Surprisingly, the K/BxNsf mice exhibited an abnormal accumulation of mature plasma cells in their spleens and a corresponding loss of bone marrow plasma cells. The plasma cells were unresponsive to the bone marrow
homing chemokine CXCL12, despite normal expression of the chemokine receptor CXCR4. Importantly, they were long-lived and less susceptible to the cytotoxic action of cyclophosphamide. click here They also expressed less Fc gamma RIIb and were less apoptotic in response to autoantigen autoantibody immune complexes. This suggests that Tregs control plasma cell susceptibility to cell death induced by engagement of Fc gamma RIIb with immune complexes. Direct cytotoxic effects of Tregs also contribute to the death of plasma cells. Thus, our results reveal that Tregs suppress the emergence of long-lived splenic plasma cells by affecting plasma cell-autonomous mechanisms as well as T cell help, thereby avoiding the persistence of humoral autoimmunity. The Journal of Immunology, 2011, 186: 1546-1553.”
“A series of new diaryl ether linked pyrrolobenzodiazepine VX-809 chemical structure (PBD) conjugates (4a-i, 5a-i and 6a-f) was synthesized and evaluated for their anticancer activity against a panel of 11 human cancer
cell lines. These conjugates exhibited significant anticancer activity with GI(50) values in the range of 0.1-3.88 mu M. Some of the potent conjugates (4b, 4h, 5h, 6b, 6c and 6e) were further investigated on cell cycle distribution. FACS analysis Ro-3306 in vitro showed the accumulation of cells in G0 phase indicating the apoptosis inducing nature of these conjugates. Moreover, compound 6b caused a
decrease in the mitochondrial membrane potential, which indicates the apoptotic nature of the compound through mitochondrial mediated pathway. Further conjugates 4b, 4h and 6b induce the activation of caspase and PARP proteins, followed by apoptotic cell death in MCF7 cell line.”
“We use a global 3-D atmospheric chemistry model (GEOS-Chem) to simulate surface and aircraft measurements of organic carbon (OC) aerosol over eastern North America during summer 2004 (ICARTT aircraft campaign), with the goal of evaluating the potential importance of a new secondary organic aerosol (SOA) formation pathway via irreversible uptake of dicarbonyl gases (glyoxal and methylglyoxal) by aqueous particles. Both dicarbonyls are predominantly produced in the atmosphere by isoprene, with minor contributions from other biogenic and anthropogenic precursors. Dicarbonyl SOA formation is represented by a reactive uptake coefficient gamma = 2.9 x 10(-3) and takes place mainly in clouds. Surface measurements of OC aerosol at the IMPROVE network in the eastern U.S. average 2.2 +/- 0.7 mu g C m(-3) for July-August 2004 with little regional structure. The corresponding model concentration is 2.8 +/- 0.