 weeks. RESULTS: Poverty was rare in households that have some assets and someone in the household that has a higher education than primary school. For these households participating in the intervention that installed piped water with water meter was most important, but also when excluding this variable, the resulting tree showed the same results. When assets were not taken into consideration, the importance of education was pronounced as a predictor for welfare. The results were further strengthened by the validation using Conditional random forest modeling showing the same variables being important as predicting the outcome in the CI tree analysis. As assets can be a result, rather than a predictor of more affluence our results in summary point specifically to the importance of education and participation in the water installation intervention as predictors for more affluence. CONCLUSION: Predictors of poverty are useful for directing interventions and in the Cuatro Santos area education seems most important to prioritize. Hopefully, the lessons learned can continue to develop the Cuatro Santos communities as well as development in similar poor rural settings around the world.
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Minería de Datos/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Evaluación de Necesidades/estadística & datos numéricos , Pobreza/estadística & datos numéricos , Adolescente , Adulto , Anciano , Árboles de Decisión , Demografía , Femenino , Encuestas Epidemiológicas/métodos , Humanos , Masculino , Persona de Mediana Edad , Nicaragua , Adulto JovenRESUMEN
BACKGROUND: Children with Down syndrome (DS) require multiple sleep studies throughout childhood to diagnose and monitor sleep disordered breathing (SDB). Previous research suggests sensors applied during polysomnography (PSG) are poorly tolerated by children with DS. The Sonomat is a contactless device previously validated in typically developing children, and adult populations. Our study aimed to compare simultaneous Sonomat and PSG recordings in children with DS to determine the suitability of the Sonomat for use in this population. METHODS: Fifty children with DS undergoing diagnostic PSG were recruited from the Queensland Children's Hospital sleep laboratory. Agreement for sleep and respiratory parameters were assessed using concordance correlation coefficients (CCC), while detection and classification of SDB were assessed using indicators such as sensitivity, specificity, likelihood ratios, and receiver operator characteristic curves. RESULTS: Comparison of parameters including the apnea-hypopnea index (CCC=89%; 95%CI 76, 93), and obstructive events index (CCC=74%; 95%CI 44, 88) showed reasonable agreement between Sonomat and PSG. The Sonomat showed outstanding ability to differentiate between the presence and absence of SDB (area under the curve [AUC]=0.97; 95%CI 0.93, 1.00), though we are uncertain of its ability to classify SDB profile and severity due to sample size limitations resulting in wide confidence intervals. CONCLUSIONS: The easy-to-use, non-invasive nature of the Sonomat make it ideal for use in the screening of SDB in children with DS. Further data are needed to determine its suitability for classifying SDB profile and severity, including within the home, and for its use in other neurodevelopmental groups.
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Síndrome de Down , Síndromes de la Apnea del Sueño , Adulto , Humanos , Niño , Polisomnografía/métodos , Sueño , Síndromes de la Apnea del Sueño/diagnóstico , Frecuencia RespiratoriaRESUMEN
Using relativistic density-functional calculations, we examine the magneto-crystalline anisotropy and exchange properties of transition-metal atoms adsorbed on 2D-GaAs. We show that single Mn and Mo atom (Co and Os) strongly bind on 2D-GaAs, and induce local out-of-plane (in-plane) magnetic anisotropy. When a pair of TM atoms is adsorbed on 2D-GaAs in a close range from each other, magnetisation properties change (become tunable) with respect to concentrations and ordering of the adatoms. In all cases, we reveal presence of strong Dzyaloshinskii-Moriya interaction. These results indicate novel pathways towards two-dimensional chiral magnetic materials by design, tailored for desired applications in magneto-electronics.
RESUMEN
First-principles calculations have been carried out to investigate the stability, structural and electronic properties of two-dimensional (2D) hydrogenated GaAs with three possible geometries: chair, zigzag-line and boat configurations. The effect of van der Waals interactions on 2D H-GaAs systems has also been studied. These configurations were found to be energetic and dynamic stable, as well as having a semiconducting character. Although 2D GaAs adsorbed with H tends to form a zigzag-line configuration, the energy differences between chair, zigzag-line and boat are very small which implies the metastability of the system. Chair and boat configurations display a [Formula: see text]-[Formula: see text] direct bandgap nature, while pristine 2D-GaAs and zigzag-line are indirect semiconductors. The bandgap sizes of all configurations are also hydrogen dependent, and wider than that of pristine 2D-GaAs with both PBE and HSE functionals. Even though DFT-vdW interactions increase the adsorption energies and reduce the equilibrium distances of H-GaAs systems, it presents, qualitatively, the same physical results on the stability and electronic properties of our studied systems with PBE functional. According to our results, 2D buckled gallium arsenide is a good candidate to be synthesized by hydrogen surface passivation as its group III-V partners 2D buckled gallium nitride and boron nitride. The hydrogenation of 2D-GaAs tunes the bandgap of pristine 2D-GaAs, which makes it a potential candidate for optoelectronic applications in the blue and violet ranges of the visible electromagnetic spectrum.
