CCR5Δ32 Genotypes in a German HIV-1 Seroconverter Cohort and Report of HIV-1 Infection in a CCR5Δ32 Homozygous Individual

Background

Homozygosity (Δ32/Δ32) for the 32 bp deletion in the chemokine receptor 5 (CCR5) gene is associated with strong resistance against HIV infection. Heterozygosity is associated with protection of HIV-1 disease progression.

Methodology/Principal Findings

We genotyped a population of 737 HIV-positive adults and 463 healthy controls for the CCR5Δ32 deletion and found heterozygous frequencies of 16.2% (HIV-negative) and 17.5% (HIV-positive) among Caucasian individuals. Analysis of CCR5Δ32 influence on disease progression showed notably lower viral setpoints and a longer time to a CD4 count of <200 µl⁻¹ in seroconverters heterozygous for the deletion. Furthermore, we identified one HIV-positive man homozygous for the Δ32 deletion.

Conclusions/Significance

The protective effect of CCR5 Δ32 heterozygosity is confimed in a large cohort of German seroconverters. The HIV-infected CCR5 Δ32 homozygous individual, however, displays extremely rapid disease progression. This is the 12th case of HIV-infection in this genotype described worldwide.     

Generation of New Hairless Alleles by Genomic Engineering at the Hairless Locus in Drosophila melanogaster

Hairless (H) is the major antagonist within the Notch signalling pathway of Drosophila melanogaster. By binding to Suppressor of Hairless [Su(H)] and two co-repressors, H induces silencing of Notch target genes in the absence of Notch signals. We have applied genomic engineering to create several new H alleles. To this end the endogenous H locus was replaced with an attP site by homologous recombination, serving as a landing platform for subsequent site directed integration of different H constructs. This way we generated a complete H knock out allele H^attP, reintroduced a wild type H genomic and a cDNA-construct (H^gwt, H^cwt) as well as two constructs encoding H proteins defective of Su(H) binding (H^LD, H^iD). Phenotypes regarding viability, bristle and wing development were recorded, and the expression of Notch target genes wingless and cut was analysed in mutant wing discs or in mutant cell clones. Moreover, genetic interactions with Notch (N⁵⁴¹⁹) and Delta (Dl^B2) mutants were addressed. Overall, phenotypes were largely as expected: both H^LD and H^iD were similar to the H^attP null allele, indicating that most of H activity requires the binding of Su(H). Both rescue constructs H^gwt and H^cwt were homozygous viable without phenotype. Unexpectedly, the hemizygous condition uncovered that they were not identical to the wild type allele: notably H^cwt showed a markedly reduced activity, suggesting the presence of as yet unidentified regulatory or stabilizing elements in untranslated regions of the H gene. Interestingly, H^gwt homozygous cells expressed higher levels of H protein, perhaps unravelling gene-by-environment interactions.     

Only-Child Status in Relation to Perceived Stress and Studying-Related Life Satisfaction among University Students in China: A Comparison with International Students

Objectives

University students in general face multiple challenges, which may affect their levels of perceived stress and life satisfaction. Chinese students currently face specific strains due to the One-Child Policy (OCP). The aim of this study was to assess (1) whether the levels of perceived stress and studying-related life satisfaction are associated with only-child (OC) status after controlling for demographic and socio-economic characteristics and (2) whether these associations differ between Chinese and international students.

Materials and Methods

A cross-sectional health survey based on a self-administrated standardised questionnaire was conducted among 1,843 (1,543 Chinese, 300 international) students at two Chinese universities in 2010–2011. Cohen’s Perceived Stress Scale (PSS-14) and Stock and Kraemer’s Studying-related Life Satisfaction Scale were used to measure perceived stress and studying-related life satisfaction respectively. Multivariable logistic regression analyses were used to examine the associations of OC status with perceived stress and studying-related life satisfaction by sex for Chinese students and international students separately.

Results

The Chinese non-only-children (NOCs) were more likely to come from small cities. Multivariable regression models indicate that the Chinese NOCs were more stressed than OCs (OR = 1.39, 1.11–1.74) with a stronger association in men (OR = 1.48, 1.08–2.02) than women (OR = 1.26, 0.89–1.77). NOCs were also more dissatisfied than their OC fellows in the Chinese subsample (OR = 1.37, 1.09–1.73). Among international students, no associations between OC status and perceived stress or studying-related life satisfaction were found.

