Perishing Paradigm: Race—1931–99

Authors of three studies (Leonard Lieberman, Blaine W. Stevenson, Larry T. Reynolds, and Matt Cartmill) agree that the concept of race has approached its lowest level of acceptance in a century. However, one of the studies (that of Cartmill) seems to show no significant change from 1965 to 1996. We analyze this paradox in terms of possible differences in the populations studied. [Keywords: race, physical anthropology, variation]     

Synthesis and structure–activity relationship of botryllamides that block the ABCG2 multidrug transporter

In previous work, botryllamides discovered from the marine ascidian Botryllus tyreus were characterized as selective inhibitors of the ABCG2 multidrug transporter. However, the structural basis for this activity could not be established. In this study, botryllamide F, the core botryllamide structure, and botryllamide G, the most potent botryllamide ABCG2 inhibitor, were synthesized along with a series of structural variants for evaluation of structure–activity relationships. The biological activity of synthetic botryllamide analogs implied that the 2-methoxy-p-coumaric acid portion, and the degree of double bond conjugation within this group, were critical for inhibition of ABCG2. However, variations in the substituents on the two aryl groups did not appear to significantly impact the potency or degree of inhibition.     

How important are climate‐induced changes in host availability for population processes in an obligate brood parasite,the European cuckoo?

In recent years, populations of long‐distance migrant birds have declined markedly. Resource availability, both on breeding and wintering grounds, is likely to be important particularly since changing climates are affecting the timing and synchrony of such resources. We use novel analytical methods to examine whether large‐scale population declines in the brood‐parasite common cuckoo Cuculus canorus are the result of changes in the abundance or timing of breeding of its host species. We find that, due to climate‐induced changes in the timing of breeding, availability of dunnock Prunella modularis nests has decreased, but that availability of reed warbler Acrocephalus scirpaceus has increased. Although there is no evidence that the timing of breeding of cuckoo has changed, these changes are likely to have had only a minimal impact on its population trend, but may explain an increase in the rate of parasitism of reed warbler nests in recent decades.     

Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential gel electrophoresis and mass spectrometry analysis

Experiments show that upon traumatic injury the composition of mesenteric lymph changes such that it initiates an immune response that can ultimately result in multiple organ dysfunction syndrome (MODS). To identify candidate protein mediators of this process we carried out a quantitative proteomic study on mesenteric lymph from a well characterized rat shock model. We analyzed three animals using analytical 2D differential gel electrophoresis. Intra-animal variation for the majority of protein spots was minor. Functional clustering of proteins revealed changes arising from several global classes that give novel insight into fundamental mechanisms of MODS. Mass spectrometry based proteomic analysis of proteins in mesenteric lymph can effectively be used to identify candidate mediators and loss of protective agents in shock models.     

Cross Validation of Liquid Chromatography–Mass Spectrometry and Lectin Array for Monitoring Glycosylation in Fed-Batch Glycoprotein Production

Glycosylation analysis of recombinant glycoproteins is of importance for the biopharmaceutical industry and the production of glycoprotein pharmaceuticals. A commercially available lectin array technology was evaluated for its ability to present a reproducible fingerprint of a recombinant CTLY4-IgG fusion glycoprotein expressed in large scale CHO-cell fermentation. The glycosylation prediction from the array was compared to traditional negative mode capillary LC-MS of released oligosaccharides. It was shown that both methods provide data that allow samples to be distinguished by their glycosylation pattern. This included information about sialylation, the presence of reducing terminal galactose β1-, terminal N-acetylglucosamine β1-, and antennary distribution. With both methods it was found that a general trend of increased sialylation was associated with an increase of the antenna and reduced amount of terminal galactose β1-, while N-acetylglucosamine β1- was less affected. LC-MS, but not the lectin array, provided valuable information about the sialic acid isoforms present, including N-acetylneuraminic acid, N-glycolylneuraminic acid and their O-acetylated versions. Detected small amounts of high-mannose structures by LC-MS correlated with the detection of the same epitope by the lectin array.     

Polymorphisms of CUL5 are associated with CD4+ T cell loss in HIV-1 infected individuals

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters of evolutionarily related haplotypes. Cox survival analysis and mixed effects models were used to assess time to AIDS outcomes and CD4(+) T cell trajectories, respectively. Relative to cluster I haplotypes, the collective cluster II haplotypes were associated with more rapid CD4(+) T cell loss (relative hazards [RH] = 1.47 and p = 0.009), in a dose-dependent fashion. This effect was mainly attributable to a single cluster II haplotype (Hap10) (RH = 2.49 and p = 0.00001), possibly due to differential nuclear protein-binding efficiencies of a Hap10-specifying SNP as indicated by a gel shift assay. Consistent effects were observed for CD4(+) T cell counts and HIV-1 viral load trajectories over time. The findings of both functional and genetic epidemiologic consequences of CUL5 polymorphism on CD4(+) T cell and HIV-1 levels point to a role for Cullin 5 in HIV-1 pathogenesis and suggest interference with the Vif-Cullin 5 pathway as a possible anti-HIV-1 therapeutic strategy.