Differences in two-component signal transduction proteins among the genus Brucella: Implications for host preference and pathogenesis

et al.Two-component systems (TCSs) are the predominant bacterial signal transduction mechanisms. Species of the genus Brucella are genetically highly related and differ mainly in mammalian host adaptation and pathogenesis. In this study, TCS proteins encoded in the available genome sequences of Brucella species have been identified using bioinformatic methods. All the Brucella species share an identical set of TCS proteins, and the number of TCS proteins in the closely related opportunistic human pathogen Ochrobactrum anthropi was higher than in Brucella species as expected from its lifestyle. O. anthropi lacks orthologs of the Brucella TCSs NodVW, TceSR and TcfSR, suggesting that these TCS proteins could be necessary for the adaptation of Brucella as an intracellular pathogen. This genomic analysis revealed the presence of a differential distribution of TCS pseudogenes among Brucella species. Moreover, there were also differences in TCS pseudogenes between strains belonging to the same Brucella species, and in particular between B. suis biovars 1 and 2.This work has been supported by research project GEN2006-27843-E of the MEC and by Institutional Grants from the Universidad Pública de Navarra.Peer reviewe

Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006–2010

Introduction: Global developmental delay (GDD) and intellectual disability (ID) are common reasons for consultation in paediatric neurology. Results from aetiological evaluations of children with GDD/ID vary greatly, and consequently, there is no universal consensus regarding which studies should be performed. Material and method: We review our experience with determining aetiological diagnoses for children with GDD/ID who were monitored by the paediatric neurology unit over the 5-year period between 2006 and 2010. Results: During the study period, 995 children with GDD/ID were monitored. An aetiological diagnosis was established for 309 patients (31%), but not in 686 (69%), despite completing numerous tests. A genetic cause was identified in 142 cases (46% of the total aetiologies established), broken down as 118 cases of genetic encephalopathy and 24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile spasms/West syndrome, or visual deficit, but more difficult in cases of autism spectrum disorders. Genetic studies provide an increasing number of aetiological diagnoses, and they are also becoming the first step in diagnostic studies. Array CGH (microarray-based comparative genomic hybridisation) is the genetic test with the highest diagnostic yield in children with unexplained GDD/ID. Discussion: The cost-effectiveness of complementary studies seems to be low if there are no clinically suspected entities. However, even in the absence of treatment, aetiological diagnosis is always important in order to provide genetic counselling and possible prenatal diagnosis, resolve family (and doctors’) queries, and halt further diagnostic studies. Resumen: Introducción: El retraso global del desarrollo (RGD) y la discapacidad intelectual (DI) son motivos de consulta frecuentes en la práctica neuropediátrica. El rendimiento de los estudios diagnósticos en niños con RGD/DI varía ampliamente y, en consecuencia, no hay acuerdo universal respecto a los estudios que se deben realizar. Material y método: Revisamos nuestra experiencia en el diagnóstico etiológico de los niños con RGD/DI valorados en la consulta de Neuropediatría durante un periodo de 5 años: 2006-2010. Resultados: Durante el periodo de estudio fueron valorados 995 niños con RGD/DI. El diagnóstico etiológico fue establecido en 309 (31%) y no en 686 (69%), a pesar de múltiples estudios realizados. En 142 niños, el 46% de los casos con diagnóstico etiológico establecido, la causa es genética: 118 encefalopatías genéticas y 24 enfermedades metabólicas hereditarias. Nuestros datos indican que establecer un diagnóstico etiológico es más fácil cuando el RGD/DI está asociado a parálisis cerebral infantil, epilepsia, espasmos infantiles/síndrome de West o déficit visual, pero más difícil en casos de trastorno del espectro autista. Los estudios genéticos están incrementando los diagnósticos etiológicos y constituyéndose en el primer escalón de estudio. El microarray comparative genomic hybridisation es la prueba con mayor rentabilidad diagnóstica en el estudio de RGD/DI. Discusión: El coste-efectividad de los exámenes complementarios es aparentemente bajo en ausencia de orientación clínica. Incluso en ausencia de tratamiento, el diagnóstico etiológico es importante para establecer un consejo genético y posible diagnóstico prenatal, resolver cuestiones a padres y profesionales, y cesar la realización de más pruebas complementarias. Keywords: Global developmental delay, Intellectual disability, Microarray comparative genomic hybridisation, Palabras clave: Retraso psicomotor global, Discapacidad intelectual, Diagnóstico etiológico, Microarray comparative genomic hybridisatio

No todo es epilepsia

Los eventos paroxísticos son un motivo muy frecuente de consulta en pediatría. Se diferencian dos grandes grupos: epilepsia (1% de la población pediátrica) y trastornos paroxísticos no epilépticos. Hasta un 20% de este segundo grupo es remitido a consultas especializadas para descartar epilepsia de difícil contro

Protocolo de actuación ante las deformidades craneales en las consultas de pediatría de atención primaria, neuropediatría y neurocirugía

The protocol under the title «Deformities in the skull and consultations Neuropediatrics Neurosurgery» consensus was for the services of Neuropediatrics, Neurosurgery and Pediatrics primary care. The protocol was submitted to pediatricians primary Scientific Meeting organized by the Pediatric Society of Aragon, La Rioja and Soria (Spars) with sponsorship from the Spanish Society of Pediatrics and Primary Care extrahospital (SEPEAP) of the Spanish Association of Pediatrics dated 8-5-08. It was approved by the Technology Committee of the Hospital Miguel Servet dated 17-6-08 with identificativo Z2-076 protocol. Its aim is to improve the «continuum of care» to a growing problem in our society.We should be understood as a working tool for its best use, and in fact is a true reflection of the original, which follows the format of clinical protocols approved by the Technology Committee of the Hospital Miguel Servet.El protocolo con el título «Deformidades craneales en las consultas de Neuropediatría y Neurocirugía» ha sido consensuado por los servicios de Neuropediatría, Neurocirugía y Pediatría de Atención Primaria. Este protocolo fue presentado a los pediatras de primaria en Reunión Científica organizada por la Sociedad de Pediatría de Aragón, La Rioja y Soria (SPARS) con el patrocinio de la Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria (SEPEAP) de la Asociación Española de Pediatría con fecha 8-5-08. Fue aprobado por la Comisión de Tecnología del Hospital Miguel Servet con fecha 17-6-08 con el identificativo de protocolo Z2-076. Su objetivo no es otro que mejorar el «continuum asistencial» ante una problemática creciente en nuestra sociedad. Creemos debe entenderse como una herramienta de trabajo para su mejor aprovechamiento, y de hecho es un fiel reflejo del original, que sigue el formato de Protocolos Clínicos aprobado por la Comisión de Tecnología del Hospital Miguel Servet

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordPlants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.The work by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The project was supported by European funds (European Regional Development Fund, ERDF), the Spanish Ministerio de Economía y Competitividad (BIO2005-25029-E, BIO2015-67148-R), and the Regional Government (Junta de Andalucía, P06-CVI-01650) to L.M.C.; Conacyt (Mexico) (FORDECYT-2012-02-193512) to A.H.-E.; the US National Science Foundation (MCB-0920581) to A.I.; and the Czech Science Foundation (13-33039S) to M.E

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication.

Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes