Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease

© 2008 Zhu et al. This article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).Maintaining tolerance of T cells to self-antigens is essential to avoid autoimmune disease. How self-reactive T cells are kept functionally inactive is, however, unknown. In this study, we show that early growth response gene 2 (Egr-2), a zinc-finger transcription factor, is expressed in CD44(high) T cells and controls their proliferation and activation. In the absence of Egr-2, CD44(high), but not CD44(low) T cells, are hyperreactive and hyperproliferative in vivo. The accumulation of activated CD4(+)CD44(high) T cells leads to the development of a late onset lupuslike autoimmune disease characterized by the accumulation of interferon (IFN)-gamma and interleukin (IL)-17-producing CD4(+) T cells, loss of tolerance to nuclear antigens, massive infiltration of T cells into multiple organs and glomerulonephritis. We found that the expression of cyclin-dependent kinase inhibitor p21cip1 was impaired in Egr-2-deficient T cells, whereas the expression of IFN-gamma and IL-17 in response to T cell receptor ligation was significantly increased, suggesting that Egr-2 activates the expression of genes involved in the negative regulation of T cell proliferation and inflammation. These results demonstrate that Egr-2 is an intrinsic regulator of effector T cells and controls the expansion of self-reactive T cells and development of autoimmune disease.The Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust

Spinor field realizations of the non-critical W2,4W_{2,4} string based on the linear W1,2,4W_{1,2,4} algebra

In this paper, we investigate the spinor field realizations of the $W_{2,4}$ algebra, making use of the fact that the $W_{2,4}$ algebra can be linearized through the addition of a spin-1 current. And then the nilpotent BRST charges of the spinor non-critical $W_{2,4}$ string were built with these realizations.Comment: 10 pages, no figures, revtex4 style, accepted by Commun.Theor.Phy

Model Building with Gauge-Yukawa Unification

In supersymmetric theories with extra dimensions, the Higgs and matter fields can be part of the gauge multiplet, so that the Yukawa interactions can arise from the gauge interactions. This leads to the possibility of gauge-Yukawa coupling unification, g_i=y_f, in the effective four dimensional theory after the initial gauge symmetry and the supersymmetry are broken upon orbifold compactification. We consider gauge-Yukawa unified models based on a variety of four dimensional symmetries, including SO(10), SU(5), Pati-Salam symmetry, trinification, and the Standard Model. Only in the case of Pati-Salam and the Standard Model symmetry, we do obtain gauge-Yukawa unification. Partial gauge-Yukawa unification is also briefly discussed.Comment: 23 page

Thermodynamic properties of thin films of superfluid 3He-A

The pairing correlations in superfluid He-3 are strongly modified by quasiparticle scattering off a surface or an interface. We present theoretical results and predictions for the order parameter, the quasiparticle excitation spectrum and the free energy for thin films of superfluid He-3. Both specular and diffuse scattering by a substrate are considered, while the free surface is assumed to be a perfectly reflecting specular boundary. The results are based on self-consistent calculations of the order parameter and quasiparticle excitation spectrum at zero pressure. We obtain new results for the phase diagram, free energy, entropy and specific heat of thin films of superfluid He-3.Comment: Replaced with an updated versio

Anomalies on orbifolds with gauge symmetry breaking

We embed two 4D chiral multiplets of opposite representations in the 5D N=2 $SU(N+K)$ gauge theory compactified on an orbifold $S^1/(Z_2\times Z'_2)$. There are two types of orbifold boundary conditions in the extra dimension to obtain the 4D N=1 $SU(N)\times SU(K)\times U(1)$ gauge theory from the bulk: in Type I, one has the bulk gauge group at $y=0$ and the unbroken gauge group at $y=\pi R/2$ while in Type II, one has the unbroken gauge group at both fixed points. In both types of orbifold boundary conditions, we consider the zero mode(s) as coming from a bulk $(K+N)$-plet and brane fields at the fixed point(s) with the unbroken gauge group. We check the consistency of this embedding of fields by the localized anomalies and the localized FI terms. We show that the localized anomalies in Type I are cancelled exactly by the introduction of a bulk Chern-Simons term. On the other hand, in some class of Type II, the Chern-Simons term is not enough to cancel all localized anomalies even if they are globally vanishing. We also find that for the consistent embedding of brane fields, there appear only the localized log FI terms at the fixed point(s) with a U(1) factor.Comment: LaTeX file of 19 pages with no figure, published versio