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The South American fur seal reproductive histophysiology is scarcely described. This study provides a histological description of prepuberal South American fur seal (Arctocephalus australis) ovaries as well as three-dimensional reconstructions of subcapsular crypts and primordial follicles. Ovaries from fresh dead animals were processed for histology and sliced into serial sections. A portion of the superficial cortex was photographed, and the images were processed using BioVis3d software in order to generate 3-dimensional reconstructions. A. australis prepuberal ovaries conform to the basic structure of pinnipedian species, with a subcapsular crypts system made up of interconnecting cisternae and tubules with multiple openings to the surface. Generally, the primordial follicles were arranged in a monolayer beneath the tunica albuginea and were closely associated with subcapsular crypts. The large number of interstitial cells distributed throughout the cortex was the main histological feature in comparison with previous reports in other seals. Three-dimensional reconstructions modelled the subcapsular crypts microarchitecture and showed the close spatial relationship between the crypts and the primordial follicles. Despite the fact that the general ovarian histological structure was similar to that of other pinnipeds, the large number of interstitial cells is a distinctive feature that raises the question about the origin and function in A. australis with regard to the steroidogenic activity reported in other seal species.
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Lobos Marinos/anatomía & histología , Folículo Ovárico/anatomía & histología , Ovario/anatomía & histología , Animales , Femenino , Tamaño de los Órganos , Folículo Ovárico/citología , Ovario/citología , Células Tecales/citologíaRESUMEN
The electronic and vibrational properties of germanane and fluorinated germanene are studied within density functional theory (DFT) and density functional perturbation theory frameworks. Different structural configurations of germanane and fluorinated germanene are investigated. The energy difference between the different configurations are consistently smaller than the energy of thermal fluctuations for all the analyzed DFT functionals LDA, GGA, and hybrid functionals, which implies that, in principle, it is possible to find these different configurations in different regions of the sample as minority phases or local defects. We calculate the Raman and infrared spectra for these configurations by using ab initio calculations and compare it with available experimental spectra for germanane. Our results show the presence of minority phases compatible with the configurations analyzed in this work. As these low energy configurations are metastable the present work shows that the synthesis of these energy competing phases is feasible by selectively changing the synthesis conditions, which is an opportunity to expand in this way the availability of new two-dimensional compounds.
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The bandgap behavior of 2D-GaAs and graphene have been investigated with van der Waals heterostructured into a yet unexplored graphene/GaAs bilayer, under both uniaxial stress along c axis and different planar strain distributions. The 2D-GaAs bandgap nature changes from [Formula: see text]-K indirect in isolated monolayer to [Formula: see text]-[Formula: see text] direct in graphene/GaAs bilayer. In the latter, graphene exhibits a bandgap of 5 meV. The uniaxial stress strongly affects the graphene electronic bandgap, while symmetric in-plane strain does not open the bandgap in graphene. Nevertheless, it induces remarkable changes on the GaAs bandgap-width around the Fermi level. However, when applying asymmetric in-plane strain to graphene/GaAs, the graphene sublattice symmetry is broken, and the graphene bandgap is open at the Fermi level to a maximum width of 814 meV. This value is much higher than that reported for just graphene under asymmetric strain. The [Formula: see text]-[Formula: see text] direct bandgap of GaAs remains unchanged in graphene/GaAs under different types of applied strain. The analyses of phonon dispersion and the elastic constants yield the dynamical and mechanical stability of the graphene/GaAs system, respectively. The calculated mechanical properties for bilayer heterostructure are better than those of their constituent monolayers. This finding, together with the tunable graphene bandgap not only by the strength but also by the direction of the strain, enhance the potential for strain engineering of ultrathin group-III-V electronic devices hybridized by graphene.
