Cytotoxic T-lymphocyte Antigen-4 Binding to SHP2 Interacting Transmembrane Adapter Protein by Phosphorylation in T-Cell

Purpose: To investigate potential cytotoxic T-lymphocyte antigen-4 (CTLA-4) binding partners and assess whether potential binding partners affect the full function of CTLA-4. .Methods: The down-regulation effects of CTLA-4 and SIT were assessed by culturing CD3 stimulated T-cells. CTLA-4 and SIT proteins were measured by immunoblot analysis and production of interlukin-2 transcription activity evaluated by luciferase assay.Results: CTLA-4 inhibited the interlukin-2 production capacity of CD3-stimulated T cells. CTLA-4 interaction with SHP2 interacting transmembrane adapter protein (SIT) in the down-regulation of the transcription of Interulin-2 required CTLA-4 binding to SIT tyrosine motifs. The SIT tyrosine mutants were significantly lower (25 – 75 %) after phosphorylation compared with WT-SIT (transfected cells, p < 0.05) and untreated control. The remaining 90 % phosphorylation in the F188ANS mutant can be explained by phosphorylation of other tyrosines in the sequence of SIT (p < 0.05). For interukin-2 transcription, F188ANS single mutant and double F148SEV mutant, increased NF-AT activity by 35 % compared with the wild type (p < 0.05).Conclusion: The findings imply that SIT transmembrane adaptor (SIT) protein, binds to CTLA-4 and thus potentiates the inhibitory role of this co-receptor. This phenomenon may lead to the development of new treatment strategies for autoimmune diseases and graft rejection.Keywords: Cytotoxic T-lymphocyte antigen-4, Interleukin-2, Nuclear factor of activated T-cells/Activator protein-1, SHP2 interacting transmembrane adapter protein, Autoimmune diseases, Graft rejectio

Towards a Model of Quarks and Leptons

We propose an extra-dimension framework on the orbifold $S^1/Z_2$ for understanding the origin of the fermion mass and mixing hierarchies. Introducing the flavor symmetry $G_F(=${\it non-Abelian}$\times${\it Abelian}) as well as the extra gauged $U(1)$ symmetries through the bulk, we regard the $SU(2)$ singlet and doublet fermions in the Standard Model (SM) to be localized at the separate 3-branes and let the extra $SU(2)$ singlet flavored fermions in the bulk couple to the SM fermions at the 3-branes. The extra $U(1)$ symmetries satisfy the $U(1)$ gravitational anomaly-free condition, playing a crucial role in achieving the desirable fermion mass and mixing hierarchies and making the flavored axion naturally light. The singlet scalar fields, the flavon fields, are responsible for the spontaneous breaking of $G_F$ on the two 3-branes, while the $SU(2)$ singlet flavored fermions are integrated out to give rise to the effective Yukawa couplings for the SM fermions, endowed with the information of $G_F$ breaking in the two sectors. The flavored axion from the PQ symmetry is also proposed for solving the strong CP problem and being a dark matter candidate in our model.Comment: 7 pages, 3 figure

A Study on the Effect on River Habitat Change by small dam removal - A Case Study of Gokreung 2 & Gotan Small Dam Removal

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Bilateral ischemic lumbosacral plexopathy from chronic aortoiliac occlusion presenting with progressive paraplegia

Spinal cord ischemia is rare but causes significant morbidity and mortality. Spinal cord ischemia has been reported after open and endovascular interventions of the thoracic and abdominal aorta, and, rarely, acute occlusion of aorta from in situ thrombosis or acute embolic occlusion. Acute interruption of the critical blood supply to the spinal cord or root contributes to this devastating neurologic deficit. However, gradually worsening lumbosacral plexopathy and consequent paraplegia related to chronic aortic occlusion is extremely rare. We present a case of a 58-year-old man with progressive lower limb paralysis from atherosclerotic aortoiliac occlusion without history of aortic surgery or evidence of thromboembolism

Prevalence and Risk Factors of Gastric Adenoma and Gastric Cancer in Colorectal Cancer Patients

Background/Aims. To evaluate the incidence of gastric adenoma and gastric cancer in colorectal cancer patients, as well as the clinicopathological features that affect their incidence. Methods. Among patients who underwent surgery after being diagnosed with colorectal cancer between January 2004 and December 2013 at Chungnam National University Hospital, 142 patients who underwent follow-up upper gastrointestinal endoscopy were assigned to the patient group. The control group included 426 subjects randomly selected. The patient group was subdivided into two: one that developed gastric adenoma or cancer and one that did not. Clinicopathological characteristics were compared between these groups. Results. In total, 35 (24.6%) colorectal cancer patients developed a gastric adenoma or gastric cancer, which was higher than the number in the control group (20 [4.7%] patients; p<0.001). Age, alcohol history, and differentiation of colorectal cancer were associated with higher risks of gastric adenoma or gastric cancer, with odds ratios of 1.062, 6.506, and 5.901, respectively. Conclusions. In colorectal cancer patients, screening with upper gastrointestinal endoscopy is important, even if no lesions are noted in the upper gastrointestinal tract at colorectal cancer diagnosis. Endoscopic screening is particularly important with increasing age, history of alcohol consumption, and poor cancer differentiation

A Study of Micronucleus Induction with Methyl Formate and 2-Methylbutane in Bone Marrow Cells of Male ICR Mice

Objectives: We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased.Methods: 7 week male ICR mice were tested at dosages of 250, 500, and 1,000mg/kg for methyl formate and 500, 1,000, and 2,000mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides.Results: As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes (PCE), all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these two chemicals.Conclusion: It was concluded that the two chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the two chemicals have no mutagenic potential under each study condition