THE PRIMARY STRUCTURE OF PANCREATIC-POLYPEPTIDE FROM A PRIMITIVE INSECTIVOROUS MAMMAL, THE EUROPEAN HEDGEHOG (ERINACEOUS-EUROPAEUS)

Pancreatic polypeptide (PP) has been isolated from extracts of the pancreas of the European hedgehog (Erinaceous europaeus) which is a representative of the order Insectivora, deemed to be the most primitive group of placental mammals. Pancreatic tissues were extracted in acidified ethanol and the peptide was purified chromatographically using a PP C-terminal hexapeptide amide specific radioimmunoassay to monitor purification. Two major PP-immunoreactive peptides were baseline-resolved following the final analytical reverse phase HPLC fractionation. Each was separately subjected to plasma desorption mass spectroscopy (PDMS) and gas-phase sequencing. The molecular masses of each peptide were similar: (I) 4237.6 +/- 4 Da and (II) 4238.2 +/- 4 Da. The full primary structures of each peptide were deduced and these were identical: VPLEPVYPGDNATPEQMAHYAAELRRYINMLTRPRY. The peptides were deemed to be amidated due to their full molar cross-reactivity with the amide-requiring PP antiserum employed in radioimmunoassay. The molecular mass (4233.8 Da) calculated from the sequence was in close agreemeent with PDMS estimates and the reason for the different retention times of each peptide is unknown at present. Hedgehog PP exhibits only 2 unique amino acid substitutions, at positions 1 (Val) and 19 (His), when compared with other mammalian analogues.

Helokinestatin-7 peptides from the venoms of Heloderma lizards

Helokinestatins 1–6 constitute a family of bradykinin antagonist peptides originally isolated from the venoms of the Gila Monster, Heloderma suspectum and the Mexican beaded lizard, Heloderma horridum. Here we report the identification, isolation and preliminary pharmacological characterization of two novel tridecapeptides, named helokinestatin-7S (FDDDSTELILEPR – 1550 Da) and helokinestatin-7H (FDDDSRKLILEPR – 1604 Da), whose primary structures were predicted from cDNAs cloned from venom libraries of respective Heloderma lizards. Computed molecular masses of putative helokinestatin-7 peptides were used as tools to locate these peptides in archived LC/MS fractions from respective venoms and sequences were confirmed by MS/MS fragmentation. A synthetic replicate of helokinestatin-7H was found to antagonize the relaxation effect of bradykinin on rat arterial smooth muscle but to have no measurable effects alone. In contrast, synthetic helokinestatin-7S was found to directly contract this preparation. Studies on related natural peptides with subtle differences in primary structure can provide the tools for structure/activity studies in pharmacological investigations directed toward unraveling the molecular basis of venom toxicity and for the evaluation of potential therapeutic leads.

Genetic analysis of the O7-polysaccharide biosynthesis region from the Escherichia coli O7:K1 strain VW187

We recently cloned biosynthesis genes for the O7-lipopolysaccharide (O7-LPS) side chain from the Escherichia coli K-1 strain VW187 (M. A. Valvano, and J. H. Crosa, Infect. Immun. 57:937-943, 1989). To characterize the O7-LPS region, the recombinant cosmids pJHCV31 and pJHCV32 were mutagenized by transposon mutagenesis with Tn3HoHo1, which carries a promoterless lac operon and can therefore generate lacZ transcriptional fusions with target DNA sequences. Cells containing mutated plasmids were examined for their ability to react by coagglutination with O7 antiserum. The LPS pattern profiles of the insertion mutants were also investigated by electrophoresis of cell envelope fractions, followed by silver staining and immunoblotting analysis. These experiments identified three phenotypic classes of mutants and defined a region in the cloned DNA of about 14 kilobase pairs that is essential for O7-LPS expression. Analysis of beta-galactosidase production by cells carrying plasmids with transposon insertions indicated that transcription occurs in only one direction along the O7-LPS region. In vitro transcription-translation experiments revealed that the O7-LPS region encodes at least 16 polypeptides with molecular masses ranging from 20 to 48 kilodaltons. Also, the O7-LPS region in VW187 was mutagenized by homologous recombination with subsets of the cloned O7-LPS genes subcloned into a suicide plasmid vector. O7-LPS-deficient mutants of VW187 were complemented with pJHCV31 and pJHCV32, confirming that these cosmids contain genetic information that is essential for the expression of the O7 polysaccharide.

Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole

An in vivo study in the laboratory rat model has been carried out to monitor morphological changes in adult Fasciola hepatica over a 4-day period resulting from co-treatment with triclabendazole (TCBZ) and ketoconazole (KTZ), a cytochrome P450 inhibitor. Rats were infected with the triclabendazole-resistant Oberon isolate of F. hepatica, dosed orally with triclabendazole at a dosage of 10mg/kg live weight and ketoconazole at a dosage of 10mg/kg live weight. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.) and changes to fluke ultrastructure were assessed using transmission electron microscopy (TEM). Results showed an increase in the severity of changes to the fluke ultrastructure with time p.t. Swelling of the basal infolds and the associated mucopolysaccharide masses became more severe with time. Golgi complexes, if present, were greatly reduced in size and number by 96 h p.t., and sub-tegumental flooding was seen from the 72 h time-period onwards. Some sloughing of the tegumental covering over the spines was observed at 96 h p.t. The results demonstrated that the Oberon isolate is more sensitive to TCBZ action in the presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug metabolism is involved in the resistance mechanism. Moreover, they support the concept that TCBZ+inhibitor combinations (aimed at altering drug pharmacokinetics and potentiating the action of TCBZ) could be used in the treatment of TCBZ-R populations of F. hepatica.

Glaciers and climate in Pacific Far NE Russia during the Last Glacial Maximum

A combined geomorphological–physical model approach is used to generate three-dimensional reconstructions of glaciers in Pacific Far NE Russia during the global Last glacial Maximum (gLGM). The horizontal dimensions of these ice masses are delineated by moraines, their surface elevations are estimated using an iterative flowline model and temporal constraints upon their margins are derived from published age estimates. The equilibrium line altitudes (ELAs) of these ice masses are estimated, and gLGM climate is reconstructed using a simple degree–day melt model. The results indicate that, during the gLGM, ice masses occupying the Pekulney, Kankaren and Sredinny mountains of Pacific Far NE Russia were of valley glacier and ice field type. These glaciers were
between 7 and 80 km in length, and were considerably less extensive than during pre-LGM phases of advance. gLGM ice masses in these regions had ELAs of between 575± 22m and 1035±41m (above sea level) – corresponding to an ELA depression of 350–740 m, relative to present. Data indicate that, in the Pekulney Mountains, this ELA depression occurred because of a 6.48°C reduction
in mean July temperature, and 200mm a¯¹ reduction in precipitation, relative to present. Thus reconstructions support a restricted view of gLGM glaciation in Pacific Far NE Russia and indicate that the region’s aridity precluded the development of large continental ice sheets.

Late Quaternary glaciations in Far NE Russia; combining moraines, topography and chronology to assess regional and global glaciation synchrony

During various periods of Late Quaternary glaciation, small ice-sheets, -caps, -fields and valley glaciers, occupied the mountains and uplands of Far NE Russia (including the Verkhoyansk, Suntar-Khayata, and Chersky Mountains; the KolymaeAnyuy and Koryak Highlands; and much of the Kamchatka and Chukchi
Peninsulas). Here, the margins of former glaciers across this region are constrained through the comprehensive mapping of moraines from remote sensing data (Landsat 7 ETM+ satellite images; ASTER Global Digital Elevation Model (GDEM2); and Viewfinder Panorama DEM data). A total of 8414 moraines
are mapped, and this record is integrated with a series of published age-estimates (n = 25), considered to chronologically-constrain former ice-margin positions. Geomorphological and chronological data are compiled in a Geographic Information System (GIS) to produce ‘best estimate’ reconstructions of ice extent during the global Last Glacial Maximum (gLGM) and, to a lesser degree, during earlier phases of glaciation. The data reveal that much of Far NE Russia (~1,092,427 km2) preserves a glaciated landscape (i.e. is bounded by moraines), but there is no evidence of former ice masses having extended more than 270 km beyond mountain centres (suggesting that, during the Late Quaternary, the region has not been occupied by extensive ice sheets). During the gLGM, specifically, glaciers occupied ~253,000 km2, and rarely extended more than 50 km in length. During earlier (pre-gLGM) periods, glaciers were more extensive, though the timing of former glaciation, and the maximum Quaternary extent, appears to have been asynchronous across the region, and out-of-phase with ice-extent maxima elsewhere in the Northern Hemisphere. This glacial history is partly explained through consideration of climatic-forcing
(particularly moisture-availability, solar insolation and albedo), though topographic-controls upon the former extent and dynamics of glaciers are also considered, as are topographic-controls upon moraine deposition and preservation. Ultimately, our ability to understand the glacial and climatic history of this region is restricted when the geomorphological-record alone is considered, particularly as directly-dated glacial deposits are few, and topographic and climatic controls upon the moraine record are difficult to
distinguish.

