Restoration and management of wildflower-rich machair for the conservation of bumblebees

Over the last half century, the widespread decline of bumblebees across the agricultural landscapes of Western Europe and North America has been well documented. This decline has undoubtedly been driven to a large extent by the intensification of agriculture, which has fragmented landscapes and removed large areas of suitable foraging habitat, nesting and hibernation sites. Consequently, some of the rarest Bombus species now persist only in isolated pockets of semi-natural habitat, which have been subjected to little agricultural intensification. Of the 25 Bombus species native to the UK, three species have gone extinct in recent decades and several others are severely threatened. Remaining populations of the UK’s rarest bumblebee, Bombus distinguendus, have become strongly associated with florally-rich machair grassland habitats found only in the North and West of Scotland and Western Ireland. Machair, a unique habitat that forms on soils rich in shell sand, has been maintained by rotational agricultural practices implemented by crofters. However, recent changes in crofting practices, which include the intensive grazing of machair in some areas, or conversely the abandonment of machair management all together in others, have resulted in sections of machair that have become degraded and consequently exhibit low floral abundance and species diversity. This has significant implications for species such as B. distinguendus, which have for the most part come to rely of the florally-rich swards of machair grassland. This thesis aimed to develop a greater understanding of how machair grassland habitats are utilised by foraging bumblebees, including B. distinguendus, and in turn examined the potential for restoring degraded areas of machair via a variety of methods. The research presented here examines the influence of current crofting practices on the abundance of bumblebees and their forage plant species and combines this information with a detailed exploration of the machair seed bank and potential machair restoration treatments. The specific foraging requirements of B. distinguendus were found to be similar to those of other long-tongued bumblebee species and the provision of plants from the Fabaceae family was found to be of particular importance. Current crofting practices implemented in the North and West of Scotland were, on the whole, found support low numbers of foraging bumblebees. Similarly, existing habitat management schemes, designed to provide early cover for corncrakes and foraging resources for bumblebees, were found to be largely ineffective in attracting B. distinguendus, when compared with florally-rich machair habitat. In addition, this research suggests that the existing machair seed bank is unlikely to provide a sufficient resource for reinstating florally-rich habitat to degraded areas of machair. However, this thesis has demonstrated that it is possible to implement seed mixes on machair which can reinstate species typical of machair plant communities and which also attract high numbers of foraging bumblebees. The findings of these habitat assessments and restoration trials are examined in full in the following chapters and implications for the future management of wildflower-rich machair are discussed throughout

Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair

Priming food intake with weight control cues: systematic review with a meta-analysis

Background A growing number of studies suggest that exposure to cues which are associated with weight control can prime or prompt controlled food intake in tempting food environments. However, findings are mixed and understanding which types of cues and for whom such cues may be most effective is needed to inform subsequent research and societal applications. A systematic review and meta-analysis were conducted to evaluate the effects of exposure to weight control cues compared with control cues on food intake. Methods PsycINFO, Medline, Embase and Web of Science were searched using key terms. Hedge’s g was used to calculate effect sizes based on mean food intake, standard deviations and sample sizes extracted from relevant publications and, a random effects model was used for the meta-analysis. Results Twenty-five articles consisting of 26 studies were eligible. Data from 25 studies (31 effect sizes) were available for the meta-analysis. Overall, weight control cues reduced food intake, albeit to a trivial effect (ES: -0.149, 95% CI: -0.271 to − 0.027). Subgroup analyses when studies which induced negative affect were removed showed that for individuals with strong weight control goals the effect was small-to-moderate (ES: -0.440, 95% CI: -0.718 to − 0.163), whereas for individuals with weak weight control goals this effect was trivial and non-significant (ES: 0.014, 95% CI: -0.249 to 0.278). Cue type and level of engagement did not significantly moderate the effect; however, specific cues (low-calorie foods and thin models) and attended engagement yielded significant effects. Caution is needed interpreting these findings as most studies were rated with high risk of bias and a number of studies could not be included in the subgroup analyses. Conclusions Based on the data available, weight control cues reduce food intake in individuals with strong weight control goals. Further research is needed to explore longer term effects of cue exposure and confirm underlying mechanisms. PROSPERO registry#CRD42016052396

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Crofting and bumblebee conservation: the impact of land management practices on bumblebee populations in northwest Scotland

