Functional consequences of sphingomyelinase-induced changes in erythrocyte membrane structure.

Inflammation enhances the secretion of sphingomyelinases (SMases). SMases catalyze the hydrolysis of sphingomyelin into phosphocholine and ceramide. In erythrocytes, ceramide formation leads to exposure of the removal signal phosphatidylserine (PS), creating a potential link between SMase activity and anemia of inflammation. Therefore, we studied the effects of SMase on various pathophysiologically relevant parameters of erythrocyte homeostasis. Time-lapse confocal microscopy revealed a SMase-induced transition from the discoid to a spherical shape, followed by PS exposure, and finally loss of cytoplasmic content. Also, SMase treatment resulted in ceramide-associated alterations in membrane-cytoskeleton interactions and membrane organization, including microdomain formation. Furthermore, we observed increases in membrane fragility, vesiculation and invagination, and large protein clusters. These changes were associated with enhanced erythrocyte retention in a spleen-mimicking model. Erythrocyte storage under blood bank conditions and during physiological aging increased the sensitivity to SMase. A low SMase activity already induced morphological and structural changes, demonstrating the potential of SMase to disturb erythrocyte homeostasis. Our analyses provide a comprehensive picture in which ceramide-induced changes in membrane microdomain organization disrupt the membrane-cytoskeleton interaction and membrane integrity, leading to vesiculation, reduced deformability, and finally loss of erythrocyte content. Understanding these processes is highly relevant for understanding anemia during chronic inflammation, especially in critically ill patients receiving blood transfusions

Fostering Research Integrity through Institutional Policies: The Case of a Selected Institution of Higher Education1

Truth, trust and integrity are essential to research at higher education institutions. These institutions have accordingly adopted several policies tofoster research integrity. This article explores the likelihood that relevant policies at a selected institution of higher education foster research integrity. The qualitative, single exploratory case study commences with a review of scholarly literature and results in a conceptual model used for a directed content analysis of relevant institutional policies. The findings indicate that these policies do complement each other in fostering research integrity. Further research will be necessary to establish whether policies indeed contribute to responsible researcher conduct

Wall-Fluid and Liquid-Gas Interfaces of Model Colloid-Polymer Mixtures by Simulation and Theory

We perform a study of the interfacial properties of a model suspension of hard sphere colloids with diameter $\sigma_c$ and non-adsorbing ideal polymer coils with diameter $\sigma_p$. For the mixture in contact with a planar hard wall, we obtain from simulations the wall-fluid interfacial free energy, $\gamma_{wf}$, for size ratios $q=\sigma_p/\sigma_c=0.6$ and 1, using thermodynamic integration, and study the (excess) adsorption of colloids, $\Gamma_c$, and of polymers, $\Gamma_p$, at the hard wall. The interfacial tension of the free liquid-gas interface, $\gamma_{lg}$, is obtained following three different routes in simulations: i) from studying the system size dependence of the interfacial width according to the predictions of capillary wave theory, ii) from the probability distribution of the colloid density at coexistence in the grand canonical ensemble, and iii) for statepoints where the colloidal liquid wets the wall completely, from Young's equation relating $\gamma_{lg}$ to the difference of wall-liquid and wall-gas interfacial tensions, $\gamma_{wl}-\gamma_{wg}$. In addition, we calculate $\gamma_{wf}, \Gamma_c$, and $\Gamma_p$ using density functional theory and a scaled particle theory based on free volume theory. Good agreement is found between the simulation results and those from density functional theory, while the results from scaled particle theory quantitatively deviate but reproduce some essential features. Simulation results for $\gamma_{lg}$ obtained from the three different routes are all in good agreement. Density functional theory predicts $\gamma_{lg}$ with good accuracy for high polymer reservoir packing fractions, but yields deviations from the simulation results close to the critical point.Comment: 23 pages, 10 figures, REVTEX. Fig 5a changed. Final versio

Rosenfeld functional for non-additive hard spheres

The fundamental measure density functional theory for hard spheres is generalized to binary mixtures of arbitrary positive and moderate negative non-additivity between unlike components. In bulk the theory predicts fluid-fluid phase separation into phases with different chemical compositions. The location of the accompanying critical point agrees well with previous results from simulations over a broad range of non-additivities and both for symmetric and highly asymmetric size ratios. Results for partial pair correlation functions show good agreement with simulation data.Comment: 8 pages with 4 figure

Spatial models of cell distribution in human lumbar dorsal root ganglia

Dorsal root ganglia (DRG), which contain the somata of primary sensory neurons, have increasingly been considered as novel targets for clinical neural interfaces, both for neuroprosthetic and pain applications. Effective use of either neural recording or stimulation technologies requires an appropriate spatial position relative to the target neural element, whether axon or cell body. However, the internal three- dimensional spatial organization of human DRG neural fibers and somata has not been quantitatively described. In this study, we analyzed 202 cross- sectional images across the length of 31 human L4 and L5 DRG from 10 donors. We used a custom semi- automated graphical user interface to identify the locations of neural elements in the images and normalize the output to a consistent spatial reference for direct comparison by spinal level. By applying a recursive partitioning algorithm, we found that the highest density of cell bodies at both spinal levels could be found in the inner 85% of DRG length, the outer- most 25- 30% radially, and the dorsal- most 69- 76%. While axonal density was fairly homogeneous across the DRG length, there was a distinct low density region in the outer 7- 11% radially. These findings are consistent with previous qualitative reports of neural distribution in DRG. The quantitative measurements we provide will enable improved targeting of future neural interface technologies and DRG- focused pharmaceutical therapies, and provide a rigorous anatomical description of the bridge between the central and peripheral nervous systems.Dorsal root ganglia (DRG) are novel targets for neural interface technologies that treat neurological disorders, such as chronic pain and spinal cord injury. The three- dimensional cellular anatomy of DRG are not well- mapped, particularly in humans, limiting the effectiveness of neurotechnology. We developed a semi- automated algorithm to quantify the three- dimensional distribution of neural elements in histologically- processed tissue. We applied this algorithm to sequential NF200- stained histology slices obtained from human lumbar DRG and demonstrated that cell bodies typically congregate around the dorsal edge of the ganglia. These results are crucial to the development of safe and effective clinical neural interface technologies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155471/1/cne24848_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155471/2/cne24848.pd

The necessity for T-cryptantigen activation screening in babies with necrotising enterocolitis

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Validity of an instrument that assesses functional abilities in people with profound intellectual and multiple disabilities:Look what I can do!

Background: Research about the psychometric properties of the Behavioural Appraisal Scales (BAS) in people with profound intellectual and multiple disabilities (PIMD) is limited. This study evaluates invariance in factor structure, item bias and convergent validity of the BAS. Methods: Data on the BAS from two studies (n = 25; n = 52) were analysed using the oblique multiple group method. The scale structure and item ordering were compared in the two groups. Convergent validity was assessed by correlating scores on the BAS with scores on two other instruments. Results: Of all items, 16–18% correlated stronger with other subscales of the BAS than the subscale they were originally assigned to. Scale structure and order of difficulty differed between groups. Correlations between the BAS and two other instruments varied from low to excellent (r = .48–.85). Conclusions: The results support the construct validity of the BAS. Removing, reassigning and adapting items may enhance construct validity