Actin Enables the Antimicrobial Action of LL-37 Peptide in the Presence of Microbial Proteases

Host defense peptides play an important host-protective role by their microcidal action, immunomodulatory functions, and tissue repair activities. Proteolysis is a common strategy of pathogens used to neutralize host defense peptides. Here, we show that actin, the most abundant structural protein in eukaryotes, binds the LL-37 host defense peptide, protects it from degradation by the proteases of Pseudomonas aeruginosa and Porphyromonas gingivalis, and enables its antimicrobial activity despite the presence of the proteases. Co-localization of LL-37 with extracellular actin was observed in necrotized regions of samples from oral lesions. Competition assays, cross-linking experiments, limited proteolysis, and mass spectrometry revealed that LL-37 binds by specific hydrophobic interactions to the His-40–Lys-50 segment of actin, located in the DNase I binding loop. The integrity of the binding site of both LL-37 and actin is a prerequisite to the binding. Our results demonstrate that actin, presumably released by dead cells and abundant in infected sites, might be utilized by the immune system to enhance spatio-temporal immunity in an attempt to arrest infection and control inflammation.     

Cis effect oflacZ sequences in transgenic mice

Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG) promoter driving theEscherichia coli -galactosidase (lacZ) gene did not display the expected ubiquitous and constitutive expression inHMG-lacZ transgenic mice. The same promoter is however able to drive ubiquitous expression of the chloramphenicol acetyltransferase (cat) gene. Two lines of doubleHMG-lacZ andHMG-cat transgenic mice were obtained in which the two constructs were integrated at the same genomic sites. These mice expressed both reporter genes, but exclusively in the testes. These results suggest that thelacZ sequence might interfere negatively with the expression of the adjacentHMG-cat transgene.     

Effect of amino acids on cryopreservation of cynomolgus monkey (Macaca fascicularis) sperm

The effects of three amino acids (proline, glutamine, and glycine) added to the freezing medium Tes-Tris-egg yolk (TTE) for cryopreservation of cynomolgus monkey (Macaca fascicularis) spermatozoa were studied. This is the first report on the effects of amino acids on nonhuman primate sperm cryopreservation. The addition of 5mM proline, 10mM glutamine, and 10 or 20mM glycine each significantly improved post-thaw sperm motility and membrane and acrosome integrity compared with the control (TTE alone). However, a significant decrease in motility and membrane/acrosome integrity was observed when amino acid concentrations increased to 60mM for proline and glutamine, and 80 mM for glycine. The results suggest that adding a limited amount of amino acids to the freezing media is beneficial for freezing cynomolgus monkey sperm.     

Phosphatidylinositol 4-kinases: old enzymes with emerging functions

Phosphoinositides account for only a tiny fraction of cellular phospholipids but are extremely important in the regulation of the recruitment and activity of many signaling proteins in cellular membranes. Phosphatidylinositol (PtdIns) 4-kinases generate PtdIns 4-phosphate, the precursor of important regulatory phosphoinositides but also an emerging regulatory molecule in its own right. The four mammalian PtdIns 4-kinases regulate a diverse array of signaling events, as well as vesicular trafficking and lipid transport, but the mechanisms by which their lipid product PtdIns 4-phosphate controls these processes is only beginning to unfold.     

Spatial population genetic structure of a bacterial parasite in close coevolution with its host

Knowledge of a species’ population genetic structure can provide insight into fundamental ecological and evolutionary processes including gene flow, genetic drift and adaptive evolution. Such inference is of particular importance for parasites, as an understanding of their population structure can illuminate epidemiological and coevolutionary dynamics. Here, we describe the population genetic structure of the bacterium Pasteuria ramosa, a parasite that infects planktonic crustaceans of the genus Daphnia. This system has become a model for investigations of host–parasite interactions and represents an example of coevolution via negative frequency‐dependent selection (aka “Red Queen” dynamics). To sample P. ramosa, we experimentally infected a panel of Daphnia hosts with natural spore banks from the sediments of 25 ponds throughout much of the species range in Europe and western Asia. Using 12 polymorphic variable number tandem repeat loci (VNTR loci), we identified substantial genetic diversity, both within and among localities, that was structured geographically among ponds. Genetic diversity was also structured among host genotypes within ponds, although this pattern varied by locality, with P. ramosa at some localities partitioned into distinct host‐specific lineages, and other localities where recombination had shuffled genetic variation among different infection phenotypes. Across the sample range, there was a pattern of isolation by distance, and principal components analysis coupled with Procrustes rotation identified congruence between patterns of genetic variation and geography. Our findings support the hypothesis that Pasteuria is an endemic parasite coevolving closely with its host. These results provide important context for previous studies of this model system and inform hypotheses for future research.     

Evolutionary pathway of child development

An evolutionary theory of socialization suggests that children from father-absent families will mature earlier, and form less-stable pair bonds, compared with those from father-present families. Using a sample of about 1,000 persons the recent study focuses on elements of father-absent children’s behavior that could be better explained by a Darwinian approach than by rival social science theories. As a result of their enhanced interest in male competition, father-absent boys were found to engage in rule-breaking behavior more intensively than father-present boys. Compared with father-present children, adolescents from widowed households (both boys and girls) showed a higher intensity of various kinds of noncompliant behavior, which can be linked to their earlier maturation. School attendance, age at marriage, and marital success proved to be influenced by the children’s early family experiences, governed by adapted evolutionary strategies. Father-absent daughters conceived more children than those whose fathers were present during their childhood. As evolutionary theory predicts, reproductive behavior of individuals from divorced households differed from that of individuals who grew up in widowed households. Finally, the strong correlation found between spontaneous abortion/stillbirths and family arrangement indicates that father absence has certain direct impacts on the neurohormonal processes of child development.