Full length talin stimulates integrin activation and axon regeneration.

Integrin function is regulated by activation involving conformational changes that modulate ligand-binding affinity and downstream signaling. Activation is regulated through inside-out signaling which is controlled by many signaling pathways via a final common pathway through kindlin and talin, which bind to the intracellular tail of beta integrins. Previous studies have shown that the axon growth inhibitory molecules NogoA and chondroitin sulfate proteoglycans (CSPGs) inactivate integrins. Overexpressing kindlin-1 in dorsal root ganglion (DRG) neurons activates integrins, enabling their axons to overcome inhibitory molecules in the environment, and promoting regeneration in vivo following dorsal root crush. Other studies have indicated that expression of the talin head alone or with kindlin can enhance integrin activation. Here, using adult rat DRG neurons, we investigate the effects of overexpressing various forms of talin on axon growth and integrin signaling. We found that overexpression of the talin head activated axonal integrins but inhibited downstream signaling via FAK, and did not promote axon growth. Similarly, co-expression of the talin head and kindlin-1 prevented the growth-promoting effect of kindlin-1, suggesting that the talin head acts as a form of dominant negative for integrin function. Using full-length talin constructs in PC12 cells we observed that neurite growth was enhanced by the expression of wild-type talin and more so by two 'activated' forms of talin produced by point mutation (on laminin and aggrecan-laminin substrates). Nevertheless, co-expression of full-length talin with kindlin did not promote neurite growth more than either molecule alone. In vivo, we find that talin is present in PNS axons (sciatic nerve), and also in CNS axons of the corticospinal tract.This work was funded by grants from the Medical Research Council (G1000864), the Henry Smith Charity, the Christopher and Dana Reeve Foundation, the John and Lucille van Geest Foundation, the European Union Framework 7 Programmes Spinal Cord Repair (201144) and Plasticise (223524), and the NIHR Cambridge Biomedical Research Centre. CLT was supported by the Merck, Sharpe and Dohme Fund. We thank Rienhardt Fassler for kindlin constructs and advice, David Critchley for talin antibodies and constructs and Mark Ginsberg for talin constructs.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.mcn.2015.03.01

Nuclear Quadrupole Hyperfine Structure in HC14N/H14NC and DC15N/D15NC Isomerization: A Diagnostic Tool for Characterizing Vibrational Localization

Large-amplitude molecular motions which occur during isomerization can cause significant changes in electronic structure. These variations in electronic properties can be used to identify vibrationally-excited eigenstates which are localized along the potential energy surface. This work demonstrates that nuclear quadrupole hyperfine interactions can be used as a diagnostic marker of progress along the isomerization path in both the HC14N/H14NC and DC15N/D15NC chemical systems. Ab initio calculations at the CCSD(T)/cc-pCVQZ level indicate that the hyperfine interaction is extremely sensitive to the chemical bonding of the quadrupolar 14N nucleus and can therefore be used to determine in which potential well the vibrational wavefunction is localized. A natural bonding orbital analysis along the isomerization path further demonstrates that hyperfine interactions arise from the asphericity of the electron density at the quadrupolar nucleus. Using the CCSD(T) potential surface, the quadrupole coupling constants of highly-excited vibrational states are computed from a one-dimensional internal coordinate path Hamiltonian. The excellent agreement between ab initio calculations and recent measurements demonstrates that nuclear quadrupole hyperfine structure can be used as a diagnostic tool for characterizing localized HCN and HNC vibrational states.Comment: Accepted by Physical Chemistry Chemical Physic

A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection

PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Pulmonary Embolism Incidence and Fatality Trends in Chinese Hospitals from 1997 to 2008: A Multicenter Registration Study

BACKGROUND: There has not been sufficient evidence to support the Asians being less susceptible to pulmonary embolism (PE) than other ethnicities, because the prevalence of PE/deep venous thrombosis (DVT) in different racial and ethnic groups has not been carefully studied until recently except in Caucasians. To test the hypothesis that the Chinese population has a lower risk for PE, this study comprehensively assessed the hospital-based incidence and case fatality rates for PE during the 1997-2008 in China. METHODS: A registration study of patients with suspected PE syndromes admitted to 60 level-3 hospitals involved in the National Cooperative Project for the Prevention and Treatment of Venous Thromboembolism (NCPPT) was conducted from January 1997 to December 2008. The only exclusion criterion was an age of less than 18 years. Helical computed tomography scan, ventilation-perfusion lung scintigraphy or pulmonary angiography was carried out before or after hospitalization. All images were reviewed and evaluated independently by two specialists. RESULTS: A total of 18,206 patients were confirmed with PE from 16,972,182 hospital admissions. The annual incidence was 0.1% (95% CI: 0.1% to 0.2%). The overall incidence of PE in male patients (0.2%, 95% CI: 0.1% to 0.3%) was higher than that in female patients (0.1% and 95% CI: 0.0% to 0.1%). An increasing incidence gradient for PE was noticed from Southern to Northern China. In addition, the case fatality rate was apparently decreasing: 25.1% (95% CI: 16.2% to 36.9%) in 1997 to 8.7% (95% CI: 3.5% to 15.8%) in 2008. CONCLUSIONS: Our findings suggest the relatively stable PE incidence and decreasing fatality trends in Chinese hospitals may be partially attributable to the implementation of the NCCPT and suggest the government should reevaluate the severity of PE so that health resources for the prevention, diagnosis and treatment of PE could be used to their fullest

Characterisation of multiple conducting permeable objects in metal detection by polarizability tensors

Realistic applications in metal detection involve multiple inhomogeneous‐conducting permeable objects, and the aim of this paper is to characterise such objects by polarizability tensors. We show that, for the eddy current model, the leading order terms for the perturbation in the magnetic field, due to the presence of N small conducting permeable homogeneous inclusions, comprises of a sum of N terms with each containing a complex symmetric rank 2 polarizability tensor. Each tensor contains information about the shape and material properties of one of the objects and is independent of its position. The asymptotic expansion we obtain extends a previously known result for a single isolated object and applies in situations where the object sizes are small and the objects are sufficiently well separated. We also obtain a second expansion that describes the perturbed magnetic field for inhomogeneous and closely spaced objects, which again characterises the objects by a complex symmetric rank 2 tensor. The tensor's coefficients can be computed by solving a vector valued transmission problem, and we include numerical examples to illustrate the agreement between the asymptotic formula describing the perturbed fields and the numerical prediction. We also include algorithms for the localisation and identification of multiple inhomogeneous objects

Selenium uptake, translocation and speciation in wheat supplied with selenate or selenite

Selenite can be a dominant form of selenium (Se) in aerobic soils; however, unlike selenate, the mechanism of selenite uptake by plants remains unclear. Uptake, translocation and Se speciation in wheat (Triticum aestivum) supplied with selenate or selenite, or both, were investigated in hydroponic experiments. The kinetics of selenite influx was determined in short-term (30 min) experiments. Selenium speciation in the water-extractable fraction of roots and shoots was determined by HPLC-ICPMS. Plants absorbed similar amounts of Se within 1 d when supplied with selenite or selenate. Selenate and selenite uptake were enhanced in sulphur-starved and phosphorus-starved plants, respectively. Phosphate markedly increased K-m of the selenite influx. Selenate and selenite uptake were both metabolically dependent. Selenite was rapidly converted to organic forms in roots, with limited translocation to shoots. Selenomethionine, selenomethionine Se-oxide, Se-methyl-selenocysteine and several other unidentified Se species were detected in the root extracts and xylem sap from selenite-treated plants. Selenate was highly mobile in xylem transport, but little was assimilated to organic forms in 1 d. The presence of selenite decreased selenate uptake and xylem transport. Selenite uptake is an active process likely mediated, at least partly, by phosphate transporters. Selenite and selenate differ greatly in the ease of assimilation and xylem transport

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Health-related quality of life in glioma patients in China

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life (HRQOL) has been increasingly emphasized in cancer patients. There are no reports comparing baseline HRQOL of different subgroups of glioma patients prior to surgery.</p> <p>Methods</p> <p>HRQOL assessments by the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0), the Mini-Mental State Examination and Karnofsky Performance Status were obtained from glioma patients prior to surgery.</p> <p>Results</p> <p>Ninety-two pathologically confirmed glioma patients were recruited. There were 84.8% patients with emotional impairment, 75% with social and cognitive impairment, 70.7% with physical impairment, and 50% with role impairment. Eighty-two percent of patients reported fatigue symptoms, 72.8% reported pain, 50% reported appetite loss, 39.1% reported insomnia, and 36.9% reported nausea/vomiting, whereas other symptoms (dyspnea, diarrhea, constipation) in the QLQ-C30 were reported by fewer than 30% of patients. Fatigue and pain symptoms and all "functioning" scales were strongly correlated with global health status/quality of life (QoL). Fatigue was strongly related to all functioning scales, pain, appetite loss, and global health status/QoL. No difference in baseline HRQOL prior to surgery was reported between females and males, among different lesion locations, or between normal- and abnormal-cognition subgroups of glioma patients. Age, KPS, WHO grade, and tumor recurrence significantly affected HRQOL in glioma patients.</p> <p>Conclusions</p> <p>These data provided the baseline HRQOL in glioma patients prior to surgery in China. Most pre-surgery glioma patients indicated emotional, social, cognitive, physical, and role impairment. Fatigue, pain, appetite loss, insomnia, and nausea/vomiting were common in these patients. The fatigue and pain symptoms and all types of functioning strongly affected global health status/QoL. Old age, worse performance status, WHO grade IV and tumor recurrence had deleterious effects on HRQOL.</p