A Chemosensory Gene Family Encoding Candidate Gustatory and Olfactory Receptors in Drosophila

AbstractA novel family of candidate gustatory receptors (GRs) was recently identified in searches of the Drosophila genome. We have performed in situ hybridization and transgene experiments that reveal expression of these genes in both gustatory and olfactory neurons in adult flies and larvae. This gene family is likely to encode both odorant and taste receptors. We have visualized the projections of chemosensory neurons in the larval brain and observe that neurons expressing different GRs project to discrete loci in the antennal lobe and subesophageal ganglion. These data provide insight into the diversity of chemosensory recognition and an initial view of the representation of gustatory information in the fly brain

SEDLIN Forms Homodimers: Characterisation of SEDLIN Mutations and Their Interactions with Transcription Factors MBP1, PITX1 and SF1

BACKGROUND: SEDLIN, a 140 amino acid subunit of the Transport Protein Particle (TRAPP) complex, is ubiquitously expressed and interacts with the transcription factors c-myc promoter-binding protein 1 (MBP1), pituitary homeobox 1 (PITX1) and steroidogenic factor 1 (SF1). SEDLIN mutations cause X-linked spondyloepiphyseal dysplasia tarda (SEDT). METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of 4 missense (Asp47Tyr, Ser73Leu, Phe83Ser and Val130Asp) and the most C-terminal nonsense (Gln131Stop) SEDT-associated mutations on interactions with MBP1, PITX1 and SF1 by expression in COS7 cells. Wild-type SEDLIN was present in the cytoplasm and nucleus and interacted with MBP1, PITX1 and SF1; the SEDLIN mutations did not alter these subcellular localizations or the interactions. However, SEDLIN was found to homodimerize, and the formation of dimers between wild-type and mutant SEDLIN would mask a loss in these interactions. A mammalian SEDLIN null cell-line is not available, and the interactions between SEDLIN and the transcription factors were therefore investigated in yeast, which does not endogenously express SEDLIN. This revealed that all the SEDT mutations, except Asp47Tyr, lead to a loss of interaction with MBP1, PITX1 and SF1. Three-dimensional modelling studies of SEDLIN revealed that Asp47 resides on the surface whereas all the other mutant residues lie within the hydrophobic core of the protein, and hence are likely to affect the correct folding of SEDLIN and thereby disrupt protein-protein interactions. CONCLUSIONS/SIGNIFICANCE: Our studies demonstrate that SEDLIN is present in the nucleus, forms homodimers and that SEDT-associated mutations cause a loss of interaction with the transcription factors MBP1, PITX1 and SF1

Comparative genomics of the eukaryotes

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease

Indicaciones de episiotomía en maternidades públicas de Neuquén, Argentina

Las indicaciones para realizar episiotomía en los partos vaginales es un tema controvertido que requere revisión en todas partes del mundo. En 1995, en la provincia de Neuquén, Argentina, se elaboraron normas para la atención del parto de bajo riesgo, una de las cuales recomendaba reservar la episiotomía para los casos de alto riesgo de desgarro. Este estudio de cohortes retrospectivo se diseñó con objeto de comparar los criterios que se utilizaron en 1996 como indicación de episiotomía en los centros de maternidad del subsector público de esa provincia así como el efecto de la paridad y otras variables en la frecuencia de esa intervención. Se examinaron 7 513 registros del Sistema Informático Perinatal, que representan 70% del total de partos atendidos ese año. Se excluyeron 830 correspondientes a partos por cesárea. Los 6683 registros restantes se dividieron en ocho grupos según la institución donde se atendió el parto. Se calcularon las tasas de incidencia de episiotomía en esos grupos y se realizó una regresión de Poisson a fin de ajustar las tasas por peso al nacer de los niños, paridad y edad de la madre, y forma de presentación y de terminación del parto. Tomando al Hospital Neuquén como base por ser el más complejo y atenderse allí el mayor número de partos, dos hospitales tuvieron incidencias de episiotomía correspondientes a 70% (IC95%, 62 a 79) y 67% (IC95%, 57 a 78) de las de ese hospital. Otros dos hospitales tuvieron incidencias más altas que el Neuquén por 28% (IC95%, 13 a 45) y 17% (IC95%, 2 a 35), mientras que en los hospitales restantes no se observaron diferencias significativas. Mediante regresión estratificada según el número de partos vaginales previos, se observó que la variable con mayor efecto en la indicación de episiotomía fue la paridad. En las nulíparas, las tasas no mostraron diferencias según el lugar donde se atendió el parto, pero en las primíparas sí hubo diferencia, aun más marcada en las multíparas. Se concluyó que todos los establecimientos incluidos en el estudio realizaban episiotomía casi de rutina en las parturientas nulíparas, que hay diferencias significativas en cuanto a su indicación en primíparas y que estas se incrementan con la paridad. Esas diferencias parecen indicar que en los centros de maternidad públicos de la provincia de Neuquén se están siguiendo distintos criterios en la indicación de episiotomía

Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication

Objective: There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R).Method: The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview.Results: Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder.Conclusions: These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice