nucleotidases as swimming proceeds raises the concentration of extracellular adenosine, which opposes ATP to reduce network excitability and terminate swimming. This entails the activation of A1 receptors and a reduction in voltage-gated Ca2+ currents without a change in the strength of synaptic transmission. By contrast, in murine spinal locomotor networks, ATP does not appear to act as a neuromodulator, whereas activation of A1 receptors depresses synaptic transmission by PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19755563 presynaptic inhibition of neurotransmitter release and hyperpolarises the resting membrane potential of ventral horn interneurons. Since ATP is consumed by neurons during activity, raising cytoplasmic adenosine levels, an efficient coupling mechanism would entail direct release of adenosine via neuronal equilibrative nucleoside transporters, with autocrine inhibition of Halofuginone manufacturer activity via A1 receptors. This mechanism does not appear to operate in mouse spinal motor networks or other systems in which the source of adenosine is ATP released into the extracellular space 13 / 17 Modulation of Spinal Motor Networks by Glia from either neurons or glia. Whether adenosine production is direct or indirect, the functional consequences of the negative feedback it provides may include the stabilisation of network activity and the prevention of excitotoxicity and metabolic exhaustion. Despite considerable evidence from in vitro brain preparations that glia sense activity in neighbouring neurons and, in turn, modulate that activity in a Ca2+-dependent manner, there is a paucity PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19755095 of evidence that gliotransmission is important for the operation of brain networks and the behaviours they direct. Rhythmically active CPGs in the brainstem and spinal cord provide a tractable model for studying the contribution of gliotransmission to network output and thus behaviour. In brainstem preparations it has been shown that glia mediate purinergic modulation of rhythmically active inspiratory networks, most likely owing to the Ca2+dependent release of glutamate, and that acidification of the extracellular medium triggers the release of ATP from glia in a Ca2+-dependent manner to stimulate activity in the phrenic nerve. It has also recently been demonstrated that glia release the Ca2+-binding protein 
S100 in a Ca2+-dependent manner to confer rhythmic bursting properties on associated neurons in the brainstem circuity for mastication. In the present study we provide evidence that activity-dependent release of ATP-adenosine from glia in the mammalian spinal cord provides negative feedback onto the circuitry that controls locomotion. This feedback may stabilise activity, delay metabolic rundown and/or have a neuroprotective role. Our findings inform understanding of the regulation of locomotor networks and provide an insight into the role of glia in shaping activity at the network level. ~~ ~~ Gastric carcinoma is the third most common cancer worldwide and is the most frequent cancer diagnosed in East Asian countries. Despite recent progress in earlier diagnosis and improved therapeutic regimens, many patients still eventually develop advanced disease and have poor clinical outcomes. The median overall survival is 810 months and 5-year survival is less than 7% for metastatic GC. With regard to standard chemotherapy, limited efficacy has spurred research into targeted therapies designed to block signaling via molecular pathways known to be important for gastric tumorigenesis. To date, two monoclonal antibodi
