RESUMEN
BACKGROUND: We examined social approachability judgments in a psychiatric population that frequently experiences interpersonal difficulties and reduced social satisfaction, individuals with generalized social phobia (gSP). METHODS: Our objective was to broaden the understanding of the social cognitive tendencies of individuals with gSP by systematically investigating their interpretation of positive facial expressions. We hypothesized that approachability ratings would be lower for positive as well as negative emotional faces in the gSP group compared to the healthy comparison group. Each participant evaluated 24 emotional faces presented on a computer screen. Participants first labeled the faces as either happy, disgust, or angry in emotional expression, and then they rated each face's approachability. Analysis of variance and post hoc analyses were used to identify group, emotion, and group by emotion rating differences. RESULTS: Happy face approachability ratings were higher than disgust and anger in both groups. The central finding was that individuals with gSP rated happy faces as less approachable than the healthy participants and that degree of social anxiety was associated with lower approachability ratings within the gSP sample. Explicit approachability judgments of negative faces did not differ as predicted. CONCLUSIONS: Consistent with earlier indirect evidence of interpretation biases of positive social emotional information, this study reveals that individuals with gSP demonstrate explicit, subjective social interpretation biases of overtly positive social feedback. The therapeutic relevance of these results is discussed.
Asunto(s)
Felicidad , Relaciones Interpersonales , Juicio , Trastornos Fóbicos/psicología , Percepción Social , Adulto , Cultura , Emociones , Expresión Facial , Retroalimentación , Femenino , Humanos , Masculino , Motivación , Reconocimiento Visual de Modelos , Trastornos Fóbicos/diagnóstico , Distancia Psicológica , Adulto JovenAsunto(s)
Causalgia/terapia , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Complicaciones Posoperatorias/terapia , Estimulación Eléctrica Transcutánea del Nervio , Ganglio del Trigémino/cirugía , Neuralgia del Trigémino/terapia , Adulto , Vías Aferentes/fisiopatología , Causalgia/fisiopatología , Cara/inervación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Umbral del Dolor/fisiología , Complicaciones Posoperatorias/fisiopatología , Umbral Sensorial/fisiología , Piel/inervación , Ganglio del Trigémino/fisiopatología , Neuralgia del Trigémino/fisiopatologíaRESUMEN
During mosquito transmission, malaria ookinetes must cross a chitin-containing structure known as the peritrophic matrix (PM), which surrounds the infected blood meal in the mosquito midgut. In turn, ookinetes produce multiple chitinase activities presumably aimed at disrupting this physical barrier to allow ookinete invasion of the midgut epithelium. Plasmodium chitinase activities are demonstrated targets for human and avian malaria transmission blockade with the chitinase inhibitor allosamidin. Here, we identify and characterize the first chitinase gene of a rodent malaria parasite, Plasmodium berghei. We show that the gene, named PbCHT1, is a structural ortholog of PgCHT1 of the avian malaria parasite Plasmodium gallinaceum and a paralog of PfCHT1 of the human malaria parasite Plasmodium falciparum. Targeted disruption of PbCHT1 reduced parasite infectivity in Anopheles stephensi mosquitoes by up to 90%. Reductions in infectivity were also observed in ookinete feeds-an artificial situation where midgut invasion occurs before PM formation-suggesting that PbCHT1 plays a role other than PM disruption. PbCHT1 null mutants had no residual ookinete-derived chitinase activity in vitro, suggesting that P. berghei ookinetes express only one chitinase gene. Moreover, PbCHT1 activity appeared insensitive to allosamidin inhibition, an observation that raises questions about the use of allosamidin and components like it as potential malaria transmission-blocking drugs. Taken together, these findings suggest a fundamental divergence among rodent, avian, and human malaria parasite chitinases, with implications for the evolution of Plasmodium-mosquito interactions.
Asunto(s)
Anopheles/parasitología , Quitinasas/genética , Eliminación de Gen , Plasmodium berghei/enzimología , Plasmodium berghei/patogenicidad , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Quitinasas/metabolismo , Interacciones Huésped-Parásitos , Malaria/parasitología , Datos de Secuencia Molecular , Plasmodium berghei/genética , Plasmodium berghei/crecimiento & desarrollo , Análisis de Secuencia de ADNRESUMEN
The major packaging signal of human immunodeficiency virus type 1 (HIV-1) RNA has been localised to the region 3' to the major splice donor within the leader sequence. Secondary structural studies for this region of the HIV-1 genome have shown the existence of a stem-loop structure capped by a purine-rich tetraloop. Extensive mapping data presented here lead to the complete characterisation of the structure of the stem-loop, including a new purine-rich internal loop in the lower part of the structure and the previously established GGAG tetraloop at its tip. Biochemical analysis reveals that both internal loop and tetraloop are primary sites for interaction with Gag polyprotein, and that binding of Gag protein leads to a conformational change which alters the RNA structure. NMR spectroscopy has been used to determine the three-dimensional structure of this complete stem-loop structure. The structural analysis reveals a significant difference between the apical part of the stem-loop structure, which adopts a well-defined conformation, and the purine-rich internal loop, which is instead very flexible. In contrast to what is generally observed for internal loop structures in RNA, this region of the encapsidation signal adopts a structure lacking stable interstrand interactions capable of stabilising a unique conformation. We suggest that the stem-loop structure represents a nucleation site for Gag protein binding, and that the protein exploits the flexibility of the internal loop to initiate the unwinding of the structure with successive addition of Gag molecules interacting with the RNA and each other through conserved I (interaction) domains.
