The capacity of cultured human monocytes to synthesize and to secrete the subcomponents of C1 and C1 inhibitor was examined. Non-stimulated monocytes secreted C1q and C1s from day 5 of culture. C1s reached a plateau immediately at its maximum level, whereas C1q secretion increased progressively until the end of the second week. Between day 12 and day 25, C1q secretion remained nearly constant (1-15 fmol/day per microgram of DNA, depending on the donor), whereas C1s secretion decreased and even in some cases stopped. C1r and C1 inhibitor were not secreted in detectable amounts by these resting cells. Stimulation of monocytes by yeasts, immunoglobulin G-opsonized sheep red blood cells or latex beads did not modify consistently C1q and C1s secretion. Activation by conditioned media from mitogen-, antigen- or allogeneic-stimulated lymphocyte cultures increased C1q production from 2 to 7 times and re-activated C1s secretion. Under the same conditions of activation, C1 inhibitor was secreted (up to 300 fmol/day per microgram of DNA) and C1r became detectable in culture supernatants. Isolated human monocytes are thus able to synthesize the whole C1 subcomponents; C1, if assembled, could be protected from non-immunological activation by locally produced C1 inhibitor. Activated monocytes appear to be a good tool for studying the assembly of C1 subcomponents and the role of C1 inhibitor in this process.
Bubonic plague (a fatal, flea-transmitted disease) remains an international public health concern. Although our understanding of the pathogenesis of bubonic plague has improved significantly over the last few decades, researchers have still not been able to define the complete set of Y. pestis genes needed for disease or to characterize the mechanisms that enable infection. Here, we generated a library of Y. pestis mutants, each lacking one or more of the genes previously identified as being up-regulated in vivo. We then screened the library for attenuated virulence in rodent models of bubonic plague. Importantly, we tested mutants both individually and using a novel, “per-pool” screening method that we have developed. Our data showed that in addition to genes involved in physiological adaption and resistance to the stress generated by the host, several previously uncharacterized genes are required for virulence. One of these genes (ympt1.66c, which encodes a putative helicase) has been acquired by horizontal gene transfer. Deletion of ympt1.66c reduced Y. pestis' ability to spread to the lymph nodes draining the dermal inoculation site – probably because loss of this gene decreased the bacteria's ability to survive inside macrophages. Our results suggest that (i) intracellular survival during the early stage of infection is important for plague and (ii) horizontal gene transfer was crucial in the acquisition of this ability.
Two experiments with preschoolers (36 to 78 months) and 8-year-old children (Experiment 1, N = 173; Experiment 2, N = 132) investigated the development of children's resource distribution in dominance contexts. On the basis of the distributive justice literature, 2 opposite predictions were tested. Children could match resource allocation with the unequal social setting they observe and thus favor a dominant individual over a subordinate 1. Alternatively, children could choose to compensate the subordinate if they consider that the dominance asymmetry should be counteracted. Two experiments using a giving task (Experiment 1) and a taking task (Experiment 2) led to the same results. In both experiments, children took dominance into account when allocating resources. Moreover, their distributive decisions were similarly affected by age: Although 3- and 4-year-old children favored the dominant individual, 5-year-old children showed no preference and 8-year-old children strongly favored the subordinate. Several mechanisms accounting for this developmental pattern are discussed. (PsycINFO Database Record
Action words referring to face, arm or leg actions activate areas along the motor strip that also control the planning and execution of the actions specified by the words. This electroencephalogram (EEG) study aimed to test the learning profile of this language-induced motor activity. Participants were trained to associate novel verbal stimuli to videos of object-oriented hand and arm movements or animated visual images on two consecutive days. Each training session was preceded and followed by a test-session with isolated videos and verbal stimuli. We measured motor-related brain activity (reflected by a desynchronization in the μ frequency bands; 8-12 Hz range) localized at centro-parietal and fronto-central electrodes. We compared activity from viewing the videos to activity resulting from processing the language stimuli only. At centro-parietal electrodes, stable action-related μ suppression was observed during viewing of videos in each test-session of the two days. For processing of verbal stimuli associated with motor actions, a similar pattern of activity was evident only in the second test-session of Day 1. Over the fronto-central regions, μ suppression was observed in the second test-session of Day 2 for the videos and in the second test-session of Day 1 for the verbal stimuli. Whereas the centro-parietal μ suppression can be attributed to motor events actually experienced during training, the fronto-central μ suppression seems to serve as a convergence zone that mediates underspecified motor information. Consequently, sensory-motor reactivations through which concepts are comprehended seem to differ in neural dynamics from those implicated in their acquisition.
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