A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation

Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase IIβ and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase IIβ and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose-response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63. Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase IIβ and that treatment with a proteasome inhibitor reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver disease.     

MODELLING RANDOM CONVEX SETS

A model is developed for convex-set valued data,which are the Minkowski sum of aconvex parameter set and a convex noise set.This model is generalized to include location and scaleparameters.A further generalization results in a model for convex sets which is analogous to aone-way analysis of variance models.In each case,estimators of the parameters are given which,under certain conditions,are shown to be consistent.Data generated from the model and theestimators are studied.An outlier detection method is examined.     

Some new data concerning effect of actinomycin D on early chick embryos

Zusammenfassung Actinomycin D führte beim Hühnerembryo zu einer deutlichen Hemmung der Herzentwicklung nach Inkubation im Nährmedium während der Entwicklungsstadien 3 und 3⁺. Nach Vorbehandlung der Stadien 3–7 und anschliessender Kultur in actinomycin D-freiem Medium fanden sich Fehlbildungen von Herz, ZNS und Somiten, die in ihrer Häufigkeit von den betroffenen Entwicklungsphasen abhängig sind.

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This study was supported by a grant from the Rutgers University Research Council No. 07-2189.     

Histone hydrolase in tadpole liver

Résumé Le cytoplasme du foie de têtard contient une enzyme qui hydrolyse spécifiquement les protéines basiques telle que la polylysine, la protamine et les histones. L'addition d'autres protéines telles que l'albumine, la globuline et l'acide polyglutamique inhibe l'activité de cette enzyme. Les résultats obtenus montrent que cette hydrolysase extraite du foie de têtard diffère des cathépsines ou de l'histone-hydrolase du rein de rat.

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This work was supported by research grants from the National Institute of Arthritis and Metabolic Diseases No. AM 09602, National Science Foundation No. GB-22663 and from the National Cancer Institute No. CA 07174.     

Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior

Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing.