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Vuilleumier P.,University of Geneva | Vuilleumier P.,University Hospitals Geneva Medical Center
Current Opinion in Neurology | Year: 2015

Purpose of review: It is increasingly recognized that affective values associated with visual stimuli can influence visual perception, attention, and eye movements. Recent research has begun to uncover the brain mechanisms mediating these phenomena. The present review summarizes the main paradigms and findings demonstrating emotional and motivational influences on visual processing. Recent findings: Several pathways have been identified for enhancing neural responses of cortical visual areas to stimuli with intrinsic emotional value (e.g., facial expressions, social scenes, and others), including projections from the amygdala and ascending modulatory neurotransmitter systems from the brainstem. These pathways can guide attention and gaze to emotionally salient information with either negative (threatening) or positive (rewarding) associations. In addition, abundant research in recent years suggests that probabilistic reward learning can lead to powerful biases in visual attention and saccade control through subcortical pathways connecting visual areas with basal ganglia and superior colliculus. Time-resolved neuroimaging using electroencephalography or magnetoencephalography has begun to tackle the time course of these effects, and can now be complemented by neuroimaging and neurophysiology recordings in monkey. Summary: These findings have implications for understanding and assessing affective biases in perception and attention in patients with psychiatric disorders, such as phobias, depression, and addiction, but also open new avenues for rehabilitation in neurological patients with attention disorders. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source


Dayer J.M.,University Hospitals Geneva Medical Center
Rheumatology (Oxford, England) | Year: 2010

RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this disease. Source


Cvetkovic-Lopes V.,University Hospitals Geneva Medical Center
PloS one | Year: 2010

In a previous study we proposed that the depolarized state of the wake-promoting hypocretin/orexin (hcrt/orx) neurons was independent of synaptic inputs as it persisted in tetrodotoxin and low calcium/high magnesium solutions. Here we show first that these cells are hyperpolarized when external sodium is lowered, suggesting that non-selective cation channels (NSCCs) could be involved. As canonical transient receptor channels (TRPCs) are known to form NSCCs, we looked for TRPCs subunits using single-cell RT-PCR and found that TRPC6 mRNA was detectable in a small minority, TRPC1, TRPC3 and TRPC7 in a majority and TRPC4 and 5 in the vast majority (∼90%) of hcrt/orx neurons. Using intracellular applications of TRPC antibodies against subunits known to form NSCCs, we then found that only TRPC5 antibodies elicited an outward current, together with hyperpolarization and inhibition of the cells. These effects were blocked by co-application of a TRPC5 antigen peptide. Voltage-clamp ramps in the presence or absence of TRPC5 antibodies indicated the presence of a current with a reversal potential close to -15 mV. Application of the non-selective TRPC channel blocker, flufenamic acid, had a similar effect, which could be occluded in cells pre-loaded with TRPC5 antibodies. Finally, using the same TRPC5 antibodies we found that most hcrt/orx cells show immunostaining for the TRPC5 subunit. These results suggest that hcrt/orx neurons are endowed with a constitutively active non-selective cation current which depends on TRPC channels containing the TRPC5 subunit and which is responsible for the depolarized and active state of these cells. Source


Saurat J.-H.,University Hospitals Geneva Medical Center
Dermatology | Year: 2015

The sequence of events and mechanisms leading to the development of the primary acne lesion, the comedone, is revisited. Recent knowledge obtained both from lineage tracing experiments in the mouse and the pilosebaceous response to xenobiotics in humans provides robust models for further understanding key biological events at the cellular roots of comedogenesis. The focus is set on the LRIG1+ sebaceous stem cells in the isthmus of the pilosebaceous duct. The master switch that transforms a normally functioning sebaceous gland into a microcomedone and the hierarchy of factors involved in this process are reviewed. The key strategic target in acne care appears to be the naïve pilosebaceous follicle that is not involved yet in the acne cycle. The prevention of the comedone switch implies that the key switching factors are adequately controlled in the long term. © 2015 The Author(s) Published by S. Karger AG, Basel. Source


Kaufmann S.H.,Max Planck Institute for Infection Biology | Hussey G.,University of Cape Town | Lambert P.-H.,University Hospitals Geneva Medical Center
The Lancet | Year: 2010

New vaccines are urgently needed if we want to reach the goal of substantially reducing the incidence of tuberculosis by 2050. Despite a steady increase in funding over the past decade, there is still a striking financial shortfall for vaccine research and development for tuberculosis. Yet, around ten vaccine candidates have left the laboratory stage and entered clinical trials. These vaccines are either aimed at replacing the present vaccine, BCG, or at enhancing immunity induced by BCG. However, these pre-exposure candidates are designed for prevention of disease and will therefore neither eradicate the pathogen, nor prevent stable infection. Long-term vaccination strategies need to target these more ambitious goals. Even though vaccine development will have a price, the return of investment will greatly exceed original costs. © 2010 Elsevier Ltd. All rights reserved. Source

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