RESUMEN
Vortices are essential to angular momentum in quantum systems such as ultracold atomic gases. The existence of quantized vorticity in bosonic systems stimulated the development of the Gross-Pitaevskii mean-field approximation. However, the true dynamics of angular momentum in finite, interacting many-body systems like trapped Bose-Einstein condensates is enriched by the emergence of quantum correlations whose description demands more elaborate methods. Herein we theoretically investigate the full many-body dynamics of the acquisition of angular momentum by a gas of ultracold bosons in two dimensions using a standard rotation procedure. We demonstrate the existence of a novel mode of quantized vorticity, which we term the phantom vortex. Contrary to the conventional mean-field vortex, can be detected as a topological defect of spatial coherence, but not of the density. We describe previously unknown many-body mechanisms of vortex nucleation and show that angular momentum is hidden in phantom vortices modes which so far seem to have evaded experimental detection. This phenomenon is likely important in the formation of the Abrikosov lattice and the onset of turbulence in superfluids.
Asunto(s)
Portador Sano/epidemiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/diagnóstico , Adulto , Portador Sano/microbiología , Estudios de Casos y Controles , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Océanos y Mares , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , ViajeRESUMEN
Gap junctions are intercellular channels which are permeable to ions and small molecules up to about 1 kDa in size. They are prominent in the skin, but their precise function there is largely unknown. Mutations in skin-expressed gap junction genes disrupt epidermal growth and differentiation. A relatively minor epidermal connexin, connexin 26 (Cx26), is associated with a wide variety of phenotypes, each specifically associated with a particular amino acid residue. How the different mutations in GJB2 lead to such distinctive phenotypes is poorly understood. Analysis of new GJB2 mutations can shed new light on pathogenesis and the apparently vital role of Cx26 in maintaining epidermal integrity.
Asunto(s)
Conexinas/genética , Mutación Missense , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Adulto , Conexina 26 , Uniones Comunicantes/genética , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/patología , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Humanos , Queratodermia Palmoplantar/genética , Queratodermia Palmoplantar/patología , Masculino , FenotipoRESUMEN
The orexins (hypocretins) play a crucial role in arousal, feeding and reward. Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward. Orexin A/hypocretin 1 (oxA/hcrt-1) can enable long-term changes associated with drugs of abuse; however, the effects of orexin B/hypocretin 2 (oxB/hcrt-2) on excitatory synaptic transmission in the VTA are unknown. We used whole-cell patch-clamp electrophysiology in rat horizontal midbrain slices to examine the effects of oxB/hcrt-2 on excitatory synaptic transmission. We observed that oxB/hcrt-2 has distinct effects from oxA/hcrt-1 in the VTA. oxB/Hcrt-2 (100 nM) increased presynaptic glutamate release in addition to a postsynaptic potentiation of NMDA receptors (NMDARs). The oxB/hcrt-2-mediated postsynaptic potentiation of NMDARs was mediated via activation of orexin/hypocretin 2 (OX2/Hcrt-2) receptors and protein kinase C (PKC). Furthermore, the increase in transmitter release probability was also PKC-dependent, but not through activation of orexin/hypocretin 1 (OX1/Hcrt-1) or OX2/Hcrt-2 receptors. Finally, oxB/hcrt-2 or the selective OX2/Hcrt-2 receptor agonist ala(11)-D-leu(15)-orexin B, significantly reduced spike-timing-induced long-term potentiation. Taken together, these results support a dual role for oxB/hcrt-2 in mediating enhanced glutamatergic transmission in the VTA, and suggest that oxA/hcrt-1 and oxB/hcrt-2 exert different functional roles in modulating the enhancement of the motivational components of arousal and feeding.
Asunto(s)
Ácido Glutámico/metabolismo , Área Hipotalámica Lateral/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuronas/metabolismo , Neuropéptidos/metabolismo , Transmisión Sináptica/fisiología , Área Tegmental Ventral/metabolismo , Animales , Apetito/fisiología , Nivel de Alerta/fisiología , Área Hipotalámica Lateral/citología , Péptidos y Proteínas de Señalización Intracelular/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Vías Nerviosas/citología , Vías Nerviosas/metabolismo , Neuropéptidos/farmacología , Receptores de Orexina , Orexinas , Técnicas de Cultivo de Órganos , Técnicas de Placa-Clamp , Fragmentos de Péptidos/farmacología , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Proteína Quinasa C/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de Neuropéptido/agonistas , Receptores de Neuropéptido/metabolismo , Transmisión Sináptica/efectos de los fármacos , Área Tegmental Ventral/citologíaRESUMEN
Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. One of the skin expressed gap junction genes is GJB2, which codes for connexin 26 and is associated with a wide variety of keratinisation disorders. Here, we report on a family with a novel GJB2 mutation (p.His73Arg) causing a syndrome of focal palmoplantar keratoderma with severe progressive sensorineural hearing impairment, a phenotype reminiscent of Vohwinkel syndrome. Using fluorescent connexin fusion proteins, we show that the mutation induces a transport defect similar to that found for the Vohwinkel syndrome mutation p.Asp66His. Co-transfection into cells expressing wild type connexin26 shows that the mutant has a dominant negative effect on connexin trafficking. We suggest that there may be a weak genotype-phenotype correlation for mutations in GJB2.