Asunto(s)
Productos del Gen gag/metabolismo , VIH-1/genética , Conformación de Ácido Nucleico , ARN Viral/química , ARN Viral/metabolismo , Ensamble de Virus/genética , Secuencia de Aminoácidos , Emparejamiento Base/genética , Sitios de Unión , Secuencia Conservada/genética , Genoma Viral , VIH-1/fisiología , Modelos Moleculares , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Docilidad , Unión Proteica , Purinas/metabolismo , Estabilidad del ARN , ARN Viral/genética , ADN Polimerasa Dirigida por ARN/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Ribonucleasas/metabolismoAsunto(s)
Clonación Molecular/métodos , Enzimas de Restricción del ADN/metabolismo , Biblioteca de Genes , Vectores Genéticos , Aphthovirus/genética , Cartilla de ADN/genética , ADN Polimerasa Dirigida por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , Nucleótidos de Desoxiadenina/metabolismo , Polimorfismo de Longitud del Fragmento de Restricción , Moldes GenéticosRESUMEN
The occurrence of many subtypes within a serotype of foot-and-mouth disease virus (FMDV) makes it difficult to control the disease by vaccination. Although inactivated vaccines are used successfully in many countries, the appearance in the field of antigenic variants against which the vaccines do not confer protection is a constant problem in vaccine manufacture. We had found previously a mixture of antigenic variants in a field isolate of serotype A12. In this report we demonstrate the presence of two variants in a plaque-isolate from this mixture. The second variant was detected only when the growth conditions were altered. Our observation points to the problems which may be encountered in the large scale growth of a virus for vaccine production.
Asunto(s)
Variación Antigénica/inmunología , Antígenos Virales/genética , Aphthovirus/aislamiento & purificación , Ensayo de Placa Viral , Vacunas Virales/genética , Secuencia de Aminoácidos , Animales , Animales Domésticos/inmunología , Antígenos Virales/inmunología , Aphthovirus/genética , Aphthovirus/inmunología , Fiebre Aftosa/prevención & control , Datos de Secuencia Molecular , Vacunas Virales/biosíntesis , Vacunas Virales/inmunologíaRESUMEN
A foot-and-mouth disease virus mutant which is stable at pH 6.4 has been isolated from a virus of serotype A. In contrast to the parent (P) virus, which gave a mixture of large and small plaques in BHK21 cells and in a bovine kidney cell line, the acid-resistant (AR) virus gave small plaques which did not increase markedly in size after 24 hr. The infectivity titer of the acid-resistant virus was about 100-fold lower in suckling mice than in BHK21 cells, whether the inoculation was made intraperitoneally or intracerebrally, whereas the parent virus gave similar titers in both systems. Furthermore, in mice the AR virus reached its end point two to three times more slowly. The diameter of the AR virus was almost 20% less than that of the P virus and it had a more distinct topography, but the two viruses cosedimented in sucrose gradients. However, the buoyant density in CsCl of the AR virus was slightly lower (1.42 compared with 1.43 g/cc) in coruns. The RNAs and capsid proteins of the two viruses gave similar profiles in sucrose gradients and by SDS-PAGE, respectively. However, isoelectric focusing of the capsid proteins revealed considerable differences between the two viruses. Whereas the P virus gave four protein bands, corresponding to VP1-VP4, the AR virus gave one band for VP4, two for VP3, two for VP2, and four for VP1. Sequence analysis of the genes coding for the capsid protein regions of the two viruses showed four changes (one silent), resulting in an Ala-3-->Ser substitution in VP1 and Glu-131-->Lys and Asp-133-->Ser substitutions in VP2.
Asunto(s)
Aphthovirus/genética , Mutación , Animales , Animales Lactantes , Aphthovirus/fisiología , Aphthovirus/ultraestructura , Línea Celular , Cricetinae , Electroforesis en Gel de Poliacrilamida , Concentración de Iones de Hidrógeno , Focalización Isoeléctrica , Ratones , Microscopía Electrónica , Análisis de Secuencia , Proteínas no Estructurales Virales/genética , Replicación ViralRESUMEN
A subgenomic cDNA clone from human rhinovirus 14 (HRV-14), comprising the 5' non-coding region and the first 1182 nucleotides of the coding sequence, has been inserted into a vector under the control of the T7 promoter, and RNA was transcribed. Deletions in the 5' non-coding sequence modulated viral polyprotein synthesis significantly in a reticulocyte lysate system. Removal of the first 491 nucleotides had little effect, but deletion of a further 55 nucleotides (491 to 546) significantly increased the efficiency of the translation process. Further deletion to nucleotide 621 almost abolished translation, suggesting an essential role for the 546 to 621 nucleotide sequence. The efficiency of the translation process can also be influenced by the addition of ribosomal salt wash prepared from uninfected HeLa cells.