Density-driven structural transformations in B2O3 glass

The method of in situ high-pressure neutron diffraction is used to investigate the structure of B2O3 glass on compression in the range from ambient to 17.5(5) GPa. The experimental results are supplemented by molecular dynamics simulations made using a newly developed aspherical ion model. The results tie together those obtained from other experimental techniques to reveal three densification regimes. In the first, BO3 triangles are the predominant structural motifs as the pressure is increased from ambient to 6.3(5) GPa, but there is an alteration to the intermediate range order which is associated with the dissolution of boroxol rings. In the second, BO4 motifs replace BO3 triangles at pressures beyond 6.3 GPa and the dissolution of boroxol rings continues until it is completed at 11–14 GPa. In the third, the B-O coordination number continues to increase with pressure to give a predominantly tetrahedral glass, a process that is completed at a pressure in excess of 22.5 GPa. On recovery of the glass to ambient from a pressure of 8.2 GPa, triangular BO3 motifs are recovered but, relative to the uncompressed material, there is a change to the intermediate range order. The comparison between experiment and simulation shows that the aspherical ion model is able to provide results of unprecedented accuracy at pressures up to at least 10 GPa

New insights into the impact of neuro-inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA

Circulating BMP9 Protects the Pulmonary Endothelium during Inflammation-induced Lung Injury in Mice.

Rationale: Pulmonary endothelial permeability contributes to the high-permeability pulmonary edema that characterizes acute respiratory distress syndrome. Circulating BMP9 (bone morphogenetic protein 9) is emerging as an important regulator of pulmonary vascular homeostasis. Objectives:To determine whether endogenous BMP9 plays a role in preserving pulmonary endothelial integrity and whether loss of endogenous BMP9 occurs during LPS challenge. Methods: A BMP9-neutralizing antibody was administrated to healthy adult mice, and lung vasculature was examined. Potential mechanisms were delineated by transcript analysis in human lung endothelial cells. The impact of BMP9 administration was evaluated in a murine acute lung injury model induced by inhaled LPS. Levels of BMP9 were measured in plasma from patients with sepsis and from endotoxemic mice. Measurements and Main Results: Subacute neutralization of endogenous BMP9 in mice (N = 12) resulted in increased lung vascular permeability (P = 0.022), interstitial edema (P = 0.0047), and neutrophil extravasation (P = 0.029) compared with IgG control treatment (N = 6). In pulmonary endothelial cells, BMP9 regulated transcriptome pathways implicated in vascular permeability and cell-membrane integrity. Augmentation of BMP9 signaling in mice (N = 8) prevented inhaled LPS-induced lung injury (P = 0.0027) and edema (P < 0.0001). In endotoxemic mice (N = 12), endogenous circulating BMP9 concentrations were markedly reduced, the causes of which include a transient reduction in hepatic BMP9 mRNA expression and increased elastase activity in plasma. In human patients with sepsis (N = 10), circulating concentratons of BMP9 were also markedly reduced (P < 0.0001). Conclusions: Endogenous circulating BMP9 is a pulmonary endothelial-protective factor, downregulated during inflammation. Exogenous BMP9 offers a potential therapy to prevent increased pulmonary endothelial permeability in lung injury

Quantitative proteomics of a B12 -dependent alga grown in coculture with bacteria reveals metabolic tradeoffs required for mutualism

The unicellular green alga Lobomonas rostrata requires an external supply of vitamin B12 (cobalamin) for growth, which it can obtain in stable laboratory cultures from the soil bacterium Mesorhizobium loti in exchange for photosynthate. We investigated changes in protein expression in the alga that allow it to engage in this mutualism. We used quantitative isobaric tagging (iTRAQ) proteomics to determine the L. rostrata proteome grown axenically with B12 supplementation or in coculture with M. loti. Data are available via ProteomeXchange (PXD005046). Using the related Chlamydomonas reinhardtii as a reference genome, 588 algal proteins could be identified. Enzymes of amino acid biosynthesis were higher in coculture than in axenic culture, and this was reflected in increased amounts of total cellular protein and several free amino acids. A number of heat shock proteins were also elevated. Conversely, photosynthetic proteins and those of chloroplast protein synthesis were significantly lower in L. rostrata cells in coculture. These observations were confirmed by measurement of electron transfer rates in cells grown under the two conditions. The results indicate that, despite the stability of the mutualism, L. rostrata experiences stress in coculture with M. loti, and must adjust its metabolism accordingly.The work in this manuscript was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK (grant BB/I013164/1, a CASE studentship for M.B.C. joint with PML Applications Ltd, Plymouth, UK, and a DTP studentship for F.B.); an EU FP7 Marie Curie ITN Photo.Comm, no. 317184 for U.J.K.; Engineering and Physical Science Research Council (EPSRC) grant EP/E036252/1; and the Natural Environment Research Council (NERC) grant NE/J024767/1

