Cromoglycate and Nedocromil: Influence on Airway Reactivity

Although basic mechanisms of bronchial hyper-responsiveness (BHR) are still incompletely understood, inflammation of airways is likely to play a fundamental role in modulating BHR in patients with asthma. The involvement of several inflammatory cells (eosinophils, mast cells, lymphocytes, neutrophils, macrophages and platelets) and of bioactive mediators secreted by these cells in the pathogenesis of asthma is well documented. Sodium cromoglycate and nedocromil sodium are two pharmacological agents which have anti-allergic and anti-inflammatory properties. Their clinical effectiveness in mild to moderate asthma, and the capacity to reduce BHR under different natural and experimental conditions, make them valuable drugs for maintenance therapy in patients with asthma

Zinc(II)-methimazole complexes: synthesis and reactivity

The tetrahedral S-coordinated complex [Zn(MeImHS)(4)](ClO4)(2), synthesised from the reaction of [Zn(ClO4)(2)] with methimazole (1-methyl-3H-imidazole-2-thione, MeImHS), reacts with triethylamine to yield the homoleptic complex [Zn(MeImS)(2)] (MeImS = anion methimazole). ESI-MS and MAS C-13-NMR experiments supported MeImS acting as a (N, S)-chelating ligand. The DFT-optimised structure of [Zn(MeImS)(2)] is also reported and the main bond lengths compared to those of related Zn-methimazole complexes. The complex [Zn(MeImS)(2)] reacts under mild conditions with methyl iodide and separates the novel complex [Zn(MeImSMe)(2)I-2] (MeImSMe = S-methylmethimazole). X-ray diffraction analysis of the complex shows a ZnI2N2 core, with the methyl thioethers uncoordinated to zinc. Conversely, the reaction of [Zn( MeImS)(2)] with hydroiodic acid led to the formation of the complex [Zn(MeImHS)(2)I-2] having a ZnI2S2 core with the neutral methimazole units S-coordinating the metal centre. The Zn-coordinated methimazole can markedly modify the coordination environment when changing from its thione to thionate form and vice versa. The study of the interaction of the drug methimazole with the complex [Zn(MeIm)(4)](2+) (MeIm = 1-methylimidazole) - as a model for Zn-enzymes containing a N-4 donor set from histidine residues shows that methimazole displaces only one of the coordinated MeIm molecules; the formation constant of the mixed complex [Zn(MeIm)(3)(MeImHS)](2+) was determined

Inhibition of IκBα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells

Adult T cell leukemia/lymphoma (ATL) can be susceptible, at least transiently, to treatments with azidothymidine (AZT) plus IFNα and/or arsenic trioxide. However, the real role of AZT in this effect is still unclear. In fact, while reverse transcriptase (RT) inhibition could explain reduction of clonal expansion and of renewal of HTLV-1 infected cells during ATL progression, this effect alone seems insufficient to justify the evident and prompt decrease of the pro-viral load in treated patients. We have previously demonstrated that AZT is endowed with an intrinsic pro-apoptotic potential towards both peripheral blood mononuclear cells from healthy donors or some tumor cell lines, but this cytotoxic potential cannot be fully achieved unless IκBα phosphorylation is inhibited. Since the constitutive activation of NF-kappa B (NF-κB) appears a common biological basis of HTLV-1-infected cells, a pharmacological inhibition of IκBα phosphorylation seems a potential strategy for treating and preventing HTLV-1 related pathologies. In this study, we have demonstrated that a combination treatment with the IκBα phosphorylation inhibitor Bay 11-7085 and AZT induced increased levels of regulated cell death (RCD) by apoptosis compared to the single treatments in HTLV-1 infected cells of different origin. Importantly, levels of RCD were considerably higher in infected cells in comparison with the uninfected ones. Inhibition of NF-κB activation following the combined treatment was confirmed by analysis of both gel-shift and functional activity of the NF-κB complex proteins, p65/p52. Moreover, a transcriptional analysis revealed that the addition of Bay 11-7085 to AZT treatment in HTLV-1-infected cells modified their transcriptional profile, by inducing the upregulation of some pro-apoptotic genes together with the downregulation of some anti-apoptotic genes. Our data suggest that addition of adequate concentrations of IκBα phosphorylation inhibitor to therapeutic regimens including AZT could be a promising strategy in ATL

