Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery

The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3′-5′ exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites

Estimation of the Effective Permeability of Heterogeneous Porous Media by Using Percolation Concepts

In this paper we present new methods to estimate the effective permeability (k_eff) of heterogeneous porous media with a wide distribution of permeabilities and various underlying structures, using percolation concepts. We first set a threshold permeability (k_th) on the permeability density function (pdf) and use standard algorithms from percolation theory to check whether the high permeable grid blocks (i.e. those with permeability higher than k_th) with occupied fraction of “p” first forms a cluster connecting two opposite sides of the system in the direction of the flow (high permeability flow pathway). Then we estimate the effective permeability of the heterogeneous porous media in different ways: a power law (k_eff=k_th p^m), a weighted power average (k_eff=[p.k_th^m+(1-p).k_g^m ]^(1/m) with k_g the geometric average of the permeability distribution) and a characteristic shape factor multiplied by the permeability threshold value. We found that the characteristic parameters (i.e. the exponent “m”) can be inferred either from the statistics and properties of percolation sub-networks at the threshold point (i.e. high and low permeable regions corresponding to those permeabilities above and below the threshold permeability value) or by comparing the system properties with an uncorrelated random field having the same permeability distribution. These physically based approaches do not need fitting to the experimental data of effective permeability measurements to estimate the model parameter (i.e. exponent m) as is usually necessary in empirical methods. We examine the order of accuracy of these methods on different layers of 10th SPE model and found very good estimates as compared to the values determined from the commercial flow simulators

Millimetron - a large Russian-European submillimeter space observatory

Millimetron is a Russian-led 12 m diameter submillimeter and far-infrared space observatory which is included in the Space Plan of the Russian Federation for launch around 2017. With its large collecting area and state-of-the-art receivers, it will enable unique science and allow at least one order of magnitude improvement with respect to the Herschel Space Observatory. Millimetron will be operated in two basic observing modes: as a single-dish observatory, and as an element of a ground-space very long baseline interferometry (VLBI) system. As single-dish, angular resolutions on the order of 3 to 12 arc sec will be achieved and spectral resolutions of up to a million employing heterodyne techniques. As VLBI antenna, the chosen elliptical orbit will provide extremely large VLBI baselines (beyond 300,000 km) resulting in micro-arc second angular resolution