Induction of antigen-specific tolerance by hepatic AAV immunotherapy regardless of T cell epitope usage or mouse strain background.

In vivo induction of antigen (Ag)-specific regulatory T cells (Treg) is considered the holy grail of therapeutic strategies for restoring tolerance in autoimmunity. Unfortunately, in the autoimmune disease multiple sclerosis, an effective and durable therapy targeting the diverse repertoire of emerging Ags without compromising the patient's natural immunity has remained elusive. To address this deficiency, we have developed an Ag-specific adeno-associated virus (AAV) immunotherapy that will restore tolerance in a Treg-dependent manner. Using multiple strains of mice with different genetic and immunological backgrounds, we demonstrate that a liver directed AAV vector expressing a single transgene can prevent experimental autoimmune encephalomyelitis from developing and effectively mitigate pre-existing or established disease that was induced by one or more auto-reactive myelin oligodendrocyte glycoprotein-derived peptides. Overall, the results suggests that AAV can efficiently restore Ag-specific immune tolerance to an immunogenic protein that is neither restricted by the major histocompatibility complex haplotype, nor by the specific antigenic epitope(s) presented. These findings may pave the way for developing a comprehensive Ag-specific immunotherapy that does not require prior knowledge of the specific immunogenic epitopes and that may prove to be universally applicable to all MS patients, and adaptable for other autoimmune diseases.

Response of benthic macroinvertebrates to dam removal in the restoration of the Boardman River, Michigan, USA.

Dam removal is an increasingly important method of stream restoration, but most removal efforts are under-studied in their effects. In order to better understand the effects of such removals on the stream ecosystem, we examined changes in stream macroinvertebrate communities from 2011-2016. Comparisons were focused above, below, and before and after the October 2012 removal of the Brown Bridge Dam on the Boardman River in Michigan (USA), as well as to new channel sites created in its former reservoir (2013-2015). Using linear mixed-effect models on the percent abundance of ecologically sensitive taxa (% Ephemeroptera, Plecoptera, Trichoptera (EPT)), total density of all macroinvertebrates, overall taxa richness, and Functional Feeding Groups, along with multivariate analyses on the community matrix, we examined differences in community composition among sites and years. EPT declined downstream of the dam immediately after dam removal, but recovered in the second year, becoming dominant within 2-4 years. Downstream sites before removal had different community composition than upstream sites and downstream sites after removal (p<0.001), while upstream and downstream sites after removal converged towards similarity. New channel (restored) %EPT, density, and taxa richness were not different from upstream sites in any year following removal, but new channel sites were the most distinct in community composition, possessing multiple indicator taxa characteristic of unique new conditions. The invasive New Zealand mud snail (Potamopyrgus antipodarum) was absent from all sites prior to dam removal, but appeared at low densities in upstream sites in 2013, had spread to all sites by 2015, and showed large increases at all sites by 2016. Managers employing dam removal for stream restoration should include post-removal monitoring for multiple years following removal and conduct risk analysis regarding potential effects on colonization of invasive invertebrate species.

A case of idiopathic GGT elevation with acute hepatitis A.

Ursodeoxycholic acid modifies the bile acid pool and its effect on lowering liver enzymes is well documented in certain cases like chronic hepatitis but on the other hand it is known to worsen when given in advanced stages of liver disease. Also, it's effects are still unknown for variety of liver insults. We hereby report a case of Idiopathic Gamma Glutaryl Transferase (GGT) elevation which responded well to Ursodeoxycholic acid.