A low accretion efficiency of planetesimals formed at planetary gap edges

Observations and models of giant planets indicate that such objects are enriched in heavy elements compared to solar abundances. The prevailing view is that giant planets accreted multiple Earth masses of heavy elements after the end of core formation. Such late solid enrichment is commonly explained by the accretion of planetesimals. Planetesimals are expected to form at the edges of planetary gaps, and here we address the question of whether these planetesimals can be accreted in large enough amounts to explain the inferred high heavy element contents of giant planets. We performed a series of N-body simulations of the dynamics of planetesimals and planets during the planetary growth phase, taking gas drag into account as well as the enhanced collision cross section caused by the extended envelopes. We considered the growth of Jupiter and Saturn via gas accretion after reaching the pebble isolation mass and we included their migration in an evolving disk. We find that the accretion efficiency of planetesimals formed at planetary gap edges is very low: less than 10% of the formed planetesimals are accreted even in the most favorable cases, which in our model corresponds to a few Earth masses. When planetesimals are assumed to form beyond the feeding zone of the planets, extending to a few Hill radii from a planet, accretion becomes negligible. Furthermore, we find that the accretion efficiency increases when the planetary migration distance is increased and that the efficiency does not increase when the planetesimal radii are decreased. Based on these results, we conclude that it is difficult to explain the large heavy element content of giant planets with planetesimal accretion during the gas accretion phase. Alternative processes most likely are required, such as accretion of vapor deposited by drifting pebbles

Multivariate calibration approach for quantitative determination of cell-line cross contamination by intact cell mass spectrometry and artificial neural networks

Cross-contamination of eukaryotic cell lines used in biomedical research represents a highly relevant problem. Analysis of repetitive DNA sequences, such as Short Tandem Repeats (STR), or Simple Sequence Repeats (SSR), is a widely accepted, simple, and commercially available technique to authenticate cell lines. However, it provides only qualitative information that depends on the extent of reference databases for interpretation. In this work, we developed and validated a rapid and routinely applicable method for evaluation of cell culture cross-contamination levels based on mass spectrometric fingerprints of intact mammalian cells coupled with artificial neural networks (ANNs). We used human embryonic stem cells (hESCs) contaminated by either mouse embryonic stem cells (mESCs) or mouse embryonic fibroblasts (MEFs) as a model. We determined the contamination level using a mass spectra database of known calibration mixtures that served as training input for an ANN. The ANN was then capable of correct quantification of the level of contamination of hESCs by mESCs or MEFs. We demonstrate that MS analysis, when linked to proper mathematical instruments, is a tangible tool for unraveling and quantifying heterogeneity in cell cultures. The analysis is applicable in routine scenarios for cell authentication and/or cell phenotyping in general

A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84.

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81 %) of T1DM-CD tested sera, but are detectable also in a fraction (27 %) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies

A Superconductor Made by a Metal Heterostructure at the Atomic Limit Tuned at the "Shape Resonance": MgB2

We have studied the variation of Tc with charge density and lattice parameters in Mg1-xAlxB2 superconducting samples at low Al doping x<8%. We show that high Tc occurs where the chemical potential is tuned at a "superconducting shape resonance" near the energy Ec of the quantum critical point (QCP) for the dimensional transition from 2D to 3D electronic structure in a particular subband of the natural superlattice of metallic atomic boron layers. At the "shape resonance" the electrons pairs see a 2D Fermi surface at EF-w0 and a 3D Fermi surface at EF+wo, where wo is the energy cut off of the pairing interaction. The resonant amplification occurs in a narrow energy range where EF-Ec is in the range of 2wo.Comment: 16 page

Shape resonance for the anisotropic superconducting gaps near a Lifshitz transition: the effect of electron hopping between layers

The multigap superconductivity modulated by quantum confinement effects in a superlattice of quantum wells is presented. Our theoretical BCS approach captures the low-energy physics of a shape resonance in the superconducting gaps when the chemical potential is tuned near a Lifshitz transition. We focus on the case of weak Cooper-pairing coupling channels and strong pair exchange interaction driven by repulsive Coulomb interaction that allows to use the BCS theory in the weak-coupling regime neglecting retardation effects like in quantum condensates of ultracold gases. The calculated matrix element effects in the pairing interaction are shown to yield a complex physics near the particular quantum critical points due to Lifshitz transitions in multigap superconductivity. Strong deviations of the ratio $2\Delta/T_c$ from the standard BCS value as a function of the position of the chemical potential relative to the Lifshitz transition point measured by the Lifshitz parameter are found. The response of the condensate phase to the tuning of the Lifshitz parameter is compared with the response of ultracold gases in the BCS-BEC crossover tuned by an external magnetic field. The results provide the description of the condensates in this regime where matrix element effects play a key role.Comment: 12 pages, 6 figure

Pennsylvania Folklife Vol. 14, No. 3

• Buckwheat Music • The Domestic Encyclopaedia of 1803-1804 • Taming the Land • Jacob Taylor and His Almanacs • Italian Immigrant Life in Northampton County, Pennsylvania, 1890-1915 • Uni Day\u27s Herb Gardenhttps://digitalcommons.ursinus.edu/pafolklifemag/1019/thumbnail.jp