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Deficits in language are a core feature of autism. The superior temporal gyrus (STG) is involved in auditory processing, including language, but also has been implicated as a critical structure in social cognition. It was hypothesized that subjects with autism would display different size-function relationships between the STG and intellectual-language-based abilities when compared to controls. Intellectual ability was assessed by either the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) or Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), where three intellectual quotients (IQ) were computed: verbal (VIQ), performance (PIQ), and full-scale (FSIQ). Language ability was assessed by the Clinical Evaluation of Language Fundamentals-Third Edition (CELF-3), also divided into three index scores: receptive, expressive, and total. Seven to 19-year-old rigorously diagnosed subjects with autism (n = 30) were compared to controls (n = 39; 13 of whom had a deficit in reading) of similar age who were matched on education, PIQ, and head circumference. STG volumes were computed based on 1.5 Tesla magnetic resonance imaging (MRI). IQ and CELF-3 performance were highly interrelated regardless of whether subjects had autism or were controls. Both IQ and CELF-3 ability were positively correlated with STG in controls, but a different pattern was observed in subjects with autism. In controls, left STG gray matter was significantly (r = .42, p < or = .05) related to receptive language on the CELF-3; in contrast, a zero order correlation was found with autism. When plotted by age, potential differences in growth trajectories related to language development associated with STG were observed between controls and those subjects with autism. Taken together, these findings suggest a possible failure in left hemisphere lateralization of language function involving the STG in autism.

). Blockage of NS3 protease activity therefore is expected to inhibit HCV replication by both direct suppression of viral protein production as well as by restoring host responsiveness to IFN. Using structure-assisted design, a ketoamide inhibitor, SCH 503034, was generated which demonstrated potent (overall inhibition constant, 14 nM) time-dependent inhibition of the NS3 protease in cell-free enzyme assays as well as robust in vitro activity in the HCV replicon system, as monitored by immunofluorescence and real-time PCR analysis. Continuous exposure of repliconbearing cell lines to six times the 90% effective concentration of SCH 503034 for 15 days resulted in a greater than 4-log reduction in replicon RNA. The combination of SCH 503034 with IFN was more effective in suppressing replicon synthesis than either compound alone, supporting the suggestion of Foy and coworkers that combinations of IFN with protease inhibitors would lead to enhanced therapeutic efficacy.

ALE-1, a homologue of lysostaphin, is a peptidoglycan hydrolase that specifically lyses Staphylococcus aureus cell walls by cleaving the pentaglycine linkage between the peptidoglycan chains. Binding of ALE-1 to S. aureus cells through its C-terminal 92 residues, known as the targeting domain, is functionally important for staphylolytic activity. The ALE-1-targeting domain belongs to the SH3b domain family, the prokaryotic counterpart of the eukaryotic SH3 domains. The 1.75 Å crystal structure of the targeting domain shows an all-␤ fold similar to typical SH3s but with unique features. The structure reveals patches of conserved residues among orthologous targeting domains, forming surface regions that can potentially interact with some common features of the Gram-positive cell wall. ALE-1-targeting domain binding studies employing various bacterial peptidoglycans demonstrate that the length of the interpeptide bridge, as well as the amino acid composition of the peptide, confers the maximum binding of the targeting domain to the staphylococcal peptidoglycan. Truncation of the highly conserved first 9 N-terminal residues results in loss of specificity to S. aureus cell wall-targeting, suggesting that these residues confer specificity to S. aureus cell wall.Lysostaphin, a peptidoglycan hydrolase, is secreted by Staphylococcus simulans biovar staphylolyticus to preferentially lyse the interpeptide bridge of the S. aureus cell wall (1-3). The enzyme can potentially be used as an antibiotic against drug-resistant S. aureus as it has been shown by both in vitro and in vivo studies to act against staphylococcal infections (4 -7). The lysostaphin proenzyme displays a three-domain modular design: an N-terminal domain of tandem repeats, a central zinc-containing metalloprotease catalytic domain, and a C-terminal targeting domain. Upon maturation, the tandem repeats are removed, leaving only the catalytic domain and the targeting domain in the mature lysostaphin (8). The C-terminal portion of lysostaphin, consisting of 92 amino acids, is thought to be the targeting domain that directs the interaction of lysostaphin with S. aureus cell walls (9). A mutant lysostaphin lacking the targeting domain loses both its abilities to bind to staphylococci and to distinguish between host cells and target cells (9). This kind of targeting domain can be found among other types of peptidoglycan hydrolases, for example, the C terminus of N-acetylmuramyl-L-alanine amidases and the N terminus of glucosaminidase, both of which are products of the S. aureus autolysin proenzyme Atl (10). These domains have been shown to direct autolysin to the equatorial surface ring of S. aureus (11). Fragments of this consensus sequence can also be mapped to some proteins secreted by other bacterial species, such as zoocin A produced by Streptococcus equi subsp. zooepidemicus, which is thought to be involved in cell wall recognition and binding (12).The targeting domain belongs to the recently identified prokaryotic SH3b domain family, the prokaryotic counter...

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