Conclusions

To promote equality between OCs and NOCs at Chinese universities, the causes of more stress and less studying-related life satisfaction among NOCs compared to OCs need further exploration.     

Munich information center for protein sequences plant genome resources: a framework for integrative and comparative analyses 1(W)

With several plant genomes sequenced, the power of comparative genome analysis can now be applied. However, genome-scale cross-species analyses are limited by the effort for data integration. To develop an integrated cross-species plant genome resource, we maintain comprehensive databases for model plant genomes, including Arabidopsis (Arabidopsis thaliana), maize (Zea mays), Medicago truncatula, and rice (Oryza sativa). Integration of data and resources is emphasized, both in house as well as with external partners and databases. Manual curation and state-of-the-art bioinformatic analysis are combined to achieve quality data. Easy access to the data is provided through Web interfaces and visualization tools, bulk downloads, and Web services for application-level access. This allows a consistent view of the model plant genomes for comparative and evolutionary studies, the transfer of knowledge between species, and the integration with functional genomics data.     

Cell invasion by Neisseria meningitidis requires a functional interplay between the focal adhesion kinase, Src and cortactin

Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells.     

Dopaminergic and noradrenergic circuit development in zebrafish

Dopaminergic and noradrenergic neurons constitute some of the major far projecting systems in the vertebrate brain and spinal cord that modulate the activity of circuits controlling a broad range of behaviors. Degeneration or dysfunction of dopaminergic neurons has also been linked to a number of neurological and psychiatric disorders, including Parkinson's disease.Zebrafish (Danio rerio) have emerged over the past two decades into a major genetic vertebrate model system,and thus contributed to a better understanding of developmental mechanisms controlling dopaminergic neuron specification and axonogenesis. In this review, we want to focus on conserved and dynamic aspects of the different catecholaminergic systems, which may help to evaluate the zebrafish as a model for dopaminergic and noradrenergic cellular specification and circuit function as well as biomedical aspects of catecholamine systems.     

Influence of Different Individual Traits on Vigilance Behaviour in European Rabbits

An animal's level of vigilance depends on various environmental factors such as predator presence or the proximity of conspecific competitors. In addition, several individual traits may influence vigilance. We investigated the effects of body condition, social rank and the state of pregnancy on individual vigilance (scanning) rates in individually marked European rabbits ( Oryctolagus cuniculus ) of a field enclosure population. We found lower rates in young rabbits than in adult females, but male and female juveniles did not differ. Vigilance of juveniles was positively correlated with their age-dependent body mass (used as a measure of body condition), i.e. young rabbits with lower body condition scanned less. We suggest that juveniles with low body condition were trading off vigilance against feeding to maximise their growth. In contrast, there was no significant correlation between body mass and vigilance in adult females. Adult females increased scanning rates during late pregnancy, which might constitute a behavioural compensation because of their lower capacity to escape predator attacks. In addition, adult females with low social ranks scanned more than high ranking individuals, likely because of their higher risk of attacks by conspecifics. In summary, our results highlight various individual characteristics that influence vigilance behaviour in European rabbits.     

Comparative analysis of the complete genome sequence of the plant growth-promoting bacterium Bacillus amyloliquefaciens FZB42

Bacillus amyloliquefaciens FZB42 is a Gram-positive, plant-associated bacterium, which stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. Its 3,918-kb genome, containing an estimated 3,693 protein-coding sequences, lacks extended phage insertions, which occur ubiquitously in the closely related Bacillus subtilis 168 genome. The B. amyloliquefaciens FZB42 genome reveals an unexpected potential to produce secondary metabolites, including the polyketides bacillaene and difficidin. More than 8.5% of the genome is devoted to synthesizing antibiotics and siderophores by pathways not involving ribosomes. Besides five gene clusters, known from B. subtilis to mediate nonribosomal synthesis of secondary metabolites, we identified four giant gene clusters absent in B. subtilis 168. The pks2 gene cluster encodes the components to synthesize the macrolactin core skeleton.