SUPERFAMILY provides structural, functional and evolutionary information for proteins from all completely sequenced genomes, and large sequence collections such as UniProt. Protein domain assignments for over 900 genomes are included in the database, which can be accessed at http://supfam.org/. Hidden Markov models based on Structural Classification of Proteins (SCOP) domain definitions at the superfamily level are used to provide structural annotation. We recently produced a new model library based on SCOP 1.73. Family level assignments are also available. From the web site users can submit sequences for SCOP domain classification; search for keywords such as superfamilies, families, organism names, models and sequence identifiers; find over- and underrepresented families or superfamilies within a genome relative to other genomes or groups of genomes; compare domain architectures across selections of genomes and finally build multiple sequence alignments between Protein Data Bank (PDB), genomic and custom sequences. Recent extensions to the database include InterPro abstracts and Gene Ontology terms for superfamiles, taxonomic visualization of the distribution of families across the tree of life, searches for functionally similar domain architectures and phylogenetic trees. The database, models and associated scripts are available for download from the ftp site.

Astrocytes are known to be critical regulators of neuronal function. However, relatively few mediators of astrocyte to neuron communication have been identified. Recent advancements in the biology of extracellular vesicles have begun to implicate astrocyte derived extracellular vesicles (ADEV) as mediators of astrocyte to neuron communication, suggesting that alterations in the release and/or composition of ADEVs could influence gliotransmission. TNFα and IL-1β are key mediators of glial activation and neuronal damage, but the effects of these cytokines on the release or molecular composition of ADEVs is unknown. We found that ADEVs released in response to IL-1β (ADEV-IL-1β) and TNFα (ADEV-TNFα) were enriched with miRNAs that target proteins involved in neurotrophin signaling. We confirmed that miR-125a-5p and miR-16-5p (both enriched in ADEV-IL-1β and ADEV-TNFα) targeted NTKR3 and its downstream effector Bcl2. Downregulation of these targets in neurons was associated with reductions in dendritic growth, dendritic complexity, reduced spike rates, and burst activity. Molecular interference of miR-125a-5p and miR-16-5p prevented ADEV-IL-1β from reducing dendritic complexity, spike, and burst rates. These findings suggest that astrocytes respond to inflammatory challenge by modifying the miRNA cargo of ADEVs to diminish the activity of target neurons by regulating the translational expression of proteins controlling programs essential for synaptic stability and neuronal excitability.

The mechanism of CD4 ؉ T-cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4 ؉ T-cell activation. We assumed that the pathogenic process of excessive CD4