The effect of interleukin-10 and transforming growth factor beta-1 on HLA-DR expression in colonic epithelial cells.

The aim of this study was to assess whether interleukin-10 (IL-10) and/or transforming growth factor beta-1 (TGFbeta1) downregulate HLA-DR expression using the HT29 cell line as a model of colonic epithelial cells. HLA-DR expression was induced in HT29 cells with gamma-interferon. The effects of IL-10 alone, TGFbeta1 alone, and IL-10 and TGFbeta1 in combination were studied. HLA-DR expression was assessed using flow cytometric analysis. Gamma-interferon induced HLA-DR expression in a dose-dependent fashion. In the absence of gamma-interferon, neither IL-10 nor TGFbeta1 induced HLA-DR expression. In isolation, neither IL-10 nor TGFbeta1 downregulated HLA-DR expression. When IL-10 and TGFbeta1 were added in combination, small (6-30%) statistically significant reductions in HLA-DR expression were seen. The biological significance is unclear

Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump

The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least ≈2 x 10(6) s(-1)

Mining routinely collected acute data to reveal non-linear relationships between nurse staffing levels and outcomes

Report of a study of routinely collected data in one NHS hospital that revealed hitherto unrecognised patterns between nurse staffing and patient outcome

A one-dimensional lattice model for a quantum mechanical free particle

Two types of particles, A and B with their corresponding antiparticles, are defined in a one dimensional cyclic lattice with an odd number of sites. In each step of time evolution, each particle acts as a source for the polarization field of the other type of particle with nonlocal action but with an effect decreasing with the distance: A -->...\bar{B} B \bar{B} B \bar{B} ... ; B --> A \bar{A} A \bar{A} A ... . It is shown that the combined distribution of these particles obeys the time evolution of a free particle as given by quantum mechanics.Comment: 8 pages. Revte

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract (GIT). Cigarette smoke (CS) exposure and chronic obstructive pulmonary disease (COPD) are risk factors for CD, although the mechanisms involved are poorly understood. We employed a mouse model of CS-induced experimental COPD and clinical studies to examine these mechanisms. Concurrent with the development of pulmonary pathology and impaired gas exchange, CS-exposed mice developed CD-associated pathology in the colon and ileum, including gut mucosal tissue hypoxia, HIF-2 stabilization, inflammation, increased microvasculature, epithelial cell turnover, and decreased intestinal barrier function. Subsequent smoking cessation reduced GIT pathology, particularly in the ileum. Dimethyloxaloylglycine, a pan-prolyl hydroxylase inhibitor, ameliorated CS-induced GIT pathology independently of pulmonary pathology. Prior smoke exposure exacerbated intestinal pathology in 2,4,6-trinitrobenzenesulfonic acid-induced (TNBS-induced) colitis. Circulating vascular endothelial growth factor, a marker of systemic hypoxia, correlated with CS exposure and CD in mice and humans. Increased mucosal vascularisation was evident in ileum biopsies from CD patients who smoke compared with nonsmokers, supporting our preclinical data. We provide strong evidence that chronic CS exposure and, for the first time to our knowledge, associated impaired gas exchange cause systemic and intestinal ischemia, driving angiogenesis and GIT epithelial barrier dysfunction, resulting in increased risk and severity of CD

Magnetic and intruder rotational bands in (113)In

©2005 American Physical SocietyExcited states in ¹¹³In were populated via the reactions ¹⁰⁰Mo(¹⁸O,p4n)¹¹³In and ¹¹⁰Pd(7Li,4n)¹¹³In. The two known ΔJ = 2 intruder bands, based on the πg7/2 ⊗ d5/2 and πh11/2 orbitals, have been extended by 8¯h to spins (49/2+)¯h and (55/2−)¯h, respectively. The previous finding of three sequences of ΔJ = 1 γ -ray transitions has been confirmed. A self-consistent cranked shell-model calculation gives a good description of the contrasting alignment patterns of the two ΔJ = 2 intruder bands. The intruder bands, the known sequences ofM1 transitions, and spherical levels together represent a coexistence of three different excitation modes in this nucleus.S. Naguleswaran, R. S. Chakrawarthy, U. Garg, K. L. Lamkin, G. Smith, J. C. Walpe, A. Galindo-Uribarri, V. P. Janzen, D. C. Radford, R. Kaczarowski, D. B. Fossan, D. R. Lafosse, P. Vaska, Ch. Droste, T. Morek, S. Pilotte, J. DeGraaf, T. Drake, and R. Wys

Braided Matrix Structure of the Sklyanin Algebra and of the Quantum Lorentz Group

Braided groups and braided matrices are novel algebraic structures living in braided or quasitensor categories. As such they are a generalization of super-groups and super-matrices to the case of braid statistics. Here we construct braided group versions of the standard quantum groups $U_q(g)$. They have the same FRT generators $l^\pm$ but a matrix braided-coproduct \und\Delta L=L\und\tens L where $L=l^+Sl^-$, and are self-dual. As an application, the degenerate Sklyanin algebra is shown to be isomorphic to the braided matrices $BM_q(2)$; it is a braided-commutative bialgebra in a braided category. As a second application, we show that the quantum double D(\usl) (also known as the `quantum Lorentz group') is the semidirect product as an algebra of two copies of \usl, and also a semidirect product as a coalgebra if we use braid statistics. We find various results of this type for the doubles of general quantum groups and their semi-classical limits as doubles of the Lie algebras of Poisson Lie groups.Comment: 45 pages. Revised (= much expanded introduction

Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy

SARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation

Oxygen uptake and denitrification in soil aggregates

A mathematical model of oxygen uptake by bacteria in agricultural soils is presented with the goal of predicting anaerobic regions in which denitrification occurs. In an environment with a plentiful supply of oxygen, microorganisms consume oxygen through normal respiration. When the local oxygen concentration falls below a threshold level, denitrification may take place leading to the release of nitrous oxide, a potent agent for global warming. A two-dimensional model is presented in which one or more circular soil aggregates are located at a distance below the ground-level at which the prevailing oxygen concentration is prescribed. The level of denitrification is estimated by computing the area of any anaerobic cores which may develop in the interior of the aggregates. The oxygen distribution throughout the model soil is calculated first for an aggregated soil for which the ratio of the oxygen diffusivities between an aggregate and its surround is small via an asymptotic analysis. Second, the case of a non-aggregated soil featuring one or more microbial hotspots, for which the diffusion ratio is arbitrary, is examined numerically using the boundary-element method. Calculations with multiple aggregates demonstrate a sheltering effect whereby some aggregates receive less oxygen than their neighbours. In the case of an infinite regular triangular network representing an aggregated soil, it is shown that there is an optimal inter-aggregate spacing which minimises the total anaerobic core area