Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.     

Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.     

Corticosteroidogenesis by isolated human adrenal cells: Effect of serotonin and serotonin antagonists

Summary The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid-particularly cortisol and aldosterone-biosynthesis.The authors are indebted to Dr. M. Kárteszi, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, for the determination of plasma ACTH by radioimmunoassay in our patients, and to Prof. P. Vecsei, Department of Pharmacology, University of Heidelberg, providing us with highly specific antisera for corticosteroids RIA-s.     

Serendipitous precise and unique staining of cell nuclei

Zusammenfassung Frischgefrorene Gewebesektionen verschiedener Gewebe wurden in Kalium-Eisen-Cyanid bei pH 5,2 inkubiert; dabei wurde eine präzise und einzigartige Färbung nur der Zellnuklei beobachtet. Die Ursache dieser selektiven Kernfärbung ist nicht verständlich, doch stellt sie höchstwahrscheinlich eine Färbung von Ferro-Verbindungen in den Nuklei dar.

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This investigation was supported in part by Public Health Service Research Grants Nos. CA 02624 and CA 02903 from the National Cancer Institute and in part by an institutional grant to the Detroit Institute of Cancer Research Division of the Michigan Cancer Foundation from the United Foundation of Greater Detroit, and Detroit General Hospital Research Corporation. Newaygo County Cancer Association. We wish to express our gratitude for stenographic assistance to Mrs.Georgette M. Bellmay.     

The indigogenic reaction for histochemical demonstration of alkaline and acid phosphatase

Résumé Le principe indigogénique à la détection histochimique des phosphates alcalins et acides a été appliqué. Ces substrates ont l'avantage de permettre une localisation précise de l'enzyme, sans ou avec minime diffusion. C'est aussi une méthode simple et directe pour la mise en évidence de ces enzymes sans passer par une réaction couplée. Un bisindigo très insoluble a lieu apparaît aux points d'activité enzymatique. Le 5-bromo-4-chlorocomposé donne un indigo bleu-vert tandis que le 5-bromo-6-chloro-composé donne un indigo magenta.     

Eine Methode zur drahtlosen Messung der Atemfrequenz and Säuglingen A Method for Wireless Telemetry of Breath-Frequency of Babies

Summary A device is introduced which allows a continuous wireless registration of breath frequency of babies.