Synchronous fire activity in the tropical high Andes: an indication of regional climate forcing

Global climate models suggest enhanced warming of the tropical mid and upper troposphere, with larger temperature rise rates at higher elevations. Changes in fire activity are amongst the most significant ecological consequences of rising temperatures and changing hydrological properties in mountainous ecosystems, and there is a global evidence of increased fire activity with elevation. Whilst fire research has become popular in the tropical lowlands, much less is known of the tropical high Andean region (>2000masl, from Colombia to Bolivia). This study examines fire trends in the high Andes for three ecosystems, the Puna, the Paramo and the Yungas, for the period 1982–2006. We pose three questions: (i) is there an increased fire response with elevation? (ii) does the El Niño- Southern Oscillation control fire activity in this region? (iii) are the observed fire trends human driven (e.g., human practices and their effects on fuel build-up) or climate driven? We did not find evidence of increased fire activity with elevation but, instead, a quasicyclic and synchronous fire response in Ecuador, Peru and Bolivia, suggesting the influence of high-frequency climate forcing on fire responses on a subcontinental scale, in the high Andes. ENSO variability did not show a significant relation to fire activity for these three countries, partly because ENSO variability did not significantly relate to precipitation extremes, although it strongly did to temperature extremes. Whilst ENSO did not individually lead the observed regional fire trends, our results suggest a climate influence on fire activity, mainly through a sawtooth pattern of precipitation (increased rainfall before fire-peak seasons (t-1) followed by drought spells and unusual low temperatures (t0), which is particularly common where fire is carried by low fuel loads (e.g., grasslands and fine fuel). This climatic sawtooth appeared as the main driver of fire trends, above local human influences and fuel build-up cyclicity

Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3

Both cholinesterases (AChE and BChE) and kinases, such as GSK-3\u3b1/\u3b2, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3\u3b1/\u3b2 (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3\u3b1/\u3b2. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp