Decidual memory T‐cell subsets and memory T‐cell stimulatory cytokines in early‐ and late‐onset preeclampsia

Problem: Preeclampsia is a major cause of fetal and maternal mortality and morbidity. Disturbed fetal-maternal immune tolerance, and therewith memory T cells, might be involved in its etiology. This study aims to give insight into memory T-cell populations and its associated cytokines in the decidual layers in early-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE). Method of Study: Lymphocytes were isolated from the decidua parietalis and basalis from EO-PE (n = 6), LO-PE (n = 8) and healthy (n = 15) pregnancies. CD4+ and CD8+ central- (CCR7+), effector- (CCR7−), tissue resident- (CD103+), and regulatory- (Foxp3+) memory cell (CD45RO+) populations and their activation status (CD69+) were analyzed using flow cytometry. qRT-PCR analysis was performed on decidua parietalis and basalis biopsies to detect mRNA expression of interferon-gamma, interleukin-1B, IL2, IL6, IL7, IL8, IL10, IL15, and IL23. Results: CD4+ central-memory (CM) cell proportions were lower in the decidua parietalis in LO-PE (P <.0001) and EO-PE (P <.01) compared to healthy pregnancies. CD8+ memory (P <.05) and CD8+ CM (P <.01) cell proportions were also lower in the decidua parietalis in EO-PE compared to healthy pregnancies. This was accompanied by higher IL15 (P <.05) and IL23 (P <.05) and lower IL7 (P <.05) mRNA expression in decidua basalis biopsies from EO-PE compared to healthy pregnancies, analyzed by qPCR. Conclusion: In conclusion, decidual memory T-cell proportions, their activation status, and associated cytokines are altered in preeclampsia and might therefore be involved in fetal-maternal immune tolerance and the pathophysiology of preeclampsia

Energy level statistics for models of coupled single-mode Bose--Einstein condensates

We study the distribution of energy level spacings in two models describing coupled single-mode Bose-Einstein condensates. Both models have a fixed number of degrees of freedom, which is small compared to the number of interaction parameters, and is independent of the dimensionality of the Hilbert space. We find that the distribution follows a universal Poisson form independent of the choice of coupling parameters, which is indicative of the integrability of both models. These results complement those for integrable lattice models where the number of degrees of freedom increases with increasing dimensionality of the Hilbert space. Finally, we also show that for one model the inclusion of an additional interaction which breaks the integrability leads to a non-Poisson distribution.Comment: 5 pages, 4 figures, revte

Universal Level dynamics of Complex Systems

. We study the evolution of the distribution of eigenvalues of a $N\times N$ matrix subject to a random perturbation drawn from (i) a generalized Gaussian ensemble (ii) a non-Gaussian ensemble with a measure variable under the change of basis. It turns out that, in the case (i), a redefinition of the parameter governing the evolution leads to a Fokker-Planck equation similar to the one obtained when the perturbation is taken from a standard Gaussian ensemble (with invariant measure). This equivalence can therefore help us to obtain the correlations for various physically-significant cases modeled by generalized Gaussian ensembles by using the already known correlations for standard Gaussian ensembles. For large $N$-values, our results for both cases (i) and (ii) are similar to those obtained for Wigner-Dyson gas as well as for the perturbation taken from a standard Gaussian ensemble. This seems to suggest the independence of evolution, in thermodynamic limit, from the nature of perturbation involved as well as the initial conditions and therefore universality of dynamics of the eigenvalues of complex systems.Comment: 11 Pages, Latex Fil

Molecular sensing with hyperpolarized 129Xe using switchable chemical exchange relaxation transfer

A new approach for hyperpolarized 129Xe molecular sensors is explored using paramagnetic relaxation agents that can be deactivated upon chemical or enzymatic reaction with an analyte. Cryptophane encapsulated 129Xe within the vicinity of the paramagnetic center experiences fast relaxation that, through chemical exchange of xenon atoms between cage and solvent pool, causes accelerated hyperpolarized 129Xe signal decay in the dissolved phase. In this work, the relaxivity of GadoliniumIII-DOTA on 129Xe in the solvent was increased eightfold through tethering of the paramagnetic molecule to a cryptophane cage. This potent relaxation agent can be ‘turned off’ specifically for 129Xe through chemical reactions that spatially separate the GdIII centre from the attached cryptophane cage. Unlike 129Xe chemical shift based sensors, the new concept does not require high spectral resolution and may lead to a new generation of responsive contrast agents for molecular MRI

Finite temperature mobility of a particle coupled to a fermion environment

We study numerically the finite temperature and frequency mobility of a particle coupled by a local interaction to a system of spinless fermions in one dimension. We find that when the model is integrable (particle mass equal to the mass of fermions) the static mobility diverges. Further, an enhanced mobility is observed over a finite parameter range away from the integrable point. We present a novel analysis of the finite temperature static mobility based on a random matrix theory description of the many-body Hamiltonian.Comment: 11 pages (RevTeX), 5 Postscript files, compressed using uufile

