Itm2a, a Target Gene of GATA-3, Plays a Minimal Role in Regulating the Development and Function of T Cells

The integral membrane protein 2a (Itm2a) is one of the BRICHOS domain-containing proteins and is structurally related to Itm2b and Itm2c. It is expressed preferentially in the T lineage among hematopoietic cells and is induced by MHC-mediated positive selection. However, its transcriptional regulation and function are poorly understood. Here we showed Itm2a to be a target gene of GATA-3, a T cell-specific transcription factor. Deficiency of Itm2a had little impact on the development and function of polyclonal T cells but resulted in a partial defect in the development of thymocytes bearing a MHC class I-restricted TCR, OT-I. In addition, Itm2a-deficient mice displayed an attenuated T helper cell-dependent immune response in vivo. We further demonstrated that Itm2b but not Itm2c was also expressed in T cells, and was induced upon activation, albeit following a kinetic different from that of Itm2a. Thus, functional redundancy between Itm2a and Itm2b may explain the minimal phenotype of Itm2a deficiency

Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus

Introduction: A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22) complementary DNA (cDNA) is associated with an increased risk of systemic lupus erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the expression of PTPN22 differs between healthy individuals and patients with lupus are poorly understood. Our objectives were to identify novel alternatively spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in healthy donors and patients with lupus. Methods: Various human PTPN22 isoforms were identified from the GenBank database or amplified directly from human T cells. The expression of these isoforms in primary T cells and macrophages was examined with real-time polymerase chain reaction. The function of the isoforms was determined with luciferase assays. Blood samples were collected from 49 subjects with SLE and 15 healthy controls. Correlation between the level of PTPN22 isoforms in peripheral blood and clinical features of SLE was examined with statistical analyses. Results: Human PTPN22 was expressed in several isoforms, which differed in their level of expression and subcellular localization. All isoforms except one were functionally interchangeable in regulating NFAT activity. SLE patients expressed higher levels of PTPN22 than healthy individuals and the levels of PTPN22 were negatively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-DI). Conclusions: The overall activity of PTPN22 is determined by the functional balance among all isoforms. The levels of PTPN22 isoforms in peripheral blood could represent a useful biomarker of SLE

Nodal superconductivity coexists with low-moment static magnetism in single-crystalline tetragonal FeS: A muon spin relaxation and rotation study

We report muon spin relaxation and rotation ($\mu$SR) measurements on hydrothermally-grown single crystals of the tetragonal superconductor~FeS, which help to clarify the controversial magnetic state and superconducting gap symmetry of this compound. $\mu$SR time spectra were obtained from 280~K down to 0.025~K in zero field (ZF) and applied fields up to 20 mT. In ZF the observed loss of initial asymmetry (signal amplitude) and increase of depolarization rate~$\Lambda_\mathrm{ZF}$ below 10~K indicate the onset of static magnetism, which coexists with superconductivity below $T_c$. Transverse-field $\mu$SR yields a muon depolarization rate $\sigma_\mathrm{sc} \propto \lambda_{ab}^{-2}$ that clearly shows a linear dependence at low temperature, consistent with nodal superconductivity. The $s{+}d$-wave model gives the best fit to the observed temperature and field dependencies. The normalized superfluid densities versus normalized temperature for different fields collapse onto the same curve, indicating the superconducting gap structure is independent of field. The $T=0$ in-plane penetration depth $\lambda_{ab}$(0) = 198(3) nm.Comment: 5 figure

Susceptibility of Human Embryonic Stem Cell-Derived Neural Cells to Japanese Encephalitis Virus Infection

Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection

Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XV. Long-Term Optical Monitoring of NGC 5548

We present the results of three years of ground-based observations of the Seyfert 1 galaxy NGC 5548, which combined with previously reported data, yield optical continuum and broad-line H-beta light curves for a total of eight years. The light curves consist of over 800 points, with a typical spacing of a few days between observations. During this eight-year period, the nuclear continuum has varied by more than a factor of seven, and the H-beta emission line has varied by a factor of nearly six. The H-beta emission line responds to continuum variations with a time delay or lag of 10-20 days, the precise value varying somewhat from year to year. We find some indications that the lag varies with continuum flux in the sense that the lag is larger when the source is brighter.Comment: 29 pages, 6 figures. Accepted for publication in ApJ (1999 Jan 10

Braggoriton--Excitation in Photonic Crystal Infiltrated with Polarizable Medium

Light propagation in a photonic crystal infiltrated with polarizable molecules is considered. We demonstrate that the interplay between the spatial dispersion caused by Bragg diffraction and polaritonic frequency dispersion gives rise to novel propagating excitations, or braggoritons, with intragap frequencies. We derive the braggoriton dispersion relation and show that it is governed by two parameters, namely, the strength of light-matter interaction and detuning between the Bragg frequency and that of the infiltrated molecules. We also study defect-induced states when the photonic band gap is divided into two subgaps by the braggoritonic branches and find that each defect creates two intragap localized states inside each subgap.Comment: LaTeX, 8 pages, 5 figure

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity