Multigenic control of Listeria monocytogenes susceptibility in mice

We have used a novel quantitative trait locus model to study the genetics of survival of F2 progeny of susceptible BALB/cByJ and resistant C57BL/6ByJ mice that have been infected with Listeria monocytogenes. This allowed us to map modifiers of L. monocytogenes susceptibility to chromosomes 5 and 13.     

Specific interactions of the adenovirus proteinase with the viral DNA,an 11-amino-acid viral peptide,and the cellular protein actin

The adenovirus proteinase (AVP) is synthesized in an inactive form that requires cofactors for activation. The interaction of AVP with two viral cofactors and with a cellular cofactor, actin, is characterized by quantitative analyses. The results are consistent with a specific model for the regulation of AVP. Late in adenovirus infection, inside nascent virions, AVP becomes partially activated by binding to the viral DNA, allowing it to cleave out an 11-amino-acid viral peptide, pVIc, that binds to AVP and fully activates it. Then, about 70 AVP-pVIc complexes move along the viral DNA, via one-dimensional diffusion, cleaving virion precursor proteins 3200 times to render a virus particle infectious. Late in adenovirus infection, in the cytoplasm, the cytoskeleton is destroyed. The amino acid sequence of the C terminus of actin is homologous to that of pVIc, and actin, like pVIc, can act as a cofactor for AVP in the cleavage of cytokeratin 18 and of actin itself. Thus, AVP may also play a role in cell lysis.Received 14 November 2002; received after revision 28 April 2003; accepted 30 April 2003     

Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation

The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making, monitoring for conflict between competing responses and predicting task difficulty. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.