The ISARM/South Eastern Europe (SEE) Programme: Sharing Data and Information

ABSTRACT Approximately 90% of the territory in South Eastern European (SEE) countries lies within shared water basins and therefore the effective management of transboundary waters is of particular importance for the region. Transboundary aquifer resources are also vital sources of freshwater. 65 Transboundary Aquifers (TA) were identified in the region in an inventory developed in 2007 by the UNESCO Chair and International Network of Water/Environment Centres for the Balkans (www.inweb.gr) at the Aristotle University of Thessaloniki, in cooperation with UNESCO/IHP, as part of the UNESCO/ISARM worldwide initiative. TA in SEE, and especially those which are karstic, are highly vulnerable to pollution from different pressure factors (agriculture, industry, mining, sewage/waste disposal and tourism). In this paper, the WEB-based metadata inventory on transboundary aquifers in SEE (the Balkans) is described. This inventory is the first step towards implementing the UNESCO/ISARM (Internationally Shared Aquifer Resources Management) programme in the region. This programme uses a multidisciplinary methodological approach and is based on an effective cooperation mechanism between countries in order to reduce groundwater and ecosystem vulnerabilities and contribute to sustainable management of transboundary groundwater resources in the SEE region. Together with the Global Environmental Facility (GEF) and other partners the cooperative project DiKTAS (Dinaric Karst Transboundary Aquifer System) was formulated specifically for the Dinaric region. The project preparation phase was completed in December 2009, and the FSP (Full Size Project) is expected to effectively start in 2010

Phosphate Homeostasis, Inflammation and the Regulation of FGF-23

Fibroblast growth factor 23 (FGF23) is released primarily from osteoblasts/osteocytes in bone. In cooperation with the transmembrane protein Klotho, FGF23 is a powerful inhibitor of 1α 25OH Vitamin D Hydroxylase (Cyp27b1) and thus of the formation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). As 1,25(OH)2D3 up-regulates intestinal calcium and phosphate absorption, the downregulation of 1,25(OH)2D3 synthesis counteracts phosphate excess and tissue calcification. FGF23 also directly inhibits renal phosphate reabsorption. Other actions of FGF23 include triggering of cardiac hypertrophy. FGF23 formation and/or release are stimulated by 1,25(OH)2D3, phosphate excess, Ca2+, PTH, leptin, catecholamines, mineralocorticoids, volume depletion, lithium, high fat diet, iron deficiency, TNFα and TGFß2. The stimulating effect of 1,25(OH)2D3 on FGF23 expression is dependent on RAC1/PAK1 induced actin-polymerisation. Intracellular signaling involved in the stimulation of FGF23 release also includes increases in the cytosolic Ca2+ concentration ([Ca2+]i) following intracellular Ca2+ release and store-operated Ca2+ entry (SOCE). SOCE is accomplished by the Ca2+ release-activated calcium channel protein 1 (Orai1) and its stimulator stromal interaction molecule 1 (STIM1). Expression of Orai1, SOCE and FGF23-formation are up-regulated by the proinflammatory transcription factor NFκB. The present brief review describes the cellular mechanisms involved in FGF23 regulation and its sensitivity to both phosphate metabolism and inflammation. The case is made that up-regulation of FGF23 by inflammatory mediators and signaling may amplify inflammation by inhibiting formation of the anti-inflammatory 1,25(OH)2D3

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy