Functional Connectivity in Tactile Object Discrimination—A Principal Component Analysis of an Event Related fMRI-Study

BACKGROUND: Tactile object discrimination is an essential human skill that relies on functional connectivity between the neural substrates of motor, somatosensory and supramodal areas. From a theoretical point of view, such distributed networks elude categorical analysis because subtraction methods are univariate. Thus, the aim of this study was to identify the neural networks involved in somatosensory object discrimination using a voxel-based principal component analysis (PCA) of event-related functional magnetic resonance images. METHODOLOGY/PRINCIPAL FINDINGS: Seven healthy, right-handed subjects aged between 22 and 44 years were required to discriminate with their dominant hand the length differences between otherwise identical parallelepipeds in a two-alternative forced-choice paradigm. Of the 34 principal components retained for analysis according to the 'bootstrapped' Kaiser-Guttman criterion, t-tests applied to the subject-condition expression coefficients showed significant mean differences between the object presentation and inter-stimulus phases in PC 1, 3, 26 and 32. Specifically, PC 1 reflected object exploration or manipulation, PC 3 somatosensory and short-term memory processes. PC 26 evinced the perception that certain parallelepipeds could not be distinguished, while PC 32 emerged in those choices when they could be. Among the cerebral regions evident in the PCs are the left posterior parietal lobe and premotor cortex in PC 1, the left superior parietal lobule (SPL) and the right cuneus in PC 3, the medial frontal and orbitofrontal cortex bilaterally in PC 26, and the right intraparietal sulcus, anterior SPL and dorsolateral prefrontal cortex in PC 32. CONCLUSIONS/SIGNIFICANCE: The analysis provides evidence for the concerted action of large-scale cortico-subcortical networks mediating tactile object discrimination. Parallel to activity in nodes processing object-related impulses we found activity in key cerebral regions responsible for subjective assessment and validation

Multidrug efflux pumps:structure, function and regulation

Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities