Cloned human TCR from patients with autoimmune disease can respond to two structurally distinct autoantigens

There is increasing evidence that the TCR can have significant plasticity in the range of Ags that a single receptor can recognize. Although it has been proposed that such TCR plasticity might contribute to autoimmunity, there have been few studies examining this possibility in either animal models or human disease. In the present study, we examined human T cell clones that were generated against two structurally dissimilar proteins, U1-70 kDa and Smith-B, that are physically associated in the U1-small nuclear ribonucleoprotein complex and that are frequent targets of autoantibodies and T cells in the same lupus patient. We found that the TCR from all clones isolated had substantial sequence homology within their complementarity-determining region 3. We molecularly cloned and expressed individual TCR/A and TCR/B genes in a TCR-negative human cell line J.RT3-T3.5. We then examined the interaction between the TCR and U1-70 kDa and Smith-B antigenic peptides. We found that there was plasticity or degeneracy of the TCR reactive with these lupus autoantigens in that two structurally dissimilar lupus autoantigenic peptides could stimulate a single TCR. These studies support an important role of plasticity of the TCR in the development of human autoimmunity.     

Roles of trehalose phosphate synthase in yeast glycogen metabolism and sporulation

Trehalose is a major storage carbohydrate in budding yeast, Saccharomyces cerevisiae. Alterations in trehalose synthesis affect carbon source-dependent growth, accumulation of glycogen and sporulation. Trehalose is synthesized by trehalose phosphate synthase (TPS), which is a complex of at least four proteins. In this work, we show that the Tps1p subunit protein catalyses trehalose phosphate synthesis in the absence of other TPS components. The tps1-H223Y allele (glc6-1) that causes a semidominant decrease in glycogen accumulation exhibits greater enzyme activity than wild-type TPS1 because, unlike the wild-type enzyme, TPS activity in tps1-H223Y cells is not inhibited by phosphate. Poor sporulation in tps1 null diploids is caused by reduced expression of meiotic inducers encoded by IME1, IME2 and MCK1. Furthermore, high-copy MCK1 or heterozygous hxk2 mutations can suppress the tps1 sporulation trait. These results suggest that the trehalose-6-phosphate inhibition of hexokinase activity is required for full induction of MCK1 in sporulating yeast cells.     

A Novel Microbial Biofilm for Bioremoval of Nickel from Aqueous Media

This study evaluated the efficacy of a microbial biofilm in removing Ni ions in aqueous media. The biofilm was developed incorporating a garden soil fungus with a bacterium isolated from Ni-rich serpentinite soil. The biofilm was characterized using microscopy, scanning electron microscopy, Fourier transform infrared (FTIR) investigations, and Boehm and potentiometric titrations. Ni removal was determined using batch experiments as a function of pH, Ni concentration, and time. The adsorption isotherm assay was conducted with varying Ni concentrations from 25 to 500 mg/L for 4 days. Isotherm and kinetic modeling were applied to the experimental data to understand the mechanisms of Ni removal. The zero point charge at pH 4.5 indicated the pH values greater than 4.5 is favorable for Ni adsorption. Acidic nature of the biofilm was reflected from Boehm titration data showing higher number of acidic groups than basic groups. With the increase in initial Ni concentration, the uptake increased from 3.43 to 38.16 mg/g. Hill, the best-fitted isotherm model, indicated a maximum adsorption capacity of 165.37 mg/g. After 4 days, the adsorption rate reached an equilibrium with a maximum sorption of ～30 mg/g for an initial concentration of 100 mg/L. Kinetic model fitting with Power function further demonstrated the chemisorptive interaction of Ni with the biofilm surface. A clear involvement of functional groups of the biofilm in Ni bonding was observed from the attenuated total reflection (ATR)-FTIR spectrum. The microbial biofilm showed an efficient but slow removal of Ni from aqueous media.     

Aurora-A Breaks Symmetry in Contractile Actomyosin Networks Independently of Its Role in Centrosome Maturation

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Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations

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Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka

Background

Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka.

Methods

1689 healthy individuals who were attending a primary health care facility were recruited. Dengue and JEV antibody status was determined in all individuals and JEV vaccination status was recorded.

Results

1152/1689 (68.2%) individuals were seropositive for dengue and only 133/1152 (11.5%) of them had been hospitalized to due to dengue. A significant and positive correlation was observed for dengue antibody seropositivity and age in children (Spearmans R = 0.84, p = 0.002) and in adults (Spearmans R = 0.96, p = 0.004). We observed a significant rise in the age stratified seroprevalence rates in children over a period of 12 years. For instance, in year 2003 the annual seroconversion rate was 1.5% per annum, which had risen to 3.79% per annum by 2014. We also found that both adults (p<0.001) and in children (p = 0.03) who were hospitalized due to dengue were more likely to be seropositive for JEV antibodies. However, 244 (91.4%) of adults who were seropositive for JEV had not had the JEV vaccine.

Conclusions

Dengue seroprevalence rates have risen significantly over the last 12 years in Sri Lanka, possibly due to increased transmission. As individuals who were hospitalized due to dengue were more likely to be seropositive for JEV, the possibility of cross-reactive assays and/or of JEV infection on immunity to the DENV and clinical disease severity should be further investigated.