An updated moraine map of Far NE Russia

Barr and Clark published a series of maps depicting the distribution of end moraines across Far NE Russia. These
moraines outlined the former distribution and dimensions of glaciers, and were identified through the analysis of
Landsat ETM+ satellite images (15- and 30-m resolution). Now, a number of freely available digital elevation
model (DEM) datasets are available, which cover the entire 4 million km2 of Far NE Russia. These include
the 30-m resolution ASTER GDEM and the 90-m resolution Viewfinder Panorama DEM. Here we use these
datasets, in conjunction with Landsat ETM+ images, to complete the process of systematically and
comprehensively mapping end moraines. With the aid of the DEMs described above, here we present a total
dataset of 8414 moraines, which almost quadruples the inventory of Barr and Clark. This increase in the
number of moraines is considered to reflect the utility of the DEMs for mapping glacial landforms. In terms of
moraine distribution, the Barr and Clark map and the one presented here are comparable, with moraines found
to cluster in highland regions and upon adjacent lowlands, attesting to the former occupation of the region by
mountain-centred ice masses. This record is considered to reflect palaeoclimatic and topographic controls upon
the extent and dynamics of palaeoglaciers, as well as spatial variability in moraine preservation.

Modelling the cycling of persistent organic pollutants (POPs) in the North Sea system: Fluxes, loading, seasonality, trends

The fate and cycling of two selected POPs is investigated for the North Sea system with an improved version of a fate and transport ocean model (FANTOM). The model uses atmospheric data from the EMEP MSC East POP model (Gusev et al., 2009), giving reasonable concentrations and seasonal distributions for the entire region, as opposed to the three observation stations that Ilyina et al. (2006) were limited to. Other model improvements include changes in the calculation of POP exchange between the water column and sediment.

We chose to simulate the fate of two POPs with very different properties, ?-HCH and PCB 153. Since the fate and cycling of POPs are strongly affected by hydrodynamic processes, a high resolution version of the Hamburg Shelf Ocean Model (HAMSOM) was developed and utilised. Simulations were made for the period 1996–2005. Both models were validated by comparing results with available data, which showed that the simulations were of very satisfactory quality.

Model results show that the North Sea is a net sink for ?-HCH and a net source to the atmosphere of PCB 153. Total masses of ?-HCH and PCB 153 in 2005 are reduced to 30% and 50%, respectively, of 1996 values.

Storms resuspending bottom sediments into the water column mobilise POPs into the atmosphere and have the potential to deliver substantial loads of these POPs into Europe.

A comparison of three bacterial phosphonoacetate hydrolases from different environmental sources

Cleavage of the carbon-phosphorus bond of the xenobiotic phosphonoacetate by phosphonoacetate hydrolase: represents a novel route for the microbial metabolism of organophosphonates, and is unique in that it: is substrate-inducible and its expression is independent of the phosphate status of the cell. The enzyme has previously only been demonstrated in cell extracts of Pseudomonas fluorescens 23F. Phosphonoacetate hydrolase activity is now reported in extracts of environmental Curtobacterium sp. and Pseudomonas sp. isolates capable of the phosphate-insensitive mineralization of phosphonoacetate as the sole source of carbon, energy and phosphorus at concentrations up to 40 mmol l(-1) and 100 mmol l(-1), respectively. The enzymes in both strains were similarly inducible by phosphonoacetate and had a unique specificity ibr this substrate. However, they differed significantly from each other, and from the previously described Ps. fluorescens 23F enzyme, in respect of their apparent molecular masses, temperature optima, thermostability, sensitivity to inhibition by chelating agents and by structural analogues of phosphonoacetate, and in their affinities for the substrate.

THE MARINE RADIOCARBON BOMB PULSE ACROSS THE TEMPERATE NORTH ATLANTIC: A COMPILATION OF Delta C-14 TIME HISTORIES FROM ARCTICA ISLANDICA GROWTH INCREMENTS

Marine radiocarbon bomb-pulse time histories of annually resolved archives from temperate regions have been underexploited. We present here series of Delta C-14 excess from known-age annual increments of the long-lived bivalve mollusk Arctica islandica from 4 sites across the coastal North Atlantic (German Bight, North Sea; Tromso, north Norway; Siglufjordur, north Icelandic shelf; Grimsey, north Icelandic shelf) combined with published series from Georges Bank and Sable Bank (NW Atlantic) and the Oyster Ground (North Sea). The atmospheric bomb pulse is shown to be a step-function whose response in the marine environment is immediate but of smaller amplitude and which has a longer decay time as a result of the much larger marine carbon reservoir. Attenuation is determined by the regional hydrographic setting of the sites, vertical mixing, processes controlling the isotopic exchange of C-14 at the air-sea boundary, C-14 content of the freshwater flux, primary productivity, and the residence time of organic matter in the sediment mixed layer. The inventories form a sequence from high magnitude-early peak (German Bight) to low magnitude-late peak (Grimsey). All series show a rapid response to the increase in atmospheric Delta C-14 excess but a slow response to the subsequent decline resulting from the succession of rapid isotopic air-sea exchange followed by the more gradual isotopic equilibration in the mixed layer due to the variable marine carbon reservoir and incorporation of organic carbon from the sediment mixed layer. The data constitute calibration series for the use of the bomb pulse as a high-resolution dating tool in the marine environment and as a tracer of coastal ocean water masses.

The changing pattern of adult primary glomerular disease

Published biopsy series have shown geographical and temporal variations in the patterns of primary glomerulonephritis (GN). IgA nephropathy is the most common type of GN in most European studies, but there is evidence suggesting that focal segmental glomerulosclerosis (FSGS) is increasingly common in the USA in all ethnic groups. We report the analysis of 30 years of native renal biopsies and the temporal pattern of primary glomerular disease in a single United Kingdom (UK) region.

WASP-52b, WASP-58b, WASP-59b, and WASP-60b: Four new transiting close-in giant planets

We present the discovery of four new transiting hot jupiters, detected mainly from SuperWASP-North and SOPHIE observations. These new planets, WASP-52b, WASP-58b, WASP-59b, and WASP-60b, have orbital periods ranging from 1.7 to 7.9 days, masses between 0.46 and 0.94 M_Jup, and radii between 0.73 and 1.49 R_Jup. Their G1 to K5 dwarf host stars have V magnitudes in the range 11.7-13.0. The depths of the transits are between 0.6 and 2.7%, depending on the target. With their large radii, WASP-52b and 58b are new cases of low-density, inflated planets, whereas WASP-59b is likely to have a large, dense core. WASP-60 shows shallow transits. In the case of WASP-52 we also detected the Rossiter-McLaughlin anomaly via time-resolved spectroscopy of a transit. We measured the sky-projected obliquity lambda = 24 (+17/-9) degrees, indicating that WASP-52b orbits in the same direction as its host star is rotating and that this prograde orbit is slightly misaligned with the stellar equator. These four new planetary systems increase our statistics on hot jupiters, and provide new targets for follow-up studies.

Detonations in sub-chandrasekhar-mass C+O white dwarfs

Explosions of sub-Chandrasekhar-mass white dwarfs (WDs) are one alternative to the standard Chandrasekhar-mass model of Type Ia supernovae (SNe Ia). They are interesting since binary systems with sub-Chandrasekhar-mass primary WDs should be common and this scenario would suggest a simple physical parameter which determines the explosion brightness, namely the mass of the exploding WD. Here we perform one-dimensional hydrodynamical simulations, associated post-processing nucleosynthesis, and multi-wavelength radiation transport calculations for pure detonations of carbon-oxygen WDs. The light curves and spectra we obtain from these simulations are in good agreement with observed properties of SNe Ia. In particular, for WD masses from 0.97 to 1.15 Msun we obtain 56Ni masses between 0.3 and 0.8 Msun, sufficient to capture almost the complete range of SN Ia brightnesses. Our optical light curve rise times, peak colors, and decline timescales display trends which are generally consistent with observed characteristics although the range of B-band decline timescales displayed by our current set of models is somewhat too narrow. In agreement with observations, the maximum light spectra of the models show clear features associated with intermediate-mass elements and reproduce the sense of the observed correlation between explosion luminosity and the ratio of the Si II lines at ?6355 and ?5972. We therefore suggest that sub-Chandrasekhar-mass explosions are a viable model for SNe Ia for any binary evolution scenario leading to explosions in which the optical display is dominated by the material produced in a detonation of the primary WD. © 2010. The American Astronomical Society.