Effects of yeast culture on broiler growth performance, nutrient digestibility and caecal microbiota

This study was conducted to evaluate the effects of yeast culture (YC) supplementation on the growth performance, apparent nutrient digestibility and caecal microflora of broiler chickens. A total of 360 one-day-old Arbor Acres broiler chickens were randomly assigned to six dietary treatments containing 0.2%, 0.4%, 0.6%, 0.8% and 1% YC. The experiment lasted for 42 days. Diet and faecal samples were collected for analysis of dry matter, crude protein, ether extract, calcium and phosphorus. Caecal microbiota on days 21 and 42 were measured using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR. Dietary supplementation with YC did not affect feed intake. On day 42, the 0.8% YC group showed optimal growth and feed efficiency, as well as higher levels of apparent digestibility of ether extract, calcium and phosphorus. On day 21, both 0.8% and 1% YC groups exhibited a significant increase in Ruminococcus, Propionibacterium clostridiales, and Bifidobacterium density. The density of Bacteroides in the YC groups was significantly higher than that of the control group. On day 42, the densities of Bacteroides, Sphingomonas and Bifidobacterium were higher in the 0.8% YC group, whereas a significant decrease was observed in the number of Enterobacteriaceae. These results serve as evidence that dietary supplementation with 0.8% YC not only moderately optimized the feed efficiency and the apparent digestibility of ether extract, calcium and phosphorus, but also positively influenced the caecal bacterial density and diversity in broiler chickens.Keywords: Arbor Acres broiler, caecal microflora, yeast culture supplementatio

Gauge-Fermion Unification and Flavour Symmetry

After we study the 6-dimensional ${\cal N} = (1, 1)$ supersymmetry breaking and $R$ symmetry breaking on $M^4\times T^2/Z_n$, we construct two ${\cal N} = (1, 1)$ supersymmetric $E_6$ models on $M^4\times T^2/Z_3$ where $E_6$ is broken down to $SO(10)\times U(1)_X$ by orbifold projection. In Model I, three families of the Standard Model fermions arise from the zero modes of bulk vector multiplet, and the $R$ symmetry $U(1)_F^{I} \times SU(2)_{{\bf 4}_-}$ can be considered as flavour symmetry. This may explain why there are three families of fermions in the nature. In Model II, the first two families come from the zero modes of bulk vector multiplet, and the flavour symmetry is similar. In these models, the anomalies can be cancelled, and we have very good fits to the SM fermion masses and mixings. We also comment on the ${\cal N}=(1, 1)$ supersymmetric $E_6$ models on $M^4\times T^2/Z_4$ and $M^4\times T^2/Z_6$, SU(9) models on $M^4\times T^2/Z_3$, and SU(8) models on $T^2$ orbifolds.Comment: Latex, 33 pages, minor change

Quasifree kaon-photoproduction from nuclei in a relativistic approach

We compute the recoil polarization of the lambda-hyperon and the photon asymmetry for the quasifree photoproduction of kaons in a relativistic impulse-approximation approach. Our motivation for studying polarization observables is threefold. First, polarization observables are more effective discriminators of subtle dynamics than the unpolarized cross section. Second, earlier nonrelativistic calculations suggest an almost complete insensitivity of polarization observables to distortions effects. Finally, this insensitivity entails an enormous simplification in the theoretical treatment. Indeed, by introducing the notion of a ``bound-nucleon propagator'' we exploit Feynman's trace techniques to develop closed-form, analytic expressions for all photoproduction observables. Moreover, our results indicate that polarization observables are also insensitive to relativistic effects and to the nuclear target. Yet, they are sensitive to the model parameters, making them ideal tools for the study of modifications to the elementary amplitude --- such as in the production, propagation, and decay of nucleon resonances --- in the nuclear medium.Comment: 15 pages and 6 figures - submitted to PR

INSIG1 influences obesity-related hypertriglyceridemia in humans

In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 × 10−3 in 1,560 individuals of the original linkage cohort, P = 8 × 10−4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 × 10−6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans