Scalarolbutenolide,a new sesterterpenoid from the marine spongeSpongia nitens

Summary A new sesterterpenoid, scalarolbutenolide (5), has been isolated from the marine spongeSpongia nitens; its structure, including the absolute stereochemistry, has been established by chemical and spectroscopic studies.This work is a part of the Progetto Finalizzato per l'Oceanografia e i Fondi Marini, C.N.R., Roma.We are indebted to A. Crispino, C. Di Pinto, G. Scognamiglio and R. Turco for their technical assistance.     

Anti-muscarinic activity of a family of C11N5 compounds isolated fromAgelas sponges

In a search for potential target sites for C₁₁N₅ compounds obtained from marine sponges of the genusAgelas we evaluated their interaction with muscarinic acetylcholine receptors from rat brain membranes. In competition experiments with³H-QNB these compounds displayed the following rank order of potency: sceptrin>oroidindibromosceptrinclathrodin. Sceptrin (50 M) was shown to be a competitive inhibitor of³H-QNB binding as revealed by Scatchard analysis. The results demonstrate the ability of these compounds to interact with multiple target molecules in the micromolar range.     

Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.     

Expression of multidrug resistance (mdr) gene(s) in primary lymphoid organs of chicken immune system during embryonic development

The presence of a multidrug resistance (MDR) related protein, P-170, in normal and pathological lymphoid cells has been described. The present report evaluates the expression of themdr 1 gene by using the reverse Polymerase Chain Reaction (PCR) on cells obtained from the thymus and bursa of chicken embryos starting from day 12 until hatching. Results show that the thymic cells are positive from day 12 to the end of the observation period. In contrast,mdr mRNA was detected in the bursa from day 14 to day 17 of embryonic life. Possible relationships between the expression ofmdr and the development of T and B lymphocytes are discussed.     

Effect of glomerulopressin on the lymphatic hearts of the toad,probably mediated by prostaglandins

Summary Glomerulopressin acts on the lymphatic hearts of toads: increasing the passage of T-1824 from the abdominal lymphatic sac to the veins in normal animals, but not in toads treated with indomethacin.