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A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4–6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece. [ABSTRACT FROM AUTHOR]

The capacity for bacterial extracellular electron transfer via secreted metabolites is widespread in natural, clinical, and industrial environments. Recently, we discovered biological oxidation of phenazine-1-carboxylic acid (PCA), the first example of biological regeneration of a naturally produced extracellular electron shuttle. However, it remained unclear how PCA oxidation was catalyzed. Here, we report the mechanism, which we uncovered by genetically perturbing the branched electron transport chain (ETC) of the soil isolate Citrobacter portucalensis MBL. Biological PCA oxidation is coupled to anaerobic respiration with nitrate, fumarate, dimethyl sulfoxide, or trimethylamine-N-oxide as terminal electron acceptors. Genetically inactivating the catalytic subunits for all redundant complexes for a given terminal electron acceptor abolishes PCA oxidation. In the absence of quinones, PCA can still donate electrons to certain terminal reductases, albeit much less efficiently. In C. portucalensis MBL, PCA oxidation is largely driven by flux through the ETC, which suggests a generalizable mechanism that may be employed by any anaerobically respiring bacterium with an accessible cytoplasmic membrane. This model is supported by analogous genetic experiments during nitrate respiration by Pseudomonas aeruginosa. Author summary: Many bacteria have extremely flexible metabolisms, and we are only beginning to understand how they manifest in the environment. Our study focuses on the role of phenazine-1-carboxylic acid (PCA), a molecule that some bacteria synthesize and secrete into their surroundings. PCA is an "extracellular electron shuttle," a molecule that readily transfers electrons between cells and oxidizing/reducing compounds or other cells. Until our investigation, the role of PCA electron-shuttling had only been studied in one direction: how it takes electrons away from cells, and the effect this has on their viability. Here we present a detailed account of the opposite process and its mechanism: what happens when PCA delivers electrons to cells? Our findings indicate that this previously underappreciated process is generalizable to any anaerobically respiring bacterium. Consequently, we expect that electron donation by PCA is widespread in environments where PCA is plentiful and oxygen is sparse, such as in some agricultural soils. The universality of the extracellular electron shuttle oxidation mechanism we describe for PCA suggests that it should also occur with similar small molecules, of which there are thousands, deepening the implication that this is a significant process in the environment and motivating further research into its consequences. [ABSTRACT FROM AUTHOR]

Heparan sulfate is ubiquitous at the cell surface, where it is expressed predominantly on proteoglycans of either the transmembrane syndecan family or the glycosylphosphatidylinositol (GPI)-anchored glypican family, and has been proposed to function as a "coreceptor" for a number of "heparin-binding" growth factors. Although little is known about functional differences between individual members of the glypican gene family, mutations in both the Drosophila gene dally and the human gene for glypican-3 strongly suggest that at least some glypicans do function in cellular growth control and morphogenesis. In particular, deletion of the human glypican-3 gene is responsible for Simpson-Golabi-Behmel syndrome, and its associated pre- and postnatal tissue overgrowth, increased risk of embryonal tumors during early childhood, and numerous visceral and skeletal anomalies. We have identified and characterized, by sequencing of EST clones and products of rapid amplification of cDNA ends (RACE), an mRNA that encodes a 572-amino-acid member of the glypican gene family (glypican-5) that is most related (50% amino acid similarity, 39% identity) to glypican-3. Glypican-5 mRNA is detected as a 3.9- and 4.4-kb transcript in adult and neonatal mouse brain total RNA, and in situ hybridization results localize transcript primarily to restricted regions of the developing central nervous system, limb, and kidney in patterns consistent with a role in the control of cell growth or differentiation. Interestingly, glypican-5 localizes to 13q31-32 of the human genome, deletions of which are associated with human 13q- syndrome, a developmental disorder with a pattern of defects that shows significant overlap with the pattern of glypican-5 expression.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.08.029 Byline: Ann Ng (a)(c), Michelle Wong (a), Beth Viviano (a), Jonathan M. Erlich (a), George Alba (a)(c), Camila Pflederer (a), Patrick Y. Jay (a)(d), Scott Saunders (a)(b) Keywords: Proteoglycans; Heparan sulfate; FGF; SHH; Vasculature; Coronary; Heart Abstract: Glypican-3 (Gpc3) is a heparan sulfate proteoglycan (HSPG) expressed widely during vertebrate development. Loss-of-function mutations cause Simpson-Golabi-Behmel syndrome (SGBS), a rare and complex congenital overgrowth syndrome with a number of associated developmental abnormalities including congenital heart disease. We found that Gpc3-deficient mice display a high incidence of congenital cardiac malformations like ventricular septal defects, common atrioventricular canal and double outlet right ventricle. In addition we observed coronary artery fistulas, which have not been previously reported in SGBS. Coronary artery fistulas are noteworthy because little is known about the molecular basis of this abnormality. Formation of the coronary vascular plexus in Gpc3-deficient embryos was delayed compared to wild-type, and consistent with GPC3 functioning as a co-receptor for fibroblast growth factor-9 (FGF9), we found a reduction in Sonic Hedgehog (Shh) mRNA expression and signaling in embryonic mutant hearts. Interestingly, we found an asymmetric reduction in SHH signaling in cardiac myocytes, as compared with perivascular cells, resulting in excessive coronary artery formation in the Gpc3-deficient animals. We hypothesize that the excessive development of coronary arteries over veins enables the formation of coronary artery fistulas. This work has broad significance to understanding the genetic basis of coronary development and potentially to molecular mechanisms relevant to revascularization following ischemic injury to the heart. Author Affiliation: (a) Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO 63110, USA (b) Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA (c) Department of Biology, Washington University, St. Louis, MO 63130, USA (d) Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA Article History: Received 26 April 2009; Revised 17 August 2009; Accepted 31 August 2009

Background: Very low birthweight (VLBW) infants must undergo transport when born at a facility unequipped for their care. Previous research suggests an increased risk for intraventricular hemorrhage (IVH) associated with transport. It is unknown whether logistical aspects of transport, particularly mode and distance, or skill level of the resuscitation team are drivers of risk. Objective: To determine if the transport vehicle, distance traveled, or absence of advanced resuscitation team increased risk for severe IVH in outborn VLBW infants. Design/methods: Outborn VLBW infants, transported by specialized team via helicopter or ambulance to a Level IV NICU, were included; inborn VLBW infants served as controls. Infants transported >24 h after birth, by referring center's team, or without head ultrasound were excluded. Baseline clinical data were collected along with IVH grade, transport vehicle, distance traveled, and skill of resuscitation team. Results: Two hundred and ninety-three outborn were matched to 293 inborn infants. Outborn infants had increased incidence of severe IVH even when controlling for antenatal steroids, race, delivery method, and surfactant use (17% vs. 11%, OR = 1.6, 95% CI = 1.1-2.7). Despite this increased incidence, severe IVH was not associated with transport vehicle (p=.90; OR = 0.76, 95% CI = 0.34-1.7), distance traveled (p=.13; OR 0.84, 95% CI = 0.60-1.2), or skill of resuscitation team (p=.18; OR = 0.49, 95% CI = 0.21-1.1). Conclusion: Compared to inborn, outborn infants had increased risk of severe IVH. Transport vehicle, distance traveled, and the skill of resuscitation team did not significantly impact risk. [ABSTRACT FROM AUTHOR]

Loss of function mutations in the gene encoding the heparan sulfate proteoglycan Glypican-3 (GPC3) causes an X-linked disorder in humans known as Simpson-Golabi-Behmel Syndrome (SGBS). This disorder includes both pre- and postnatal overgrowth, a predisposition to certain childhood cancers, and a complex assortment of congenital defects including skeletal abnormalities. In this study, we have identified a previously unrecognized delay in endochondral ossification associated with the loss of Gpc3 function. Gpc3 knockout animals show a marked reduction in calcified trabecular bone, and an abnormal persistence of hypertrophic chondrocytes at embryonic day 16.5 (E16.5). These hypertrophic chondrocytes down-regulate Type X collagen mRNA expression and undergo apoptosis, suggesting a normal progression of hypertrophic chondrocyte cell fate. However, replacement of these cells by mineralized bone is delayed in association with a marked delay in the appearance of osteoclasts in the bone in vivo. This delay in vivo correlates with a significant reduction in the capacity to form osteoclasts from bone marrow macrophage precursors in vitro in response to M-CSF and RANKL, and with a reduction in the numbers of bone-marrow-derived cells expressing the markers CD11b and Gr-1. Together, these results indicate selective impairment in the development of the common hematopoietic lineage from which monocyte/macrophages and PMNs are derived. This is the first report of a requirement for heparan sulfate, and specifically Gpc3, in the lineage-specific differentiation of these cell types in vivo. Keywords: Heparan sulfate; Proteoglycans; Glypican-3; Endochondral ossification; Osteoclasts; Hematopoiesis