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PURPOSE: Report effects on knowledge of sexual health and gender from an intervention using peer methodology in Nicaragua. DESIGN: A prepost nonequivalent control group design. SETTING: Ciudad Sandino, Managua, Nicaragua. SUBJECTS: A total of 599 girls were surveyed, 60% nonintervened and 40% intervened. INTERVENTION: Peer methodology consisted of (1) meetings in which girls talked and worked with other girls, (2) mothers taking an active role in the peer groups, and/or (3) girls watching the soap opera "Sexto Sentido." MEASURES: Indices measuring changes in sexual knowledge and gender vision. RESULTS: Girls participating in the peer groups were twice as likely to have satisfactory sexual health-related self-esteem as those who did not participate. Eleven percent of the girls achieved satisfactory self-esteem as a result of the (peer groups x mothers) interaction and 15% due to the (peer groups x mothers x "Sexto Sentido") interaction. Girls participating in the peer groups were three times as likely to have satisfactory gender visions; if exposed to all three components, they were almost four times as likely to develop satisfactory gender visions. CONCLUSIONS: Peer methodology, participation of a female family member, and an educational soap opera seem beneficial in promoting sexual health-related knowledge and gender vision in young girls.
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Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Estado de Salud , Grupo Paritario , Evaluación de Programas y Proyectos de Salud , Autoimagen , Conducta Sexual , Adolescente , Niño , Femenino , Encuestas Epidemiológicas , Humanos , Nicaragua , Proyectos Piloto , Desarrollo de Programa , Factores Sexuales , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
The intestines and mesentery of the nutria (Myocastor coypus) have not been fully described. In the present study 30 adult nutrias were studied using gross dissection. The small intestine was divided into the duodenum, jejunum and ileum as usual. The duodenum started at the pylorus with a cranial portion, which dilated forming a duodenal ampulla. The ileum was located within the concavity of the caecum and attached to the coiled caecum by means of the iliocaecal fold. The ascending colon had two ansae, one proximal and one distal. The proximal ansa was fixed to the caecum by the caecocolic fold. The base of the caecum and a short proximal part of the ascending colon belonging to the proximal ansa were attached to the mesoduodenum descendens. The distal ansa of the ascending colon had a proximal part which was sacculated and a distal part which was smooth. The two parts of the distal ansa of the ascending colon were parallel and joined by a flexure of variable localisation. The smooth part of the distal ansa of the ascending colon was attached to the initial portion of the descending colon by a peritoneal fold. The short transverse colon was directly attached to the mesoduodenum and greater omentum. In conclusion, we have described the anatomy of the intestines of the nutria and its mesentery in detail, and provided a nomenclature list adapted to the Nomina Anatomica Veterinaria.
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Intestinos/anatomía & histología , Mesenterio/anatomía & histología , Roedores/anatomía & histología , Animales , Peso Corporal , Ciego/anatomía & histología , Colon/anatomía & histología , Sistema Digestivo/anatomía & histología , Disección/métodos , Duodeno/anatomía & histología , Femenino , Íleon/anatomía & histología , Masculino , Epiplón/anatomía & histología , Estómago/anatomía & histologíaRESUMEN
This research is a study about the arterial vascularization of pelvic cavity and pelvic limb in pampas deer. For this study, 25 dead animals were used. The vascularization of the organs was investigated using a latex injection technique. Two animals were injected in the common carotid artery with contrast to cardiac angiography, and then, radiographs were taken. The aorta showed the two external iliac arteries, and after a short course, the aorta ended in two internal iliac arteries. The median sacral artery was originated from the dorsal surface cranially to the emergence of the internal iliac arteries. The last one gave off parietal (iliolumbar, cranial and caudal gluteal arteries) and visceral (umbilical and internal pudendal arteries) branches. The external iliac artery gave as first branch the deep circumflex iliac artery which was divided into a cranial and a caudal branch. After a short distance from the external iliac artery, the femoral and deep femoral arteries were originated. The deep femoral artery gave origin to the pudendoepigastric trunk and to the medial femoral circumflex artery. Based on the arterial distribution of the pelvic cavity and pelvic limb in the pampas deer, it is concluded that the internal iliac artery has a pattern of intermediate development. In reference to the distribution of the external iliac artery and its branches, the pattern of development is the cranial tibial type.
