Surprisingly, not only did conversion of AAV8 to AAV2 cap sequences increase the transduction efficiency and change tissue tropism but so did the reciprocal conversion of AAV2 to AAV8. Insertion of new peptide

motifs at position 590 in AAV8 also enabled retargeting of AAV8 capsids to specific tissues, suggesting that these sequences can interact with receptors on the cell surface. However, a neutralizing monoclonal antibody that binds to amino acids (588)QQNTA(592) of AAV8 does not prevent cell binding and virus uptake, indicating that this region is not necessary for receptor binding but rather that the antibody interferes with an essential step of postattachment processing in which the 3-fold protrusion is also involved. This study supports a multifunctional role of the 3-fold PS-341 region of AAV capsids in the infection process.”
“Although inhibition plays a major role in the function of the mammalian

neocortex, the circuit connectivity of GABAergic check details interneurons has remained poorly understood. The authors review recent studies of the connections made to and from interneurons, highlighting the overarching principle of a high density of unspecific connections in inhibitory connectivity. Whereas specificity remains in the subcellular targeting of excitatory neurons by interneurons, the general strategy appears to be for interneurons to provide a global “”blanket of inhibition”" to nearby neurons. In the review, the authors highlight the fact that the function of interneurons, which remains elusive, will be informed by understanding the structure of their connectivity as well as the dynamics

of inhibitory synaptic connections. In a last section, the authors describe briefly the link between dense inhibitory networks and different interneuron functions described in the neocortex.”
“STAT4 is an important transcription factor that contributes to the incidence and severity of different autoimmune SB525334 diseases and is implicated in the antiviral immune responses in mice. In this study, we evaluated the role of STAT4 in human and murine herpes simplex virus 2 (HSV-2) infections. We show that STAT4 regulates antiviral gamma interferon (IFN-gamma) responses and disease severity during chronic HSV-2 infections in humans and vaccine-induced IFN-gamma-mediated protection against HSV-2 infection in mice. In a cohort of 228 HSV-2-infected individuals, representing both patients with recurrent disease and asymptomatic HSV-2 carriers, we found that genetic variations in the STAT4 gene were associated with asymptomatic HSV-2 infection, as well as with increased in vitro secretion of IFN-gamma in response to the virus. Mice that lacked STAT4 had impaired HSV-2-specific IFN-gamma production and delayed-type hypersensitivity responses following vaccination, which led to impaired viral clearance in the genital tract of vaccinated animals after a genital HSV-2 challenge.