036) and potency (P < 0.0001).

The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16.”
“The human and mouse homologs of the rat thyroid hormone responsive protein (THRP), c-abl-interacting protein 2 (Abi-2), are critically involved in neurological development. The Abi-2 gene is evolutionarily conserved invertebrates, and is also found in Xenopus laevis and Drosophila melanogaster. The THRP gene is one of the few genes regulated by thyroid hormone in adult animals. Sequence analysis of the 5′-flanking region of the THRP gene identified a putative thyroid selleck screening library hormone response element (TRE) that is conserved between rat and human. To determine whether or not THRP regulates neural growth and development, THRP was constitutively expressed in transgenic X. laevis. Growth of most animals was halted in early neurulation while the few animals that survived the process developed into grossly malformed

tadpoles. In contrast, control animals reached late embryonic stage 25. These observations suggest that THRP overexpression in early development is not compatible with completion of early embryogenesis and that a different strategy needs to be employed to investigate THRP function in this model. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The 86-kDa immediate-early this website 2 (IE2) protein of human cytomegalovirus (HCMV) is a promiscuous transactivator essential for viral gene expression. IE2 is covalently modified by SUMO at two lysine residues (K175 and K180) and also interacts noncovalently

with SUMO. Although SUMOylation of IE2 has been shown to enhance its transactivation activity, the role of SUMO binding is not clear. Here we showed that SUMO binding by IE2 is necessary for its efficient transactivation function and for viral growth. IE2 bound physically to SUMO-1 through a SUMO-interacting motif (SIM). Mutations in SIM (mSIM) or in both SUMOylation sites and SIM (KR/mSIM), significantly reduced IE2 transactivation effects on Dichloromethane dehalogenase viral early promoters. The replication of IE2 SIM mutant viruses (mSIM or KR/mSIM) was severely depressed in normal human fibroblasts. Analysis of viral growth curves revealed that the replication defect of the mSIM virus correlated with low-level accumulation of SUMO-modified IE2 and of viral early and late proteins. Importantly, both the formation of viral transcription domains and the association of IE2 with viral promoters in infected cells were significantly reduced in IE2 SIM mutant virus infection.