Direct manipulation of T lymphocytes by proteins of gastrointestinal bacterial pathogens

Gastrointestinal bacterial infection represents a significant threat to human health, as well as a burden on food animal production and welfare. Although there is advanced knowledge about the molecular mechanisms underlying pathogenesis, including the development of immune responses to these pathogens, gaps in knowledge persist. It is well established that gastrointestinal bacterial pathogens produce a myriad of proteins that affect the development and effectiveness of innate immune responses. However, relatively few proteins that directly affect lymphocytes responsible for humoral or cell-mediated immunity and memory have been identified. Here, we review factors produced by gastrointestinal bacterial pathogens that have direct T cell interactions and what is known about their functions and mechanisms of action. T cell interacting bacterial proteins that have been identified to date mainly target three major T cell responses: activation and expansion, chemotaxis or apoptosis. Further, the requirement for more focused studies to identify and understand additional mechanisms used by bacteria to directly affect the T cell immune response and how these may contribute to pathogenesis is highlighted. Increased knowledge in this area will help to drive development of better interventions in prevention and treatment of gastrointestinal bacterial infection.</p

Direct excitation of the forbidden clock transition in neutral 174Yb atoms confined to an optical lattice

We report direct single-laser excitation of the strictly forbidden (6s^2)^1S_0 -(6s6p)^3P_0 clock transition in the even 174Yb isotope confined to a 1D optical lattice. A small (~1.2 mT) static magnetic field was used to induce a nonzero electric dipole transition probability between the clock states at 578.42 nm. Narrow resonance linewidths of 20 Hz (FHWM) with high contrast were observed, demonstrating a record neutral-atom resonance quality factor of 2.6x10^13. The previously unknown ac Stark shift-canceling (magic) wavelength was determined to be 759.35+/-0.02 nm. This method for using the metrologically superior even isotope can be easily implemented in current Yb and Sr lattice clocks, and can create new clock possibilities in other alkaline earth-like atoms such as Mg and Ca.Comment: Submitted to Physics Review Letter

Young's modulus, Poisson's ratio, and residual stress and strain in (111)-oriented scandium nitride thin films on silicon

Epitaxial scandium nitride films (225 nm thick) were grown on silicon by molecular beam epitaxy, using ammonia as a reactive nitrogen source. The main crystallographic orientation of ScN with respect to Si is (111)(ScN)parallel to(111)(Si) and [1-10](ScN)parallel to[0-11](Si); however, some twinning is also present in the films. The films displayed a columnar morphology with rough surfaces, due to low adatom mobility during growth. The strain-free lattice parameter of ScN films grown under optimized conditions was found to be 4.5047 +/- 0.0005 A, as determined using high-resolution x-ray diffraction (HRXRD). In-plane and out-of-plane strains were subsequently evaluated using HRXRD and were used to determine the Poisson ratio of ScN along the direction, which is found to be 0.188 +/- 0.005. Wafer curvature measurements were made and combined with the strain information to determine the average Young's modulus of the films, which is found to be 270 +/- 25 GPa. Residual film stresses ranged from -1 to 1 GPa (depending on film growth temperature and film thickness) due to competition between the tensile stress (induced by the differential thermal contraction between the ScN film and the Si substrate) and intrinsic compressive stresses generated during growth

Critical Exponent for the Density of Percolating Flux

This paper is a study of some of the critical properties of a simple model for flux. The model is motivated by gauge theory and is equivalent to the Ising model in three dimensions. The phase with condensed flux is studied. This is the ordered phase of the Ising model and the high temperature, deconfined phase of the gauge theory. The flux picture will be used in this phase. Near the transition, the density is low enough so that flux variables remain useful. There is a finite density of finite flux clusters on both sides of the phase transition. In the deconfined phase, there is also an infinite, percolating network of flux with a density that vanishes as $T \rightarrow T_{c}^{+}$. On both sides of the critical point, the nonanalyticity in the total flux density is characterized by the exponent $(1-\alpha)$. The main result of this paper is a calculation of the critical exponent for the percolating network. The exponent for the density of the percolating cluster is $\zeta = (1-\alpha) - (\varphi-1)$. The specific heat exponent $\alpha$ and the crossover exponent $\varphi$ can be computed in the $\epsilon$-expansion. Since $\zeta < (1-\alpha)$, the variation in the separate densities is much more rapid than that of the total. Flux is moving from the infinite cluster to the finite clusters much more rapidly than the total density is decreasing.Comment: 20 pages, no figures, Latex/Revtex 3, UCD-93-2

Frequency evaluation of the doubly forbidden 1S0→3P0^1S_0\to ^3P_0 transition in bosonic 174^{174}Yb

