The presence of astrocytes enhances beta amyloid-induced neurotoxicity in hippocampal cell cultures.

A characteristic feature of neuritic plaques in Alzheimer's disease is represented by the presence of activated astrocytes, surrounding dystrophic neurons and beta-amyloid deposition. To explore the role of astrocytes in in vitro beta-amyloid neurotoxicity, we studied the effect of beta-amyloid treatment in hippocampal neurons in two different cell models: pure cultures, where neurons were grown in absence of astrocytes and mixed cultures, where neurons were seeded on a confluent layer of astrocytes. We evaluated two characteristic aspects of in vitro beta-amyloid neurotoxicity: reduction of cell viability and degeneration of the neuritic tree. We demonstrated that neurons growing on astrocytes were more prone to the detrimental effect of the amyloid peptide, with respect to neurons grown in absence of the glial component. Our results support the hypothesis that beta-amyloid-astrocyte interaction can adversely condition neurons and contribute to neuronal damage in Alzheimer's disease.

[Circadian biological clocks: molecular self-generating mechanisms which keep the rhythm]. / Orologi biologici circadiani: meccanismi molecolari autorigeneranti che mantengono il ritmo.

Biological circadian clocks are endogenous self-sustaining oscillators, where periodically expressed genes control functions at all levels of biological organization. These mechanisms are detectable from prokaryotes to humans, and their basic molecular components are common in most living organisms. This review focuses on the basic properties of biological circadian clocks and their possible involvement in human diseases.

A new candidate region for the positional cloning of the XLP gene.

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterised by selective susceptibility to Epstein-Barr virus and frequent association with malignant lymphomas chiefly located in the ileocecal region, liver, kidney and CNS. Taking advantage of a large bacterial clone contig, we obtained a genomic sequence of 197620 bp encompassing a deletion (XLP-D) of 116 kb in an XLP family, whose breakpoints were identified. The study of potential exons from this region in 40 unrelated XLP patients did not reveal any mutation. To define the critical region for XLP and investigate the role of the XLP-D deletion, detailed haplotypes in a region of approximately 20 cM were reconstructed in a total of 87 individuals from 7 families with recurrence of XLP. Two recombination events in a North American family and a new microdeletion (XLP-G) in an Italian family indicate that the XLP gene maps in the interval between DXS1001 and DXS8057, approximately 800 kb centromeric to the previously reported familial microdeletion XLP-D.

Physical map and cosmid contig encompassing a new interstitial deletion of the X-linked lymphoproliferative syndrome region.

The X-linked lymphoproliferative syndrome (XLP) is an inherited immuno-deficiency to Epstein-Barr virus infection that has been mapped to chromosome Xq25. Molecular analysis of XLP patients from ten different families identified a small interstitial constitutional deletion in 1 patient (XLP-D). This deletion, initially defined by a single marker, DF83, known to map to interval Xq24-q26.1, is nested within a previously reported and much larger deletion in another XLP patient (XLP-739). A cosmid minilibrary was constructed from a single mega-YAC and used to establish a contig encompassing the whole XLP-D deletion and a portion of the XLP-739 deletion. Based on this contig, the size of the XLP-D deletion can be estimated at 130 kb. The identification of this minimal deletion, within which at least a portion of the XLP gene is likely to reside, should greatly facilitate efforts in isolating the gene.

cDNA sequence for bovine ribosomal protein L3 carrying a bipartite nuclear targeting motif, identified also in many other ribosomal proteins.

A full-length cDNA encoding bovine ribosomal protein L3 was isolated and sequenced. The deduced protein sequence comprises 403 amino acids and shows a high level of identity with the other known mammalian L3 proteins. Southern blot analysis of bovine genomic DNA suggests that the bovine genome contains at least 4 copies of the L3 gene. A single hybridisation band of about 1.3 kb is detectable by Northern blot analysis. Within the amino acid sequence, two potential nuclear targeting sequences were detected: one at the N-terminal end and the other, consisting in a bipartite motif (amino acids 341 to 358), present and not previously noticed also in the other known mammalian L3 proteins. A search on all the available mammalian ribosomal proteins revealed the presence of this bipartite motif in many of these proteins.

Assignment of the human connexin 32 gene (GJB1) to band Xq13.

The chromosomal localization of the human gene coding for connexin 32 (GJB1) was determined by in situ suppression hybridization (ISSH). The results allowed assignment of the gene to band Xq13, thus refining previous localization data obtained by means of somatic cell hybrid analysis.

Detection of bovine leukaemia virus (BLV) infection by DNA probe technology.

Classical serological methods and Southern blot hybridization for the diagnosis of bovine leukaemia virus (BLV) infection have been compared during the first nine months of life of offspring from BLV serum-negative and serum-positive dams belonging to a Friesian dairy herd in Italy. At birth, 9/13 calves analysed showed serum positivity for anti-gp60 BLV antibodies by agar immunodiffusion and/or by ELISA. However, only two calves were positive for BLV integrated proviruses in their lymphocyte DNA. At six months of age, anti-gp60 BLV antibodies and proviral DNA positivities were simultaneously shown only by the two cattle identified as DNA-positive at birth. This pattern remained constant up to nine months of age. Furthermore, analysis of the molecular characteristics of BLV integrated proviruses, carried out by using, as probes, the almost complete proviral genome (Belgian isolate) or a subclone of the env gene radioactively labelled or chemically modified, revealed that the calves under study were infected by a different isolate (Japanese isolate) and that, in one of the cattle, the majority of integrated proviruses was characterized by deletions probably located in the 5' half of the proviral genome.

Linkage in human heterochromatin between highly divergent Sau3A repeats and a new family of repeated DNA sequences (HaeIII family).

The hybridization of human DNA with three non-cross-hybridizing monomers (68 bp in length) of the heterochromatic Sau3A family of DNA repeats, indicates the coexistence within a Sau3A-positive genomic block of divergent Sau3A units as well as of unrelated sequences. To gain some insight into the structure of these human heterochromatic DNA regions, three previously cloned Sau3A-positive genomic fragments (with a total length of approximately 1900 base-pairs (bp] were sequenced. The analysis of the sequences showed the presence of clustered Sau3A units with different degrees of divergence and of two DNA regions of approximately 100 bp and 291 bp in length, unrelated to the family of repeats. A consensus sequence derived from the 24 identified Sau3A monomers presents, among highly variable regions, two less variant regions of 8 bp and 10 bp in length, respectively. The Sau3A-unrelated DNA fragment 291 bp in length, used as a probe on genomic DNA digested with a series of restriction enzymes, defines a "new" family of DNA repeats possessing periodicities for HaeIII (HaeIII family). Sau3A and HaeIII repeats display a high degree of linkage in a collection of Sau3A-positive genomic recombinant phages.

Goldenhar syndrome: a case report with review of literature.

A case of Goldenhar Syndrome, in an adult male, with the typical triad of auricular appendages, epibulbar dermoid and vertebral anomalies is presented. The relevent literature is review. The differential diagnosis of this Syndrome from a few similar syndromes is stressed.