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Angiografía Coronaria/veterinaria , Ciervos/anatomía & histología , Pelvis/irrigación sanguínea , Animales , Aorta Abdominal/anatomía & histología , Femenino , Arteria Femoral/anatomía & histología , Arteria Ilíaca/anatomía & histología , MasculinoRESUMEN
This research presents the first anatomical description of the tongue and lingual papillae of the mountain lion (puma). The tongues of three adult male pumas were used in this study. The tongues were dissected and studied firstly by gross and stereomicroscopy. Samples of each part were processed by study with scanning electron microscopy. The margins of the lingual apex were surrounded by numerous filiform papillae, which had a bulky papillary body and a bifurcated tip. On the dorsal surface of the lingual apex, filiform papillae were remarkably pointed and had many secondary projections, which emerged from the base of the main papilla. In the rostral half of the lingual body, filiform papillae were longer, cylindrical and had blunt tips. On the caudal half of the lingual body, filiform papillae gave place to conical ones exhibiting a pointed tip. The fungiform papillae were scattered on the whole dorsal surface of the tongue. On each lateral half of the tongue, four circumvallate papillae were observed and each circumvallate papilla was surrounded by thick and horseshoe-like annular pad, which were composed by pointed conical papillae on the caudal border of the lingual body. The dorsal surface of the circumvallate papilla was covered by many finger-like protrusion, and the tip of each protrusion had a central orifice. Anatomical distribution of lingual papillae was different to other carnivores and represents the adaptation to the feeding habits of this mammal. General morphology of the lingual structures was similar to those of the tiger.
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Puma/anatomía & histología , Lengua/anatomía & histología , Animales , Conducta Alimentaria/fisiología , Masculino , Microscopía Electrónica de Rastreo/veterinaria , Conducta Predatoria/fisiología , Puma/fisiología , Glándulas Salivales Menores/ultraestructura , Lengua/ultraestructuraRESUMEN
The available information about anatomical characteristics of the cardiovascular system of the alpaca (Vicugna pacos, Linnaeus 1758) is scarce. The general objective of this work was to describe its heart anatomy. We dissected six adult animals and five neonates. The heart of the alpaca was located in the middle mediastinum, with a craniocaudal extension from the third to the sixth rib. No ligament that connected the fibrous pericardium to the sternum or to the diaphragm was detected. In the right atrium, there was a developed crista terminalis and small pectinate muscles. In the right ventricle, the septomarginal trabecula was very large. From the proximities of the interventricular septum arose small septomarginal trabeculae that ended in carnous trabeculae of the septal wall. The left atrium included little developed pectinate muscles. On the left ventricle, both papillary muscles were bilobed. Two left septomarginal trabeculas were detected in this ventricle. The left subclavian artery was originated from the aortic arch separately from the brachiocephalic trunk, and bicarotid trunk was present. The other branches of the subclavian artery were similar to the domestic ruminants. The arterial supply of the heart was of the right type. In conclusion, the heart anatomy of alpaca and the irrigation of thoracic cavity were more similar to those of old world camels and different from domestic ruminants.
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Camélidos del Nuevo Mundo/anatomía & histología , Disección/veterinaria , Atrios Cardíacos/anatomía & histología , Ventrículos Cardíacos/anatomía & histología , Cavidad Torácica/irrigación sanguínea , Animales , Aorta Torácica/anatomía & histología , Femenino , Masculino , Miocardio , Músculos Papilares/anatomía & histología , Arteria Subclavia/anatomía & histologíaRESUMEN
The aims of this study were to describe the anatomy of the mouth and pharynx of the pampas deer, and to consider its evolutionary feeding niche according to those characteristics. Gross dissections of the mouth and pharynx were performed in 15 animals, 10 adult females and five young animals under 1 year (three males and two females), all dead by causes unrelated to this anatomical region. The upper lip entered in the constitution of a pigmented nasolabial plane. The masseter muscles weighed 43.8 ± 3.5 g and represented 0.23% of body weight, which corresponds to ruminants of feeders intermediate to grazers and browsers. Parotid glands represented 0.08% of the body weight, characteristic that also categorize the pampas deer as belonging to the intermediate feeding group. The dental formula was the same of the domestic ruminants. The upper incisors and canines were absent, and instead of them, there was a dental pad (Pulvinus dentalis). The upper canine teeth were present only in the deciduous dentition. The existence of a brachydont dentition turns Ozotoceros very vulnerable to continuous use as there is no compensatory teeth growth. The particular anatomy of the mouth and lips of this animal was adapted to a very selective feeding, taking highly nutritious sprouts beyond plant category. In conclusion and in addition to previous studies of anatomy of the digestive organs in this species, pampas deer may be categorized as belonging to the intermediate type of feeding.