Design and characterization of Squalene-Gusperimus nanoparticles for modulation of innate immunity

Immunosuppressive drugs are widely used for the treatment of autoimmune diseases and to prevent rejection in organ transplantation. Gusperimus is a relatively safe immunosuppressive drug with low cytotoxicity and reversible side effects. It is highly hydrophilic and unstable. Therefore, it requires administration in high doses which increases its side effects. To overcome this, here we encapsulated gusperimus as squalene-gusperimus nanoparticles (Sq-GusNPs). These nanoparticles (NPs) were obtained from nanoassembly of the squalene gusperimus (Sq-Gus) bioconjugate in water, which was synthesized starting from squalene. The size, charge, and dispersity of the Sq-GusNPs were optimized using the response surface methodology (RSM). The colloidal stability of the Sq-GusNPs was tested using an experimental block design at different storage temperatures after preparing them at different pH conditions. Sq-GusNPs showed to be colloidally stable, non-cytotoxic, readily taken up by cells, and with an anti-inflammatory effect sustained over time. We demonstrate that gusperimus was stabilized through its conjugation with squalene and subsequent formation of NPs allowing its controlled release. Overall, the Sq-GusNPs have the potential to be used as an alternative in approaches for the treatment of different pathologies where a controlled release of gusperimus could be required

Феномен самодостатності містико-естетичного досвіду: місце в розумінні подібності християнства, даосизму, релігії давніх українців і сучасного містицизму

Correlative light and electron microscopy is an increasingly popular technique to study complex biological systems at various levels of resolution. Fluorescence microscopy can be employed to scan large areas to localize regions of interest which are then analyzed by electron microscopy to obtain morphological and structural information from a selected field of view at nm-scale resolution. Previously, an integrated approach to room temperature correlative microscopy was described. Combined use of light and electron microscopy within one instrument greatly simplifies sample handling, avoids cumbersome experimental overheads, simplifies navigation between the two modalities, and improves the success rate of image correlation. Here, an integrated approach for correlative microscopy under cryogenic conditions is presented. Its advantages over the room temperature approach include safeguarding the native hydrated state of the biological specimen, preservation of the fluorescence signal without risk of quenching due to heavy atom stains, and reduced photo bleaching. The potential of cryo integrated light and electron microscopy is demonstrated for the detection of viable bacteria, the study of in vitro polymerized microtubules, the localization of mitochondria in mouse embryonic fibroblasts, and for a search into virus-induced intracellular membrane modifications within mammalian cells

In Vitro Studies of Squalene-Gusperimus Nanoparticles in Islet-Containing Alginate Microcapsules to Regulate the Immune Response in the Immediate Posttransplant Period

Grafting of microencapsulated pancreatic islets has been proposed as an alternative to exogenous insulin for the treatment of type 1 diabetes mellitus. Microencapsulated islets are protected from direct contact with immune cells and larger immune‐active molecules such as immunoglobulins. Unfortunately, many islet cells in the microcapsules are lost in the immediate period after transplantation due to an early host immune response limiting long‐term function of the graft. Gusperimus has shown to reduce the inflammatory responses to grafted encapsulated islets, but it cannot be appropriately used because it is easily hydrolyzed leading to loss of activity. To temporarily modulate the inflammatory response directly after implantation and stabilize gusperimus, squalene‐gusperimus nanoparticles (Sq‐GusNPs) are developed and incorporated in human islets‐containing alginate‐based microcapsules. A prolonged and continuous release of gusperimus is achieved. This offers an anti‐inflammatory microenvironment in the vicinity of the microcapsules and a reduction of cytokine secretion by lipopolysaccharides‐activated human macrophages. Release of gusperimus from Sq‐GusNPs does not affect the in vitro viability or function of human pancreatic islets. The data illustrate that incorporation of Sq‐GusNPs in alginate microcapsules offers an opportunity to temporarily modulate the immediate immune response after the grafting procedure of encapsulated islets cells and reduce loss of islet cells

In vitro determination of the immunosuppressive effect, internalization, and release mechanism of squalene-gusperimus nanoparticles for managing inflammatory responses

Gusperimus is an anti-inflammatory drug that has shown to be effective in managing autoimmunity and preventing graft rejection. This is unstable and easily broken down into cytotoxic components. We encapsulated gusperimus binding it covalently to squalene obtaining squalene-gusperimus nanoparticles (Sq-GusNPs). These nanoparticles enhanced the immunosuppressive effect of gusperimus in both mouse macrophages and T cells. The half-maximal inhibitory concentration in macrophages was 9-fold lower for Sq-GusNPs compared with the free drug. The anti-inflammatory effect of the Sq-GusNPs was maintained over time without cytotoxicity. By studying nanoparticles uptake by cells with flow cytometry, we demonstrated that Sq-GusNPs are endocytosed by macrophages after binding to low-density lipoprotein receptors (LDLR). In presence of cathepsin B or D release of gusperimus is increased demonstrating the participation of proteases in the release process. Our approach may allow the application of Sq-GusNPs for effective management of inflammatory disorders including autoimmunity and graft rejection