Airway inflammation frequently found in congenital and mice efficiently transfected primarily the lungs and to a acquired lung diseases may interfere with gene delivery by lesser extent, heart, spleen, kidney and liver. The other direct administration through either instillation or aerosol.vectors mediated lower to undetectable levels of luciferase Systemic delivery by the intravenous administration repexpression in the lungs, with DOTAP Ͼ GL67/DOPE Ͼ PEI resents an alternative route of delivery that might bypass 25K Ͼ DOTMA/DOPE. A double injection protocol with a this barrier. A nonviral approach for transfecting various 15-min interval between the two doses of DOTAP/DNA airway-derived cell lines in vitro showed that cationic polycomplexes was investigated and showed a relevant role of mers (PEI 22K and 25K) and lipids (DOTAP, GL-67/DOPE) the first injection in transfecting the lungs. A two log are able to transfect with high efficiency the reporter genes increase in luciferase expression was obtained either when firefly luciferase and E. coli lacZ. Notably, two properties the two doses were comprised of luciferase plasmid or predicted that cationic vectors would be useful for a syswhen an irrelevant plasmid was used in the first injection. temic gene delivery approach to the lung: (1) transfectionThe double injection of luciferase/PEI 22K complexes was not inhibited or increased when cells were incubated determined higher transgene levels than a single dose, but with cationic lipids or polymers in the presence of serum; a clear difference using an irrelevant plasmid as first dose and (2) cationic vectors protected plasmid DNA from was not observed. Using lacZ as a reporter gene, it was DNase degradation. A single injection of DNA complexed shown that only cells in the alveolar region, including type II to the cationic polymer PEI 22K into the tail vein of adult penumocytes, stained positively for the transgene product.

No abstract

The processes of neurite extension and remodeling require a close coordination between the cytoskeleton and the cell membranes. The small GTPase ARF6 (ADP-ribosylation factor 6) has a central role in regulating membrane traffic and actin dynamics, and its activity has been demonstrated to be involved in neurite elaboration. EFA6A has been shown to act as a guanine nucleotide exchange factor (GEF) for ARF6. Here, we report that two distinct isoforms of the EFA6A gene are expressed in murine neural tissue: a long isoform of 1025 amino acids (EFA6A), and a short isoform of 393 amino acids (EFA6As). EFA6A encompasses proline-rich regions, a Sec7 domain (mediating GEF activity on ARF6), a PH domain, and a C-terminal region with coiled-coil motifs. EFA6As lacks the Sec7 domain, and it comprises the PH domain and the C-terminal region. The transcript encoding EFA6As is the result of alternative promoter usage. EFA6A and EFA6As have distinct biological activities: upon overexpression in HeLa cells, EFA6A induces membrane ruffles, whereas EFA6As gives rise to cell elongation; in primary cortical neurons EFA6A promotes neurite extension, whereas EFA6As induces dendrite branching. Our findings suggest that EFA6A could participate in neuronal morphogenesis through the regulated expression of two functionally distinct isoforms.

This research was stimulated by the need to extend in time the record of Italy's largest earthquakes, which commonly have repeat times of the same order as the length of the available historical record. As a test case we used the 1908 Straits of Messina earthquake, a large event that geologists assume to recur at intervals of roughly a millennium but whose predecessors are as yet unknown. The 1908 earthquake caused enormous territorial upheaval and left signs in the settlements that are still largely recognizable today. We hypothesized that the Straits of Messina, which were densely populated even in ancient times, may similarly retain evidence of one or more much older 'upheavals' of the settlement network, and that this evidence may be recognized through a careful analysis of archaeological observations. We found evidence that the settled area around the Straits of Messina contracted substantially around the middle of the fourth century AD, when many sites were abandoned or relocated. This contraction can hardly be justified by the then current economic and military setting. Specific archaeological findings within the cities of Messina and Reggio Calabria also suggest a serious decline of the region during the same period. The archaeological hypothesis is in good agreement with the available historical and palaeoseismological evidence and suggests that a large earthquake, perhaps similar to the 1908 event, took place in the area surrounding the Straits of Messina around the middle of the fourth century AD.One of the most important findings of earthquake studies in Italy over the past decade is that the repeat time of individual large earthquakes is of the order of one or more millennia. Similar results had previously been obtained for many seismic areas in the world, but the frequency of large historical earthquakes in Italy had brought seismologists to the conclusion that Italian earthquakes repeated themselves every few centuries or so. Some Italian cities indeed appear to have been struck several times in their history, but results supplied by palaeoseismology (a recently developed discipline aimed at uncovering and dating any direct surface evidence of large earthquakes of the past) suggest that this is due to multiplicity of destructive seismogenic sources rather than to the frequency with which individual sources generate large earthquakes (see, e.g. Boschi et al. 1994).

To investigate whether transcription factors of the NF‐κB family could play a role in early mammalian development, we have analyzed the expression of nfkb1, nfkb2, c‐Rel, RelA, RelB, and bcl‐3 from 6.5‐ to 10.5‐day mouse embryo implantation sites. Our study shows that nfkb2 mRNA and protein are specifically localized in trophoblast giant cells throughout the stages analyzed. Trophoblast giant cells obtained upon in vitro cultures of 7.5‐day ectoplacental cones display NF‐κB DNA‐binding activity that is supershifted by the anti‐NF‐κB2 antibody. Trophoblast giant cells are embryo‐derived cells that form an interface between embryonic and maternal tissues during early mouse development; they are involved in decidual remodeling and expansion of the embryonic cavity, placenta formation, and possibly avoidance of maternal immune response to the embryo. Our study suggests that NF‐κB2 could play a role in the modulation of genes expressed in trophoblast giant cells during the course of early embryogenesis, and therefore be relevant for tissue remodeling and morphogenesis of placenta. Dev. Genet. 25:23–30, 1999. © 1999 Wiley‐Liss, Inc.