MASPs were not detected in BAL, and were not produced by alveolar or tissue macrophages. MBL
significantly increased macrophage expression of Rac1/2/3. We provide evidence for Rac1/2/3 involvement in the MBL-mediated improvement in efferocytosis, and a rationale for investigating MBL as a supplement to existing therapies in smoking-related lung inflammation.”
“Co-stimulatory signaling pathway triggered by the binding of B7.1/B7.2 (CD80/86) of antigen-presenting cells (APCs) to CD28 of T cells is required for optimal T-cell activation. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Ipilimumab, a monoclonal antibody against CTLA-4, has shown positive efficacy in a pivotal clinical trial for the treatment of metastatic melanoma and buy MLN4924 was approved by FDA. However, the cost of monoclonal antibody-based therapeutics might limit the number of patients treated. To develop a novel therapeutics specifically targeting CTLA-4, we constructed a DNA vaccine by cloning the sequence of CTLA-4 fused with a transmembrane domain sequence of placental
alkaline phosphatase (PLAP) into a mammalian expression plasmid, pVAC-1. Immunization with the resulting construct, pVAC-1-hCTLA-4, elicited antibody specific to human CTLA-4 with cross reactivity to murine CTLA-4, which was sufficient for inhibiting B16F10 tumor growth in c57BL/6 mice in the absence of measurable toxicity. Coupling liposome with pVAC-1-mCTLA-4 ST-1571 Mesylate could break tolerance to self-antigen in BALB/c mice and induce potent immunity against murine CTLA-4, and suppress growth of subcutaneous renal cell
carcinoma (Renca). (C) 2013 Elsevier Inc. All Bucladesine rights reserved.”
“We present a complete phylogeny of macroperforate planktonic foraminifer species of the Cenozoic Era (similar to 65 million years ago to present). The phylogeny is developed from a large body of palaeontological work that details the evolutionary relationships and stratigraphic (time) distributions of species-level taxa identified from morphology (‘morphospecies’). Morphospecies are assigned to morphogroups and ecogroups depending on test morphology and inferred habitat, respectively. Because gradual evolution is well documented in this clade, we have identified many instances of morphospecies intergrading over time, allowing us to eliminate ‘pseudospeciation’ and ‘pseudoextinction’ from the record and thereby permit the construction of a more natural phylogeny based on inferred biological lineages. Each cladogenetic event is determined as either budding or bifurcating depending on the pattern of morphological change at the time of branching. This lineage phylogeny provides palaeontologically calibrated ages for each divergence that are entirely independent of molecular data.