Double-detonation sub-Chandrasekhar supernovae: Synthetic observables for minimum helium shell mass models

In the double-detonation scenario for Type Ia supernovae, it is suggested that a detonation initiates in a shell of helium-rich material accreted from a companion star by a sub-Chandrasekhar-mass white dwarf. This shell detonation drives a shock front into the carbon-oxygen white dwarf that triggers a secondary detonation in the core. The core detonation results in a complete disruption of the white dwarf. Earlier studies concluded that this scenario has difficulties in accounting for the observed properties of Type Ia supernovae since the explosion ejecta are surrounded by the products of explosive helium burning in the shell. Recently, however, it was proposed that detonations might be possible for much less massive helium shells than previously assumed (Bildsten et al.). Moreover, it was shown that even detonations of these minimum helium shell masses robustly trigger detonations of the carbon-oxygen core (Fink et al.). Therefore, it is possible that the impact of the helium layer on observables is less than previously thought. Here, we present time-dependent multi-wavelength radiative transfer calculations for models with minimum helium shell mass and derive synthetic observables for both the optical and ? -ray spectral regions. These differ strongly from those found in earlier simulations of sub-Chandrasekhar-mass explosions in which more massive helium shells were considered. Our models predict light curves that cover both the range of brightnesses and the rise and decline times of observed Type Ia supernovae. However, their colors and spectra do not match the observations. In particular, their B - V colors are generally too red. We show that this discrepancy is mainly due to the composition of the burning products of the helium shell of the Fink et al. models which contain significant amounts of titanium and chromium. Using a toy model, we also show that the burning products of the helium shell depend crucially on its initial composition. This leads us to conclude that good agreement between sub-Chandrasekhar-mass explosions and observed Type Ia supernovae may still be feasible but further study of the shell properties is required.

2D simulations of the double-detonation model for thermonuclear transients from low-mass carbon-oxygen white dwarfs

Thermonuclear explosions may arise in binary star systems in which a carbon-oxygen (CO) white dwarf (WD) accretes helium-rich material from a companion star. If the accretion rate allows a sufficiently large mass of helium to accumulate prior to ignition of nuclear burning, the helium surface layer may detonate, giving rise to an astrophysical transient. Detonation of the accreted helium layer generates shock waves that propagate into the underlying CO WD. This might directly ignite a detonation of the CO WD at its surface (an edge-lit secondary detonation) or compress the core of the WD sufficiently to trigger a CO detonation near the centre. If either of these ignition mechanisms works, the two detonations (helium and CO) can then release sufficient energy to completely unbind the WD. These 'double-detonation' scenarios for thermonuclear explosion of WDs have previously been investigated as a potential channel for the production of Type Ia supernovae from WDs of ~ 1 M . Here we extend our 2D studies of the double-detonation model to significantly less massive CO WDs, the explosion of which could produce fainter, more rapidly evolving transients. We investigate the feasibility of triggering a secondary core detonation by shock convergence in low-mass CO WDs and the observable consequences of such a detonation. Our results suggest that core detonation is probable, even for the lowest CO core masses that are likely to be realized in nature. To quantify the observable signatures of core detonation, we compute spectra and light curves for models in which either an edge-lit or compression-triggered CO detonation is assumed to occur. We compare these to synthetic observables for models in which no CO detonation was allowed to occur. If significant shock compression of the CO WD occurs prior to detonation, explosion of the CO WD can produce a sufficiently large mass of radioactive iron-group nuclei to significantly affect the light curves. In particular, this can lead to relatively slow post-maximum decline. If the secondary detonation is edge-lit, however, the CO WD explosion primarily yields intermediate-mass elements that affect the observables more subtly. In this case, near-infrared observations and detailed spectroscopic analysis would be needed to determine whether a core detonation occurred. We comment on the implications of our results for understanding peculiar astrophysical transients including SN 2002bj, SN 2010X and SN 2005E. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.