Asunto(s)
Conexinas/genética , Conexinas/metabolismo , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/genética , Queratodermia Palmoplantar/complicaciones , Queratodermia Palmoplantar/genética , Mutación Missense , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Conexina 26 , Secuencia Conservada , Cartilla de ADN/genética , ADN Complementario/genética , Femenino , Uniones Comunicantes/metabolismo , Genotipo , Células HeLa , Pérdida Auditiva Sensorineural/metabolismo , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Queratodermia Palmoplantar/metabolismo , Queratodermia Palmoplantar/patología , Masculino , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Linaje , Fenotipo , Transporte de Proteínas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Aminoácido , Síndrome , TransfecciónRESUMEN
Oculo-dento-digital dysplasia (ODDD, OMIM no.164210) is a pleiotropic disorder caused by mutations in the GJA1 gene that codes for the gap junction protein connexin 43. While the gene is highly expressed in skin, ODDD is usually not associated with skin symptoms. We recently described a family with ODDD and palmoplantar keratoderma. Interestingly, mutation carriers had a novel dinucleotide deletion in the GJA1 gene that resulted in truncation of part of the C-terminus. We speculated, that truncation of the C-terminus may be uniquely associated with skin disease in ODDD. Here, we describe a patient with ODDD and palmar hyperkeratosis caused by a novel dinucleotide deletion that truncates most of the connexin 43 C-terminus. Thus, our findings support the notion that such mutations are associated with the occurrence of skin symptoms in ODDD and provide the first evidence for the existence of a genotype-phenotype correlation.
Asunto(s)
Anomalías Múltiples/genética , Conexina 43/genética , Queratosis/genética , Eliminación de Secuencia , Adulto , Análisis Mutacional de ADN , Anomalías del Ojo/genética , Femenino , Humanos , Queratosis/patología , Deformidades Congénitas de las Extremidades/genética , Fenotipo , Anomalías Cutáneas/genética , Sindactilia/genética , Anomalías Dentarias/genéticaRESUMEN
The renewal of Pavlovian-conditioned responses may provide a model for the relapse of fear following extinction-based treatments for anxiety disorders. Renewal can be observed if conditional stimulus (CS) and unconditional stimulus (US) pairings are given in one context, extinction trials of CS presentations in a second context, prior to test trials of CS presentations in the original acquisition context (ABA renewal). We examined ABA renewal in humans by using a fear-conditioning procedure with an unpleasant shock US. A renewal of rated shock expectancy was demonstrated with this procedure. Conducting extinction treatment in multiple contexts was expected to attenuate the renewal effect. However, the renewal of shock expectancy persisted when extinction treatment was given across three or five different contexts. With the current renewal design, learning task, and measure of conditioned behaviour, extinction treatment does not appear to readily generalise to the test context. The use of multiple extinction treatments in a clinical setting may not necessarily reduce the likelihood of relapse via a renewal effect.
Asunto(s)
Condicionamiento Clásico , Extinción Psicológica , Miedo/psicología , Adolescente , Adulto , Electrochoque/psicología , Femenino , Respuesta Galvánica de la Piel/fisiología , Generalización Psicológica , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/métodos , RecurrenciaRESUMEN
Cominicamos nuestra experiencia en remplazo vesical con distintos segmentos del tracto gastro intestinal. Efectuamos un estudio retrospectivo en aquellos pacientes que requirieron de algún tipo de derivación urinaria entre mayo de 1991 y agosto 2001. Se analizaron las indicaciones quirúrgicas, el tipo y la evolución clínic de estas derivaciones. El grupo de estudio se compuso de 29 pacientes que fueron sometidos a 30 cirugías de sustitución vesical: nueve (30 por ciento), Indiana pouch, ocho (26,6 por ciento), reservorios ileales uretras, ocho (26,6 por ciento), cistoplastias ileales, tres (19 por ciento) gastrocistoplastias, una (3,4 por ciento), cistoplastia con sigmoides y un (4,4 por ciento), reservorio ileal de Studer. La mortalidad perioperatoria fue de 6,6 por ciento (2 pacientes), y la morbilidad global de 26,4 por ciento (8 pacientes). Las derivaciones urinarias ofrecen en la actualidad técnicas operatorias seguras al paciente aunque no exentas de morbimortalidad y probablemente debemos establecer una selección de los casos clínicos más óptimos para el tratamiento quirúrgico.
