General synthesis and biological evaluation of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides)

A general synthesis of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of alpha-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of alpha-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.     

Smooth tests for the zero-inflated poisson distribution

In this article we construct three smooth goodness-of-fit tests for testing for the zero-inflated Poisson (ZIP) distribution against general smooth alternatives in the sense of Neyman. We apply our tests to a data set previously claimed to be ZIP distributed, and show that the ZIP is not a good model to describe the data. At rejection of the null hypothesis of ZIP, the individual components of the test statistic, which are directly related to interpretable parameters in a smooth model, may be used to gain insight into an alternative distribution.     

Modulation of prolactin but not corticosterone responses to stress in relation to parental effort in a long-lived bird

We tested the hypothesis that parental effort modulates the magnitude of corticosterone and prolactin responses to stress in a long-lived bird, the Black-legged kittiwake (Rissa tridactyla). To do so, we compared corticosterone and prolactin responses to capture/restraint stress between chick-rearing birds and failed breeders (no parental effort). We predicted that (1) the increase in plasma corticosterone levels in response to stress should be lower in chick-rearing birds, (2) the decrease in plasma prolactin levels in response to stress should be lower in chick-rearing birds, and (3) as both sexes care for the chick, there should be no sex difference in the hormonal response to stress. Baseline plasma corticosterone and prolactin levels were higher in chick-rearing birds and were not influenced by body condition. Failed breeders were in better condition than chick-rearing individuals. Corticosterone response to stress was unaffected by parental effort as both chick-rearing and failed birds exhibited a robust corticosterone increase. Prolactin response to stress was however clearly influenced by parental effort: chick-rearing birds showed a modest 9% prolactin decrease whereas in failed birds prolactin concentrations fell by 41%. Body condition did not influence hormonal responses to stress. When facing stressful condition, breeding kittiwakes attenuate their prolactin response to stress while enhancing their secretion of corticosterone. Increasing corticosterone secretion triggers foraging efforts and diminishes nest attendance whereas an attenuation of prolactin response to stress maintains parental behavior. We suggest that this hormonal mechanism facilitates a flexible time-budget that has been interpreted as a buffer against environmental variability.     

Oxo-rhenium(V) complexes with analogs of bis(diphenylphosphino)ethane

Compounds of the types ReOCl₃(L-L) and ReOCl₂(OEt)(L-L) with bis(diphenylphosphino)ethene (dppen) and bis(diphenylphosphino)ferrocene (dppf) were prepared by reacting the diphosphine with ReOCl₃(OPPh₃)(Me₂S). The ReOCl₃(L-L) compound with bis(diphenylarsino)ethane (dpae) was prepared similarly. Crystallographic work on ReOCl₃(dppen) and ReOCl₃(dpae) confirmed the approximate octahedral environment of the metal and the presence of a Cl ligand trans to the ReO bond. The ReOCl₂(OEt)(L-L) compounds contain a transORe-OEt unit. The visible spectra of both types of compounds include a two-component d-d absorption pattern originating from the spin-allowed excitation of a d electron from the interaxial d orbital in the equatorial plane to the empty d_xz and d_yz orbitals. For ReOCl₂(OEt)(dppf), these bands are masked by strong transitions taking place in the ferrocene moiety. The absorptions of the other systems are not greatly displaced compared to the similar dppe compounds, a small decrease in the transition energy being noted for the dpae complex.     

Fishing for biodiversity: novel methanopterin-linked C transfer genes deduced from the Sargasso Sea metagenome

The recently generated database of microbial genes from an oligotrophic environment populated by a calculated 1800 major phylotypes (the Sargasso Sea metagenome-SSM) presents a great source for expanding local databases of genes indicative of a specific function. In this article we analyse the SSM for the presence of methanopterin-linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest are present in this environment. The sequences representative of these major phylotypes do not appear to belong to any known microbial group capable of methanopterin-linked C1 transfer. Instead, these sequences separate from all known sequences on phylogenetic trees, pointing toward their affiliation with novel microbial phyla. These data imply a broader distribution of methanopterin-linked functions in the microbial world than has been previously known.     

Development and application of polymerase chain reaction primers based on fhcD for environmental detection of methanopterin-linked C1-metabolism in bacteria

In this work we describe development and testing of a novel pair of environmental primers targeting fhcD, a conserved gene in the H4MTP-linked C1-transfer pathway, and demonstrate that these primers enable confident detection of a broad variety of fhcD genes originating from phylogenetically diverse bacteria. The new primer pair was employed to analyse fhcD diversity in Lake Washington sediment, uncovering the presence of 40 fhcD phylotypes. Based on phylogenetic analyses, the phylotypes identified were affiliated with alpha-, beta- and gamma-proteobacteria, and Planctomycetes, while a number of sequences formed deep branches suggesting the presence of unknown groups of microorganisms. To assess the physiological potential and the possible substrate repertoire of the fhcD-containing species in Lake Washington, we conducted enrichments of natural populations on a variety of C1 substrates, and observed specific shifts in community structure in response to different C1 substrates. A specific shift in community structure was also observed in the presence of humic acids suggesting that C1 transfer metabolism linked to H4MPT may be part of the degradation pathway for this natural polymer, possibly involving formaldehyde production. Overall, our data suggest that C1 oxidation reactions linked to H4MPT are much more widespread in natural environments than previously thought.     

Diversity of functional genes of methanogens, methanotrophs and sulfate reducers in deep-sea hydrothermal environments

To contribute to the identification of methanogens, methanotrophs and sulfate-reducing bacteria (SRB) in microbial communities from the 13 degrees N (East Pacific Rise) and Rainbow (Mid-Atlantic Ridge) hydrothermal vent fields, we investigated the diversity of mcrA, pmoA and dsrAB genes sequences. Clone libraries were obtained using DNA isolated from fragments of diffuse vents, sediment and in situ samplers. The clones were categorized by restriction fragment length polymorphism, and representatives of each group were sequenced. Sequences were related to that of hyperthermophilic (order Methanopyrales and family Methanocaldococcaceae), thermophilic and mesophilic (family Methanococcaceae) methanogens, thermophilic (proposed genus 'Methylothermus') and mesophilic type I methanotrophs, and hyperthermophilic (order Archaeoglobales), thermophilic (order Thermodesulfobacteriales) and mesophilic (family Desulfobulbaceae) SRB. Several of the obtained sequences were distantly related to the genes of cultivated organisms, providing evidence of the existence of novel lineages in the three functional groups. This study provides for the first time an insight into the diversity of several functional genes of deep-sea hydrothermal system microorganisms.