Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.

Light chain-associated amyloidosis is a fatal disease characterized by the aggregation and pathologic deposition of monoclonal light chain-related fragments as amyloid fibrils in organs or tissues throughout the body. Notably, it has been observed that proteins encoded by the lambda variable light chain (V(L)) gene segment 6a are invariably associated with amyloid deposition; however, the contribution of the gene to this phenomenon has not been established. In this regard, we have determined the thermodynamic stability and kinetics of in vitro fibrillogenesis of a recombinant (r) V(L) protein, designated 6aJL2, which contains the predicted sequences encoded by the 6a and JL2 germline genes. Additionally, we studied a 6a mutant (6aJL2-Arg25Gly), that is present in approximately 25% of all amyloid-associated lambda6 light chains. Remarkably, the wild-type 6aJL2 protein was more stable than were all known amyloidogenic kappa and lambda light chains for which stability parameters are available; more importantly, it was even more so (and less fibrillogenic) than the only clinically proven nonamyloidogenic lambda6 protein, Jto. Conversely, the mutated 6aJL2-R25G molecule was considerably less stable and more fibrillogenic than was the native 6aJL2. Our data indicate that the propensity of lambda6 light chains to form amyloid can not be attributed to thermodynamic instability of the germline-encoded Vlambda6 domain, but rather, is dependent on sequence alterations that render such proteins amyloidogenic.

PM, PM, precursor gas, and upper-air meteorological measurements were taken in Mexico City, Mexico, from February 23 to March 22, 1997, to understand concentrations and chemical compositions of the city's particulate matter (PM). Average 24-hr PM concentrations over the period of study at the core sites in the city were 75 H g/m. The 24-hr standard of 150 μ g/m was exceeded for seven samples taken during the study period; the maximum 24-hr concentration measured was 542 μ g/m. Nearly half of the PM was composed of fugitive dust from roadways, construction, and bare land. About 50% of the PM consisted of PM, with higher percentages during the morning hours. Organic and black carbon constituted up to half of the PM. PM concentrations were highest during the early morning and after sunset, when the mixed layers were shallow. Meteorological measurements taken during the field campaign show that on most days air was transported out of the Mexico City basin during the afternoon with little day-to-day carryover.

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Twenty-five MiniVol samplers were operated throughout the Mexico City metropolitan region from February 22 through March 22, 1997, to evaluate the variability of PM 10 concentrations and composition. The highest PM 10 concentrations were found in neighborhoods with unpaved or dirty roads, and elements related to crustal material were the main cause of differences from nearby (<200 m) monitors that were not adjacent to the roadbed. SO 4 2-concentrations were homogeneous across the city. SO 4 2-measured at the city boundaries was about two-thirds of the concentrations measured within the urbanized area, indicating that most SO 4 2-is of regional origin. Elemental carbon (EC) and organic carbon (OC) concentrations were highly variable, with higher concentrations in areas that had high diesel traffic and older vehicles. Spatial correlations among PM 10 concentrations were high, even though absolute concentrations were variable, indicating a common effect of meteorology on the concentration or dispersion of local emissions.