Getting in touch: segregated somatosensory what and where pathways in humans revealed by electrical neuroimaging.

Whether the somatosensory system, like its visual and auditory counterparts, is comprised of parallel functional pathways for processing identity and spatial attributes (so-called what and where pathways, respectively) has hitherto been studied in humans using neuropsychological and hemodynamic methods. Here, electrical neuroimaging of somatosensory evoked potentials (SEPs) identified the spatio-temporal mechanisms subserving vibrotactile processing during two types of blocks of trials. What blocks varied stimuli in their frequency (22.5 Hz vs. 110 Hz) independently of their location (left vs. right hand). Where blocks varied the same stimuli in their location independently of their frequency. In this way, there was a 2x2 within-subjects factorial design, counterbalancing the hand stimulated (left/right) and trial type (what/where). Responses to physically identical somatosensory stimuli differed within 200 ms post-stimulus onset, which is within the same timeframe we previously identified for audition (De Santis, L., Clarke, S., Murray, M.M., 2007. Automatic and intrinsic auditory "what" and "where" processing in humans revealed by electrical neuroimaging. Cereb Cortex 17, 9-17.). Initially (100-147 ms), responses to each hand were stronger to the what than where condition in a statistically indistinguishable network within the hemisphere contralateral to the stimulated hand, arguing against hemispheric specialization as the principal basis for somatosensory what and where pathways. Later (149-189 ms) responses differed topographically, indicative of the engagement of distinct configurations of brain networks. A common topography described responses to the where condition irrespective of the hand stimulated. By contrast, different topographies accounted for the what condition and also as a function of the hand stimulated. Parallel, functionally specialized pathways are observed across sensory systems and may be indicative of a computationally advantageous organization for processing spatial and identity information.

Le code-switching comme ressource stratégique pour la gestion de l'interaction multilingue : coordination et leadership dans un groupe de travail

In this article, we analyze a multilingual interaction in a students' working group and hypothesize a correlation between management of languages in interaction and leadership. We consider Codeswitching as one of the most relevant observables in multilingual interaction and attempt to analyze how it is used by speakers. After a brief presentation of three theoretical and analytical conceptions of Code-switching in interaction (Auer, Mondada & Myers Scotton), we define Code-switching as an interactional, strategical, multilingual resource exploited by speakers to achieve various interactionaland non interactional goals. We then show in two CA-like analysis how multilingual strategical resources occur in the interactional practices of the analyzed working group, and how they are exploited by speakers in order to organize interaction, work, tasks, and to construct one's leadership.We also consider the metadiscourses of the students about their own practices and multilingualism in general, in order to confront them to their actual multilingual practices. We draw the hypothesis that discrepancies observed between metadiscourses and practices can be explained through the development of (meta)discourses showing a unilingual conception in describing multilingual practices.

Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

Switching between apparently redundant iron-uptake mechanisms benefits bacteria in changeable environments.

Bacteria often possess multiple siderophore-based iron uptake systems for scavenging this vital resource from their environment. However, some siderophores seem redundant, because they have limited iron-binding efficiency and are seldom expressed under iron limitation. Here, we investigate the conundrum of why selection does not eliminate this apparent redundancy. We focus on Pseudomonas aeruginosa, a bacterium that can produce two siderophores-the highly efficient but metabolically expensive pyoverdine, and the inefficient but metabolically cheap pyochelin. We found that the bacteria possess molecular mechanisms to phenotypically switch from mainly producing pyoverdine under severe iron limitation to mainly producing pyochelin when iron is only moderately limited. We further show that strains exclusively producing pyochelin grew significantly better than strains exclusively producing pyoverdine under moderate iron limitation, whereas the inverse was seen under severe iron limitation. This suggests that pyochelin is not redundant, but that switching between siderophore strategies might be beneficial to trade off efficiencies versus costs of siderophores. Indeed, simulations parameterized from our data confirmed that strains retaining the capacity to switch between siderophores significantly outcompeted strains defective for one or the other siderophore under fluctuating iron availabilities. Finally, we discuss how siderophore switching can be viewed as a form of collective decision-making, whereby a coordinated shift in behaviour at the group level emerges as a result of positive and negative feedback loops operating among individuals at the local scale.

