Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility.

The flexibility of different regions of HIV-1 protease was examined by using a database consisting of 73 X-ray structures that differ in terms of sequence, ligands or both. The root-mean-square differences of the backbone for the set of structures were shown to have the same variation with residue number as those obtained from molecular dynamics simulations, normal mode analyses and X-ray B-factors. This supports the idea that observed structural changes provide a measure of the inherent flexibility of the protein, although specific interactions between the protease and the ligand play a secondary role. The results suggest that the potential energy surface of the HIV-1 protease is characterized by many local minima with small energetic differences, some of which are sampled by the different X-ray structures of the HIV-1 protease complexes. Interdomain correlated motions were calculated from the structural fluctuations and the results were also in agreement with molecular dynamics simulations and normal mode analyses. Implications of the results for the drug-resistance engendered by mutations are discussed briefly.

How a haemosporidian parasite of bats gets around: the genetic structure of a parasite, vector and host compared.

Parasite population structure is often thought to be largely shaped by that of its host. In the case of a parasite with a complex life cycle, two host species, each with their own patterns of demography and migration, spread the parasite. However, the population structure of the parasite is predicted to resemble only that of the most vagile host species. In this study, we tested this prediction in the context of a vector-transmitted parasite. We sampled the haemosporidian parasite Polychromophilus melanipherus across its European range, together with its bat fly vector Nycteribia schmidlii and its host, the bent-winged bat Miniopterus schreibersii. Based on microsatellite analyses, the wingless vector, and not the bat host, was identified as the least structured population and should therefore be considered the most vagile host. Genetic distance matrices were compared for all three species based on a mitochondrial DNA fragment. Both host and vector populations followed an isolation-by-distance pattern across the Mediterranean, but not the parasite. Mantel tests found no correlation between the parasite and either the host or vector populations. We therefore found no support for our hypothesis; the parasite population structure matched neither vector nor host. Instead, we propose a model where the parasite's gene flow is represented by the added effects of host and vector dispersal patterns.

Localization and fine structure of a vaccinia virus gene encoding an envelope antigen.

The major antigen on the envelope of extracellular vaccinia virus particles is a polypeptide with an apparent molecular weight of 37,000 (p37K; G. Hiller and K. Weber, J. Virol. 55:651-659, 1985). The gene encoding p37K was mapped in the vaccinia virus genome by hybrid selection of RNA followed by in vitro translation. p37K was then identified among the in vitro translation products by immunoprecipitation with a monoclonal antibody. The gene is located close to the right-hand end of the HindIII F fragment. The corresponding region of the DNA was sequenced, and an open reading frame encoding a polypeptide of 41,748 daltons was observed. The 5' end of the mRNA, as defined by nuclease S1 analysis, maps within only a few nucleotides of the translation initiation codon. Examination of the DNA sequence around the putative initiation site of transcription revealed a characteristic sequence, TAAATG, which includes the ATG translation initiation codon and which is conserved in all but one late gene so far analyzed. It is therefore likely that this sequence is an important regulatory signal for late gene expression in vaccinia virus.

Vulnerability as a heuristic for interdisciplinary research: Assessing the thematic and methodological structure of empirical life-course studies

Changes in human lives are studied in psychology, sociology, and adjacent fields as outcomes of developmental processes, institutional regulations and policies, culturally and normatively structured life courses, or empirical accounts. However, such studies have used a wide range of complementary, but often divergent, concepts. This review has two aims. First, we report on the structure that has emerged from scientific life course research by focusing on abstracts from longitudinal and life course studies beginning with the year 2000. Second, we provide a sense of the disciplinary diversity of the field and assess the value of the concept of 'vulnerability' as a heuristic tool for studying human lives. Applying correspondence analysis to 10,632 scientific abstracts, we find a disciplinary divide between psychology and sociology, and observe indications of both similarities of-and differences between-studies, driven at least partly by the data and methods employed. We also find that vulnerability takes a central position in this scientific field, which leads us to suggest several reasons to see value in pursuing theory development for longitudinal and life course studies in this direction.

Population structure of three Psammodromus species in the Iberian Peninsula.

The knowledge of a species' population structure is essential for the development of adequate conservation actions as well as for the understanding of its evolution. The population structure is unknown in all species of the Genus Psammodromus, including the Western Sand Racer (Psammodromus occidentalis; a recently described species), the Edward's Sand Racer (P. edwardsianus) and the Spanish Sand Racer (P. hispanicus). In this article, the genetic variability and population structure of Psammodromus edwardsianus, P. hispanicus, and P. occidentalis were studied in the Iberian Peninsula covering their natural geographic distribution. Mitochondrial DNA showed genetically different units in all species with higher genetic variability in their southern populations (latitudinal variation). Genetic differentiation was different among species and contrasted to those of species with similar characteristics. Our results therefore highlight the importance of species-specific studies analysing population structure.