Androstadienone odor thresholds in adolescents

A sex-related difference in olfactory sensitivity to androstenone has been reported to occur during adolescence. More males than females exhibited anosmia to androstenone, or an increase in androstenone threshold with age. The current study addressed the question whether similar, sexually dimorphic effects of aging over puberty can also be found for androstadienone. A total of 102 subjects participated (36 females, 66 males). Similar to previous investigations, subjects were divided into a group of 47 individuals with a mean age of 13.3 years, defined as pre/peri-pubertal, and a group of 55 subjects with a mean age of 17.1 years, defined as post-pubertal. All subjects underwent tests for verbal abilities, general olfactory function, and measurements of androstadienone thresholds. The study provided the following major results: (1) Male subjects exhibited higher androstadienone sensitivity in the pre/peri-pubertal group as compared to the post-pubertal group. This difference was not observed in female subjects. Correspondingly, a negative correlation between age and androstadienone sensitivity was found for male subjects, but not for female subjects. (2) In contrast to this sex-specific change of the androstadienone odor threshold, verbal skills and odor identification abilities increased with age in all subjects regardless of their sex. In conclusion, the present observations confirm previous research on sex-differentiated effects of aging during puberty on sensitivity towards odorous steroids. While the underlying causes are unknown, it may be hypothesized that the decreased sensitivity could result from the increased endogenous levels of androstadienone in male subjects. Future studies should include both steroid and non-steroid odorants to further explore these age-related changes.     

Exoribonuclease R interacts with endoribonuclease E and an RNA helicase in the psychrotrophic bacterium Pseudomonas syringae Lz4W

Endoribonuclease E, a key enzyme involved in RNA decay and processing in bacteria, organizes a protein complex called degradosome. In Escherichia coli, Rhodobacter capsulatus, and Streptomyces coelicolor, RNase E interacts with the phosphate-dependent exoribonuclease polynucleotide phosphorylase, DEAD-box helicase(s), and additional factors in an RNA-degrading complex. To characterize the degradosome of the psychrotrophic bacterium Pseudomonas syringae Lz4W, RNase E was enriched by cation exchange chromatography and fractionation in a glycerol density gradient. Most surprisingly, the hydrolytic exoribonuclease RNase R was found to co-purify with RNase E. Co-immunoprecipitation and Ni(2+)-affinity pull-down experiments confirmed the specific interaction between RNase R and RNase E. Additionally, the DEAD-box helicase RhlE was identified as part of this protein complex. Fractions comprising the three proteins showed RNase E and RNase R activity and efficiently degraded a synthetic stem-loop containing RNA in the presence of ATP. The unexpected association of RNase R with RNase E and RhlE in an RNA-degrading complex indicates that the cold-adapted P. syringae has a degradosome of novel structure. The identification of RNase R instead of polynucleotide phosphorylase in this complex underlines the importance of the interaction between endo- and exoribonucleases for the bacterial RNA metabolism. The physical association of RNase E with an exoribonuclease and an RNA helicase apparently is a common theme in the composition of bacterial RNA-degrading complexes.     

CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation

Atopic dermatitis represents a chronically relapsing skin disease with a steadily increasing prevalence of 10-20% in children. Skin-infiltrating T cells, dendritic cells (DC), and mast cells are thought to play a crucial role in its pathogenesis. We report that the expression of the CC chemokine CCL1 (I-309) is significantly and selectively up-regulated in atopic dermatitis in comparison to psoriasis, cutaneous lupus erythematosus, or normal skin. CCL1 serum levels of atopic dermatitis patients are significantly higher than levels in healthy individuals. DC, mast cells, and dermal endothelial cells are abundant sources of CCL1 during atopic skin inflammation and allergen challenge, and Staphylococcus aureus-derived products induce its production. In vitro, binding and cross-linking of IgE on mast cells resulted in a significant up-regulation of this inflammatory chemokine. Its specific receptor, CCR8, is expressed on a small subset of circulating T cells and is abundantly expressed on interstitial DC, Langerhans cells generated in vitro, and their monocytic precursors. Although DC maintain their CCR8+ status during maturation, brief activation of circulating T cells recruits CCR8 from intracytoplamic stores to the cell surface. Moreover, the inflammatory and atopy-associated chemokine CCL1 synergizes with the homeostatic chemokine CXCL12 (SDF-1alpha) resulting in the recruitment of T cell and Langerhans cell-like DC. Taken together, these findings suggest that the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation.     

