Children\u27s Exposure to Metals: A Community-Initiated Study

In 2007, it was shown that the shipping of lead (Pb) through Esperance Port in Western Australia resulted in contamination and increased Pb concentrations in children. A clean-up strategy was implemented; however, little attention was given to other metals. In consultation with the community, a cross-sectional exposure study was designed. Thirty-nine children aged 1 to 12 years provided samples of hair, urine, drinking water, residential soil and dust. Concentrations of nickel (Ni) and Pb were low in biological and environmental samples. Hair aluminium (Al) (lower than the detection limit [DL] to 251 μg/g) and copper (Cu) (7 to 415 μg/g), as well as urinary Al ( μg/L), manganese (Mn) (μg/L), and Cu (μg/L), were increased for a small number of participants. Concentrations of nickel (Ni) in urine, soil, and dust decreased with increasing distance from the port, as did soil Pb concentrations. The results suggest exposure to Ni and Pb was limited in children at the time of sampling in 2009. Further investigation is required to determine the source(s) and significance of other increased metals concentrations

Action video games improve direction discrimination of parafoveal translational global motion but not reaction times

Playing action video games enhances visual motion perception. However, there is psychophysical evidence that action video games do not improve motion sensitivity for translational global moving patterns presented in fovea. This study investigates global motion perception in action video game players and compares their performance to that of non-action video game players and non-video game players. Stimuli were random dot kinematograms presented in the parafovea. Observers discriminated the motion direction of a target random dot kinematogram presented in one of the four visual quadrants. Action video game players showed lower motion coherence thresholds than the other groups. However, when the task was performed at threshold, we did not find differences between groups in terms of distributions of reaction times. These results suggest that action video games improve visual motion sensitivity in the near periphery of the visual field, rather than speed response

The Role of Organic Carbon in the Southern Uplands-Down-Longford Terrane Accretionary Prism, Scotland and Ireland

Fluid inclusions were measured by M. Baron. Electron Microscopy was performed with the help of J. Still in the ACEMAC Facility at the University of Aberdeen. Skilled technical support was also provided by J. Johnston & C. Taylor. P. Carey and A. Lings assisted field sampling. The manuscript benefitted from careful reviews by I. Scotchman and W. Meredith. The research was partly supported by NERC grant NE/T003677/1.Peer reviewedPublisher PD

Rapid Prototyping of Reconfigurable Microfluidic Channels in Undercooled Metal Particle-Elastomer Composites

Conventional fabrication of microfluidic channels/devices are faced with challenges such as single use channels and/or significant time consumption. We propose a flexible platform for fabricating microfluidic channels simply through indentation on a smart composite—the so-called ST3R (Stiffness tuning through thermodynamic relaxation) composite. The application of ST3R composite allows rapid fabrication of microfluidic channels by hand or with a prefabricated stamp, and precise prototyping of complex designs using a 2D plotter. Indenter geometry, applied stress, filler loading, and number of repeated indentations affect channel dimensions and/or shape. These channels further exhibit; i) Substantial improvement against swelling by organic solvent, in part due to the high modulus of the solidified metal network. ii) Channel reconfigurability by heating the solidified undercooled metals. ST3R composite slabs have the potential to serve as microfluidic ‘breadboards’, from which complex channels can be integrated in a flexible manner

The stable isotope (C, O, S) record of Paleoproterozoic marbles, Scotland

Paleoproterozoic marbles occur widely in NW Scotland. The isotopically heavy carbonate carbon (⁠δ 13C >3‰) in marbles that characterizes the worldwide Lomagundi–Jatuli Event (2.3–2.05 Ga) is recognized in the Laurentian Foreland, the Moine Nappe and the Sgurr Beag Nappe, over a 150 km transect across the Caledonian thrust belt. A light oxygen isotope composition distinguishes marbles that have been sheared and retrogressed by ingress of meteoric water, possibly during both Laxfordian and Caledonian orogenesis. The shearing of marbles also contributed to graphite formation (mean δ 13C −7.2‰). Pyrite in the marbles contains isotopically heavy sulfur, typical of Paleoproterozoic diagenetic sulfides precipitated from low-sulfate seawater. These data show that the c. 2 Ga marbles in Scotland are a high-quality archive of information on their depositional and post-depositional history. The data emphasize a continuum of a Paleoproterozoic marble–graphite–sulfide-bearing assemblage from eastern Canada and Greenland through Scotland to Scandinavia

Regional-scale paleofluid system across the Tuscan Nappe–Umbria–Marche Apennine Ridge (northern Apennines) as revealed by mesostructural and isotopic analyses of stylolite–vein networks

We report the results of a multiproxy study that combines structural analysis of a fracture–stylolite network and isotopic characterization of calcite vein cements and/or fault coating. Together with new paleopiezometric and radiometric constraints on burial evolution and deformation timing, these results provide a first-order picture of the regional fluid systems and pathways that were present during the main stages of contraction in the Tuscan Nappe and Umbria–Marche Apennine Ridge (northern Apennines). We reconstruct four steps of deformation at the scale of the belt: burial-related stylolitization, Apenninic-related layer-parallel shortening with a contraction trending NE–SW, local extension related to folding, and late-stage fold tightening under a contraction still striking NE–SW. We combine the paleopiezometric inversion of the roughness of sedimentary stylolites – that constrains the range of burial depth of strata prior to layer-parallel shortening – with burial models and U–Pb absolute dating of fault coatings in order to determine the timing of development of mesostructures. In the western part of the ridge, layer-parallel shortening started in Langhian time (∼15 Ma), and then folding started at Tortonian time (∼8 Ma); late-stage fold tightening started by the early Pliocene (∼5 Ma) and likely lasted until recent/modern extension occurred (∼3 Ma onward). The textural and geochemical (δ18O, δ13C, Δ47CO2 and 87Sr∕86Sr) study of calcite vein cements and fault coatings reveals that most of the fluids involved in the belt during deformation either are local or flowed laterally from the same reservoir. However, the western edge of the ridge recorded pulses of eastward migration of hydrothermal fluids (>140 ∘C), driven by the tectonic contraction and by the difference in structural style of the subsurface between the eastern Tuscan Nappe and the Umbria–Marche Apennine Ridge

Netazepide inhibits expression of Pappalysin 2 in type-1 gastric neuroendocrine tumors

Background & Aims: In patients with autoimmune atrophic gastritis and achlorhydria, hypergastrinemia is associated with the development of type 1 gastric neuroendocrine tumors (gNETs). Twelve months of treatment with netazepide (YF476), an antagonist of the cholecystokinin B receptor (CCKBR or CCK2R), eradicated some type 1 gNETs in patients. We investigated the mechanisms by which netazepide induced gNET regression using gene expression profiling. Methods: We obtained serum samples and gastric corpus biopsy specimens from 8 patients with hypergastrinemia and type 1 gNETs enrolled in a phase 2 trial of netazepide. Control samples were obtained from 10 patients without gastric cancer. We used amplified and biotinylated sense-strand DNA targets from total RNA and Affymetrix (Thermofisher Scientific, UK) Human Gene 2.0 ST microarrays to identify differentially expressed genes in stomach tissues from patients with type 1 gNETs before, during, and after netazepide treatment. Findings were validated in a human AGS GR gastric adenocarcinoma cell line that stably expresses human CCK2R, primary mouse gastroids, transgenic hypergastrinemic INS-GAS mice, and patient samples. Results: Levels of pappalysin 2 (PAPPA2) messenger RNA were reduced significantly in gNET tissues from patients receiving netazepide therapy compared with tissues collected before therapy. PAPPA2 is a metalloproteinase that increases the bioavailability of insulin-like growth factor (IGF) by cleaving IGF binding proteins (IGFBPs). PAPPA2 expression was increased in the gastric corpus of patients with type 1 gNETs, and immunohistochemistry showed localization in the same vicinity as CCK2R-expressing enterochromaffin-like cells. Up-regulation of PAPPA2 also was found in the stomachs of INS-GAS mice. Gastrin increased PAPPA2 expression with time and in a dose-dependent manner in gastric AGS GR cells and mouse gastroids by activating CCK2R. Knockdown of PAPPA2 in AGS GR cells with small interfering RNAs significantly decreased their migratory response and tissue remodeling in response to gastrin. Gastrin altered the expression and cleavage of IGFBP3 and IGFBP5. Conclusions: In an analysis of human gNETS and mice, we found that gastrin up-regulates the expression of gastric PAPPA2. Increased PAPPA2 alters IGF bioavailability, cell migration, and tissue remodeling, which are involved in type 1 gNET development. These effects are inhibited by netazepide

Effect of surface morphologies and chemistry of paper on deposited collagen

Paper-based platforms for biological studies have received significant attention given that cellulose is ubiquitous, biocompatible, and can be readily organized into tunable fibrous structures. In the latter form, effect of complexity in surface morphologies (roughness, porosity and fiber organization) on cell-substrate interaction has not been thoroughly explored. We infer that altering the properties of a fibrous material should lead to significant changes in cellular microenvironment and direct the deposition of structurally analogous extracellular matrix (fiber-fiber templating) like collagen. Here, we elucidate the effect of varying paper roughness and surface chemistry on NIH/3T3 fibroblasts via organization of excreted collagen. Collagen intensity was found to increase linearly with paper porosity, indicating a 3D culture platform. The intensity, however, decays over time due to biodegradation of the substrate. Stability can be improved by introducing fluorinated alkyl silanes to yield hydrophobic paper. This process concomitantly transforms the substrate to a 2D-like scaffold where collagen is predominantly assembled on the surface, thus changing the cellular microenvironment. Altering surface energy also led to fluctuations in collagen intensity and organization over time for smooth (calendered) paper substrates. We infer that the increased roughness improves collagen adsorption through capillary driven petal effect. In general, the influence of the substrate simultaneously affects its ability to host collagen and guide orientation. These findings offer insights into the effects of secondary structures and chemistry of fibrous polymeric materials on cell culture, which we propose as vital parameters when using paper-based platforms

The short term debt vs. long term debt puzzle: a model for the optimal mix

This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

Gastrin-induced miR-222 promotes gastric tumor development by suppressing p27kip1

Background and Aims: Elevated circulating concentrations of the hormone gastrin contribute to the development of gastric adenocarcinoma and types-1 and 2 gastric neuroendocrine tumors (NETs). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate proteins which in turn influence various biological processes. We hypothesised that gastrin induces the expression of specific gastric miRNAs within CCK2 receptor (CCK2R) expressing cells and that these mediate functionally important actions of gastrin. Results: Gastrin increased miR-222 expression in AGSGR cells, with maximum changes observed at 10 nM G17 for 24 h. Signalling occurred via CCK2R and the PKC and PI3K pathways. miR-222 expression was increased in the serum and gastric corpus mucosa of hypergastrinemic INS-GAS mice and hypergastrinemic patients with autoimmune atrophic gastritis and type 1 gastric NETs; it decreased in patients following treatment with the CCK2R antagonist netazepide (YF476). Gastrin-induced miR-222 overexpression resulted in reduced expression and cytoplasmic mislocalisation of p27kip1, which in turn caused actin remodelling and increased migration in AGSGR cells. Materials and Methods: miRNA PCR arrays were used to identify changes in miRNA expression following G17 treatment of human gastric adenocarcinoma cells stably transfected with CCK2R (AGSGR). miR-222 was further investigated using primer assays and samples from hypergastrinemic mice and humans. Chemically synthesised mimics and inhibitors were used to assess cellular phenotypical changes associated with miR-222 dysregulation. Conclusions: These data indicate a novel mechanism contributing to gastrin-associated gastric tumor development. miR-222 may also be a promising biomarker for monitoring gastrin induced premalignant changes in the stomach