Identification of Potent and Long-Acting Single-Chain Peptide Mimetics of Human Relaxin-2 for Cardiovascular Diseases.

The insulin-like peptide human relaxin-2 was identified as a hormone that, among other biological functions, mediates the hemodynamic changes occurring during pregnancy. Recombinant relaxin-2 (serelaxin) has shown beneficial effects in acute heart failure, but its full therapeutic potential has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. In this study, we report the development of long-acting potent single-chain relaxin peptide mimetics. Modifications in the B-chain of relaxin, such as the introduction of specific mutations and the trimming of the sequence to an optimal size, resulted in potent, structurally simplified peptide agonists of the relaxin receptor Relaxin Family Peptide Receptor 1 (RXFP1) (e.g., 54). Introduction of suitable spacers and fatty acids led to the identification of single-chain lipidated peptide agonists of RXFP1, with sub-nanomolar activity, high subcutaneous bioavailability, extended half-lives, and in vivo efficacy (e.g., 64).

Wind farm development on peatlands increases fluvial macronutrient loading.

Wind farms can help to mitigate increasing atmospheric carbon (C) emissions. However, disturbance caused by wind farm development must not have lasting deleterious impacts on landscape C sequestration. To understand the effects of wind farm development on peatlands, we monitored streamwater at Europe's second largest onshore wind farm (539 MW), Whitelee, Scotland, for 31 months. Using nested catchment sampling to understand impacts on water quality, increasing macronutrient concentrations and exports were associated with wind farm development, particularly forest-felling and borrow pits. Low/poor water quality occurred in small headwater catchments most disturbed by development. At the site exit, dissolved organic C and soluble reactive phosphorus (SRP) concentrations increased during construction, though [SRP] recovery occurred within 2 years. Since C was lost and streamwater quality negatively affected, we propose future good practice measures for wind farm development, including limiting total disturbance within individual catchments and locating borrow pits, where deemed necessary, off site avoiding peatlands.

The potential for modelling peatland habitat condition in Scotland using long-term MODIS data.

Globally, peatlands provide an important sink of carbon in their near natural state but potentially act as a source of gaseous and dissolved carbon emission if not in good condition. There is a pressing need to remotely identify peatland sites requiring improvement and to monitor progress following restoration. A medium resolution model was developed based on a training dataset of peatland habitat condition and environmental covariates, such as morphological features, against information derived from the Moderate Resolution Imaging Spectroradiometer (MODIS), covering Scotland (UK). The initial, unrestricted, model provided the probability of a site being in favourable condition. Receiver operator characteristics (ROC) curves for restricted training data, limited to those located on a peat soil map, resulted in an accuracy of 0.915. The kappa statistic was 0.8151, suggesting good model fit. The derived map of predicted peatland condition at the suggested 0.56 threshold was corroborated by data from other sources, including known restoration sites, areas under known non-peatland land cover and previous vegetation survey data mapped onto inferred condition categories. The resulting locations of the areas of peatland modelled to be in favourable ecological condition were largely confined to the North and West of the country, which not only coincides with prior land use intensity but with published predictions of future retraction of the bioclimatic space for peatlands. The model is limited by a lack of spatially appropriate ground observations, and a lack of verification of peat depth at training site locations, hence future efforts to remotely assess peatland condition will require more appropriate ground-based monitoring. If appropriate ground-based observations could be collected, using remote sensing could be considered a cost-efficient means to provide data on changes in peatland habitat condition.

The effects of soil horizons and faunal excrement on bacterial distribution in an upland grassland soil.

The density and spatial location of bacteria were investigated within different horizons of an upland grassland soil before and after a liming treatment to increase the numbers of large soil fauna. Bacterial cells were located by image analysis of stained thin sections and densities calculated from these data. Excrement from macro- and meso-fauna was identified using micromorphology and the densities of bacteria on specific areas of excrement measured by image analysis. There were significant differences among horizons in the density of bacterial cells, with the minimum density found in the horizon with least evidence of earthworm activity, but no difference in density between the organic H and organo-mineral Ah horizons. Soil improvement by liming significantly increased bacterial densities in all three horizons, with the greatest increase found in the horizon with the smallest density before liming. There were no differences in bacterial density between areas dominated by excrement from earthworms and excrement from enchytraeids, although densities in both areas were significantly increased by liming. Variability in bacterial density at spatial scales of less than 1 mm was linked to the occurrence of excrement. Bacterial densities within areas of both types of excrement were significantly greater than those in the surrounding soil. However, the frequency distribution of the ratios of density in excrement to that in the soil was bimodal, with a majority of occurrences having a ratio near 1 and only some 20-30% having a much larger ratio. These variations can probably be explained by variations in the age of the excrement and its suitability as a substrate.

Determination of rhizosphere 13C pulse signals in soil thin sections by laser ablation isotope ratio mass spectrometry.

In grassland ecosystems, soil animals act as key soil engineers and architects. The diversity of soil animals is also a regulator of ecosystem carbon flow. However, our understanding of the link between soil animals, carbon fluxes and soil physical organisation remains poor. An integrated approach based on soil micromorphology and laser ablation stable isotope ratio mass spectrometry (LA-IRMS) was developed to provide spatially distributed data of pulse-derived (13)C tracer from roots in the soil environment. This paper describes the development and testing of a LA-IRMS (13)C/(12)C analytical method on soil thin sections as a means to determine the fate of root carbon derived from photosynthesis into soil. Results from this work demonstrated (1) that micro-scale delta(13)C (per thousand) analysis could be made on targeted features located within a soil thin section and (2) that LA-IRMS delta(13)C (per thousand) measurements made on samples obtained from (13)CO(2) pulse labelled plant-soil blocks confirmed the presence of recent photosynthates in the rhizosphere (1 and 4 weeks post-pulse).