Crop yield loss due to flooding is a threat to food security. Submergence-induced hypoxia in plants results in stabilization of group VII ETHYLENE RESPONSE FACTORs (ERF-VIIs), which aid survival under these adverse conditions. ERF-VII stability is controlled by the N-end rule pathway, which proposes that ERF-VII N-terminal cysteine oxidation in normoxia enables arginylation followed by proteasomal degradation. The PLANT CYSTEINE OXIDASEs (PCOs) have been identified as catalysts of this oxidation. ERF-VII stabilization in hypoxia presumably arises from reduced PCO activity. We directly demonstrate that PCO dioxygenase activity produces Cys-sulfinic acid at the N terminus of an ERF-VII peptide, which then undergoes efficient arginylation by an arginyl transferase (ATE1). This provides molecular evidence of N-terminal Cys-sulfinic acid formation and arginylation by N-end rule pathway components, and a substrate of ATE1 in plants. The PCOs and ATE1 may be viable intervention targets to stabilize N-end rule substrates, including ERF-VIIs, to enhance submergence tolerance in agriculture.

IntroductionChronic lymphocytic leukemia (CLL) is a clonal B-cell disorder that is not curable by conventional chemoimmunotherapies. The leukemic transformation may be initiated by specific genomic alterations (eg, del13q) that may cause the deletion of specific micro-RNA genes (eg, miR15 and miR16) and increase the resistance of B cells toward apoptosis. 1,2 Survival of CLL cells depends on a permissive microenvironment composed of cellular components, such as macrophages, T cells, or stromal follicular dendritic cells. [3][4][5] This microenvironment provides various chemokines and angiogenic factors, which interact with leukemic cells via appropriate surface receptors and adhesion molecules. 2,5 Macrophage migration inhibitory factor (MIF) is a proinflammatory and immunoregulatory cytokine that seems to be involved in the pathogenesis of various malignant diseases. 6-9 MIF was identified as a product of T cells 10 but also other cells of the immune system (B cells, monocytes/macrophages). 11 Later, MIF was found to be an almost ubiquitous mediator secreted by a wide variety of cells in the mammalian organism, such as endothelial cells, epithelial cells, or fibroblasts. 12 Macrophages are considered to be a prime source for MIF, as they are able to secrete large amounts of MIF in response to various stimuli. 13 MIF binds to the surface receptors CD74 and CXCR2/CXCR4, thereby stimulating signaling pathways, such as MAPK, NF-B, and AKT. [14][15][16] In B cells, activation of the surface receptor complex CD74/CD44 by MIF induces the proteolytic release of the intracellular domain of CD74, which in turn initiates a signaling cascade composing Syk, AKT, and NF-B; this leads to the production of IL-8 and to an increased resistance to apoptosis via the up-regulation of BCL-2. 17,18 Thus, the MIF-MIF receptor system may be seen as a part of the B-cell costimulatory signals that are required for full B-cell activation and maturation. MIF-deficient mice do not show developmental abnormalities and appear to have normal numbers of B cells. 6 However, they exhibit a number of immune dysfunctions when challenged by antigens or infectious agents. [19][20][21][22] Even more importantly, MIF seems to be required for bone marrow-derived dendritic cells to maintain mature B cells in the bone marrow compartment. 23 Submitted May 22, 2012; accepted October 14, 2012. Prepublished online as Blood First Edition paper, November 1, 2012; DOI 10.1182/blood-2012-05-431452.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. MIF is overexpressed in a variety of malignancies compared with the respective primary tissues (eg, prostate, 24 colon, 25 melanoma, 26 glioblastoma, 27 breast cancer 28,29 ). This overexpression might be caused by the tumor-activated HSP90 chaperone complex that protects MIF from degradation, a...

In most bacteria and archaea, filaments of FtsZ protein organize cell division. FtsZ forms a ring structure at the division site and starts the recruitment of 10 to 20 downstream proteins that together form a multiprotein complex termed the divisome. The divisome is thought to facilitate many of the steps required to make two cells out of one. FtsQ and FtsB are part of the divisome, with FtsQ being a central hub, interacting with most of the other divisome components. Here we show for the first time in detail how FtsQ interacts with its downstream partner FtsB and show that mutations that disturb the interface between the two proteins effectively inhibit cell division.

Extended rituximab exposure compared with eight 2-week applications in combination with 6×R-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6×R-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.