Derivation of soil-specific streaming potential electrical parameters from hydrodynamic characteristics of partially saturated soils

Water movement in unsaturated soils gives rise to measurable electrical potential differences that are related to the flow direction and volumetric fluxes, as well as to the soil properties themselves. Laboratory and field data suggest that these so-called streaming potentials may be several orders of magnitudes larger than theoretical predictions that only consider the influence of the relative permeability and electrical conductivity on the self potential (SP) data. Recent work has improved predictions somewhat by considering how the volumetric excess charge in the pore space scales with the inverse of water saturation. We present a new theoretical approach that uses the flux-averaged excess charge, not the volumetric excess charge, to predict streaming potentials. We present relationships for how this effective excess charge varies with water saturation for typical soil properties using either the water retention or the relative permeability function. We find large differences between soil types and the predictions based on the relative permeability function display the best agreement with field data. The new relationships better explain laboratory data than previous work and allow us to predict the recorded magnitudes of the streaming potentials following a rainfall event in sandy loam, whereas previous models predict values that are three orders of magnitude too small. We suggest that the strong signals in unsaturated media can be used to gain information about fluxes (including very small ones related to film flow), but also to constrain the relative permeability function, the water retention curve, and the relative electrical conductivity function.

Gains from switching and evolutionary stability in multi-player matrix games.

In this paper we unify, simplify, and extend previous work on the evolutionary dynamics of symmetric N-player matrix games with two pure strategies. In such games, gains from switching strategies depend, in general, on how many other individuals in the group play a given strategy. As a consequence, the gain function determining the gradient of selection can be a polynomial of degree N-1. In order to deal with the intricacy of the resulting evolutionary dynamics, we make use of the theory of polynomials in Bernstein form. This theory implies a tight link between the sign pattern of the gains from switching on the one hand and the number and stability of the rest points of the replicator dynamics on the other hand. While this relationship is a general one, it is most informative if gains from switching have at most two sign changes, as is the case for most multi-player matrix games considered in the literature. We demonstrate that previous results for public goods games are easily recovered and extended using this observation. Further examples illustrate how focusing on the sign pattern of the gains from switching obviates the need for a more involved analysis.

Hypoxia/hypoglycemia preconditioning prevents the loss of functional electrical activity in organotypic slice cultures.

In cerebral ischemic preconditioning (IPC), a first sublethal ischemia increases the resistance of neurons to a subsequent severe ischemia. Despite numerous studies, the mechanisms are not yet fully understood. Our goal is to develop an in vitro model of IPC on hippocampal organotypic slice cultures. Instead of anoxia, we chose to apply varying degrees of hypoxia that allows us various levels of insult graded from mild to severe. Cultures are exposed to combined oxygen and glucose deprivation (OGD) of varying intensities, ranging from mild to severe, assessing both the electrical activity and cell death. IPC was accomplished by exposure to the mildest ischemia condition (10% of O2 for 15 min) 24 h before the severe deprivation (5% of O2 for 30 min). Interestingly, IPC not only prevented delayed ischemic cell death 6 days after insult but also the transient loss of evoked potential response. The major interest and advantage of this system over both the acute slice preparation and primary cell cultures is the ability to simultaneously measure the delayed neuronal damage and neuronal function.

PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes.

Mice in which peroxisome proliferator-activated receptor beta (PPARbeta) is selectively ablated in skeletal muscle myocytes were generated to elucidate the role played by PPARbeta signaling in these myocytes. These somatic mutant mice exhibited a muscle fiber-type switching toward lower oxidative capacity that preceded the development of obesity and diabetes, thus demonstrating that PPARbeta is instrumental in myocytes to the maintenance of oxidative fibers and that fiber-type switching is likely to be the cause and not the consequence of these metabolic disorders. We also show that PPARbeta stimulates in myocytes the expression of PGC1alpha, a coactivator of various transcription factors, known to play an important role in slow muscle fiber formation. Moreover, as the PGC1alpha promoter contains a PPAR response element, the effect of PPARbeta on the formation and/or maintenance of slow muscle fibers can be ascribed, at least in part, to a stimulation of PGC1alpha expression at the transcriptional level.

Reverse-transcriptase-associated RNaseH activity mediates template switching during reverse transcription in vitro.

