Dynamic features of allosteric Ca2+ sensor in tissue-specific NCX variants

The Na(+)-Ca(2+) exchanger (NCX) mediated Ca(2+) fluxes are essential for handling Ca(2+) homeostasis in many cell-types. Eukaryotic NCX variants contain regulatory CBD1 and CBD2 domains, whereas in distinct variants the Ca(2+) binding to Ca3-Ca4 sites of CBD1 results either in sustained activation, inhibition or no effect. CBD2 contains an alternatively spliced segment, which is expressed in a tissue-specific manner although its impact on allosteric regulation remains unclear. Recent studies revealed that the Ca(2+) binding to Ca3-Ca4 sites results in interdomain tethering of CBDs, which rigidifies CBDs movements with accompanied slow dissociation of "occluded" Ca(2+). Here we investigate the effects of CBD2 variants on Ca(2+) occlusion in the two-domain construct (CBD12). Mutational studies revealed that both sites (Ca3 and Ca4) contribute to Ca(2+) occlusion, whereas after dissociation of the first Ca(2+) ion the second Ca(2+) ion becomes occluded. This mechanism is common for the brain, kidney and cardiac splice variants of CBD12, although the occluded Ca(2+) exhibits 20-50-fold difference in off-rates among the tested variants. Therefore, the spliced exons on CBD2 affect the rate-limiting step of the occluded Ca(2+) dissociation at the primary regulatory sensor to shape dynamic features of allosteric regulation in NCX variants.     

Correction to: Dose–responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003

Radiation and Environmental Biophysics - The article Dose–responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003, written by Helmut...     

The heat shock protein HSP70 promotes mouse NK cell activity against tumors that express inducible NKG2D ligands

The stress-inducible heat shock protein (HSP) 70 is known to function as an endogenous danger signal that can increase the immunogenicity of tumors and induce CTL responses. We show in this study that HSP70 also activates mouse NK cells that recognize stress-inducible NKG2D ligands on tumor cells. Tumor size and the rate of metastases derived from HSP70-overexpressing human melanoma cells were found to be reduced in T and B cell-deficient SCID mice, but not in SCID/beige mice that lack additionally functional NK cells. In the SCID mice with HSP70-overexpressing tumors, NK cells were activated so that they killed ex vivo tumor cells that expressed NKG2D ligands. In the tumors, the MHC class I chain-related (MIC) A and B molecules were found to be expressed. Interestingly, a counter selection was observed against the expression of MICA/B in HSP70-overexpressing tumors compared with control tumors in SCID, but not in SCID/beige mice, suggesting a functional relevance of MICA/B expression. The melanoma cells were found to release exosomes. HSP70-positive exosomes from the HSP70-overexpressing cells, in contrast to HSP70-negative exosomes from the control cells, were able to activate mouse NK cells in vitro to kill YAC-1 cells, which express NKG2D ligands constitutively, or the human melanoma cells, in which MICA/B expression was induced. Thus, HSP70 and inducible NKG2D ligands synergistically promote the activation of mouse NK cells resulting in a reduced tumor growth and suppression of metastatic disease.     

Spring migration dynamics and sex-specific patterns in stopover strategy in the Wood Sandpiper Tringa glareola

