Binding between the neural cell adhesion molecules axonin-1 and Nr- CAM/Bravo is involved in neuron-glia interaction

Neural cell adhesion molecules of the immunoglobulin superfamily mediate cellular interactions via homophilic binding to identical molecules and heterophilic binding to other family members or structurally unrelated cell-surface glycoproteins. Here we report on an interaction between axonin-1 and Nr-CAM/Bravo. In search for novel ligands of axonin-1, fluorescent polystyrene microspheres conjugated with axonin-1 were found to bind to peripheral glial cells from dorsal root ganglia. By antibody blockage experiments an axonin-1 receptor on the glial cells was identified as Nr-CAM. The specificity of the interaction was confirmed with binding studies using purified axonin-1 and Nr-CAM. In cultures of dissociated dorsal root ganglia antibodies against axonin-1 and Nr-CAM perturbed the formation of contacts between neurites and peripheral glial cells. Together, these results implicate a binding between axonin-1 of the neuritic and Nr-CAM of the glial cell membrane in the early phase of axon ensheathment in the peripheral nervous system

Assessing the conversion of electronic medical record data into antibiotic stewardship indicators.

BACKGROUND Measuring the appropriateness of antibiotic use is crucial for antibiotic stewardship (ABS) programmes to identify targets for interventions. OBJECTIVES To assess the technical feasibility of converting electronic medical record (EMR) data into ABS indicators. METHODS In this observational feasibility study covering a period of 2 years, the EMRs of patients hospitalized at a large non-university hospital network and receiving at least one dose of a systemic antibiotic were included. ABS indicators measuring steps in the process of antibiotic prescription proposed by the literature were collected and rephrased or defined more specifically to be calculable if needed. Algorithms were programmed in R to convert EMR data into ABS indicators. The indicators were visualized in an interactive dashboard and the plausibility of each output value was assessed. RESULTS In total, data from 25 337 hospitalizations from 20 723 individual patients were analysed and visualized in an interactive dashboard. Algorithms could be programmed to compute 89% (25/28) of all pre-selected indicators assessing treatment decisions automatically out of EMR data, with good data quality for 46% (13/28) of these indicators. According to the data quality observed, the most important issues were (i) missing or meaningless information on indication (e.g. 'mild infection') and (ii) data processing issues such as insufficiently categorized metadata. CONCLUSIONS The calculation of indicators assessing treatment decisions from EMRs was feasible. However, better data structure and processing within EMR systems are crucial for improving the validity of the results

When humans and computers induce social stress through negative feedback: Effects on performance and subjective state

People increasingly work with autonomous systems, which progressively take over functions previously performed exclusively by humans. This may lead to situations in which automated agents give negative performance feedback, which represents an important work-related social stressor. Little is known about how negative feedback provided by computers (as opposed to humans) affects human performance and subjective state. A first experiment (N = 60) focused on the influence of human feedback on performance. After participants had performed a cognitive task, they received a manipulated performance feedback (either positive or negative) from a human (comparing to a control with no feedback) and subsequent performance on several cognitive tasks and the participants' subjective state was measured. The results showed that while negative feedback had a negative influence on several subjective state measures, performance remained unimpaired. In a second experiment (N = 89), participants received manipulated negative feedback by a human or by a computer (or no feedback at all) after having completed an ability test. Subsequent performance was measured on attention tasks and creativity tasks and participants' subjective state was assessed. Although participants felt stressed by both negative computer and human feedback, subsequent performance was again not impaired. However, computer feedback was rated as being less fair than human feedback. Overall, our findings show that there are costs of protecting one's performance against negative feedback and they call for caution regarding the use of negative feedback by both human and automated agents in work settings

Behaviour of adenylic and pyridinic compounds in gingival tissue after a short-term exposure to air

Biochemical variations of adenine and pyridine compounds in human gingival grafts during the period between excision and implantation have been studied. These groups of compounds are considered as «indicators» of the metabolic and energetic status of the living cells. Adenylic compounds such as ATP, ADP and AMP are involved in numerous metabolic processes as «modulators» of allosteric enzymes.NAD+ and NADP+ are involved in the carbohydrate metabolism as co-factors of many reactions of oxydoreduction. The exposure to air of the gingival tissue induces modifications in the energy state of the cells as well as in the ox-reox system. No variation is detectable in the intermediates of the pyridine compounds cycle.Dans des gencives humaines prélevées pour des greffes, ont été étudiées, à certains intervalles de temps entre le prélèvement et la greffe, les variations biochimiques des composés adényliques et pyridiniques, qui sont les «indicateurs» des conditions énergétiques et métaboliques du tissu. Des composés comme l’ATP, l’ADP et l’AMP participent à de nombreux processus métaboliques comme «modulateurs» des enzymes allostériques. NAD+ et NADP + participent au métabolisme des carbohydrates comme co-facteurs de nombreuses réactions d’oxydoréduction. Une brève exposition de la gencive à l’air provoque des changements dans le métabolisme des cellules et du système d’oxydoréduction. Il n’y a pas de variation notable dans les composés intermédiaires du cycle pyridinique

The axonally secreted protein axonin-1 is a potent substratum for neurite growth

Axonin-1 is a neuronal glycoprotein occurring both as a membrane-bound and a secreted form. Membrane-bound axonin-1 is predominantly located in membranes of developing nerve fiber tracts and has recently been characterized as a cell adhesion molecule; the soluble form is secreted from axons and accumulates in the cerebrospinal fluid and the vitreous fluid of the eye. In the present study, we addressed the question as to whether secreted axonin-1 was released in a functionally competent form and we found that it strongly promotes neurite outgrowth when presented to neurons as an immobilized substratum. Neurite lengths elaborated by embryonic dorsal root ganglia neurons on axonin-1 were similar to those on the established neurite-promoting substrata L1 and laminin. Fab fragments of axonin-1 antibodies completely inhibited neurite growth on axonin-1, but not on other substrata. In soluble form, axonin-1 had an anti-adhesive effect, as revealed by perturbation of neurite fasciculation. In view of their structural similarity, we conclude that secreted and membrane-bound axonin-1 interact with the same growth-promoting neuritic receptor. The fact that secreted axonin-1 is functionally active, together with our previous findings that it is secreted from an internal cellular pool, suggests a functional dualism between membrane-bound and secreted axonin-1 at the site of secretion, which is most likely the growth cone. The secretion of adhesion molecules could represent a powerful and rapidly acting regulatory element of growth cone-neurite interactions in the control of neurite elongation, pathway selection, and possibly target recognition

Masses and widths of scalar-isoscalar multi-channel resonances from data analysis

Peculiarities of obtaining parameters for broad multi-channel resonances from data are discussed analyzing the experimental data on processes $\pi\pi\to\pi\pi,K\bar{K}$ in the $I^GJ^{PC}=0^+0^{++}$ channel in a model-independent approach based on analyticity and unitarity and using an uniformization procedure. We show that it is possible to obtain a good description of the $\pi\pi$ scattering data from the threshold to 1.89 GeV with parameters of resonances cited in the PDG tables as preferred. However, in this case, first, representation of the $\pi\pi$ background is unsatisfactory; second, the data on the coupled process $\pi\pi\to K\bar{K}$ are not well described even qualitatively above 1.15 GeV when using the resonance parameters from the only $\pi\pi$ scattering analysis. The combined analysis of these coupled processes is needed, which is carried out satisfactorily. Then both above-indicated flaws, related to the analysis of solely the $\pi\pi$-scattering, are cured. The most remarkable change of parameters with respect to the values of only $\pi\pi$ scattering analysis appears for the mass of the $f_0 (600)$ which is now in some accordance with the Weinberg prediction on the basis of mended symmetry and with an analysis using the large-$N_c$ consistency conditions between the unitarization and resonance saturation. The obtained $\pi\pi$-scattering length $a_0^0$ in case when we restrict to the analysis of the $\pi\pi$ scattering or consider so-called A-solution (with a lower mass and width of $f_0(600)$ meson) agrees well with prediction of chiral perturbation theory (ChPT) and with data extracted at CERN by the NA48/2 Collaboration from the analysis of the $K_{e4}$ decay and by the DIRAC Collaboration from the measurement of the $\pi^+\pi^-$ lifetime.Comment: 21 pages, 3 figures, 6 table

Characterization of yeast mutants lacking alkaline ceramidases YPC1 and YDC1

Humans and yeast possess alkaline ceramidases located in the early secretory pathway. Single deletions of the highly homologous yeast alkaline ceramidases YPC1 and YDC1 have very little genetic interactions or phenotypes. Here, we performed chemical-genetic screens to find deletions/conditions that would alter the growth of ypc1∆ydc1∆ double mutants. These screens were essentially negative, demonstrating that ceramidase activity is not required for cell growth even under genetic stresses. A previously reported protein targeting defect of ypc1∆ could not be reproduced and reported abnormalities in sphingolipid biosynthesis detected by metabolic labeling do not alter the mass spectrometric lipid profile of ypc1∆ydc1∆ cells. Ceramides of ypc1∆ydc1∆ remained normal even in presence of aureobasidin A, an inhibitor of inositolphosphorylceramide synthase. Moreover, in caloric restriction conditions Ypc1p reduces chronological life span. A novel finding is that, when working backwards as a ceramide synthase in vivo, Ypc1p prefers C24 and C26 fatty acids as substrates, whereas it prefers C16:0, when solubilized in detergent and working in vitro. Therefore, its physiological activity may not only concern the minor ceramides containing C14 and C16. Intriguingly, so far the sole discernable benefit of conserving YPC1 for yeast resides with its ability to convey relative resistance toward H₂O₂

Time-resolved cathodoluminescence of InGaAs/AlGaAs tetrahedral pyramidal quantum structures

An original time resolved cathodoluminescence set up has been used to investigate the optical properties and the carrier transport in quantum structures located in InGaAs/AlGaAs tetrahedral pyramids. An InGaAs quantum dot formed just below the top of the pyramid is connected to four types of low-dimensional barriers: InGaAs quantum wires on the edges of the pyramid, InGaAs quantum wells on the (111)A facets and segregated AlGaAs vertical quantum wire and AlGaAs vertical quantum wells formed at the centre and at the pyramid edges. Experiments were performed at a temperature of 92K, an accelerating voltage of 10kV and a beam probe current of 10pA. The cathodoluminescence spectrum shows five luminescence peaks. Rise and decay times for the different emission wavelengths provide a clear confirmation of the peak attribution (previously done with other techniques) to the different nanostructures grown in a pyramid. Moreover, experimental results suggest a scenario where carriers diffuse from the lateral quantum structures towards the central structures (the InGaAs quantum dot and the segregated AlGaAs vertical quantum wire) via the InGaAs quantum wires on the edges of the pyramid. According to this hypothesis, we have modeled the carrier diffusion along these quantum wires. An ambipolar carrier mobility of 1400cm2/V s allows to obtain a good fit to all temporal dependence