TAK1 maintains the survival of immunoglobulin λ‐chain‐positive B cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/1/gtc12442-sup-0001-FigS1-S6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/2/gtc12442.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/3/gtc12442_am.pd

Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases

Activation of the B cell receptor complex in B lymphocytes causes Ca2+ release from intracellular stores, which, in turn, activates ion channels known as Icrac. We investigated the mechanisms that link Ca2+ store release to channel gating in DT40 B lymphocyte cell lines genetically manipulated to suppress the expression of several tyrosine kinases: Btk, Lyn, Syk, and the Blnk adaptor molecule. The simultaneous but not the independent suppression of Lyn and Syk expression prevents the activation of Icrac without interfering with thapsigargin-sensitive Ca2+ store release. Icrac activation by Ca2+ is reversed in mutant cells by the homologous expression of the missing kinases. Pharmacological inhibition of kinase activity by LavendustinA and PP2 cause the same functional deficit as the genetic suppression of enzyme expression. Biochemical assays demonstrate that kinase activity is required as a tonic signal: targets must be phosphorylated to link Ca2+ store release to Icrac gating. The action of kinases on Icrac activation does not arise from control of the expression level of the stromal interaction molecule 1 and Orai1 proteins

A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells

BACKGROUND: Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-γ2 (PLCγ2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCγ2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCγ2-deficient DT40 B cell line. RESULTS: Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCγ2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCγ2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCγ2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis. CONCLUSIONS: These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCγ2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types

Exact diagonalization study of Mott transition in the Hubbard model on an anisotropic triangular lattice

We study Mott transition in the two-dimensional Hubbard model on an anisotropic triangular lattice. We use the Lanczos exact diagonalization of finite-size clusters up to eighteen sites, and calculate Drude weight, charge gap, double occupancy and spin structure factor. We average these physical quantities over twisted boundary conditions in order to reduce finite-size effects. We find a signature of the Mott transition in the dependence of the Drude weight and/or charge gap on the system size. We also examine the possibility of antiferromagnetic order from the spin structure factor. Combining these information, we propose a ground-state phase diagram which has a nonmagnetic insulating phase between a metallic phase and an insulating phase with antiferromagnetic order. Finally, we compare our results with those reported in the previous theoretical studies, and discuss the possibility of an unconventional insulating state.Comment: 10 pages, 11 figure

Falling behind and catching up : India’s transition from a colonial economy

India fell behind during colonial rule. The absolute and relative decline of Indian GDP per capita with respect to Britain began before colonization and coincided with the rising textile trade with Europe in the 18th century. The decline of traditional industries was not the main driver Indian decline and stagnation. Inadequate investment in agriculture and consequent decline in yield per acre stalled economic growth. Modern industries emerged and grew relatively fast. The falling behind was reversed after independence. Policies of industrialization and a green revolution in agriculture increased productivity growth in agriculture and industry, but Indian growth has been led by services. A strong focus on higher education under colonial policy had created an advantage for the service sector, which today has a high concentration of human capital. However, the slow expansion in primary education was a disadvantage in comparison with the high growth East Asian economies