IntroductionChronic lymphocytic leukemia (CLL) represents 30% of adult leukemia and is an incurable B-cell malignancy. Malignant CLL cells use a limited repertoire of immunoglobulin heavy and light chain genes to manufacture their BCRs, [1][2][3] and are very responsive to in vitro anti-IgM stimulation. 4,5 Thus, Ag stimulation has been proposed to drive malignant progression of CLL.The functions of the endoplasmic reticulum (ER) and its associated molecules in CLL have not attracted extensive investigative efforts because CLL cells do not exhibit a readily prominent ER structure like professional secretory cells. Although no protein Ag has been shown to drive malignant progression of CLL in vivo, exposure to Toll-like receptor ligands activates CLL cells, allowing rapid proliferation, 6,7 a cellular process accompanied by robust production and folding of membrane receptors and secretory proteins in the ER. We hypothesize that the ER may play an important role in malignant progression of CLL. First, electron microscopy examinations of human CLL cells showed clear ER expansions and immunoglobulin staining in the ER. [8][9][10] Second, treatments that target ER-Golgi protein transport or inhibit BiP (HSP70 in the ER) and GRP94 (HSP90 in the ER) can sensitize CLL cells to drug-induced apoptosis. 9,11,12 The IRE-1/XBP-1 pathway is activated in response to stress conditions like proteotoxicity or hypoxia in the ER, but it also plays important roles in maintaining basal cellular functions. 13,14 IRE-1 is an ER-resident transmembrane protein that contains a stress sensor domain in the lumen of the ER, and a serine/threonine kinase domain linked to an RNase domain in the cytoplasm. On stress conditions, IRE-1 oligomerizes via its luminal domains in the ER, bringing together the cytoplasmic kinase domains which can undergo autophosphorylation and up-regulate IRE-1's RNase activity. The IRE-1 RNase then splices 26 nucleotides from the mature XBP-1 mRNA, allowing the spliced XBP-1 mRNA to encode the functional 54-kDa transcription factor XBP-1. [15][16][17] XBP-1 regulates a panel of important genes 18 and can crosstalk with other B-cell transcription factors, such as IRF4 and Blimp-1. 19 Overexpression of XBP-1 in B cells has been shown to cause monoclonal gammopathy of undetermined significance, a precursor condition for multiple myeloma. 20 Here, we investigate the roles of the ER stress response in the E-TCL1 CLL mouse model, in which the TCL1 gene is under the control of the immunoglobulin heavy chain promoter/enhancer driving TCL1 overexpression in B cells. 21 TCL1 is expressed in ϳ 90% human CLL patients, 22 and its overexpression is associated with strong BCR signaling, 23,24 allowing malignant CLL cells to undergo high-rate proliferation. E-TCL1 mice initially develop a preleukemic state with clear CD5 ϩ IgM ϩ B-cell characteristics in the blood, spleen, lymph nodes, and bone marrow, and slowly progress to the full-blown monoclonal CLL stage with all clinical features of aggressive human CLL. 21,25 Similar to huma...

The conformational heterogeneity of backbone N-substituted peptides limits their ability to adopt stable secondary structures. Herein, we describe a practical synthesis of backbone aminated peptides that readily adopt β-sheet folds. Data derived from model N-amino peptides suggest that extended conformations are stabilized through cooperative steric, electrostatic, and hydrogen-bonding interactions.

This research was conducted to compare the meat characteristics of Korean native duck and imported commercial duck. The Korean native ducks and imported commercial ducks (broiler duck: Grimaud) were raised under identical rearing and feeding conditions for 8 wk and 6 wk, respectively. At the end of the rearing period, ten ducks from each group were slaughtered, and breast and leg meat were obtained 24 h after slaughtering for analyses of meat characteristics. The results showed that the breast of Korean native ducks contained lower moisture and fat, and higher protein and water holding capacity (WHC) than those of imported commercial ducks (p<0.05). The breast of Korean native ducks also had higher CIE a* and lower CIE L* (p<0.05). After cooking, the breast meat of Korean native ducks had higher shear-force, sensory attributes of texture, taste and overall likeness (p<0.05). Also, the breast meat of Korean native ducks contained a higher percentage of palmitic acid (C 16:0 ) and arachidonic acid (C 20:4 ) (p<0.05) than those of imported commercial ducks. Furthermore, the leg meat of Korean native ducks contained higher percentages of total unsaturated fatty acid and lower percentages of total saturated fatty acid (p<0.05). It is concluded that the meat from Korean native ducks, especially breast meat, had better quality parameters and contained higher amounts of unsaturated fatty acids.

The synthesis of the terpyridine derivative 1 tethered to a DNA oligonucleotide and its use for the preparation of two-way branched metal-organic modules capable of self-assembling into DNA triangles are described.