The Relaxin Gene Knockout Mouse: A Model of Progressive Scleroderma

Relaxin is a peptide hormone with anti-fibrotic properties. To investigate the long-term effects of relaxin deficiency on the ageing skin, we compared structural changes in the skin of ageing relaxin-deficient (RLX-/-) and normal (RLX+/+) mice, by biochemical, histological, and magnetic resonance imaging analyses. Skin biopsies from RLX+/+ and RLX-/- mice were obtained at different ages and analyzed for changes in collagen expression and distribution. We demonstrated an age-related progression of dermal fibrosis and thickening in male and female RLX-/- mice, associated with marked increases in types I and III collagen. The increased collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer. Additionally, fibroblasts from the dermis of RLX-/- mice were shown to produce increased collagen in vitro. Recombinant human gene-2 (H2) relaxin treatment of RLX-/- mice resulted in the complete reversal of dermal fibrosis, when applied to the early onset of disease, but was ineffective when applied to more established stages of dermal scarring. These combined findings demonstrate that relaxin provides a means to regulate excessive collagen deposition in disease states characterized by dermal fibrosis and with our previously published work demonstrate the relaxin-null mouse as a model of progressive scleroderma

The protein kinases AtMAP3Kε1 and BnMAP3Kε1 are functional homologues of S. pombe cdc7p and may be involved in cell division

We identified an Arabidopsis thaliana gene, AtMAP3Kε1, and a Brassica napus cDNA, BnMAP3Kε1, encoding functional protein serine/threonine kinases closely related to cdc7p and Cdc15p from Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. This is the first report of cdc7-related genes in non-fungal eukaryotes; no such genes have as yet been identified in Metazoans. The B. napus protein is able to partially complement a cdc7 loss of function mutation in S. pombe. RT–PCR and in situ hybridisation revealed that the A. thaliana and B. napus genes are expressed in both the sporophytic and the gametophytic tissues of the respective plant species and revealed further that expression is highest in dividing cells. Moreover, AtMAP3Kε1 gene expression is cell cycle-regulated, with higher expression in G2-M phases. Our results strongly suggest that the plant cdc7p-related protein kinases are involved in a signal transduction pathway similar to the SIN pathway, which positively regulates cytokinesis in S. pombe.This work was mainly supported by a EU grant (SIME project BIOTEC-RTD-CEE PL 960275). The authors also acknowledge the financial support of the MERS and CNRS to UMR 8618, and DGESIG PB98–0678

Routes to sustainability in public food procurement: An investigation of different models in primary school catering

Increasingly, policymakers are setting ambitious goals for sustainability in public procurement, integrated across different pillars. Such ambitions are apparent in public catering services, where procurement models have been shifting towards greater localisation of supply chains and purchasing of more organically grown food. To date however, few studies have examined empirically what the impacts of different procurement models are across these multiple pillars of sustainability. This research aimed to fill the gap, by measuring and comparing the environmental, economic and nutritional outcomes of different models of school meals procurement. Case studies were undertaken of ten primary school meals services in five European countries, capturing different procurement model types. Results showed carbon emissions ranged from 0.95 kgs CO2e per meal in the lowest case to 2.41 kgs CO2e in the highest case, with adoption of low carbon food waste disposal methods and reduction of the amount of ruminant meat in the menus being the most important actions for lowering emissions. In terms of economic impact, local economic multiplier ratios ranged from 1.59 to 2.46, and although the level of local food sourcing contributed to these ratios, the effect was eclipsed, in some cases, by investment in local catering staff. Meanwhile, implementation of a robust standards regime and improving canteen environment and supervision were the most important actions for nutritional quality and intake. The paper discusses the implications of the findings for integrated, sustainable models of food procurement

Improving access to large-scale digital libraries through semantic-enhanced search and disambiguation

With 13,000,000 volumes comprising 4.5 billion pages of text, it is currently very difficult for scholars to locate relevant sets of documents that are useful in their research from the HathiTrust Digital Libary (HTDL) using traditional lexically-based retrieval techniques. Existing document search tools and document clustering approaches use purely lexical analysis, which cannot address the inherent ambiguity of natural language. A semantic search approach offers the potential to overcome the shortcoming of lexical search, but even if an appropriate network of ontologies could be decided upon it would require a full semantic markup of each document. In this paper, we present a conceptual design and report on the initial implementation of a new framework that affords the benefits of semantic search while minimizing the problems associated with applying existing semantic analysis at scale. Our approach avoids the need for complete semantic document markup using pre-existing ontologies by developing an automatically generated Concept-in-Context (CiC) network seeded by a priori analysis of Wikipedia texts and identification of semantic metadata. Our Capisco system analyzes documents by the semantics and context of their content. The disambiguation of search queries is done interactively, to fully utilize the domain knowledge of the scholar. Our method achieves a form of semantic-enhanced search that simultaneously exploits the proven scale benefits provided by lexical indexing

The Latin American Social Medicine database

BACKGROUND: Public health practitioners and researchers for many years have been attempting to understand more clearly the links between social conditions and the health of populations. Until recently, most public health professionals in English-speaking countries were unaware that their colleagues in Latin America had developed an entire field of inquiry and practice devoted to making these links more clearly understood. The Latin American Social Medicine (LASM) database finally bridges this previous gap. DESCRIPTION: This public health informatics case study describes the key features of a unique information resource intended to improve access to LASM literature and to augment understanding about the social determinants of health. This case study includes both quantitative and qualitative evaluation data. Currently the LASM database at The University of New Mexico brings important information, originally known mostly within professional networks located in Latin American countries to public health professionals worldwide via the Internet. The LASM database uses Spanish, Portuguese, and English language trilingual, structured abstracts to summarize classic and contemporary works. CONCLUSION: This database provides helpful information for public health professionals on the social determinants of health and expands access to LASM

Exploring the contribution of alternative food networks to food security. A comparative analysis

[EN] Food (in)security has become a challenge not only for developing economies but also for High Income Countries. In parallel, food scholars have actively investigated the contribution of alternative food networks (AFNs) to the development of more sustainable and just food systems, paying attention to drivers, initiatives and policies supporting the development of alternatives to the dominant industrialised food system and its detrimental environmental and socio-economic impacts. However, few studies have directly addressed the contribution of AFNs to food security in the Global North. This paper aims to establish new linkages between food security debates and critical AFNs literature. For that purpose, we conduct a place-based approach to food security in a comparative analysis of initiatives of three different European contexts: Cardiff city-region (UK), the Flemish Region (Belgium) and the peri-urban area of the city of Valencia (Spain). The results unfold: i) how AFNs weave a more localised socio-economic fabric that creates new relationships between food security outcomes and specific territories, ii) hybridization processes within alternative but also conventional systems and iii) the role of advocacy and collective action at different levels. The analysis allows identification of key elements on which food security debates hinge and provides new insights to ground conceptual discussions on territorial and place-based food security approaches.This research is part of the project "Assessment of the impact of global drivers of change on Europe's food security" (TRANSMANGO), granted by the EU under 7th Framework Programme; theme KBBE.2013.2.5-01; Grant agreement no: 613532. Dr. Ana Moragues-Faus also acknowledges the funding of the European Commission and the Welsh Government that currently supports her Ser Cymru fellowship. 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Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required