Systemic dysregulation of CEACAM1 in melanoma patients

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(?) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.     

Trade-offs in plankton species richness arising from drought: insights from long-term data of a National Park wetland (central Spain)

Wetlands are considered vulnerable ecosystems of both high species richness and socio-economic value. In semi-arid regions, these ecosystems often experience long drought periods that are usually aggravated by local water overexploitation. Drought leads to: (i) reduced flooding area, (ii) isolation of water bodies, (iii) increased areas of dry sediments and shoreline length, and (iv) increased ionic concentration. These processes affect aquatic populations in a species-specific way and can have antagonistic effects on taxon richness. Here, we highlight long-term (1997–2008) trade-off effects on plankton species richness linked to drought in a semi-arid wetland (Las Tablas de Daimiel National Park, central Spain). Annual average phytoplankton species richness increased from wet- (1997–1998) to dry years (2001–2002) and taxon richness diminished again when drought was more severe (2007–2008). Zooplankton changes were more complex depending on taxonomic groups and the body size of the organisms, total species loss being related to hydrological conditions. Half of the algal species recorded in 2007–2008 and one-tenth of total zooplankton taxa were new comers in the wetland, because salinization, eutrophication and submerged macrophytes occurring in different sites enhanced species turnover and mitigated homogenization of beta diversity. Maintenance of one water body with a constant water level and macrophytes was the key to preventing the collapse of plankton richness. Our study has demonstrated that plankton can be very useful for tracking environmental changes of wetlands, thus giving the environmental manager another tool to enhance the conservation of wetlands and their biota.     

Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis

MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds.     

Housing arrangement and location determine the likelihood of housing loss due to wildfire

Surging wildfires across the globe are contributing to escalating residential losses and have major social, economic, and ecological consequences. The highest losses in the U.S. occur in southern California, where nearly 1000 homes per year have been destroyed by wildfires since 2000. Wildfire risk reduction efforts focus primarily on fuel reduction and, to a lesser degree, on house characteristics and homeowner responsibility. However, the extent to which land use planning could alleviate wildfire risk has been largely missing from the debate despite large numbers of homes being placed in the most hazardous parts of the landscape. Our goal was to examine how housing location and arrangement affects the likelihood that a home will be lost when a wildfire occurs. We developed an extensive geographic dataset of structure locations, including more than 5500 structures that were destroyed or damaged by wildfire since 2001, and identified the main contributors to property loss in two extensive, fire-prone regions in southern California. The arrangement and location of structures strongly affected their susceptibility to wildfire, with property loss most likely at low to intermediate structure densities and in areas with a history of frequent fire. Rates of structure loss were higher when structures were surrounded by wildland vegetation, but were generally higher in herbaceous fuel types than in higher fuel-volume woody types. Empirically based maps developed using housing pattern and location performed better in distinguishing hazardous from non-hazardous areas than maps based on fuel distribution. The strong importance of housing arrangement and location indicate that land use planning may be a critical tool for reducing fire risk, but it will require reliable delineations of the most hazardous locations.     

Evaluation of deep eutectic solvents as new media for Candida antarctica B lipase catalyzed reactions

This study aimed at analyzing the advantages and limitations of several deep eutectic solvents (DESs) as ‘green solvents’ for biotransformation using immobilized Candida antarctica lipase B as catalyst. The transesterification of vinyl laurate was chosen as model reaction and the influence of substrate polarity was assessed using alcohols of various chain lengths. Results showed that grinding of immobilized lipase was essential parameters for good lipase activity. Moreover, in our model reaction some hydrogen-bond donor component from the DES can compete with the alcoholysis reaction. Indeed, side reactions were observed with DES based on dicarboxylic acid or ethylene glycol, leading to some limitations of their use. However, the results showed that other DESs such as choline chloride:urea and choline chloride:glycerol could exhibit high activity and selectivity making them promising solvents for lipase-catalyzed reactions. Finally, the best DES's specific activity – and stability up to five days incubation time – were analyzed and compared with conventional organic solvents. Experiments revealed that iCALB is less influenced by the chain length of alcohol in DES than organic solvents and it is preserves its activity with minimally destructive to protein structure.     

Functional anatomy of the female reproductive systems of two spider crabs (Decapoda,Majoidea)

To better understand the mating systems of majoid crabs, we studied the functional anatomy of the female reproductive systems of the spider crabs Leurocyclus tuberculosus and Libinia spinosa, comparing them with those of other Majoidea. Adult females were measured and dissected, and their reproductive systems described macroscopically and histologically. In females of both species, the seminal receptacles are paired globular structures of ecto‐mesodermal origin. The mesoderm‐derived region is lined by a stratified epithelium. The anchoring, proliferative, and secretory strata are clearly recognizable . The ectoderm‐derived region is lined by a simple cylindrical epithelium underlying a cuticle that increases in thickness toward the vagina. The transition between the ectoderm and mesoderm‐derived regions is abrupt, with differences between the studied species: Li. spinosa has a “velum,” whereas Le. tuberculosus presents prominent “folds.” In both species, the position in which the oviduct is connected to the seminal receptacles is intermediate between the dorsal and ventral types previously described in other eubrachyurans. The seminal receptacles of the studied species show four different conditions, which can be distinguished macroscopically based on their shape and amount of sperm stored. We compare our data with those from other Majoidea in an attempt to determine whether the morphology of the seminal receptacles is related to different mating strategies or behaviors.