Due to being a virtually monomorphic wader species, migration dynamics and sex-related migration patterns in the Wood Sandpiper (Tringa glareola) have rarely been investigated. We captured spring migrants at an important stopover site in northeastern Austria. Birds were individually color-marked, and sex was determined by an analysis of DNA from tail feather material. Among temporary residents (birds seen again after day of capture), males migrated on average 3 days earlier than females. However, since sexes did not differ in fat score, the length of stay and the proportion of transients (birds not seen again after day of capture) and temporary residents, we suggest that males and females adopt similar migration strategies in the spring. The large number of transients captured as well as shorter stopover durations in later temporary residents indicate that Wood Sandpipers minimize time at this stage of their northbound migration. Temporary residents earlier in the season exhibited lower fat stores than later ones. Nevertheless, since the fat stores of transients and temporary residents were similar even after the progress of the season had been accounted for, we assume that Wood Sandpipers may afford to exhibit individual flexibility in migration strategy and the use of stopover sites, especially early in the season. This variability may be a necessary adaptation to cope with possible varying environmental conditions at dynamic and unpredictable inland stopover sites. After having reached North Mediterranean regions, mean body mass of spring migrants gradually increases during successive stopovers, indicating that Wood Sandpipers follow a ‘hopping’ migration strategy. This emphasizes the high conservation value of even small artificial mudflat pools as important stepping stones in order to maintain a continuous network of wetland habitats for this continental migrant.     

Clinical studies on the appearance of natural anterior teeth in young and old adults

Objectives: To evaluate the typical appearance of natural anterior teeth in young and elderly people and to develop guidelines for the natural appearance of dentures. Design: Clinical examination and photography. Inclusion criteria were a dental state with natural anterior teeth and no more than two crowns. Subjects: A study group (SG) consisting of 64 patients ranging in age from 60 to 86 years (67.3 ± 5.8) and a control group (CG) composed of 64 dental students aged 21–33 years (25.8 ± 2.4). Setting: Dental schools of the Johannes‐Gutenberg‐University Mainz and the University of Leipzig. Results: Most participants were content with the appearance of their own natural teeth. With relaxed lips a mean of 1.5 (±0.19) mm of upper incisors and 1.6 (±0.19) mm of lower incisors were visible in the SG compared with 2.5 (±0.16) and 0.4 (±0.07) mm in the CG, respectively. The subjects in the SG showed a greater diversity in position of teeth in the anterior arch and this was more often with incisors than with canines. Features such as stains, cracks and defects were much more noticeable in the SG. An inter‐dental ‘black triangle’ seemed to be a typical feature of an aged dental appearance. Conclusion: The majority of people older than 60 years who still have their own natural anterior teeth would not wish for a change in appearance if they needed a prosthodontic reconstruction. Thus techniques for customisation should be promoted to obtain a natural appearance in dentures.     

Forest Modification Affects Diversity (But Not Dynamics) of Speciose Tropical Pyraloid Moth Communities

We studied temporal and spatial dynamics of extremely diverse moth ensembles (Lepidoptera: Pyraloidea) along a gradient of forest disturbance ranging from undisturbed primary tropical rain forest to different kinds of modified forest and open cultivated land at the margin of Mount Kinabalu National Park (Sabah, East Malaysia). We sampled moths by light trapping during two periods (March‐May and August‐September 1997). We collected a total of 7724 individuals representing 680 species during 78 light‐trapping nights at six study sites. Species diversity (Fisher's α) of ensembles in undisturbed primary forest was distinctly higher than in disturbed or secondary forest. More pyraloid moths were attracted in undisturbed primary forest. Samples from disturbed primary or old‐growth secondary forest were statistically indistinguishable from the undisturbed primary forest ensemble in regard to species composition. Thus, pyraloid ensembles from disturbed forest with tall trees remaining appeared to represent impoverished subsets of the undisturbed primary forest community. The more heavily disturbed sites had a distinct fauna and showed a stronger faunal differentiation among each other. Four species of the genus Eoophyla, in which aquatic larvae feed on algae in fast‐running streams benefited prominently from forest disturbance. Temporal variation of ensembles was remarkably concordant across the disturbance gradient. Relative abundance variation of the commonest species was identical at all sites. Overall, pyraloid moths responded more sensitively to anthropogenic habitat alteration than most other moth taxa studied thus far in tropical regions and allowed for an analysis of diversity patterns at a high temporal resolution.     