Asymmetric control of short day response in European hamsters

The European hamster (Cricetus cricetus) is a circannual species in which the synchronization of the circannual cycle to the natural year occurs during 2 annual phases of sensitivity. Around the summer solstice, the animals are sensitive to a shortening of photoperiod. During this sensitive phase, pronounced changes in circadian output parameters are observed, indicating a different functional state of the circadian system. This special state is assumed to be necessary to develop the extreme sensitivity to short day length in European hamsters during this phase. In natural conditions, the animals are able to recognize the shortening of photoperiod already in mid-July, when the photoperiod is reduced only by 30 min. To investigate the short-day response in sensitive European hamsters on the basis of the 2-coupled oscillator model of Pittendrigh and Daan (1976), daily activity and the reproductive state of European hamsters were recorded after an asymmetrical reduction of photoperiod from long (LD 16:08) to short (LD 08:16) photoperiods. The activity pattern of the animals showed an immediate response to the short photoperiod at the day of transfer when the night was extended only into the evening, but there was a significant delay in the response time when the night was extended into the morning. Thus, the evening oscillator E is more important in inducing the photoperiodic response than the morning oscillator M. Moreover, the broad intragroup variation in the latter conditions strongly suggests that the changes in the activity pattern were endogenously induced and that the animals were not able to recognize a lengthening of the night into the morning. Gonadal regression started in both groups 3 weeks after the change in the activity pattern, indicating that this process is initiated when the circadian system has received the short-day signal either through changes in photoperiod or through the circannual clock.     

Characterization of native and reconstituted exosome complexes from the hyperthermophilic archaeon Sulfolobus solfataricus

The eukaryotic exosome is a protein complex with essential functions in processing and degradation of RNA. Exosome-like complexes were recently found in Archaea. Here we characterize the exosome of Sulfolobus solfataricus. Two exosome fractions can be discriminated by density gradient centrifugation. We show that the Cdc48 protein is associated with the exosome from the 30S-50S fraction but not with the exosome of the 11.3S fraction. While only some complexes contain Cdc48, the archaeal DnaG-like protein was found to be a core exosome subunit in addition to Rrp4, Rrp41, Rrp42 and Csl4. Assays with depleted extracts revealed that the exosome is responsible for major ribonucleolytic activity in S. solfataricus. Various complexes consisting of the Rrp41-Rrp42 hexameric ring and Rrp4, Csl4 and DnaG were reconstituted. Dependent on their composition, different complexes showed variations in RNase activity indicating functional interdependence of the subunits. The catalytic activity of these complexes and of the native exosome can be ascribed to the Rrp41-Rrp42 ring, which degrades RNA phosphorolytically. Rrp4 and Csl4 do not exhibit any hydrolytic RNase activity, either when assayed alone or in context of the complex, but influence the activity of the archaeal exosome.     

Evolution of resistance during clonal expansion

Acquired drug resistance is a major limitation for cancer therapy. Often, one genetic alteration suffices to confer resistance to an otherwise successful therapy. However, little is known about the dynamics of the emergence of resistant tumor cells. In this article, we consider an exponentially growing population starting from one cancer cell that is sensitive to therapy. Sensitive cancer cells can mutate into resistant ones, which have relative fitness alpha prior to therapy. In the special case of no cell death, our model converges to the one investigated by Luria and Delbrück. We calculate the probability of resistance and the mean number of resistant cells once the cancer has reached detection size M. The probability of resistance is an increasing function of the detection size M times the mutation rate u. If Mu < 1, then the expected number of resistant cells in cancers with resistance is independent of the mutation rate u and increases with M in proportion to M(1-1/alpha) for advantageous mutants with relative fitness alpha>1, to l nM for neutral mutants (alpha = 1), but converges to an upper limit for deleterious mutants (alpha<1). Further, the probability of resistance and the average number of resistant cells increase with the number of cell divisions in the history of the tumor. Hence a tumor subject to high rates of apoptosis will show a higher incidence of resistance than expected on its detection size only.     

Drivers of litter mass loss and faunal composition of detritus patches change over time

Decomposition of vegetal detritus is one of the most fundamental ecosystem processes. In complex landscapes, the fate of litter of terrestrial plants may depend on whether it ends up decomposing in terrestrial or aquatic conditions. However, (1) to what extent decomposition rates are controlled by environmental conditions or by detritus type, and (2) how important the composition of the detritivorous fauna is in mediating decomposition in different habitats, remain as unanswered questions. We incubated two contrasting detritus types in three distinct habitat types in Coastal Georgia, USA, to test the hypotheses that (1) the litter fauna composition depends on the habitat and the litter type available, and (2) litter mass loss (as a proxy for decomposition) depends on environmental conditions (habitat) and the litter type. We found that the abundance of most taxa of the litter fauna depends primarily on habitat. Litter type became a stronger driver for some taxa over time, but the overall faunal composition was only weakly affected by litter type. Decomposition also depends strongly on habitat, with up to ca. 80% of the initial detrital mass lost over 25 months in the marsh and forest habitats, but less than 50% lost in the creek bank habitat. Mass loss rates of oak versus pine litter differed initially but converged within habitat types within 12 months. We conclude that, although the habitat type is the principle driver of the community composition of the litter fauna, litter type is a significant driver of litter mass loss in the early stages of the decomposition process. With time, however, litter types become more and more similar, and habitat becomes the dominating factor in determining decomposition of older litter. Thus, the major driver of litter mass loss changes over time from being the litter type in the early stages to the habitat (environmental conditions) in later stages.