Specialized odorant receptors in social insects that detect cuticular hydrocarbon cues and candidate pheromones.

Eusocial insects use cuticular hydrocarbons as components of pheromones that mediate social behaviours, such as caste and nestmate recognition, and regulation of reproduction. In ants such as Harpegnathos saltator, the queen produces a pheromone which suppresses the development of workers' ovaries and if she is removed, workers can transition to a reproductive state known as gamergate. Here we functionally characterize a subfamily of odorant receptors (Ors) with a nine-exon gene structure that have undergone a massive expansion in ants and other eusocial insects. We deorphanize 22 representative members and find they can detect cuticular hydrocarbons from different ant castes, with one (HsOr263) that responds strongly to gamergate extract and a candidate queen pheromone component. After systematic testing with a diverse panel of hydrocarbons, we find that most Harpegnathos saltator Ors are narrowly tuned, suggesting that several receptors must contribute to detection and discrimination of different cuticular hydrocarbons important in mediating eusocial behaviour.Cuticular hydrocarbons (CHC) mediate the interactions between individuals in eusocial insects, but the sensory receptors for CHCs are unclear. Here the authors show that in ants such as H. saltator, the 9-exon subfamily of odorant receptors (HsOrs) responds to CHCs, and ectopic expression of HsOrs in Drosophila neurons imparts responsiveness to CHCs

Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails

Department of Biochemistry and Biophysics, Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA; Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, US

Aggregate Unemployment Decreases Individual Returns to Education

On the basis of a theoretical model, we argue that higher aggregate unemployment affects individual returns to education. We therefore include aggregate unemployment and an interaction term between unemployment and the individual education level in a standard Mincer equation. Our results show that an increase in regional unemployment by 1% decreases the returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour market changes with respect to their jobs but encounter larger wage changes than less skilled employees. Differences in regional unemployment can in addition almost fully explain the observed large differences in regional returns to education. We use representative individual data and regional panel variation in unemployment between different German regions and for different employee groups. We demonstrate that our results are robust with respect to aggregation bias, time lags and potential endogeneity of the unemployment variable

Ctk1 promotes dissociation of basal transcription factors from elongating RNA polymerase II

As RNA polymerase II (RNApII) transitions from initiation to elongation, Mediator and the basal transcription factors TFIID, TFIIA, TFIIH, and TFIIE remain at the promoter as part of a scaffold complex, whereas TFIIB and TFIIF dissociate. The yeast Ctk1 kinase associates with elongation complexes and phosphorylates serine 2 in the YSPTSPS repeats of the Rpb1 C-terminal domain, a modification that couples transcription to mRNA 3′-end processing. The higher eukaryotic kinase Cdk9 not only performs a similar function, but also functions at the 5′-end of genes in the transition from initiation to elongation. In strains lacking Ctk1, many basal transcription factors cross-link throughout transcribed regions, apparently remaining associated with RNApII until it terminates. Consistent with this observation, preinitiation complexes formed on immobilized templates with transcription extracts lacking Ctk1 leave lower levels of the scaffold complex behind after escape. Taken together, these results suggest that Ctk1 is necessary for the release of RNApII from basal transcription factors. Interestingly, this function of Ctk1 is independent of its kinase activity, suggesting a structural function of the protein

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5–98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1–16 h after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS–MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle

Epigenetic regulation of centromeric chromatin: old dogs, new tricks?

The assembly of just a single kinetochore at the centromere of each sister chromatid is essential for accurate chromosome segregation during cell division. Surprisingly, despite their vital function, centromeres show considerable plasticity with respect to their chromosomal locations and activity. The establishment and maintenance of centromeric chromatin, and therefore the location of kinetochores, is epigenetically regulated. The histone H3 variant CENP-A is the key determinant of centromere identity and kinetochore assembly. Recent studies have identified many factors that affect CENP-A localization, but their precise roles in this process are unknown. We build on these advances and on new information about the timing of CENP-A assembly during the cell cycle to propose new models for how centromeric chromatin is established and propagated

Custom affinity probes reveal DNA-damage-induced, ssDNA-independent chromatin SUMOylation in budding yeast

The small ubiquitin-related modifier SUMO regulates cellular processes in eukaryotes either by modulating individual protein-protein interactions or with relaxed substrate selectivity by group modification. Here, we report the isolation and characterization of designed ankyrin repeat protein (DARPin)-based affinity probes directed against budding yeast SUMO (Smt3). We validate selected DARPins as compartment-specific inhibitors or neutral detection agents. Structural characterization reveals a recognition mode distinct from that of natural SUMO interactors. In vivo application pinpoints Smt3's essential function to the nucleus and demonstrates DARPin-mediated sensitization toward various stress conditions. A subset of selected clones is validated as SUMOylation reporters in cells. In this manner, we identify a DNA-damage-induced nuclear SUMOylation response that-in contrast to previously reported chromatin group SUMOylation-is independent of single-stranded DNA and the SUMO-E3 Siz2 but depends on Mms21 and likely reflects late intermediates of homologous recombination. Thus, Smt3-specific DARPins can provide insight into the dynamics of SUMOylation in defined subcellular structures

Food biofortification : reaping the benefits of science to overcome hidden hunger

Biofortification is a process of increasing the density of minerals and vitamins in a food crop through conventional plant breeding, genetic engineering, or agronomic practices (primarily use of fertilizers and foliar sprays). Biofortified staple food crops, when substituted consistently for non-biofortified staple food crops, can generate measurable improvements in human nutrition and health. This monograph describes the progress made in developing, testing, and disseminating biofortified staple food crops, primarily through the use of conventional plant breeding, summarizing the activities of two consortiums of inter-disciplinary collaborating institutions led the HarvestPlus program and the International Potato Center (CIP). We focus on laying out the evidence base proving the effectiveness and impact to date of biofortified crops. Results of a large number of nutritional bioavailability and efficacy trials are summarized (Chapter 2), crop development techniques and activities are presented and variety releases documented for a dozen staple food crops in low and middle income countries (LMICs) in Africa, Asia, and Latin America (Chapter 3), and strategies for promoting the uptake of specific biofortified crops are discussed, concurrent with policy advocacy to encourage key institutions to mainstream the promotion, and use of biofortified crops in their core activities (Chapters 4 and 5). Statistics will be presented on numbers of farm households adopting biofortified crops (Chapters 3 and 4), now available to farmers in 40 low and middle income countries (LMICs). Each section will outline the way forward on additional future activities required to enhance the development and impact the biofortification through conventional plant breeding. No biofortified staple food crop developed through transgenic techniques has been fully de-regulated for release to farmers in LMICs. Yet transgenic techniques hold the potential for a several-fold increase in the impact/benefits of biofortified crops. This potential is described in Chapter 6 which discusses developmental research already completed, including achieving higher densities of single nutrients than is possible with conventional breeding, combining multiple nutrient traits in single events, slowing down/reducing the level of degradation of vitamins after harvesting, and combining superior agronomic traits with nutrient traits in single events. A final chapter summarizes and discusses key questions and issues that will influence the ultimate mainstreaming of biofortified crops in food systems in LMICs and will allow maximization of the benefits of biofortification

Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization

The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1