Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA.

Long-term expression of coagulation factor IX (FIX) has been observed in murine and canine models following administration of recombinant adeno-associated viral (rAAV) vectors into either the portal vein or muscle. These studies were designed to evaluate factors that influence rAAV-mediated FIX expression. Stable and persistent human FIX (hFIX) expression (> 22 weeks) was observed from 4 vectors after injection into the portal circulation of immunodeficient mice. The level of expression was dependent on promoter with the highest expression, 10% of physiologic levels, observed with a vector containing the cytomegalovirus (CMV) enhancer/beta-actin promoter complex (CAGG). The kinetics of expression after injection of vector particles into muscle, tail vein, or portal vein were similar with hFIX detectable at 2 weeks and reaching a plateau by 8 weeks. For a given dose, intraportal administration of rAAV CAGG-FIX resulted in a 1.5-fold or 4-fold higher level of hFIX compared to tail vein or intramuscular injections, respectively. Polymerase chain reaction analysis demonstrated predominant localization of the rAAV FIX genome in liver and spleen after tail vein injection with a higher proportion in liver after portal vein injection. Therapeutic levels of hFIX were detected in the majority of immunocompetent mice (21 of 22) following intravenous administration of rAAV vector without the development of anti-hFIX antibodies, but hFIX was not detected in 14 immunocompetent mice following intramuscular administration, irrespective of strain. Instead, neutralizing anti-hFIX antibodies were detected in all the mice. These observations may have important implications for hemophilia B gene therapy with rAAV vectors

Crime scene and body alterations caused by arthropods: implications in death investigation

The activity of arthropods on corpses has been largely investigated, since they can produce information to reconstruct the peri-mortem events. However, the feeding/movement activity of insects around the crime scene, among the clothes and on the body, can also cause some alterations that can lead to wrong reconstruction and misinterpretations. This article summarises all the post-mortem arthropods artefacts related to the scene (i.e. fly artefacts and floor stripes) and the body (i.e. skin and other soft tissue alterations, bone alterations and hair alterations) that can mislead the forensic pathologist, discussing macroscopic and microscopic findings derived from forensic casework and from experimental laboratory studies, in order to provide a useful instrument to avoid misinterpretations and evaluation errors. Finally, some procedural notes for the documentation and the interpretation of findings are proposed

Graphene on metals: a Van der Waals density functional study

We use density functional theory (DFT) with a recently developed van der Waals density functional (vdW-DF) to study the adsorption of graphene on Al, Cu, Ag, Au, Pt, Pd, Co and Ni(111) surfaces. In constrast to the local density approximation (LDA) which predicts relatively strong binding for Ni,Co and Pd, the vdW-DF predicts weak binding for all metals and metal-graphene distances in the range 3.40-3.72 \AA. At these distances the graphene bandstructure as calculated with DFT and the many-body G$_0$W$_0$ method is basically unaffected by the substrate, in particular there is no opening of a band gap at the $K$-point.Comment: 4 pages, 3 figure