Activity of broadly neutralizing antibodies, including PG9, PG16, and VRC01, against recently transmitted subtype B HIV-1 variants from early and late in the epidemic

For the development of a neutralizing antibody-based human immunodeficiency virus type 1 (HIV-1) vaccine, it is important to characterize which antibody specificities are most effective against currently circulating HIV-1 variants. We recently reported that HIV-1 has become more resistant to antibody neutralization over the course of the epidemic, and we here explore whether this increased neutralization resistance is also observed for the newly identified broadly neutralizing antibodies (BrNAbs) PG9, PG16, and VRC01. Furthermore, we performed a comprehensive analysis of the neutralizing sensitivity of currently circulating recently transmitted subtype B viruses to the currently most known BrNAbs. Virus variants isolated less than 6 months after seroconversion from individuals who seroconverted between 2003 and 2006 (n = 21) were significantly more resistant to neutralization by VRC01 than viruses from individuals who seroconverted between 1985 and 1989 (n = 14). In addition, viruses from contemporary seroconverters tended to be more resistant to neutralization by PG16, which coincided with the presence of more mutations at positions in the viral envelope that may potentially influence neutralization by this antibody. Despite this increased neutralization resistance, all recently transmitted viruses from contemporary seroconverters were sensitive to at least one BrNAb at concentrations of ≤5 μg/ml, with PG9, PG16, and VRC01 showing the greatest breadth of neutralization at lower concentrations. These results suggest that a vaccine capable of eliciting multiple BrNAb specificities will be necessary for protection of the population against HIV-1 infection.     

No inbreeding depression but increased sexual investment in highly inbred ant colonies

Inbreeding can lead to the expression of deleterious recessive alleles and to a subsequent fitness reduction. In Hymenoptera, deleterious alleles are purged in haploid males moderating inbreeding costs. However, in these haplodiploid species, inbreeding can result in the production of sterile diploid males. We investigated the effects of inbreeding on the individual and colony level in field colonies of the highly inbred ant Hypoponera opacior. In this species, outbreeding winged sexuals and nest‐mating wingless sexuals mate during two separate reproductive periods. We show that regular sib‐matings lead to high levels of homozygosity and the occasional production of diploid males, which sporadically sire triploid offspring. On the individual level, inbreeding was associated with an increased body size in workers. On the colony level, we found no evidence for inbreeding depression as productivity was unaffected by the level of homozygosity. Instead, inbred colonies altered their allocation strategies by investing more resources into sexuals than into workers. This shift towards sexual production was due to an increased investment in both males and queens, which was particularly pronounced in the dispersive generation. The absence of inbreeding depression combined with increased reproductive investment, especially in outbreeding sexuals, suggests that these ants have evolved active strategies to regulate the extent and effects of frequent inbreeding.     

Sequence correlations between Cro recognition helices and cognate O(R) consensus half-sites suggest conserved rules of protein-DNA recognition

The O(R) regions from several lambdoid bacteriophages contain the three regulatory sites O(R)1, O(R)2 and O(R)3, to which the Cro and CI proteins can bind. These sites show imperfect dyad symmetry, have similar sequences, and generally lie on the same face of the DNA double helix. We have developed a computational method, which analyzes the O(R) regions of additional phages and predicts the location of these three sites. After tuning the method to predict known O(R) sites accurately, we used it to predict unknown sites, and ultimately compiled a database of 32 known and predicted O(R) binding site sets. We then identified sequences of the recognition helices (RH) for the cognate Cro proteins through manual inspection of multiple sequence alignments. Comparison of Cro RH and consensus O(R) half-site sequences revealed strong one-to-one correlations between two amino acids at each of three RH positions and two bases at each of three half-site positions (H1-->2, H3-->5 and H6-->6). In each of these three cases, one of the two amino acid/base-pairings corresponds to a contact observed in the crystal structure of a lambda Cro/consensus operator complex. The alternate amino acid/base combinations were rationalized using structural models. We suggest that the pairs of amino acid residues act as binary switches that efficiently modulate specificity for different consensus half-site variants during evolution. The observation of structurally reasonable amino acid-to-base correlations suggests that Cro proteins share some common rules of recognition despite their functional and structural diversity.     

Physical Fitness and Physical Activity in Obese and Nonobese Flemish Youth

Objective: To assess different aspects of physical fitness and physical activity in obese and nonobese Flemish youth. Research Methods and Procedures: A random sample of 3214 Flemish schoolchildren was selected and divided into an “obese” and “nonobese” group based on body mass index and sum of skinfolds. Physical fitness was assessed by the European physical fitness test battery. Physical activity was estimated by a modified version of the Baecke Questionnaire. Results: Obese subjects had inferior performances on all tests requiring propulsion or lifting of the body mass (standing‐broad jump, sit‐ups, bent‐arm hang, speed shuttle run, and endurance shuttle run) compared with their nonobese counterparts (p < 0.001). In contrast, the obese subjects showed greater strength on handgrip (p < 0.001). Both groups had similar levels of leisure‐time physical activity; however, nonobese boys had a higher sport index than their obese counterparts (p < 0.05). Discussion: Results of this study show that obese subjects had poorer performances on weight‐bearing tasks, but did not have lower scores on all fitness components. To encourage adherence to physical activity in obese youth, it is important that activities are tailored to their capabilities. Results suggest that weight‐bearing activities should be limited at the start of an intervention with obese participants and alternative activities that rely more on static strength used.