During the first steps of reverse transcription of the retroviral genome, sequences present at the extremities of the RNA are used to reconstitute a host cell PolII promoter. The assembly of the promoter occurs by template switching, which takes advantage of a direct repeat at the ends of the RNA molecule. These steps are catalysed by the viral reverse transcriptase, which carries an intrinsic RNaseH activity that is probably also involved therein. To study the role of the RNaseH activity in this first template-switching event, an in vitro system has been developed based on primer extensions of synthetic RNAs. When an RNA was reverse transcribed with wild-type reverse transcriptase in the presence of a second RNA the 3' part of which was repeated at the 5' end of the first one, extension products could be observed corresponding to a chimeric cDNA comprising both RNA species. This template switching could not be detected when a mutant reverse transcriptase lacking the RNaseH activity was used. The results show that the RNaseH activity is needed to remove the 5' RNA sequences from the cDNA:RNA hybrid thereby enabling its translocation to another RNA containing an appropriate complementary target sequence.

FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases.

FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division septum. FtsK(50C) also promotes a complete Xer recombination reaction between dif sites by switching the state of activity of the XerCD recombinases so that XerD makes the first pair of strand exchanges to form Holliday junctions that are then resolved by XerC. The reaction between directly repeated dif sites in circular DNA leads to the formation of uncatenated circles and is equivalent to the formation of chromosome monomers from dimers.

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy.

PURPOSE: To study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. METHODS: Eight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. RESULTS: The distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. CONCLUSION: Decrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs.

Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed.

The borehole-fluid effect in electrical resistivity imaging

Fluid that fills boreholes in crosswell electrical resistivity investigations provides the necessary electrical contact between the electrodes and the rock formation but it is also the source of image artifacts in standard inversions that do not account for the effects of the boreholes. The image distortions can be severe for large resistivity contrasts between the rock formation and borehole fluid and for large borehole diameters. We have carried out 3D finite-element modeling using an unstructured-grid approach to quantify the magnitude of borehole effects for different resistivity contrasts, borehole diameters, and electrode configurations. Relatively common resistivity contrasts of 100:1 and borehole diameters of 10 and 20 cm yielded, for a bipole length of 5 m, apparent resistivity underestimates of approximately 12% and 32% when using AB-MN configurations and apparent resistivity overestimates of approximately 24% and 95% when using AM-BN configurations. Effects are generally more severe at shorter bipole spacings. We report the results obtained by either including or ignoring the boreholes in inversions of 3D field data from a test site in Switzerland, where approximately 10,000 crosswell resistivity-tomography measurements were made across six acquisition planes among four boreholes. Inversions of raw data that ignored the boreholes filled with low-resistivity fluid paradoxically produced high-resistivity artifacts around the boreholes. Including correction factors based on the modeling results fora ID model with and without the boreholes did not markedly improve the images. The only satisfactory approach was to use a 3D inversion code that explicitly incorporated the boreholes in the actual inversion. This new approach yielded an electrical resistivity image that was devoid of artifacts around the boreholes and that correlated well with coincident crosswell radar images.

Le code-switching comme ressource stratégique pour la gestion de l'interaction multilingue : coordination et leadership dans un groupe de travail

In this article, we analyze a multilingual interaction in a students' working group and hypothesize a correlation between management of languages in interaction and leadership. We consider Codeswitching as one of the most relevant observables in multilingual interaction and attempt to analyze how it is used by speakers. After a brief presentation of three theoretical and analytical conceptions of Code-switching in interaction (Auer, Mondada & Myers Scotton), we define Code-switching as an interactional, strategical, multilingual resource exploited by speakers to achieve various interactional and non interactional goals. We then show in two CA-like analysis how multilingual strategical resources occur in the interactional practices of the analyzed working group, and how they are exploited by speakers in order to organize interaction, work, tasks, and to construct one's leadership. We also consider the metadiscourses of the students about their own practices and multilingualism in general, in order to confront them to their actual multilingual practices. We draw the hypothesis that discrepancies observed between metadiscourses and practices can be explained through the development of (meta)discourses showing a unilingual conception in describing multilingual practices.

TNFα in synaptic function: switching gears.

Pathological brain states are known to induce massive production of proinflammatory cytokines, including tumor necrosis factor alpha (TNFα). At much lower levels, these cytokines are also present in the healthy brain, where it is increasingly being recognized that they exert regulatory influences. Recent studies suggest that TNFα plays important roles in controlling synaptic transmission and plasticity. Here, we discuss the evidence in support of synaptic regulation by TNFα and the underlying cellular mechanisms, including control of AMPA receptor trafficking and glutamate release from astrocytes. These findings suggest that increases in TNFα levels (caused by nervous system infection, injury, or disease) transform the physiological actions of the cytokine into deleterious ones. This functional switch may contribute to cognitive alterations in several brain pathologies.