Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration

Cyclin-dependent kinase 5 (Cdk5) is required for proper development of the mammalian central nervous system. To be activated, Cdk5 has to associate with its regulatory subunit, p35. We have found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease. This accumulation correlates with an increase in Cdk5 kinase activity. Unlike p35, p25 is not readily degraded, and binding of p25 to Cdk5 constitutively activates Cdk5, changes its cellular location and alters its substrate specificity. In vivo the p25/Cdk5 complex hyperphosphorylates tau, which reduces tau's ability to associate with microtubules. Moreover, expression of the p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis. These findings indicate that cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases.     

Zonaroic acid from the brown seaweedDictyopteris undulata (=zonarioides)

Summary A sesquiterpene-substituted 4-hydroxybenzoic acid, zonaroic acid (5), is described from the brown seaweedDictyopteris undulata (=zonarioides). The absolute stereochemistry in the zonarol (1)-chromazonarol (2) and zonaroic acid (5) series has also been defined. The occurrence of5 along with zonarol (1), the corresponding sesquiterpene-substituted hydroquinone, suggests that 4-hydroxybenzoic acid is the ring precursor as in ubiquinone biogenesis.     

On the ovary development in queenless worker bees (Apis mellifica L.)

Zusammenfassung Gruppen von 50 Jungbienen wurden in kleinen Versuchskäfigen im Thermostaten bei 30°C gehalten und mit Zuckerteig + 15% Pollen gefüttert. Bei Anwesenheit einer Königin entwickelten sich ihre Ovarien nicht. Ohne Königin waren jedoch die Ovarien bei Tötung nach 3 Wochen deutlich entwickelt. Die hemmende Wirkung geht nicht nur von der lebenden Königin aus: auch bei Anwesenheit einer toten Königin unterbleibt die Ovarienentwicklung. Es genügte sogar bloss deren Kopf oder Abdomen; der Thorax hingegen war nicht deutlich wirksam. Für das Zustandekommen der hemmenden Wirkung ist direkter Kontakt jeder einzelnen Arbeiterin mit der Königin bzw. deren erwähnten Körperteilen erforderlich. Mit Alkohol oder Azeton extrahierte Königinnen waren unwirksam; nach Imprägnierung mit der Extraktflüssigkeit wirkten sie wieder hemmend.Aus den Versuchen scheint somit hervorzugehen, dass die Entwicklung der Arbeiterinnen-Ovarien normalerweise deshalb unterbleibt, weil jede einzelne Arbeiterin in direktem Kontakt vom Körper der Königin eine Substanz aufnimmt, welche die Ovarienentwicklung hemmt.     

Occurrence of a physalaemin-like polypeptide (Uperolein) and other active polypeptides in the skin ofUperoleia rugosa

Riassunto Gli estratti metanolici della pelle diUperoleia rugosa, piccolo anfibio australiano, contengono, oltre ad eventuali costituenti attivi minori, due polipeptidi altamente attivi. Il primo è caratterizzato da una intensa azione stimolante sul colon e sull'utero di ratto; il secondo, per il quale viene proposto il nome diuperoleina, è dotato di potente azione ipotensiva nel cane e nel coniglio, di potente azione stimolante sul colon di coniglio e di potente azione scialagoga nel ratto. L'uperoleina è strettamente vicina da un punto di vista biologico, e presumibilmente anche chimico, alla eledoisina e alla fisalemina.     

Effects of prolactin and growth hormone on DNA synthesis of rat mammary carcinomas in vitro

Summary Explants derived from mammary carcinomas of DMBA-treated female Sprague-Dawley rats were cultured for 5 days in Medium 199 containing insulin and corticosterone. The addition of ovine prolactin to the culture media resulted in a consistent significant increase in H³-thymidine incorporation into DNA. DNA synthesis of explants treated with either ovine or human growth hormone was intermediary to prolactin-treated cultures and control cultures. A combination of prolactin and human growth hormone often increased DNA synthesis above either hormone alone, suggesting a possible growth synergism between these peptides.Supported by NIH research grant No. CA-13777 and American Cancer Society research grant No. ET-59.NIH Research Career Development Awardee No. CA-35027.     

Progressive antithrombin activity in rabbit plasma. Role of alpha macroglobulins]

Immunological methods associated with a kinetic study of blood coagulation allowed us to show the influence of the 2 rabbit alpha macroglobulins on the plasma progressive antithrombin activity. This study allowed the authors to discuss the participation of the alpha macroglobulins during the fibrinoformation and to think that these proteins have an immediate antithrombin activity.