The G Protein regulators EGL-10 and EAT-16, the Giα GOA-1 and the Gqα EGL-30 modulate the response of the C. elegans ASH polymodal nociceptive sensory neurons to repellents

<p>Abstract</p> <p>Background</p> <p>Polymodal, nociceptive sensory neurons are key cellular elements of the way animals sense aversive and painful stimuli. In <it>Caenorhabditis elegans</it>, the polymodal nociceptive ASH sensory neurons detect aversive stimuli and release glutamate to generate avoidance responses. They are thus useful models for the nociceptive neurons of mammals. While several molecules affecting signal generation and transduction in ASH have been identified, less is known about transmission of the signal from ASH to downstream neurons and about the molecules involved in its modulation.</p> <p>Results</p> <p>We discovered that the regulator of G protein signalling (RGS) protein, EGL-10, is required for appropriate avoidance responses to noxious stimuli sensed by ASH. As it does for other behaviours in which it is also involved, <it>egl-10 </it>interacts genetically with the G_o/iα protein GOA-1, the G_qα protein EGL-30 and the RGS EAT-16. Genetic, behavioural and Ca²⁺imaging analyses of ASH neurons in live animals demonstrate that, within ASH, EGL-10 and GOA-1 act downstream of stimulus-evoked signal transduction and of the main transduction channel OSM-9. EGL-30 instead appears to act upstream by regulating Ca²⁺transients in response to aversive stimuli. Analysis of the delay in the avoidance response, of the frequency of spontaneous inversions and of the genetic interaction with the diacylglycerol kinase gene, <it>dgk-1</it>, indicate that EGL-10 and GOA-1 do not affect signal transduction and neuronal depolarization in response to aversive stimuli but act in ASH to modulate downstream transmission of the signal.</p> <p>Conclusions</p> <p>The ASH polymodal nociceptive sensory neurons can be modulated not only in their capacity to detect stimuli but also in the efficiency with which they respond to them. The Gα and RGS molecules studied in this work are conserved in evolution and, for each of them, mammalian orthologs can be identified. The discovery of their role in the modulation of signal transduction and signal transmission of nociceptors may help us to understand how pain is generated and how its control can go astray (such as chronic pain) and may suggest new pain control therapies.</p

Remote monitoring of the Comba Citrin landslide using discontinuous GBInSAR campaigns

This paper describes the use of the discontinuous Ground-Based Interferometric Synthetic Aperture Radar technique (GBInSAR) to monitor the displacement of the Comba Citrin landslide in the North Western Italian Alps. Two GBInSAR surveys were carried out respectively during the summer and the fall of 2015 separated by a temporal baseline of 63 days. For each GBInSAR survey, which lasted respectively 166.2 h (6 dd, 22 h, 12′) and 238.3 h (9 dd, 22 h, 18′), two sets of 139 and 275 SAR images were acquired. After the selection of a specific stack of Persistent Scatterers, the SAR images of each survey were analyzed separately and in combination with the images of the other survey to detect the possible displacements occurred both in every single survey as well as in the elapsed time between the two different campaigns. The displacement maps showed that two different sectors of the monitored slope were affected by millimetres to centimetres movements during the monitoring period. The results obtained for the Comba Citrin landslide show that the discontinuous GBInSAR can be reliably adopted to monitor the displacement of landslides moving at an average rate of few centimetres per year

Migration and Development. Some Reflections on Current Legal Issues

The issue of the link between migration and development is increasingly relevant in the global political agenda. However, the scientific discussion concerning the increased migratory flows seems to be more focused on the questions regarding admission and / or rejection of migrants on the territory of receiving countries than on the general topic of the contribution of migrants to the financial, social and cultural development of societies (of origin, transit, or destination). The volume aims at offering food for thought for the analysis of the changes occurring in modern societies, that are asked to answer thoroughly to economic and forced migration. The goal of the volume is to open discussion among experts, scholars and policy-makers, on the problematic questions, outcomes, implications and achievements on migration and development

Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation

Human liver stem cells (HLSCs) are a mesenchymal stromal cell-like population resident in the adult liver. Preclinical studies indicate that HLSCs could be a good candidate for cell therapy. The aim of the present study was to evaluate the immunogenicity and the immunomodulatory properties of HLSCs on T-lymphocytes, natural killer cells (NKs), and dendritic cells (DCs) in allogeneic experimental settings. We found that HLSCs inhibited T-cell proliferation by a mechanism independent of cell contact and dependent on the release of prostaglandin E2 (PGE2) and on indoleamine 2,3-dioxygenase activity. When compared with mesenchymal stromal cells (MSCs), HLSCs were more efficient in inhibiting T-cell proliferation. At variance with MSCs, HLSCs did not elicit NK degranulation. Moreover, HLSCs inhibited NK degranulation against K562, a NK-sensitive target, by a mechanism dependent on HLA-G release. When tested on DC generation from monocytes, HLSCs were found to impair DC differentiation and DCs ability to induce T-cell proliferation through PGE2. This study shows that HLSCs have immunomodulatory properties similar to MSCs, but, at variance with MSCs, they do not elicit a NK response