Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis

Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development.     

Genetic variation in selenoprotein S influences inflammatory response

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.     

Short-lived orogenic cycles and the eclogitization of cold crust by spasmodic hot fluids

Collision tectonics and the associated transformation of continental crust to high-pressure rocks (eclogites) are generally well-understood processes, but important contradictions remain between tectonothermal models and petrological-isotopic data obtained from such rocks. Here we use 40Ar-39Ar data coupled with a thermal model to constrain the time-integrated duration of an orogenic cycle (the burial and exhumation of a particular segment of the crust) to be less than 13 Myr. We also determine the total duration of associated metamorphic events to be approximately 20 kyr, and of individual heat pulses experienced by the rocks to be as short as 10 years. Such short timescales are indicative of rapid tectonic processes associated with catastrophic deformation events (earthquakes). Such events triggered transient heat advection by hot fluid along deformation (shear) zones, which cut relatively cool and dry subducted crust. In contrast to current thermal models that assume thermal equilibrium and invoke high ambient temperatures in the thickened crust, our non-steady-state cold-crust model satisfactorily explains several otherwise contradictory geological observations.     

Organizing for Research and Action: Implementing Action Researcher Networks

The article describes and analyzes the process by which action researchers transcend boundaries—including discipline and institutional boundaries, as well as those between academia and industry—to develop effective action researcher networks. The particular empirical setting explored is that defined by the CO-IMPROVE project, a European Union-funded project which addresses the facilitation of collaborative improvement of operations practice and performance in the extended manufacturing enterprise through collaborative action learning among both managers and researchers.     

Fluorescein-concanavalin A conjugates distinguish between normal and malignant human cells: A preliminary report

Summary A method is described for using a fluorescein isothiocyanate concanavalin A conjugate to stain human cell membranes in formalin fixed paraffin embedded tissue. 57 neoplastic and normal tissue sites were examined. In 34 malignant tumours, bright green fluorescence was confined to the cell membranes while in 23 benign tumours and normal tissue sites, the membranes were unstained or showed a diminished level of fluorescence. The distinction between malignant and hyperplastic or normal cells was clear cut and definite.     

Recherches sur la fraction Y des protéines de muscles de Lapin

Summary The proteinic material corresponding toDubuisson's electrophoretic gradient has been prepared by a new method. This fraction migrates as a single peak in the U-tube, but is heterogeneous in the ultra-centrifugation.     

Autoradiographic localization of 5-hydroxytryptamine in monkey pineal gland

Zusammenfassung Die Verteilung von aus 5-Hydroxy-Tryptophan entstandenem Serotonin in der Zirbeldrüse von Affen wird beschrieben.     

Polyvinylchloride (PVC) particles implantation in mouse liver. A technique for experimental study of schistosome eggs-induced liver pathology

Summary An injection of suspended PVC particles in the caecal vein of mice induces a foreign-body portal granuloma reaction in the liver. Plastic casts of the portal system, after PVC particles implantation, show modifications in the portal bed and are compared with plastic casts obtained in mice infested bySchistosoma mansoni. This technique can be useful to study the cellular dynamics of the portal granuloma and can be a model for schistosomal eggs induced liver pathology.This work was supported by an ATP (INSERM) 18.75.41 and a scholarship from the Société d'Hépatologie Expérimentale.