Antibody neutralization and escape by HIV-1

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.     

An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.     

INFORMATION CHARACTERIZATION OF COMMUNICATION CHANNELS FOR SYSTEM IDENTIFICATION

This paper studies identification of systems in which the system output is quantized, transmitted through a digital communication channel, and observed afterwards. The concept of the CR Ratio is introduced to characterize impact of communication channels on identification. The relationship between the CR Ratio and Shannon channel capacity is discussed. Identification algorithms are further developed when the channel error probability is unknown.     

Colony isolation and isozyme variability of the western seep fritillary, Speyeria nokomis apacheana (Nymphalidae), in the western Great Basin

Thirteen Speyeria nokomis apacheana (Edwards) (Nymphalidae) populations from the western Great Basin were assayed for isozyme variability using starch-gel electrophoresis. Eight of the 25 presumptive isozyme loci analyzed were found to be polymorphic. Collections made in 1991and 1992 allowed for between-year comparisons of heterozygosity and the estimation of effective population size for five of the sampled populations. Speyeria nokomis apacheana populations exhibit lower mean heterozygosity levels than other nymphalids. This may be attributed to genetic drift in apparently isolated populations with small effective sizes.     

Temperature-related behavior of some migrant birds in the desert

Behavior of migrant birds in relation to temperature was studied and compared to that of resident species in the northern Mojave Desert. Migrants reduced foraging intensity above 30 C, but resident species showed no striking decrease in intensity of foraging at temperatures up to 35 C. Migrant species shifted activities to shaded microhabitats at temperatures between 20 and 30 C; the resident Verdin showed a similar shift at 35 C. Most migrants decreased the amount of time spent foraging at temperatures above 30; Verdins showed a similar but stronger response to temperatures about 30 C. Significant reductions in the use of hovering and hawking maneuvers were found among migrants at temperatures above 30 C. Migrants showed similar types of behavioral adjustments to temperatures as did resident desert species, but they responded earlier in the daily temperature cycle. Desert birds appear to correlate their daily activity strongly with temperature, but nondesert species may respond either to temperature or time of day.     

Linking innate and adaptive immunity

The evolution of mechanisms to fight pathogens in plants and animals is reflected in the complexity of the components of their so-called immune systems. Higher vertebrates have evolved     

中国〖XC5XHCC.TIF〗目二新种(笛〖XC18.TIF〗科: 长角枝〖XC18.TIF〗亚科, 短角棒〖XC18.TIF〗亚科)

 记述中国〖XC5XCC.TIF〗目2新种, 井冈山无齿股〖XC5XCC.TIF〗Parasipyloideajinggangshanensis Ho, sp nov.及七州瘦〖XC5XCC.TIF〗Macellina qizhouense Ho, sp nov。新种模式标本存放于广州中山大学生物博物馆。