second model, the two main conditions were parametrically modulated by the two categories, respectively (SOM, S5.1). The activation of the precuneus was higher for hard dominance-solvable games than for easy ones ( Fig. 4A and table S10). The activation of the insula was higher for the highly focal coordination games than for less focal ones ( Fig. 4B and table S11). Previous studies also found that precuneus activity increased when the number of planned moves increased (40, 41). The higher demand for memory-related imagery and memory retrieval may explain the greater precuneus activation in hard dominance-solvable games. In highly focal coordination games, the participants may have felt quite strongly that the pool students must notice the same salient feature. This may explain why insula activation correlates with NCI.Participants might have disagreed about which games were difficult. We built a third model to investigate whether the frontoparietal activation correlates with how hard a dominance-solvable game is and whether the activation in insula and ACC correlates with how easy a coordination game is. Here, the two main conditions were parametrically modulated by each participant's probability of obtaining a reward in each game (SOM, S2.2 and S5.2). We found a negative correlation between the activation of the precuneus and the participant's probability of obtaining a reward in dominance-solvable games ( Fig. 4C and table S12), which suggests that dominance-solvable games that yielded lower payoffs presented harder mental challenges. In a previous study on working memory, precuneus activity positively correlated with response times, a measure of mental effort (24). Both findings are consistent with the interpretation that subjective measures reflecting harder tasks (higher efforts) correlate with activation in precuneus. A positive correlation between insula activation and the participant's probability of obtaining a reward again suggests that coordination games with a highly salient feature strongly activated the "gut feeling" reported by many participants (Fig. 4D and table S13). A previous study found that the subjective rating of "chills intensity" in music correlates with activation of insula (42). Both findings are consistent with the interpretation that the subjective intensity of how salient a stimulus is correlates with activation in insula.As mentioned, choices were made significantly faster in coordination games than in dominancesolvable games. The results of the second and third models provide additional support for the idea that intuitive and deliberative mental processes have quite different properties. The "slow and effortful" process was more heavily taxed when the dominance-solvable games were harder. The "fast and effortless" process was more strongly activated when coordination was easy.

SUMMARYBrucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-c (IFN-c), perforin or b 2 -microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the ®rst week after infection. However, only the IFN-c knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-c gene were infected they had more splenic CFU at one week postinfection than control mice but the increase was not statistically signi®cant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-c knock-out mice between 6 and 10 . 5 weeks, although they died at 10 . 5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-c gene disrupted mice coincided with symptoms of cachexia and macrophages comprised i 75% of the splenic leucocytes.

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings.

Brucella spp. are intracellular gram-negative bacteria that include a number of virulent species that cause chronic infections in a variety of mammalian hosts. Human infections are proportional to the level of disease in domestic animals because humans are infected zoonotically after contact with infected animals or their products. The chronicity of infection results from the ability of some brucellae to survive reactive oxygen intermediate and nitric oxide killing in host phagocytes, following which they activate bacterial genes in response to the acidic phagosome environment, prevent phagolysosomal fusion by remodeling the intracellular compartment, and subsequently replicate intracellularly. The crucial component of immunity that results in survival of the host and thus maintenance of this chronic infective state is interferon-gamma (IFN-gamma). Production of IFN-gamma results from the ability of brucella components, including lipid A, to interact with Toll-like receptors for the production of IL-12 and TNF-alpha, although the regulatory cytokine IL-10 is also produced and decreases control of the infection. Although CD4 and CD8 T cells are clearly involved in the production of IFN-gamma, and CD8 T cells may be cytotoxic, a role for NK cells and cytotoxicity in protective immunity to brucellosis has not been substantiated experimentally. Moreover, antibodies have been shown to have a limited role in passive transfer studies.

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Outer membrane proteins were derived from one rough and four smooth strains of Brucella abortus by sequential extraction of physically disrupted cells with N-lauroylsarcosinate and dipolar ionic detergent. Extraction of outer membrane proteins was ineffective, however, without predigestion with lysozyme. Three groups of proteins were present and could be separated in their native state by sequential anion-exchange chromatography and gel filtration. Membrane proteins contained substantial quantities of tightly adherent lipopolysaccharide which could be reduced but not eliminated by extraction of cells with trichloroacetic acid before disruption. Group 2 proteins, apparently trimers in their native state, gave rise to 43,000- and 41,000-molecular-weight bands after complete denaturation in sodium dodecyl sulfate. They were antigenically identical among all the strains, showed close resemblance in amino acid composition to each other and a general similarity to OmpF of Escherichia coli, and are proposed to be the porins of B. abortus. Group 3 proteins occurred as 30,000-molecular-weight bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, although additional bands were frequently observed in this region. In none of the strains did group 3 proteins manifest heat-modifiable characteristics. Proteins of different strains bore a high degree of similarity to each other in amino acid composition, except in methionine, isoleucine, tyrosine, and histidine. Differences occurred consistently in amino acid composition between group 2 and 3 proteins, and some of these correspond to differences between OmpF and OmpA. Group 2 and 3 proteins were antigenically distinct from each other, but the principal group 3 antigens were shared among all the strains. Despite the lack of heat modifiability, perhaps influenced by adherent lipopolysaccharide, group 3 proteins are proposed as counterparts to OmpA. Most of the group 1 proteins, minor components, were physically associated with those of group 3 unless in sodium dodecyl sulfate. Group 1 proteins produced a major band at 94,000 and exhibited heat modifiability. No evidence was found of a low-molecular-weight lipoprotein in the outer membrane of B. abortus, but this is not taken to exclude its occurrence.

WC1 molecules are transmembrane glycoproteins belonging to the scavenger receptor cysteine-rich family and uniquely expressed on γδ T cells. Although participation of WC1+ γδ T cells in immune responses is well established, very little is understood regarding the significance of expressing different forms of the WC1 molecule. Two forms previously identified by mAbs, i.e., WC1.1 and WC1.2, are expressed by largely nonoverlapping subpopulations of γδ T cells. In this study it was shown that expression of the WC1.1 coreceptor was the main indicator of proliferation and IFN-γ production in response to autologous and bacterial Ags as well as for IFN-γ production without proliferation in Th1-polarizing, IL-12-containing cultures. Nevertheless, after culture in either Th1-polarizing or neutral conditions, mRNA was present for both T-bet and GATA-3 as well as for IL-12Rβ2 in WC1.1+ and WC1.2+ subpopulations, and neither produced IL-4 under any conditions. Although the steady decrease in the proportion of WC1.1+ cells, but not WC1.2+ cells, within PBMC with animal aging suggested that the two subpopulations may have different roles in immune regulation, cells bearing either WC1.1 or WC1.2 expressed mRNA for regulatory cytokines IL-10 and TGF-β, with TGF-β being constitutively expressed by ex vivo cells. Overall, the results demonstrate that the form of the WC1 coreceptor expressed on γδ T cells divides them into functional subsets according to IFN-γ production and proliferative capacity to specific stimuli as well as with regard to representation within PBMC. Finally, evidence is provided for minor differences in the intracytoplasmic tail sequences of WC1.1 and WC1.2 that may affect signaling.