Catecholamine Metabolism in Paraganglioma and Pheochromocytoma: Similar Tumors in Different Sites?

Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL.     

Landscape structure and the genetic effects of a population collapse

Both landscape structure and population size fluctuations influence population genetics. While independent effects of these factors on genetic patterns and processes are well studied, a key challenge is to understand their interaction, as populations are simultaneously exposed to habitat fragmentation and climatic changes that increase variability in population size. In a population network of an alpine butterfly, abundance declined 60–100% in 2003 because of low over-winter survival. Across the network, mean microsatellite genetic diversity did not change. However, patch connectivity and local severity of the collapse interacted to determine allelic richness change within populations, indicating that patch connectivity can mediate genetic response to a demographic collapse. The collapse strongly affected spatial genetic structure, leading to a breakdown of isolation-by-distance and loss of landscape genetic pattern. Our study reveals important interactions between landscape structure and temporal demographic variability on the genetic diversity and genetic differentiation of populations. Projected future changes to both landscape and climate may lead to loss of genetic variability from the studied populations, and selection acting on adaptive variation will likely occur within the context of an increasing influence of genetic drift.     

Use of space and habitats by meadow voles at the home range,patch and landscape scales

Using capture/recapture methods, we examined the spatial usage patterns of Microtus pennsylvanicus within and between experimentally created habitat patches of three sizes (1.0, 0.25 and 0.0625 ha) and between a 20-ha fragmented and a 20-ha continuous habitat landscape. We tested the prediction that home ranges near patch edges would be qualitatively different from those in patch interiors, and that the edge:interior habitat ratio could be used to make predictions concerning the dispersion and spatial use of individuals occupying different sized patches and between landscapes with different habitat structure. We found adult females on patch edges to have larger and more exclusive home ranges, larger body sizes, longer residence times, and to reproduce at a higher frequency than those in patch interiors. These edge effects also appeared to be largely responsible for the greater proportion of larger, reproductive females we found in small than larger patches and in the fragmented than in the continuous habitat (control) landscape. The selection of higher quality edge habitats by dominant females and the relegation of sub-dominants to patch interiors provides an explanation for the observed differences in the distribution and performance of females over patches and between landscapes.     

Reproductive asynchrony in natural butterfly populations and its consequences for female matelessness

1. Reproductive asynchrony, where individuals in a population are short-lived relative to the population-level reproductive period, has been identified recently as a theoretical mechanism of the Allee effect that could operate in diverse plant and insect species. The degree to which this effect impinges on the growth potential of natural populations is not yet well understood. 2. Building on previous models of reproductive timing, we develop a general framework that allows a detailed, quantitative examination of the reproductive potential lost to asynchrony in small natural populations. 3. Our framework includes a range of biologically plausible submodels that allow details of mating biology of different species to be incorporated into the basic reproductive timing model. 4. We tailor the parameter estimation methods of the full model (basic model plus mating biology submodels) to take full advantage of data from detailed field studies of two species of Parnassius butterflies whose mating status may be assessed easily in the field. 5. We demonstrate that for both species, a substantial portion of the female population (6.5-18.6%) is expected to die unmated. These analyses provide the first direct, quantitative evidence of female reproductive failure due to asynchrony in small natural populations, and suggest that reproductive asynchrony exerts a strong and largely unappreciated influence on the population dynamics of these butterflies and other species with similarly asynchronous reproductive phenology.     

Population changes in Czech passerines are predicted by their life‐history and ecological traits

A species’ susceptibility to environmental change might be predicted by its ecological and life‐history traits. However, the effects of such traits on long‐term bird population trends have not yet been assessed using a comprehensive set of explanatory variables. Moreover, the extent to which phylogeny affects patterns in the interspecific variability of population changes is unclear. Our study focuses on the interspecific variability in long‐term population trends and annual population fluctuations of 68 passerine species in the Czech Republic, assessing the effects of eight life‐history and five ecological traits. Ordination of life‐history traits of 68 species revealed a life‐history gradient, from ‘r‐selected’ (e.g. small body mass, short lifespan, high fecundity, large clutch size) to ‘K‐selected’ species. r‐selected species had more negative population trends than K‐selected species, and seed‐eaters declined compared with insectivores. We suggest that the r‐selected species probably suffer from widespread environmental changes, and the seed‐eaters from current changes in agriculture and land use. Populations of residents fluctuated more than populations of short‐distance migrants, probably due to the effect of winter climatic variability. Variance partitioning at three taxonomic levels showed that whereas population trends, population fluctuations and habitat specialization expressed the highest variability at the species level, most life‐history traits were more variable at higher taxonomic levels. These results explain the loss of statistical power in the relationship between life histories and population trends after controlling for phylogeny. However, we argue that a lack of significance after controlling for phylogeny should not reduce the value of such results for conservation purposes.     

Cell biology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in cell biology.     

Asynchronous transport to the cell surface of intestinal brush border hydrolases is not due to differential trimming of N-linked oligosaccharides

Intestinal brush border enzyme glycoproteins are transported to the microvillar membrane at different rates in the differentiated intestinal cell line Caco-2. This asynchronism is due to at least two rate-limiting events, a pre- and an intra-Golgi step (Stieger B., Matter, K., Baur, B., Bucher, K., H?chli, M., and Hauri, H.P. (1988) J. Cell Biol. 106, 1853-1861). A possible cause for the asynchronous protein transport might be differential trimming of N-linked oligosaccharide side chains. The effects of two trimming inhibitors on the intracellular transport of sucrase-isomaltase, a slowly migrating hydrolase, and dipeptidylpeptidase IV, a rapidly migrating hydrolase, are described. 1-Deoxymannojirimycin, an inhibitor of Golgi alpha-mannosidase I, had no influence on the rate of appearance of these hydrolases in the brush border membrane as assessed by subcellular fractionation. In the presence of N-methyl-1-deoxynojirimycin, an inhibitor of glucosidase I, 30-40% of the newly synthesized molecules appeared at the cell surface, and half-time for appearance of this pool was identical to that found in control cells. The reduced maximal transport to the cell surface observed with N-methyl-1-deoxynojirimycin may suggest that proper glycosylation is necessary for an efficient transport from the Golgi apparatus to the microvillar membrane. Inhibition of glucosidase I does not prevent the acquisition of endoglycosidase H resistance. Furthermore, evidence is presented that the processing in the presence of N-methyl-1-deoxynojirimycin leads to glycosylated endoglycosidase H-resistant glycoproteins.     

Neutrophil chemotaxis and enzyme release competitive inhibition by a diazoacetamide pepsin inhibitor

Treatment of human neutrophils with a reagent (diazoacetylnorleucine methyl ester plus copper ion) which covalently labels the active site of the acid proteases, pepsin and cathepsin D, inhibits neutrophil chemotaxis and enzyme release stimulated by the chemoattractants pepstatin and formylmethiony peptides. In contrast, chemotaxis and enzyme release in response to zymosan activated serum are not affected. Furthermore, diazoacetylnorleucine methy ester plus copper competes with [3H]formylmethionyl leucylphenylalanine for binding to neutrophils. Since pepstatin shares binding sites with formylmethionyl leucylphenylalanine, the present data suggest that diazoacetylnorleucine methyl ester plus copper reacts with the neutrophil receptor for pepstatin and formylmethionyl peptides, and thus may be useful in further characterization of this structure.