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Ciervos/anatomía & histología , Disección/veterinaria , Conducta Alimentaria/fisiología , Boca/anatomía & histología , Faringe/anatomía & histología , Animales , Evolución Biológica , Femenino , Masculino , Diente/anatomía & histologíaRESUMEN
Information about gonadal asymmetries in ruminants is very scarce. In this work, we performed three complementary studies to compare characteristics of both testes: (i) weight and size of offspring and adult dead males; (ii) the tissue:fluid relationship determined by ultrasound scanning; and (iii) the spermatogenic status using fine needle aspiration cytology. The right testis was heavier than the left one in both offspring and adult animals and had greater width and volume in adult males than the left one. The ultrasound pixel intensity was similar in both testes. The right testis tended to have more spermatogonia (p = .06) and had a greater percentage of early spermatids (p = .004) than the left testis. On the other hand, the left testis had a greater percentage of spermatozoa (p = .05). The left testis had a greater spermatozoa/spermatogonia ratio (p = .02) and tended to have more spermatozoa/Sertoli cells ratio (p = .07). The spermatogenic index tended to be greater in the left than in the right testis (p = .06). Overall, we concluded that the right testis of pampas deer males is bigger but according to the cytology, it seems to be less spermatogenically effective than the left one, but these differences are not explained by different tissue:fluid ratio in each testis. Although differences were greater in adults than in offspring, asymmetry was observed even in just born offspring.
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Ciervos/anatomía & histología , Espermatogénesis/fisiología , Testículo/anatomía & histología , Factores de Edad , Animales , Biopsia con Aguja Fina/veterinaria , Ciervos/fisiología , Masculino , Células de Sertoli/citología , Espermátides/citología , Espermatogonias/citología , Espermatozoides/citología , Testículo/diagnóstico por imagen , Testículo/patología , Testículo/fisiología , Ultrasonografía/veterinaria , UruguayRESUMEN
For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immunosuppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor transplants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from >1-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, >1-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding probabilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplantation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor.
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Anemia Aplásica/terapia , Trasplante de Médula Ósea , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA/análisis , Humanos , Lactante , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
A disparity was noted in the transport of rhodamine 123 among nine MXR/BCRP/ABCP-overexpressing cells studied; all demonstrated mitoxantrone transport, whereas only two effluxed rhodamine 123. When the MXR/BCRP/ABCP gene was sequenced in the cell lines studied, differences were noted at amino acid 482, predicted to be at the start of the third transmembrane domain. Sequencing genomic DNA revealed wild-type MXR/BCRP/ABCP to have an arginine at position 482. Cells having a threonine or glycine at position 482 were able to efflux rhodamine 123, whereas cells having an arginine were not. A vaccinia virus expression system confirmed that rhodamine as well as doxorubicin efflux is observed with R482T or R482G but not with the wild-type R482; all three MXR/BCRP/ABCP forms transported mitoxantrone. Cross-resistance studies suggest that, compared with wild-type MXR/BCRP/ABCP, cells having an R482T mutation have higher anthracycline resistance, whereas an R482G mutation seems to confer relatively less resistance to SN-38 and topotecan. These results suggest that amino acid 482 has a crucial role in MXR/BCRP/ABCP function and that mutation of a single amino acid residue significantly changes substrate specificity, thus altering the drug resistance phenotype.
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Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Mutación , Proteínas de Neoplasias , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/biosíntesis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Camptotecina/análogos & derivados , Camptotecina/farmacología , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos , Genes MDR/genética , Vectores Genéticos/genética , Células HeLa , Humanos , Irinotecán , Mitoxantrona/farmacocinética , Mitoxantrona/farmacología , ARN Mensajero/genética , Rodamina 123/farmacocinética , Especificidad por Sustrato , Topotecan/farmacología , Transfección , Células Tumorales Cultivadas , Virus Vaccinia/genéticaRESUMEN
Based on gross dissection of fifteen adult animals (11 females, 4 males), we described the arterial supply of the stomach and intestines of the pampas deer (Ozotoceros bezoarticus), a South American endangered species. The coeliac artery emitted the splenic, left gastric and hepatic arteries. The splenic artery directed towards the spleen, and the right ruminal artery, which is its only collateral directed towards the stomach, being the main artery of the rumen. The left gastric artery gave origin to the left ruminal, the reticular and the left gastroepiploic arteries. The left gastroepiploic artery originated the reticular accessory artery. Both arteries, gastric and left gastroepiploic, anastomosed their right counterparts derived from the hepatic artery on the curvatures of the abomasum. The cranial mesenteric artery irrigated the second half of the duodenum until the beginning of the descending colon. The thickest branch emitted by the cranial mesenteric artery was the ileocolic artery, which was destined to the ascending colon, caecum and ileum. The colic branches and the right colic arteries were irradiated on the right surface of the spiral loop of the ascending colon and distributed to both centripetal and centrifugal coils of the ascending colon; the colic branches were also anastomosed with the last jejunals and ileals and with the right colic arteries. There were no variations in the origin of any of the main branches derived from the coeliac and cranial mesenteric arteries. This species had a basic pattern of arterial distribution similar to small domestic ruminants.