Functional Expression of the Extracellular Calcium Sensing Receptor (CaSR) in Equine Umbilical Cord Matrix Size-Sieved Stem Cells

The present study investigates the effects of high external calcium concentration ([Ca(2+)](o)) and the calcimimetic NPS R-467, a known calcium-sensing receptor (CaSR) agonist, on growth/proliferation of two equine size-sieved umbilical cord matrix mesenchymal stem cell (eUCM-MSC) lines. The involvement of CaSR on observed cell response was analyzed at both the mRNA and protein level.A large (>8 µm in diameter) and a small (<8 µm) cell line were cultured in medium containing: 1) low [Ca(2+)](o) (0.37 mM); 2) high [Ca(2+)](o) (2.87 mM); 3) NPS R-467 (3 µM) in presence of high [Ca(2+)](o) and 4) the CaSR antagonist NPS 2390 (10 µM for 30 min.) followed by incubation in presence of NPS R-467 in medium with high [Ca(2+)](o). Growth/proliferation rates were compared between groups. In large cells, the addition of NPS R-467 significantly increased cell growth whereas increasing [Ca(2+)](o) was not effective in this cell line. In small cells, both higher [Ca(2+)](o) and NPS R-467 increased cell growth. In both cell lines, preincubation with the CaSR antagonist NPS 2390 significantly inhibited the agonistic effect of NPS R-467. In both cell lines, increased [Ca(2+)](o) and/or NPS R-467 reduced doubling time values.Treatment with NPS R-467 down-regulated CaSR mRNA expression in both cell lines. In large cells, NPS R-467 reduced CaSR labeling in the cytosol and increased it at cortical level.In conclusion, calcium and the calcimimetic NPS R-467 reduce CaSR mRNA expression and stimulate cell growth/proliferation in eUCM-MSC. Their use as components of media for eUCM-MSC culture could be beneficial to obtain enough cells for down-stream purposes

Precision charge control for isolated free-falling test masses: LISA pathfinder results

The LISA Pathfinder charge management device was responsible for neutralizing the cosmic-ray-induced electric charge that inevitably accumulated on the free-falling test masses at the heart of the experiment. We present measurements made on ground and in flight that quantify the performance of this contactless discharge system which was based on photoemission under UV illumination. In addition, a two-part simulation is described that was developed alongside the hardware. Modeling of the absorbed UV light within the Pathfinder sensor was carried out with the Geant4 software toolkit and a separate Matlab charge transfer model calculated the net photocurrent between the test masses and surrounding housing in the presence of AC and DC electric fields. We confront the results of these models with observations and draw conclusions for the design of discharge systems for future experiments like LISA that will also employ free-falling test masses

Phénomènes biologiques résultant de la suppression du contact occlusal Intérêt thérapeutique

Dans le cadre du processus combiné de l'égression et de la migration physiologique des dents, l'homéostasie de l'os alvéolaire est assurée par l'activité des enveloppes cellulaires bordantes, à savoir les enveloppes périostée, desmodontale et endostée. La suppression du contact occlusal entraîne une hypofonction occlusale et un phénomène d'égression passive, ce qui se traduit par une balance osseuse temporairement négative au niveau de l'endoste et du périoste, et une balance temporairement positive au niveau du desmodonte. Les tissus gingivaux accompagnent la dent au cours du mouvement d'égression. L'hypofonction occlusale entraîne cependant une augmentation de l'accumulation de la plaque bactérienne, facteur étiologique majeur des parodontopathies. L'intérêt thérapeutique du mouvement d'égression est discuté en tenant compte de ces données physiologiques et des facteurs anatomiques

