Infection by Toxoplasma gondii down-regulates the host innate immune responses, such as proinflammatory cytokine production, in a Stat3-dependent manner. A forward genetic approach recently demonstrated that the type II strain fails to suppress immune responses because of a potential defect in a highly polymorphic parasite-derived kinase, ROP16. We generated ROP16-deficient type I parasites by reverse genetics and found a severe defect in parasite-induced Stat3 activation, culminating in enhanced production of interleukin (IL) 6 and IL-12 p40 in the infected macrophages. Furthermore, overexpression of ROP16 but not ROP18 in mammalian cells resulted in Stat3 phosphorylation and strong activation of Stat3-dependent promoters. In addition, kinase-inactive ROP16 failed to activate Stat3. Comparison of type I and type II ROP16 revealed that a single amino acid substitution in the kinase domain determined the strain difference in terms of Stat3 activation. Moreover, ROP16 bound Stat3 and directly induced phosphorylation of this transcription factor. These results formally establish an essential and direct requirement of ROP16 in parasite-induced Stat3 activation and the significance of a single amino acid replacement in the function of type II ROP16.

The nucleon's strange-quark vector current form factors are studied from the perspective of chiral symmetry. It is argued that chiral perturbation theory cannot yield a prediction for the strangeness radius and magnetic moment. Arrival at definite predictions requires the introduction of additional, modeldependent assumptions which go beyond the framework of chiral perturbation theory. A variety of such model predictions is surveyed, and the credibility of each is evaluated. The most plausible prediction appears in a model where the unknown chiral counterterms are identified with t-channel vector meson exchange amplitudes. The corresponding prediction for the mean square Dirac strangeness radius is r 2 s = 0.24 fm 2 , which would be observable in up-coming semileptonic determinations of the nucleon's strangeness form factors.

A monoclonal antibody against protein kinase C (PKC) was used for immunocytochemical studies of the type I PKC encoded by gamma-cDNA sequence (gamma-subspecies) in rat Purkinje cells. Dense gamma-subspecies-like immunoreactivity was found on the cell membrane and in the cytoplasm except within cell organelles of the perikaryon, dendrites, axon, and axon terminals. The nucleus was also stained but less heavily, and the nucleoli remained unstained. Synaptic vesicles in the axon terminals were densely stained. The results suggest that gamma-subspecies might be functionally involved in modulation of nuclear function and of pre- and postsynaptic functions including transmitter release in the rat Purkinje cells.

Electromagnetic form factors for the p-ir^y an d ^^7 vertices, estimated from quark loop diagrams, differ considerably from the monopole form factors obtained from vector meson dominance, and significantly alter the predictions for the elastic electromagnetic form factors of the deuteron.PACS numbers: 25.30. Bf, 13.40.Fn, 24.85.+p, 27.10.+h A number of experimental measurements, the most famous being the electrodisintegration of the deuteron at threshold, have established the existence of isovector meson exchange currents [1]. In contrast, the nature and size of isoscalar exchange currents are still issues of some controversy. The ptr^ interaction (related to the AVV anomaly [2]) certainly leads to an isoscalar exchange current, but because of the large mass and width of the p and the comparatively small size of the p-ivy coupling, such a current is hard to distinguish from other short range interaction currents, including those which might arise from quark exchange forces [3]. Use of the cva^y isoscalar exchange interaction is more dubious. Both the very short range nature of this current and the phenomenological status of the a make it hard to justify, singling it out for special consideration.The simplest system in which to look for isoscalar exchange currents is the deuteron. The deuteron structure functions A(Q 2 ) and B(Q 2 ) have been calculated using a variety of relativistic schemes for treating the nuclear dynamics [4][5][6][7][8], and good deuteron wave functions can be derived from realistic models of the NN interaction based on meson field theory [9,10]. The relativistic theory for electron-deuteron elastic scattering is therefore fairly reliable. In the context of a Bethe-Salpeter one boson exchange (OBE) model of the nuclear force, the form factors can be calculated from only two contributions: the relativistic impulse approximation (RIA) in which the photon couples directly to one of the bound nucleons [shown in Fig. 1 (a)], and the meson exchange current (MEC) contribution in which the photon couples to the exchanged mesons [shown in Fig. 1(b)]. Because the deuteron is an isospin zero target, only the isoscalar MEC can contribute, and in the context of the OBE model the pn^f and uor^y currents are two likely candidates.The ptvy and LUCTJ exchange currents make small contributions to the magnetic and quadrupole moments (which are the values of the magnetic and quadrupole form factors at Q 2 = 0, where Q 2 is the square of the fourmomentum transferred by the photon), but these contributions are much less than \% [11]. They are therefore masked by the significantly larger (and uncertain) relativistic corrections, which are about 5% for the magnetic moment and 1.5% for the quadrupole moment [9]. The situation is more favorable at large Q 2 , where these MEC contributions are expected to be large (because they provide a mechanism for sharing the incoming photon momentum equally between the two nucleons) [12][13][14], and where previous calculations of the RIA [4, 5,11] have underestimated A{Q 2 ) by ...

No abstract