Two Novel Fish Paralogs Provide Insights Into the Rid Family of Imine Deaminases Active in Pre-Empting enamine/imine Metabolic Damage

Reactive Intermediate Deaminase (Rid) protein superfamily includes eight families among which the RidA is conserved in all domains of life. RidA proteins accelerate the deamination of the reactive 2-aminoacrylate (2AA), an enamine produced by some pyridoxal phosphate (PLP)-dependent enzymes. 2AA accumulation inhibits target enzymes with a detrimental impact on fitness. As a consequence of whole genome duplication, teleost fish have two ridA paralogs, while other extant vertebrates contain a single-copy gene. We investigated the biochemical properties of the products of two paralogs, identified in Salmo salar. SsRidA-1 and SsRidA-2 complemented the growth defect of a Salmonella enterica ridA mutant, an in vivo model of 2AA stress. In vitro, both proteins hydrolyzed 2-imino acids (IA) to keto-acids and ammonia. SsRidA-1 was active on IA derived from nonpolar amino acids and poorly active or inactive on IA derived from other amino acids tested. In contrast, SsRidA-2 had a generally low catalytic efficiency, but showed a relatively higher activity with IA derived from L-Glu and aromatic amino acids. The crystal structures of SsRidA-1 and SsRidA-2 provided hints of the remarkably different conformational stability and substrate specificity. Overall, SsRidA-1 is similar to the mammalian orthologs whereas SsRidA-2 displays unique properties likely generated by functional specialization of a duplicated ancestral gene

Gender and Administration

Summary Public administration in development has been a poor instrument for implementing gender policies. Rural development administration in particular has tended to be indifferently accountable to female ‘publics’ in agrarian economies. Conventionally, this particular feature of institutional failure is explained by the suggestion that public administrations reflect gender relations in society. This paper, however, argues that the role of public administration in the organization of gender provokes questions about the gender of organization. It sketches out the conceptual premises for a theory of the gender of organization, looking at the way organizational structures, cultures, and purposes institutionalize male dominance. This perspective may help illuminate the processes and relationships through which other inequalities, such as those of class, race, and the North?South divide, are reproduced in public administration. Résumé Le Genre et l'insuccès des institutions dans le développement: l'organisation du Genre et le Genre dans l'organisation Au sein du développement, les administrations publiques ont constitué un outil peu utile pour la mise en oeuvre des politiques relatives au genre. Les administrations de développement rural notamment ont eu tendance à comptabiliser de manière indifférente les ‘publics’ féminins dans les économies agraires. Classiquement, et notoirement, cette caractéristique de l'insuccès des institutions est expliquée par la suggestion que les administrations publiques reflètent les rapports entre les genres dans la société. Le présent article, par contre, revendique que le rôle des administrations publiques dans l'organisation des genres soulève certaines questions le genre dans l'organisation même. L'auteur ébauche les prémisses d'une éventuelle théorie du genre dans l'organisation, et examine comment les structures, les cultures et les objectifs mêmes de ces organisations tendent à institutionnaliser la dominance masculine. Cette perspective veut aider à mettre en lumière des procédés et des rapports par l'influence desquels d'autres inégalités, par exemples celles des classes, des races et du partage nord?sud, viennent à se reproduire dans les administrations publiques. Resumen El Género y las fallas institucionales en el desarrollo: la organización del género y el género de la organización La administración pública en el desarrollo ha sido un instrumento muy pobre para la implementación de criterios relativos al género. En las economías agrarias en particular la administración del desarrollo rural tiende a ser poco responsable para con el ‘público’ femenino. Tradicionalmente, este rasgo característico del fracaso institucional se explica sugiriendo que la administración pública refleja las relaciones entre los sexos en la sociedad. Este artículo, sin embargo, argumenta que el papel de la administración pública en la organización del género suscita interrogantes sobre el género de la organización. Se bosquejan las premisas conceptuales para una teoría del género en la organización, analizando la forma en que las culturas, estructuras organizativas y objetivos institucionalizan la dominación masculina. Esta perspectiva puede arrojar luz sobre los procesos y relaciones a través de los cuales otras desigualdades — clase, raza, la división Norte?Sur — se reproducen en la administración pública

Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition

Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4

An extensive theoretical study is performed for wide bandgap crystalline oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}: $\alpha$-quartz, $\alpha$- and $\beta$-cristobalite and stishovite, for GeO_{2}: $\alpha$-quartz, and rutile, for Al_{2}O_{3}: $\alpha$-phase, for Si_{3}N_{4} and Ge_{3}N_{4}: $\alpha$- and $\beta$-phases. This work constitutes a comprehensive account of both electronic structure and the elastic properties of these important insulating oxides and nitrides obtained with high accuracy based on density functional theory within the local density approximation. Two different norm-conserving \textit{ab initio} pseudopotentials have been tested which agree in all respects with the only exception arising for the elastic properties of rutile GeO_{2}. The agreement with experimental values, when available, are seen to be highly satisfactory. The uniformity and the well convergence of this approach enables an unbiased assessment of important physical parameters within each material and among different insulating oxide and nitrides. The computed static electric susceptibilities are observed to display a strong correlation with their mass densities. There is a marked discrepancy between the considered oxides and nitrides with the latter having sudden increase of density of states away from the respective band edges. This is expected to give rise to excessive carrier scattering which can practically preclude bulk impact ionization process in Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure

Prevalence, clinical investigation, and management of gallbladder disease in Rett syndrome

AIM: This study determined the prevalence of cholelithiasis and/or cholecystectomy in Rett syndrome, described gallbladder function in a clinical cohort, and identified recommendations for assessment and management of gallbladder disease. METHOD The incidence of cholelithiasis/cholecystectomy was estimated from data describing 270 and 681 individuals with a pathogenic MECP2 mutation in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database respectively. Gallbladder function in 25 females (mean age 16y 5mo, SD 20y 7mo, range 3y 5mo–47y 10mo) with Rett syndrome (RTT) was evaluated with clinical assessment and ultrasound of the gallbladder. The Delphi technique was used to develop assessment and treatment recommendations. RESULTS: The incidence rate for cholelithiasis and/or cholecystectomy was 2.3 (95% confidence interval [CI] 1.1–4.2) and 1.8 (95% CI 1.0–3.0) per 1000 person-years in the Australian and International Databases respectively. The mean contractility index of the gallbladder for the clinical sample was 46.5% (SD 38.3%), smaller than for healthy individuals but similar to children with Down syndrome, despite no clinical symptoms. After excluding gastroesophageal reflux, gallbladder disease should be considered as a cause of abdominal pain in RTT and cholecystectomy recommended if symptomatic. INTERPRETATION: Gallbladder disease is relatively common in RTT and should be considered in the differential diagnosis of abdominal pain in RTT

Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models

Cyclin-dependent-like kinase 5 (Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signaling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder

Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis

Background: Rheumatoid arthritis (RA) and periodontitis are both chronic inflammatory diseases, which demonstrate similarities in terms of mechanism, histopathology, and demography. An association between these conditions has been demonstrated previously but has been called into question more recently. Methods: The published databases, such as MEDLINE, EMBASE, and PsycINFO, were searched using search terms related to RA and periodontitis. Articles were selected if they included data on the number of people with RA diagnosed with periodontitis (or periodontal disease parameters) compared to a control comparison group. Review articles, case reports, animal model studies, non-English language, and articles with unavailable abstracts were excluded. Data were extracted, critically appraised using the Downs and Black tool, and a random-effect Mantel–Haenszel meta-analysis was performed. Results: Twenty-one papers met the eligibility criteria and provided data for the meta-analysis; 17 studies (including a total of 153,492 participants) comparing RA to healthy controls and 4 (including a total of 1378 participants) comparing RA to osteoarthritis (OA). There was a significantly increased risk of periodontitis in people with RA compared to healthy controls (relative risk: 1.13; 95% CI: 1.04, 1.23; p = 0.006; N = 153,277) with a significantly raised mean probing depth, risk of bleeding on probing (BOP), and absolute value of clinical attachment loss in those with RA. When comparing RA and OA, there was no significant difference in the prevalence of periodontitis; however, the risk of BOP was greater in OA than RA. Conclusion: A significant association between RA and periodontitis is supported by the results of our systematic review and meta-analysis of studies comparing RA to healthy controls. In our meta-analysis, however, this is not replicated when comparing RA to OA controls

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states