We report an uncertainty evaluation of an optical lattice clock based on the $^1S_0\leftrightarrow^3P_0$ transition in the bosonic isotope $^{174}$Yb by use of magnetically induced spectroscopy. The absolute frequency of the $^1S_0\leftrightarrow^3P_0$ transition has been determined through comparisons with optical and microwave standards at NIST. The weighted mean of the evaluations is $\nu$($^{174}$Yb)=518 294 025 309 217.8(0.9) Hz. The uncertainty due to systematic effects has been reduced to less than 0.8 Hz, which represents $1.5\times10^{-15}$ in fractional frequency.Comment: 4 pages, 3 figure -Submitted to PRA Rapid Communication

Superfluid, Mott-Insulator, and Mass-Density-Wave Phases in the One-Dimensional Extended Bose-Hubbard Model

We use the finite-size density-matrix-renormalization-group (FSDMRG) method to obtain the phase diagram of the one-dimensional ($d = 1$) extended Bose-Hubbard model for density $\rho = 1$ in the $U-V$ plane, where $U$ and $V$ are, respectively, onsite and nearest-neighbor interactions. The phase diagram comprises three phases: Superfluid (SF), Mott Insulator (MI) and Mass Density Wave (MDW). For small values of $U$ and $V$, we get a reentrant SF-MI-SF phase transition. For intermediate values of interactions the SF phase is sandwiched between MI and MDW phases with continuous SF-MI and SF-MDW transitions. We show, by a detailed finite-size scaling analysis, that the MI-SF transition is of Kosterlitz-Thouless (KT) type whereas the MDW-SF transition has both KT and two-dimensional-Ising characters. For large values of $U$ and $V$ we get a direct, first-order, MI-MDW transition. The MI-SF, MDW-SF and MI-MDW phase boundaries join at a bicritical point at ($U, V) = (8.5 \pm 0.05, 4.75 \pm 0.05)$.Comment: 10 pages, 15 figure

Anti-proliferative effect of main dietary phytosterols and \u3b2-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 \u2013 and oxidative stress induced apoptosis

\u3b2-cryptoxanthin (\u3b2-Cx) and phytosterols (Ps) have potential against different cancer types,including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with \u3b2-Cx and/or main dietary Ps (\u3b2-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initial triggers. Ps and \u3b2-Cx, alone or in combination showed anti-proliferative activity against human colon adenocarcinoma Caco-2 cells through the mitochondrial pathway of apoptosis. No additive or synergistic effects were observed.The importance of bioactivity-guided assays with mixtures of dietary bioactive compounds to determine their eventual interactions in the functional food context is demonstrated

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease

BACKGROUND: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. OBJECTIVES: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. ANIMALS: Records of 174 client-owned cats with IRIS stage 2-4 CKD. METHODS: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999-2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. RESULTS: Plasma tMg (reference interval, 1.73-2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, -0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35-5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54-5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04-154; P = .009) lost significance in multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation

In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth

Insulin-like growth factor binding proteins initiate cell death and extracellular matrix remodeling in the mammary gland

We have demonstrated that insulin-like growth factor binding protein-5 (IGFBP-5) production by mammary epithelial cells increases dramatically during forced involution of the mammary gland in rats, mice and pigs. We proposed that growth hormone (GH) increases the survival factor IGF-I, whilst prolactin (PRL) enhances the effects of GH by decreasing the concentration of IGFBP-5, which would otherwise inhibit the actions of IGFs. To demonstrate a causal relationship between IGFBP-5 and cell death, we created transgenic mice expressing IGFBP-5, specifically, in the mammary gland. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. The concentrations of the pro-apoptotic molecule caspase-3 was increased in transgenic animals whilst the concentrations of two pro-survival molecules Bcl-2 and Bcl-x were both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I, we examined IGF receptor- and Akt-phoshorylation and showed that both were inhibited. These studies also indicated that the effects of IGFBP-5 could be mediated in part by IGF-independent effects involving potential interactions with components of the extracellular matrix involved in tissue remodeling, such as components of the plasminogen system, and the matrix metallo-proteinases (MMPs). Mammary development was normalised in transgenic mice by R3-IGF-I, an analogue of IGF-I which binds weakly to IGFBPs, although milk production was only partially restored. In contrast, treatment with prolactin was able to inhibit early involutionary processes in normal mice but was unable to prevent this in mice over-expressing IGFBP-5, although it was able to inhibit activation of MMPs. Thus, IGFBP-5 can simultaneously inhibit IGF action and activate the plasminogen system thereby coordinating cell death and tissue remodeling processes. The ability to separate these properties, using mutant IGFBPs, is currently under investigatio