Asunto(s)
Humanos , Derivación Urinaria/instrumentación , Derivación Urinaria/métodos , Procedimientos Quirúrgicos del Sistema Digestivo , Técnicas de InvestigaciónRESUMEN
Comunicamos nuestra experiencia en el tratamiento quirúrgico radical del Cáncer de Próstata. Revisamos la historia de 100 pacientes sometidos a Prostatectomía Radical Retropúbica en 10 años (1991-2000). Alizamos las principales características clínicas y patológicas. El período de seguimiento fue de 3 años en promedio (0,5-9). la edad media de los pacientes fue 64,6 años (51-79). El PSA preoperatorio fue de 18:79ng/ml (1,3-70). Un 54 por ciento de los pacientes presentó estadio patológico pT2, un 22 por ciento pT3 y un 24 por ciento pN1. La sobrevida cáncer específica fue 96 por ciento en estadios pT2, 90 por ciento en estadios pT3 y 89 por ciento en estadios pN1. La Prostatectomía Radical Retropública es, en nuestra experiencia, una técnica segura, baja mortalidad perioperatoria y es un muy buen tratamiento para el cáncer prostático aún en casos localmente extendidos.
Asunto(s)
Humanos , Masculino , Próstata , Neoplasias de la Próstata , ProstatectomíaRESUMEN
The use of transcatheter uterine artery embolization as a treatment for uterine fibroids represents a new approach to the management of this common problem. Early reports of uterine artery embolization as a treatment of symptomatic fibroids have indicated significant symptomatic improvement as well as reduction in the size of fibroids. We have been performing this procedure for two years at the Christiana Care Hospital. We describe two representative cases with clinical follow up on 12 of our patients and briefly review the literature on uterine artery embolization for uterine fibroids.
Asunto(s)
Embolización Terapéutica/métodos , Leiomioma/terapia , Neoplasias Uterinas/terapia , Adulto , Angiografía , Femenino , Humanos , Leiomioma/diagnóstico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Uterinas/diagnóstico , Útero/irrigación sanguíneaRESUMEN
A functional skeletal system requires the coordinated development of many different tissue types, including cartilage, bones, joints, and tendons. Members of the Bone morphogenetic protein (BMP) family of secreted signaling molecules have been implicated as endogenous regulators of skeletal development. This is based on their expression during bone and joint formation, their ability to induce ectopic bone and cartilage, and the skeletal abnormalities present in animals with mutations in BMP family members. One member of this family, Growth/differentiation factor 5 (GDF5), is encoded by the mouse brachypodism locus. Mice with mutations in this gene show reductions in the length of bones in the limbs, altered formation of bones and joints in the sternum, and a reduction in the number of bones in the digits. The expression pattern of Gdf5 during normal development and the phenotypes seen in mice with single or double mutations in Gdf5 and Bmp5 suggested that Gdf5 has multiple functions in skeletogenesis, including roles in joint and cartilage development. To further understand the function of GDF5 in skeletal development, we assayed the response of developing chick and mouse limbs to recombinant GDF5 protein. The results from these assays, coupled with an analysis of the development of brachypodism digits, indicate that GDF5 is necessary and sufficient for both cartilage development and the restriction of joint formation to the appropriate location. Thus, GDF5 function in the digits demonstrates a link between cartilage development and joint development and is an important determinant of the pattern of bones and articulations in the digits.
Asunto(s)
Proteínas Morfogenéticas Óseas , Huesos/embriología , Sustancias de Crecimiento/fisiología , Articulaciones/embriología , Proteínas del Tejido Nervioso , Proteínas Represoras , Dedos del Pie/embriología , Transactivadores , Proteínas de Xenopus , Animales , Proteínas de Unión al Calcio/metabolismo , Cartílago/embriología , Cartílago/metabolismo , Embrión de Pollo , Colágeno/metabolismo , Colágeno Tipo II , Proteínas de Unión al ADN/metabolismo , Factor 5 de Diferenciación de Crecimiento , Proteínas Hedgehog , Hibridación in Situ , Factores de Transcripción de Tipo Kruppel , Ratones , Modelos Biológicos , Técnicas de Cultivo de Órganos , Proteínas/metabolismo , Factores de Tiempo , Factores de Transcripción/metabolismo , Alas de Animales/metabolismo , Proteína Gli3 con Dedos de ZincRESUMEN
The mouse brachypodism locus encodes a bone morphogenetic protein (BMP)-like molecule called growth/differentiation factor 5 (GDF5). Here we show that Gdf5 transcripts are expressed in a striking pattern of transverse stripes within many skeletal precursors in the developing limb. The number, location and time of appearance of these stripes corresponds to the sites where joints will later form between skeletal elements. Null mutations in Gdf5 disrupt the formation of more than 30% of the synovial joints in the limb, leading to complete or partial fusions between particular skeletal elements, and changes in the patterns of repeating structures in the digits, wrists and ankles. Mice carrying null mutations in both Gdf5 and another BMP family member, Bmp5, show additional abnormalities not observed in either of the single mutants. These defects include disruption of the sternebrae within the sternum and abnormal formation of the fibrocartilaginous joints between the sternebrae and ribs. Previous studies have shown that members of the BMP family are required for normal development of cartilage and bone. The current studies suggest that particular BMP family members may also play an essential role in the segmentation process that cleaves skeletal precursors into separate elements. This process helps determine the number of elements in repeating series in both limbs and sternum, and is required for normal generation of the functional articulations between many adjacent structures in the vertebrate skeleton.
