CD5L is a canonical component of circulatory IgM

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L

A resource constraint approach for one global constraint MINLP

Many industrial optimization problems are sparse and can be formulated as block-separable mixed-integer nonlinear programming (MINLP) problems, where low-dimensional sub-problems are linked by a (linear) knapsack-like coupling constraint. This paper investigates exploiting this structure using decomposition and a resource constraint formulation of the problem. The idea is that one outer approximation master problem handles sub-problems that can be solved in parallel. The steps of the algorithm are illustrated with numerical examples which shows that convergence to the optimal solution requires a few steps of solving sub-problems in lower dimension

SrPt3In2 \u2013 an orthorhombically distorted coloring variant of SrIn5

The new intermetallic phase SrPt3In2 was synthesized by induction-melting of the elements in a sealed tantalum ampoule followed by long-term annealing for crystal growth. The SrPt3In2 structure was refined from single crystal X-ray diffraction data: Imma, a = 1674.7(6), b = 921.2(4), c = 971.2(4) pm, wR(2) = 0.0551, 1192 F-2 values and 55 variables. Electronic structure calculations indicate strong covalent Pt-In bonding and a substantial charge transfer from the strontium atoms to the three-dimensional [Pt3In2](delta-) polyanionic network. The strontium atoms fill larger cavities within the network and the bonding of strontium to the polyanion is of the electrostatic type. The Bader charge calculations classify SrPt3In2 as a ternary platinide. The close relationship between the SrPt3In2 structure and the aristotype CaCu5 is discussed on the basis of a group-subgroup scheme in the Barnighausen formalism along with other CaCu5 coloring variants and superstructures