Stimulation of cell proliferation by calcium and a calcimimetic compound

Some mesenchymal cells respond to stimulation by specific cations with increased cell proliferation. In the present study we have investigated whether the parathyroid/kidney/brain calcium-sensing receptor (PCaR) can mediate such mitogenic responses. We have expressed the recombinant rat PCaR in CCL39 hamster fibroblasts, which do not express a detectable endogenous cation sensor. The transfected cells responded to increased extracellular calcium concentrations ([Ca2+](e)) with strong inositol phosphate (IP) formation, which was insensitive to pertussis toxin treatment of cells. We could not detect negative coupling of the receptor to adenylyl cyclase. The calcimimetic NPS R-568 left-shifted the concentration-response curve for [Ca2+](e)-induced IP formation and increased the maximal response. In [H-3]thymidine incorporation experiments, increasing [Ca2+](e) from 1 to 4 mM was found to stimulate DNA synthesis weakly, but significantly. A strong potentiation of this response was observed in the presence of NPS R-568. [Ca2+](e) and NPS R-568 also synergized to increase cell numbers in cultures maintained in defined medium. In contrast to our expectations, no significant stimulation of IP formation or cell proliferation could be observed after stimulation of cells with the reported PCaR agonist gadolinium (Gd3+) or with aluminum (Al3+), which stimulates osteoblast proliferation. Gd3+ actually inhibited IP formation stimulated by increased [Ca2+](e) as well as by thrombin and AlF4-, indicating toxicity. However, submaximal receptor stimulation by Gd3+ was evident when intracellular calcium transients were measured in fluo-3-loaded cells. Our data show that PCaR can stimulate cell proliferation when expressed in an appropriate cellular context. However, it is unlikely that PCaR mediates the strong mitogenic effects elicited by the cations Gd3+ and Al3+ observed in osteoblasts

Critical Analysis of ISRU Plants Integration in Complex Architectures for Planetary Human Colonies Development

A sustainable expansion of human presence in space should be based on the development of self-sustaining outposts and permanent bases, and therefore on the capability of producing part, or possibly the entire amount, of necessary resources in situ. Most useful resources can be extracted from local materials (e.g. from the lunar regolith or the martian atmosphere), by means of dedicated In-Situ Resources Utilization (ISRU) plants which must be included within the overall surface architecture. These plants might require different mobile elements (e.g. miners and haulers) to extract and transport raw materials from the excavation site to the plant, to transport by-products to secondary plants or to containment facilities, and, possibly, to transport the produced resources to storage facilities. EVA activities might be required for servicing and maintenance activities or, in case of man-tended plants, to manage and control the ISRU process phases. Thus, the integration of an ISRU plant into a manned base involves several surface elements together with the planning, scheduling and management of activities and operations. This paper presents an analysis of the requirements, constraints, and risks which characterize and drive that integration and describes the synergies and the interfaces which must be considered in developing the build-up and maintenance process of manned surface architectures including ISRU systems. A trade off analysis between completely autonomous plants and man-tended ones is proposed, including safety and reliability considerations. The critical analysis here presented is supported by parametrical models of ISRU production requirements and performances to support a manned base, exploiting a library of dynamic models of ISRU plants, Environmental Control and Life Support Systems (ECLSSs) and power provision systems developed at Politecnico di Milano - DIA

Painful peripheral neuropathies : an overview of their pathophysiology and newer approaches to treatment

Peripheral neuropathies are extremely heterogeneous nosological entities. One of the most common symptoms is pain, the underlying mechanisms of which are numerous and complex. Inflammation, reparative processes, and anatomical and gene expression alterations lead to chronic pain, the persistence of which is sustained by peripheral and central sensitisation mechanisms. Treatment of peripheral neuropathies is targeted to its symptomatic and aetiological features. For pain relief, several types of drugs may be used, notably antidepressants (e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, and both serotonin and noradrenaline [norepinephrine] reuptake inhibitors), antiepileptic drugs (e.g. carbamazepine, phenytoin, lamotrigine, valproic acid, gabapentin, topiramate and pregabalin), NSAIDs and opioid analgesics. Aetiological therapy is aimed at modifying the pathophysiological mechanisms underlying the neuropathy, some of which are common in different neuropathic conditions. Certain drugs are known to exert more than one action on different pathophysiological mechanisms. This is the case with acetyl-L-carnitine (ALC), which can be considered both a symptomatic therapy that can be used in any kind of painful neuropathy, and an aetiological therapy, at least in diabetic neuropathy and neuropathies induced by nucleoside reverse transcriptase inhibitors and cancer chemotherapeutic agents. ALC acts via several mechanisms, inducing regeneration of injured nerve fibres, reducing oxidative stress, supporting DNA synthesis in mitochondria, and enhancing nerve growth factor concentrations in neurons