New 1-aryl-3-substituted propanol derivatives as antimalarial agents

This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 μM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria

Critical Dynamics in Genetic Regulatory Networks: Examples from Four Kingdoms

The coordinated expression of the different genes in an organism is essential to sustain functionality under the random external perturbations to which the organism might be subjected. To cope with such external variability, the global dynamics of the genetic network must possess two central properties. (a) It must be robust enough as to guarantee stability under a broad range of external conditions, and (b) it must be flexible enough to recognize and integrate specific external signals that may help the organism to change and adapt to different environments. This compromise between robustness and adaptability has been observed in dynamical systems operating at the brink of a phase transition between order and chaos. Such systems are termed critical. Thus, criticality, a precise, measurable, and well characterized property of dynamical systems, makes it possible for robustness and adaptability to coexist in living organisms. In this work we investigate the dynamical properties of the gene transcription networks reported for S. cerevisiae, E. coli, and B. subtilis, as well as the network of segment polarity genes of D. melanogaster, and the network of flower development of A. thaliana. We use hundreds of microarray experiments to infer the nature of the regulatory interactions among genes, and implement these data into the Boolean models of the genetic networks. Our results show that, to the best of the current experimental data available, the five networks under study indeed operate close to criticality. The generality of this result suggests that criticality at the genetic level might constitute a fundamental evolutionary mechanism that generates the great diversity of dynamically robust living forms that we observe around us

Forest Biomass Density across Large Climate Gradients in Northern South America is related to Water Availability but not with Temperature

Understanding and predicting the likely response of ecosystems to climate change are crucial challenges for ecology and for conservation biology. Nowhere is this challenge greater than in the tropics as these forests store more than half the total atmospheric carbon stock in their biomass. Biomass is determined by the balance between biomass inputs (i.e., growth) and outputs (mortality). We can expect therefore that conditions that favor high growth rates, such as abundant water supply, warmth, and nutrient-rich soils will tend to correlate with high biomass stocks. Our main objective is to describe the patterns of above ground biomass (AGB) stocks across major tropical forests across climatic gradients in Northwestern South America. We gathered data from 200 plots across the region, at elevations ranging between 0 to 3400 m. We estimated AGB based on allometric equations and values for stem density, basal area, and wood density weighted by basal area at the plot-level. We used two groups of climatic variables, namely mean annual temperature and actual evapotranspiration as surrogates of environmental energy, and annual precipitation, precipitation seasonality, and water availability as surrogates of water availability. We found that AGB is more closely related to water availability variables than to energy variables. In northwest South America, water availability influences carbon stocks principally by determining stand structure, i.e. basal area. When water deficits increase in tropical forests we can expect negative impact on biomass and hence carbon storage

Model-based geostatistical mapping of the prevalence of onchocerca volvulus in West Africa.

Background: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings: Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance: This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Amazon tree dominance across forest strata

The forests of Amazonia are among the most biodiverse plant communities on Earth. Given the immediate threats posed by climate and land-use change, an improved understanding of how this extraordinary biodiversity is spatially organized is urgently required to develop effective conservation strategies. Most Amazonian tree species are extremely rare but a few are common across the region. Indeed, just 227 ‘hyperdominant’ species account for >50% of all individuals >10 cm diameter at 1.3 m in height. Yet, the degree to which the phenomenon of hyperdominance is sensitive to tree size, the extent to which the composition of dominant species changes with size class and how evolutionary history constrains tree hyperdominance, all remain unknown. Here, we use a large floristic dataset to show that, while hyperdominance is a universal phenomenon across forest strata, different species dominate the forest understory, midstory and canopy. We further find that, although species belonging to a range of phylogenetically dispersed lineages have become hyperdominant in small size classes, hyperdominants in large size classes are restricted to a few lineages. Our results demonstrate that it is essential to consider all forest strata to understand regional patterns of dominance and composition in Amazonia. More generally, through the lens of 654 hyperdominant species, we outline a tractable pathway for understanding the functioning of half of Amazonian forests across vertical strata and geographical locations

Femtosecond filamentation in sapphire with diffractive lenses

In this paper, we demonstrate novel properties in the phenomenology of supercontinuum generation in sapphire with diffractive lenses and provide a complete spatial, spectral, and temporal characterization of the so-generated pulses. Filament formation inside the sample is analyzed and related to the measured spectra, finding that clipping of the filament results in blueshifted spectra. For comparison, filament formation with refractive lenses is also examined, and the roles of diffraction and extension of the focusing region are inspected. The tunability achieved in the anti-Stokes side of the spectrum is also extended to the ultraviolet by frequency mixing with infrared femtosecond pulses