Causes of variation in mineral soil C content and turnover in differently managed beech dominated forests

Background and aims

Forest soils are important carbon stores and considered as net CO₂ sinks over decadal to centennial time scales. Intensive forest management is thought to reduce the carbon sequestration potential of forest soils. Here we study the effects of decades of forest management (as unmanaged forest, forest under selection cutting, forest under age class management) on the turnover of mineral associated soil organic matter (MOM) in German beech (Fagus sylvatica L.) dominated forests.

Methods

Radiocarbon contents were determined by accelerator mass spectrometry (AMS) in 79 Ah horizon MOM fractions of Cambisols (n?=?13), Luvisols (n?=?51) and Stagnosols (n?=?15). Mean residence times (MRTs) for soil organic carbon (SOC) were estimated with a 2-pool model using the litter input derived from a forest inventory.

Results

MOM fractions from Ah horizons contained 64?±?8.8 % of the bulk SOC. The radiocarbon content of MOM fractions in Ah horizons, expressed as Δ¹⁴C, ranged between ?2.8?‰ and 114?‰ for the three soil groups. Almost all samples contained a detectable proportion of ‘bomb’ carbon fixed from the atmosphere since 1963. Under the assumption that depending on the soil texture between 19 % and 24 % of the SOC from the labile pool is transferred to the stable SOC pool, the corresponding MRTs ranged between 72 and 723 years, with a median of 164 years.

Conclusions

Our results indicate that the MOM fraction of Ah horizons from beech forests contained a high proportion of young carbon, but we did not find a significant decadal effect of forest management on the radiocarbon signature and related turnover times. Instead, both variables were controlled by clay contents and associated SOC concentrations (p?<?0.01). This underlines the importance of pedogenic properties for SOC turnover in the MOM fraction.     

Structure-activity relationship studies on 1-(5-carboxyindol-1-yl)-propan-2-one inhibitors of human cytosolic phospholipase A2α: variation of the activated ketone moiety

Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 have been found to be potent inhibitors of human cytosolic phospholipase A₂α (cPLA₂α). In course of structure-activity relationship studies, we investigated the effect of the substitution of the electrophilic ketone group in the middle part of the molecule by other polar residues, such as hydroxyimino, azido, acyloxy, acylamino, urea and carbamate, on enzyme inhibition. With an IC₅₀ of 1.7 μM against cPLA₂α from human platelets, the 4-fluorophenylcarbamate derivative 23f was the most active of the compounds tested.     

5 alpha-androstane-3 beta,17 beta-diol hydroxylating enzymes in stroma and epithelium of human benign prostatic hyperplasia (BPH)

As enzymatic hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) may be a factor in controlling the 5 alpha-dihydrotestosterone (DHT) content in the prostate, we were interested in activity and distribution of these enzymes in epithelium and stroma of human benign prostatic hyperplasia (BPH). The enzyme activities were measured after mechanical separation of BPH tissue from 15 patients of various ages into stroma and epithelium, and optimization of the in vitro transformation of 3 beta-diol to hydroxylated products, which were analyzed by HPLC. The main results were: (1) 3 beta-diol was hydroxylated at C-7 alpha, C-7 beta, C-6 alpha, and C-6 beta. (2) The mean Michaelis constant Km (nM +/- SEM) for hydroxylation at C-7 alpha(beta) (168 +/- 21) was significantly lower than at C-6 alpha(beta) (601 +/- 43) without differences between stroma and epithelium. (3) Hydroxylation at alpha position dominated significantly over that at beta. (4) The mean maximal metabolic rate Vmax (pmol . mg protein-1 . h-1) of hydroxylation at C-6 alpha was about 7-fold lower in stroma (3.4 +/- 0.2) than in epithelium (23.8 +/- 4.1), concerning the other hydroxylations, Vmax was about 1.6-fold lower in stroma. (5) With increasing age of the patients there was a significant decrease of the 3 beta-diol hydroxylation in stroma and epithelium. It is discussed that the significantly lower activity of 3 beta-diol hydroxylation in stroma compared to epithelium and the decrease of activity with increasing age might potentiate the DHT accumulation in stroma of BPH.