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

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

While the association between low birth weight (LBW

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

First Results from The GlueX Experiment

The GlueX experiment at Jefferson Lab ran with its first commissioning beam in late 2014 and the spring of 2015. Data were collected on both plastic and liquid hydrogen targets, and much of the detector has been commissioned. All of the detector systems are now performing at or near design specifications and events are being fully reconstructed, including exclusive production of $\pi^{0}$, $\eta$ and $\omega$ mesons. Linearly-polarized photons were successfully produced through coherent bremsstrahlung and polarization transfer to the $\rho$ has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015 Conference, Newport News VA, September 201

Soil seal development under simulated rainfall: structural, physical and hydrological dynamics

This study delivers new insights into rainfall-induced seal formation through a novel approach in the use of X-ray Computed Tomography (CT). Up to now seal and crust thickness have been directly quantified mainly through visual examination of sealed/crusted surfaces, and there has been no quantitative method to estimate this important property. X-ray CT images were quantitatively analysed to derive formal measures of seal and crust thickness. A factorial experiment was established in the laboratory using open-topped microcosms packed with soil. The factors investigated were soil type (three soils: silty clay loam - ZCL, sandy silt loam - SZL, sandy loam - SL) and rainfall duration (2-14 minutes). Surface seal formation was induced by applying artificial rainfall events, characterised by variable duration, but constant kinetic energy, intensity, and raindrop size distribution. Soil porosities derived from CT scans were used to quantify the thickness of the rainfall-induced surface seals and reveal temporal seal micro-morphological variations with increasing rainfall duration. In addition, the water repellency and infiltration dynamics of the developing seals were investigated by measuring water drop penetration time (WDPT) and unsaturated hydraulic conductivity (Kun). The range of seal thicknesses detected varied from 0.6 - 5.4 mm. Soil textural characteristics and OM content played a central role in the development of rainfall-induced seals, with coarser soil particles and lower OM content resulting in thicker seals. Two different trends in soil porosity vs. depth were identified: i) for SL soil porosity was lowest at the immediate soil surface, it then increased constantly with depth till the median porosity of undisturbed soil was equalled; ii) for ZCL and SL the highest reduction in porosity, as compared to the median porosity of undisturbed soil, was observed in a well-defined zone of maximum porosity reduction c. 0.24 - 0.48 mm below the soil surface. This contrasting behaviour was related to different dynamics and processes of seal formation which depended on the soil properties. The impact of rainfall-induced surface sealing on the hydrological behaviour of soil (as represented by WDTP and Kun) was rapid and substantial: an average 60% reduction in Kun occurred for all soils between 2 and 9 minutes rainfall, and water repellent surfaces were identified for SZL and ZCL. This highlights that the condition of the immediate surface of agricultural soils involving rainfall-induced structural seals has a strong impact in the overall ability of soil to function as water reservoir

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function

Accuracy of both virtual and printed 3-dimensional models for volumetric measurement of alveolar clefts prior to alveolar bone grafting compared to a validated algorithm:a preliminary investigation

Objective: To determine the accuracy of virtual 3D and 3D printed models derived from cone-beam computed tomography (CBCT) scans for volumetric measurement of alveolar clefts prior to bone grafting Design: Cohort studySetting: University dental hospitalParticipants: Fifteen subjects with unilateral cleft lip and palate Methods: Subjects had i-CAT CBCT scans recorded at 0.2mm voxel and sectioned transversely into 0.2mm slices using i-CAT Vision (Imaging Sciences International, Hatfield, Pennsylvania). Main outcome measures: Alveolar cleft volumes were calculated using: (1) validated algorithm (MATLAB, The Mathworks Inc, Natwik, Massachusetts), (2) commercially available virtual 3D model software (Volume Graphics Studio Max 2.2 (VGSM), Volume Graphics, Heidelberg, Germany) and (3) 3D printed models, which were micro-CT scanned and analyzed using VGSM. For inter-observer reliability, a two-way mixed model intraclass correlation coefficient (ICC) evaluated the reproducibility of identifying the cranial and caudal limits of the clefts between three observers. A Friedman Test (p&lt;0.05) determined differences between the volume methods (SPSS Statistics 19.0, IBM Corporation, New York). Results: Inter-observer reliability was almost perfect (ICC = 0.987). There were no significant differences between the three methods (p&gt;0.05) although virtual 3D models were the most precise with the smallest standard deviations and confidence intervals. Conclusion: In this preliminary investigation, virtual 3D and 3D printed models were as precise as the validated computer algorithm for calculating alveolar cleft volumes prior to bone grafting but virtual 3D models were the most accurate and subject to further investigation could be a useful adjunct in clinical practice. <br/