Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

Evaluation of three physical mixing methods of nanoparticles to orthodontic primer

Background: Demineralization and white spot lesions are the most common complications in fixed orthodontic treatment. It is useful to enhance the remineralization properties of the orthodontic primer by the addition of remineralizing agents. Fluoride and calcium are regarded as the main component of enamel fluorohydroxyapatite crystals. This pilot study compared three mixing methods of calcium fluoride nanoparticles (nCaF2) with conventional orthodontic primer (Transbond XT™) to develop a primer with enamel remineralization properties. Materials and methods: The nanoparticles were added to Transbond XT™ primer to form 20% (w/w) of the final solution. Three dark plastic bottles were prepared and stored until mixing. The first sample was mixed by a Vortex machine, the second was mixed with an electric agitator, and the third one was mixed with a customized plastic spatula adapted to a dental engine and a straight handpiece. Cured blocks of the developed primer were prepared and were examined for homogeneity, cracks, and agglomeration of the nanoparticles within the primer using Field Emission Scanning Electron Microscopy (FESM). Results: The third Sample showed a continuous distribution of nanoparticles with no apparent cracks or agglomeration of nanoparticles. In contrast, a higher agglomeration was seen in the first sample than in the other two. Conclusion: Mixing of nCaF2 with Transbond XT™ orthodontic primer was best achieved by the customized plastic spatula adapted to a dental engine compared to Vortex and electric agitator machines.</p

Evaluation of three physical mixing methods of nanoparticles to orthodontic primer

Background: Demineralization and white spot lesions are the most common complications in fixed orthodontic treatment. It is useful to enhance the remineralization properties of the orthodontic primer by the addition of remineralizing agents. Fluoride and calcium are regarded as the main component of enamel fluorohydroxyapatite crystals. This pilot study compared three mixing methods of calcium fluoride nanoparticles (nCaF2) with conventional orthodontic primer (Transbond XT™) to develop a primer with enamel remineralization properties. Materials and methods: The nanoparticles were added to Transbond XT™ primer to form 20% (w/w) of the final solution. Three dark plastic bottles were prepared and stored until mixing. The first sample was mixed by a Vortex machine, the second was mixed with an electric agitator, and the third one was mixed with a customized plastic spatula adapted to a dental engine and a straight handpiece. Cured blocks of the developed primer were prepared and were examined for homogeneity, cracks, and agglomeration of the nanoparticles within the primer using Field Emission Scanning Electron Microscopy (FESM). Results: The third Sample showed a continuous distribution of nanoparticles with no apparent cracks or agglomeration of nanoparticles. In contrast, a higher agglomeration was seen in the first sample than in the other two. Conclusion: Mixing of nCaF2 with Transbond XT™ orthodontic primer was best achieved by the customized plastic spatula adapted to a dental engine compared to Vortex and electric agitator machines.</p

Effect of birth weight on adulthood renal function: a bias-adjusted meta-analytic approach

While the association between low birth weight (LBW

NB 3 SN BLOCK-COIL DIPOLE FOR HIGH-FIELD SUBSTITUTION IN THE LHC LATTICE*

Abstract A design is being developed to prototype for a dipole for this purpose: a block-coil dipole with 13 T shortsample field, 11 T working field, and 6 cm aperture. The dipole is a natural application of the high-field dipole strategy developed at Texas A&amp;M, using simple pancake windings, flux-plate suppression of low-field multipoles, and bladder preloading. A short model dipole is planned

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale

Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy

Pliocene Te Aute limestones, New Zealand: Expanding concepts for cool-water shelf carbonates

Acceptance of a spectrum of warm- through cold-water shallow-marine carbonate facies has become of fundamental importance for correctly interpreting the origin and significance of all ancient platform limestones. Among other attributes, properties that have become a hallmark for characterising many Cenozoic non-tropical occurrences include: (1) the presence of common bryozoan and epifaunal bivalve skeletons; (2) a calcite-dominated mineralogy; (3) relatively thin deposits exhibiting low rates of sediment accumulation; (4) an overall destructive early diagenetic regime; and (5) that major porosity destruction and lithification occur mainly in response to chemical compaction of calcitic skeletons during moderate to deep burial. The Pliocene Te Aute limestones are non-tropical skeletal carbonates formed at paleolatitudes near 40-42°S under the influence of commonly strong tidal flows along the margins of an actively deforming and differentially uplifting forearc basin seaway, immediately inboard of the convergent Pacific-Australian plate boundary off eastern North Island, New Zealand. This dynamic depositional and tectonic setting strongly influenced both the style and subsequent diagenetic evolution of the limestones. Some of the Te Aute limestones exhibit the above kinds of "normal" non-tropical characteristics, but others do not. For example, many are barnacle and/or bivalve dominated, and several include attributes that at least superficially resemble properties of certain tropical carbonates. In this regard, a number of the limestones are infaunal bivalve rich and dominated by an aragonite over a calcite primary mineralogy, with consequently relatively high diagenetic potential. Individual limestone units are also often rather thick (e.g., up to 50-300 m), with accumulation rates from 0.2 to 0.5 m/ka, and locally as high as 1 m/ka. Moreover, there can be a remarkable array of diagenetic features in the limestones, involving grain alteration and/or cementation to widely varying extents within any, or some combination of, the marine phreatic, burial, and meteoric diagenetic environments, including locally widespread development of meteoric cement sourced from aragonite dissolution. The message is that non-tropical shelf carbonates include a more diverse array of geological settings, of skeletal and mineralogical facies, and of diagenetic features than current sedimentary models mainly advocate. While several attributes positively distinguish tropical from non-tropical limestones, continued detailed documentation of the wide spectrum of shallow-marine carbonate deposits formed outside tropical regions remains an important challenge in carbonate sedimentology