Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD <sup>+</sup> LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD <sup>+</sup> B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD <sup>+</sup> DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD <sup>+</sup> BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies

Adaptive evolution of drug targets in producer and non-producer organisms

Mycophenolic acid (MPA) is an immunosuppressive drug produced by several fungi in Penicillium subgenus Penicillium. This toxic metabolite is an inhibitor of IMP dehydrogenase (IMPDH). The MPA biosynthetic cluster of P. brevicompactum contains a gene encoding a B-type IMPDH, IMPDH-B, which confers MPA-resistance. Surprisingly, all members of subgenus Penicillium contain genes encoding IMPDHs of both the A and B type, regardless of their ability to produce MPA. Duplication of the IMPDH gene occurred prior to and independent of the acquisition of the MPA biosynthetic cluster. Both P. brevicompactum IMPDHs are MPA-resistant while the IMPDHs from a nonproducer are MPA-sensitive. Resistance comes with a catalytic cost: while P. brevicompactum IMPDH-B is >1000-fold more resistant to MPA than a typical eukaryotic IMPDH, its value of k(cat)/K(m) is 0.5% of “normal”. Curiously, IMPDH-B of Penicillium chrysogenum, which does not produce MPA, is also a very poor enzyme. The MPA binding site is completely conserved among sensitive and resistant IMPDHs. Mutational analysis shows that the C-terminal segment is a major structural determinant of resistance. These observations suggest that the duplication of the IMPDH gene in Pencillium subgenus Penicillium was permissive for MPA production and that MPA production created a selective pressure on IMPDH evolution. Perhaps MPA production rescued IMPDH-B from deleterious genetic drift

Oxidation of thioketenes by singlet oxygen

This article does not have an abstract

ChemInform Abstract: OXIDATION OF THIOKETENES BY SINGLET OXYGEN

Di‐tertnbutyl‐tfiioketen (I) wird mit Singulett‐Sauerstoff in Methylenchlorid zu einem Gemisch aus (II)‐(V), in Methanol zu (II) und (‐III) sowie (VI) und (VII) umgesetzt

Multiple wave packets running in the photon number space

If a two-level system coupled to a single-mode cavity is strongly driven by an external laser, instead of a continuous accumulation of photons in the cavity, oscillations in the mean photon number occur. These oscillations correspond to peaks of finite width running up and down in the photon number distribution, reminiscent of wave packets in linear chain models. A single wave packet is found if the cavity is resonant to the external laser. Here, we show that for finite detuning, multiple packet structures can exist simultaneously, oscillating at different frequencies and amplitudes. We further study the influence of dissipative effects resulting in the formation of a stationary state, which, depending on the parameters, can be characterized by a bimodal photon number distribution. While we give analytical limits for the maximally achievable photon number in the absence of any dissipation, surprisingly, dephasing processes can push the photon occupations towards higher photon numbers.</p

Multiple wave packets running in the photon number space

If a two-level system coupled to a single-mode cavity is strongly driven by an external laser, instead of a continuous accumulation of photons in the cavity, oscillations in the mean photon number occur. These oscillations correspond to peaks of finite width running up and down in the photon number distribution, reminiscent of wave packets in linear chain models. A single wave packet is found if the cavity is resonant to the external laser. Here, we show that for finite detuning, multiple packet structures can exist simultaneously, oscillating at different frequencies and amplitudes. We further study the influence of dissipative effects resulting in the formation of a stationary state, which, depending on the parameters, can be characterized by a bimodal photon number distribution. While we give analytical limits for the maximally achievable photon number in the absence of any dissipation, surprisingly, dephasing processes can push the photon occupations towards higher photon numbers.</p