The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4+ T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4+ T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell–specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4+ T-cell activation via epigenetic regulation of Kv1.3 expression.
BACKGROUND: Barley straw is a potential lignocellulosic biomass for the production of bioethanol because of its high cellulose and hemicelluloses content. Ethanosolv pretreatment catalyzed with inorganic acids has some undesirable effects, and thus, inorganic salts, such as FeCl 3 , were studied as the catalyst in order to enhance enzymatic digestibility.
The current ethanol production processes using crops such as corn and sugar cane are well established. However, the utilization of cheaper biomasses such as lignocellulose could make bioethanol more competitive with fossil fuels, without the ethical concerns associated with the use of potential food resources. A cassava stem, a lignocellulosic biomass, was pretreated using dilute acid to produce bioethanol. The pretreatment conditions were evaluated using response surface methodology (RSM). As a result, the optimal conditions were 177 o C, 10 min and 0.14 M for the temperature, reaction time and acid concentration, respectively. The enzymatic digestibility of the pretreated cassava stem was examined at various enzyme loadings (10-40 FPU/g cellulose of cellulase and 30 CbU/g of β-glucosidase). With respect to economic feasibility, 20 FPU/g cellulose of cellulase and 30 CbU/g of β-glucosidase were selected for the test concentration and led to a saccharification yield of 70%. The fermentation of the hydrolyzed cassava stem using Saccharomyces cerevisiae resulted in an ethanol concentration of 7.55 g/L and a theoretical fermentation yield of 89.6%. This study made a significant contribution to the production of bioethanol from a cassava stem. Although the maximum ethanol concentration was low, an economically efficient overall process was carried out to convert a lignocellulosic biomass to bioethanol.
BACKGROUND: Current ethanol production processes using crops such as corn and sugar cane are well established. However, the utilization of cheaper biomasses such as lignocellulose could make bioethanol more competitive with fossil fuels while avoiding the ethical concerns associated with using potential food resources.
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