Spontaneous reversal of ethinyl estradiol-induced cholestasis in the rat

Summary The spontaneous reversal of ethinyl estradiol-induced cholestasis has been documented 7 days after the last estrogen administration in the rat. This finding supports the hypothesis that estrogens produce only a transient functional failure of the hepatocytic structures responsible for bile secretion.Supported by Research grant CT-77, 0153304 from Consiglio Nazionale delle Ricerche, Rome, Italy.     

Effects of ionizing radiation on myelinogenesis in the chicken

Résumé Chez le poulet, l'irradiation (1600 R rayons gamma) retarde la croissance de l'organisme in toto et de plusieurs organes, et affecte sélectivement les constituants individuels de la myéline plutôt que le processus global de myélinisation, l'accumulation de la sphingomyéline étant plus retardée que celle de la cérébroside et du cholestérol.     

Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites

The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A?site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A?site. The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner. Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P?site) on the 30S head and simultaneously establishes interaction with the exit site (E?site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain?IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process.     

Which neurological abnormalities and neuropsychological impairments share the same substrate in psychosis?

Approximately 60% of subjects with schizophrenia present minor neurological signs (neurological soft signs, NSS), which include abnormalities in sensory and motor performance indicative of a non-specific cerebral dysfunction. These are also present in healthy individuals and relatives of patients with psychosis, at significantly lower rates. The excess of NSS in psychosis may be a potential endophenotype for this disorder, and reflect the same neurodevelopmental brain dysfunction that also underlies the cognitive deficits consistently reported in psychosis. To establish whether neurological and cognitive dysfunction meet the essential criterion required for a refined endophenotype for psychosis, the association with the illness, we explored evidence that certain neurological and cognitive deficits co-occur in affected individuals. This evidence suggests that signs of motor dysfunctions may be specific to patients with psychosis, in whom they are associated with dysfunction in cognitive tasks requiring motor skills. Thus, they may form a promising candidate endophenotype for psychosis.     

The endocannabinoid system in rat gliosomes and its role in the modulation of glutamate release

The endocannabinoid system and endocannabinoid receptor-driven modulation of glutamate release were studied in rat brain cortex astroglial gliosomes. These preparations contained the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, as well their major biosynthetic (N-acyl-phosphatidylethanolamines-hydrolyzing-phospholipase D and diacylglycerol-lipase) and catabolic (fatty acid amide-hydrolase and monoacylglycerol-lipase) enzymes. Gliosomes expressed type-1 (CB1R), type-2 (CB2R) cannabinoid, and type-1 vanilloid (TRPV1) receptors, as ascertained by Western blotting and confocal microscopy. Methanandamide, a stable analogue of anandamide acting as CB1R, CB2R, and TRPV1 agonist, stimulated or inhibited the depolarization-evoked gliosomal [³H]d-aspartate release, at lower and higher concentrations, respectively. Experiments with ACEA (arachidonyl-2′-chloroethylamide), JWH133 ((6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]-pyran) and capsaicin, selective agonists at CB1R, CB2R and TRPV1, respectively, demonstrated that potentiation of [³H]d-aspartate release was due to CB1R while inhibition to CB2R and TRPV1 engagement. These findings were confirmed by using selective receptor antagonists. Furthermore, CB1R activation caused increase of intracellular IP3 and Ca²⁺ concentration, suggesting an involvement of phospholipase C.     

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na⁺ channels and amplitude of Ca⁺⁺ currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases.     

Role of kinetin in the dormancy ofCercis siliquastrum seeds

Summary Studies conducted onCercis siliquastrum seeds treated with kinetin confirm that this hormone does not interrupt dormancy in either whole seeds or those decoated at the radical pole. Seeds totally decoated or decoated at the cotyledon pole only demonstrated atypical germinations linked to cotyledon growth, permitting the embryo to escape the inhibitory action present in the endosperm; this does not occur when the cotyledon surface is experimentally reduced.This investigation was supported by the Italian National Research Council (C.N.R.) Project Biology of Reproduction.