Asunto(s)
Tipificación del Cuerpo/genética , Proteínas Morfogenéticas Óseas/genética , Huesos/anomalías , Sustancias de Crecimiento/genética , Articulaciones/anomalías , Animales , Factor 5 de Diferenciación de Crecimiento , Deformidades Congénitas de las Extremidades , Ratones , Ratones Endogámicos , Ratones Mutantes , Fenotipo , Esternón/anomalíasAsunto(s)
Huesos/anomalías , Huesos/embriología , Proteínas/fisiología , Animales , Evolución Biológica , Proteínas Morfogenéticas Óseas , Regulación del Desarrollo de la Expresión Génica , Sustancias de Crecimiento/fisiología , Ratones , Ratones Mutantes , Mutación , Fenotipo , Biosíntesis de Proteínas , VertebradosRESUMEN
Using video-enhanced microscopy and a pulse-radiolabeling paradigm, we show that proteins synthesized in the medial giant axon cell body of the crayfish (Procambarus clarkii) are delivered to the axon via fast (approximately 62 mm/day) and slow (approximately 0.8 mm/day) transport components. These data confirm that the medial giant axon cell body provides protein to the axon in a manner similar to that reported for mammalian axons. Unlike mammalian axons, the distal (anucleate) portion of a medial giant axon remains intact and functional for > 7 months after severance. This axonal viability persists long after fast transport has ceased and after the slow wave front of radiolabeled protein has reached the terminals. These data are consistent with the hypothesis that another source (i.e., local glial cells) provides a significant amount of protein to supplement that delivered to the medial giant axon by its cell body.
Asunto(s)
Astacoidea/metabolismo , Axones/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Axones/ultraestructura , Transporte Biológico , Desnervación , Orgánulos/metabolismo , Factores de TiempoRESUMEN
Protein maintenance and degradation are examined in the severed distal (anucleate) portions of crayfish medial giant axons (MGAs), which remain viable for over 7 months following axotomy. On polyacrylamide gels, the silver-stained protein banding pattern of anucleate MGAs severed from their cell bodies for up to 4 months remains remarkably similar to that of intact MGAs. At 7 months postseverance, some (but not all) proteins are decreased in anucleate MGAs compared to intact MGAs. To determine the half-life of axonally transported proteins, we radiolabeled MGA cell bodies and monitored the degradation of newly synthesized transported proteins. Assuming exponential decay, proteins in the fast component of axonal transport have an average half-life of 14 d in anucleate MGAs and proteins in the slow component have an average half-life of 17 d. Such half-lives are very unlikely to account for the ability of anucleate MGAs to survive for over 7 months after axotomy.
Asunto(s)
Axones/fisiología , Proteínas del Tejido Nervioso/metabolismo , Actinas/metabolismo , Animales , Astacoidea , Transporte Biológico , Supervivencia Celular , Desnervación , Factores de Tiempo , Tubulina (Proteína)/metabolismoRESUMEN
The mutation brachypodism (bp) alters the length and number of bones in the limbs of mice but spares the axial skeleton. It illustrates the importance of specific genes in controlling the morphogenesis of individual skeletal elements in the tetrapod limb. We now report the isolation of three new members of the transforming growth factor-beta (TGF-beta) superfamily (growth/differentiation factors (GDF) 5,6 and 7) and show by mapping, expression patterns and sequencing that mutations in Gdf5 are responsible for skeletal alterations in bp mice. GDF5 and the closely related GDF6 and GDF7 define a new subgroup of factors related to known bone- and cartilage-inducing molecules, the bone morphogenetic proteins (BMPs). Studies of Bmp5 mutations in short ear mice have shown that at least one other BMP gene is also required for normal skeletal development. The highly specific skeletal alterations in bp and short ear mice suggest that different members of the BMP family control the formation of different morphological features in the mammalian skeleton.