The northwest of Scotland is a stronghold for two of the UK's rarest bumblebee species, Bombus distinguendus and Bombus muscorum. The predominant form of agricultural land management in this region is crofting, a system specific to Scotland in which small agricultural units (crofts) operate rotational cropping and grazing regimes. Crofting is considered to be beneficial to a wide range of flora and fauna. However, currently there is a lack of quantitative evidence to support this view with regard to bumblebee populations. In this study we assessed the effect of land management on the abundance of foraging bumblebees and the availability of bumblebee forage plants across crofts in northwest Scotland. The results of our study show that current crofting practices do not support high densities of foraging bumblebees. Traditional crofting practice was to move livestock to uplands in the summer, but this has been largely abandoned. Summer sheep grazing of lowland pasture had a strong negative impact on bumblebee abundance and forage plant availability throughout the survey period. The use of specific 'bird and bee' conservation seed mixes appears to improve forage availability within the crofted landscape, although the number of bees observed remained low. Of the forage plants available, the three most frequently visited species were from the Fabaceae. We therefore conclude that the creation of agri-environment schemes which promote the use of Fabaceae-rich seed mixes and encourage the removal of sheep grazing on lowland areas throughout the summer are essential in order to conserve bumblebee populations within crofted areas. © 2009 Elsevier Ltd. All rights reserved

Additional file 2: of Priming food intake with weight control cues: systematic review with a meta-analysis

Risk of bias assessment. Description: Table showing risk of bias assessment for each study (DOCX 19 kb)

Thymosin beta 4 - a novel regulator of low density lipoprotein receptor related protein 1 (LRP1) in vascular disease

Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). Injury-induced growth factors stimulate a phenotypic switching of VSMCs, from their quiescent contractile state to a more active synthetic phenotype that proliferate and migrate. Chronic VSMC dedifferentiation leads to vascular thickening and stiffness, exacerbates inflammation and promotes atherosclerotic lesion development and susceptibility to abdominal aortic aneurysm (AAA). Inhibiting VSMC phenotypic transformation has thus been shown to attenuate progression of vascular disease. We previously identified Thymosin β4 (Tβ4) as a key regulator of embryonic VSMC differentiation. TMSB4X, encoding Tβ4, is the most abundant transcript in healthy and AAA aorta, therefore we hypothesised that Tβ4 may additionally function to maintain vasculature and protect against disease throughout postnatal life. We identified an interaction between Tβ4 and Low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of PDGFR? signalling which controls VSMC proliferation. LRP1 variants have been identified by GWAS as major risk loci for AAA and coronary artery disease. Adult Tβ4-null mice displayed aortic VSMC and elastin defects, phenocopying LRP1 mutants and suggesting compromised vascular integrity. During development, Tβ4 functions in a paracrine manner, secreted from endothelial cells (ECs) to induce mesoderm to VSMC differentiation. To distinguish between cell-autonomous and paracrine roles for Tβ4, and simultaneously discern adult maintenance versus developmental requirements, we selectively induced deletion of Tβ4 from VSMCs or ECs at 3 weeks of age. Histological assessment of aortas at 12 weeks demonstrated that VSMC-specific Tβ4 knockdown recapitulated the global KO phenotype, revealing a postnatal requirement for Tβ4 to maintain healthy vasculature. In keeping with this, we confirmed predisposition of these mice to disease in models of atherosclerosis and AAA. Aneurysmal aorta and plaques of Tβ4KO were characterised by accelerated contractile-synthetic VSMC switching, elastin degradation and augmented PDGFR? signalling. In vitro, enhanced sensitivity to PDGF-BB, upon loss of Tβ4, coincided with increased cell surface recycling of LRP1-PDGFR? complexes and reduced lysosomal targeting, suggesting that dysregulated endocytosis underlies enhanced phenotypic switching and proliferation. Given the VSMC differentiation, anti-inflammatory and anti-apoptotic roles of Tβ4, we sought to determine the vasculoprotective potential of exogenous Tβ4. In the AAA model, Tβ4 treatment significantly reduced aortic dilatation and rupture, and preserved VSMC phenotype and elastin integrity, associated with normalisation of PDGFR? signalling. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, providing insight that may reveal useful therapeutic targets for modulation of VSMC phenotypic switching and disease progression

Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor.

African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection