Sensitivity of primary R5 HTV-1 to inhibition by RANTES correlates with sensitivity to small-molecule R5 inhibitors

In approximately 50% of HIV-1 subtype B-infected individuals, progression to AIDS is preceded by the emergence of CXCR4-using (X4) variants, whereas the rest progress to AIDS in the presence of CCR5-using (R5) variants only. In a previous study, we showed that during disease progression in the presence of R5 variants only, HIV-1 variants emerge with a decreased sensitivity to inhibition by RANTES, a natural ligand of CCR5 that inhibits cellular entry of R5 variants. This observation was of potential clinical relevance as HIV-1 small-molecule R5 entry inhibitors are a new class of drugs that, in analogy to RANTES, target the binding and subsequent entry of HIV into the target cell. Here we show that R5 HIV-1 sensitivity to RANTES correlates with sensitivity to the R5 small-molecule inhibitor AD101. HIV-1 small-molecule entry inhibitors are a new class of drugs that target the binding and subsequent entry of HIV into the target cell. Furthermore, we found that R5 variants obtained from individuals who later developed X4 variants were less sensitive to AD101 inhibition compared with R5 variants obtained from individuals who never developed X4 variants. These results may have implications for the evaluation of R5 inhibitors in future clinical trial

Ribonuclease H1 maps to chromosome 2 and has at least three pseudogene loci in the human genome

We have analyzed the genomic structure of ribonuclease H1 (RNase H1) loci in the human genome. Human PAC library screening combined with database searches indicated that several loci are present. The transcribed gene is localized on chromosome 2p25. This was confirmed by RNA analysis of a monochromosomal hybrid cell line that expressed human chromosome 2. These data contradict a previous report, as well as the current Human Genome Project (HGP) annotation, which had placed the gene on chromosome 17p11.2. This location represents a pseudogene. Another highly similar pseudogene is present at a separate locus located more distal on chromosome 17p, while a third pseudogene is localized on chromosome 1

Long-Term Outcome for People with Severe Intellectual Disabilities: Impact of Social Impairment

Results from a 25-year follow-up study of the Camberwell Cohort (L. Wing & Gould, 1978, 1979) were presented. Ninety-one people, ranging in age from 27 to 41 years, were traced, and an outcome measure was developed incorporating independent functioning, residential placement, employment, and quality of life. Outcome was rated as either poor (53%) or fair (43%), with only 3% having a good outcome. Using logistic regression methods, we found that the best predictor of outcome was social impairment, with those who were socially impaired, particularly those in the aloof category, having a poorer outcome. Higher IQ at Time 1 and lower challenging behavior were also predictive of better outcome. An in-depth look at social impairment revealed that social impairment remained stable over time