Eddy transport of organic carbon and nutrients from the Chukchi Shelf : impact on the upper halocline of the western Arctic Ocean

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): C05011, doi:10.1029/2006JC003899.In September 2004 a detailed physical and chemical survey was conducted on an anticyclonic, cold-core eddy located seaward of the Chukchi Shelf in the western Arctic Ocean. The eddy had a diameter of ∼16 km and was centered at a depth of ∼160 m between the 1000 and 1500 m isobaths over the continental slope. The water in the core of the eddy (total volume of 25 km3) was of Pacific origin, and contained elevated concentrations of nutrients, organic carbon, and suspended particles. The feature, which likely formed from the boundary current along the edge of the Chukchi Shelf, provides a mechanism for transport of carbon, oxygen, and nutrients directly into the upper halocline of the Canada Basin. Nutrient concentrations in the eddy core were elevated compared to waters of similar density in the deep Canada Basin: silicate (+20 μmol L−1), nitrate (+5 μmol L−1), and phosphate (+0.4 μmol L−1). Organic carbon in the eddy core was also elevated: POC (+3.8 μmol L−1) and DOC (+11 μmol L−1). From these observations, the eddy contained 1.25 × 109 moles Si, 4.5 × 108 moles NO3 −, 5.5 × 107 moles PO3 −, 1.2 × 108 moles POC, and 1.9 × 109 moles DOC, all available for transport to the interior of the Canada Basin. This suggests that such eddies likely play a significant role in maintaining the nutrient maxima observed in the upper halocline. Assuming that shelf-to-basin eddy transport is the dominant renewal mechanism for waters of the upper halocline, remineralization of the excess organic carbon transported into the interior would consume 6.70 × 1010 moles of O2, or one half the total oxygen consumption anticipated arising from all export processes impacting the upper halocline.This work was supported by the National Science Foundation, and office of Naval Research; DH OPP-0124900, NB OPP-0124868, DK OPP 0124872, RP N00014-02-1-0317

An intergenerational study of perceptions of changes in active free play among families from rural areas of Western Canada

Background: Children's engagement in active free play has declined across recent generations. Therefore, the purpose of this study was to examine perceptions of intergenerational changes in active free play among families from rural areas. We addressed two research questions: (1) How has active free play changed across three generations? (2) What suggestions do participants have for reviving active free play? Methods: Data were collected via 49 individual interviews with members of 16 families (15 grandparents, 16 parents, and 18 children) residing in rural areas/small towns in the Province of Alberta (Canada). Interview recordings were transcribed verbatim and subjected to thematic analysis guided by an ecological framework of active free play. Results: Factors that depicted the changing nature of active free play were coded in the themes of less imagination/more technology, safety concerns, surveillance, other children to play with, purposeful physical activity, play spaces/organized activities, and the good parenting ideal. Suggestions for reviving active free play were coded in the themes of enhance facilities to keep kids entertained, provide more opportunities for supervised play, create more community events, and decrease use of technology. Conclusions: These results reinforce the need to consider multiple levels of social ecology in the study of active free play, and highlight the importance of community-based initiatives to revive active free play in ways that are consistent with contemporary notions of good parentin

Standards recommendations for the Earth BioGenome Project

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met

Functional similarities between pigeon \u27milk\u27 and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon &lsquo;milk&rsquo; and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon &lsquo;milk&rsquo;. Therefore, using a chicken model, we investigated the effect of pigeon &lsquo;milk&rsquo; on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon &lsquo;milk&rsquo; had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon &lsquo;milk&rsquo;-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon &lsquo;milk&rsquo;-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon &lsquo;milk&rsquo;, as well as being directly seeded by bacteria present in pigeon &lsquo;milk&rsquo;. Our results demonstrate that pigeon &lsquo;milk&rsquo; has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon &lsquo;lactation&rsquo; and mammalian lactation evolved independently but resulted in similarly functional products