Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Orientational Defects in Ice Ih: An Interpretation of Electrical Conductivity Measurements

We present a first-principles study of the structure and energetics of Bjerrum defects in ice Ih and compare the results to experimental electrical conductivity data. While the DFT result for the activation energy is in good agreement with experiment, we find that its two components have quite different values. Aside from providing new insight into the fundamental parameters of the microscopic electrical theory of ice, our results suggest the activity of traps in doped ice in the temperature regime typically assumed to be controlled by the free migration of L defects.Comment: 4 pages, 4 Figures, 1 Tabl

Comparing league formats with respect to match importance in Belgian football

Recently, most clubs in the highest Belgian football division have become convinced that the format of their league should be changed. Moreover, the TV station that broadcasts the league is pleading for a more attractive competition. However, the clubs have not been able to agree on a new league format, mainly because they have conflicting interests. In this paper, we compare the current league format, and three other formats that have been considered by the Royal Belgian Football Association. We simulate the course of each of these league formats, based on historical match results. We assume that the attractiveness of a format is determined by the importance of its games; our importance measure for a game is based on the number of teams for which this game can be decisive to reach a given goal. Furthermore, we provide an overview of how each league format aligns with the expectations and interests of each type of club

Толерантный подход к теме греко-турецких взаимоотношений в новейшей греческой прозе

Целью данной статьи стало рассмотрение нового видения дихотомии «грек-турок» в романах греческих писателей второй половины ХХ века

Speeds and arrival times of solar transients approximated by self-similar expanding circular fronts

The NASA STEREO mission opened up the possibility to forecast the arrival times, speeds and directions of solar transients from outside the Sun-Earth line. In particular, we are interested in predicting potentially geo-effective Interplanetary Coronal Mass Ejections (ICMEs) from observations of density structures at large observation angles from the Sun (with the STEREO Heliospheric Imager instrument). We contribute to this endeavor by deriving analytical formulas concerning a geometric correction for the ICME speed and arrival time for the technique introduced by Davies et al. (2012, ApJ, in press) called Self-Similar Expansion Fitting (SSEF). This model assumes that a circle propagates outward, along a plane specified by a position angle (e.g. the ecliptic), with constant angular half width (lambda). This is an extension to earlier, more simple models: Fixed-Phi-Fitting (lambda = 0 degree) and Harmonic Mean Fitting (lambda = 90 degree). This approach has the advantage that it is possible to assess clearly, in contrast to previous models, if a particular location in the heliosphere, such as a planet or spacecraft, might be expected to be hit by the ICME front. Our correction formulas are especially significant for glancing hits, where small differences in the direction greatly influence the expected speeds (up to 100-200 km/s) and arrival times (up to two days later than the apex). For very wide ICMEs (2 lambda > 120 degree), the geometric correction becomes very similar to the one derived by M\"ostl et al. (2011, ApJ, 741, id. 34) for the Harmonic Mean model. These analytic expressions can also be used for empirical or analytical models to predict the 1 AU arrival time of an ICME by correcting for effects of hits by the flank rather than the apex, if the width and direction of the ICME in a plane are known and a circular geometry of the ICME front is assumed.Comment: 15 pages, 5 figures, accepted for publication in "Solar Physics

A multi-organ transcriptome resource for the Burmese Python (Python molurus bivittatus)

<p>Abstract</p> <p>Background</p> <p>Snakes provide a unique vertebrate system for studying a diversity of extreme adaptations, including those related to development, metabolism, physiology, and venom. Despite their importance as research models, genomic resources for snakes are few. Among snakes, the Burmese python is the premier model for studying extremes of metabolic fluctuation and physiological remodelling. In this species, the consumption of large infrequent meals can induce a 40-fold increase in metabolic rate and more than a doubling in size of some organs. To provide a foundation for research utilizing the python, our aim was to assemble and annotate a transcriptome reference from the heart and liver. To accomplish this aim, we used the 454-FLX sequencing platform to collect sequence data from multiple cDNA libraries.</p> <p>Results</p> <p>We collected nearly 1 million 454 sequence reads, and assembled these into 37,245 contigs with a combined length of 13,409,006 bp. To identify known genes, these contigs were compared to chicken and lizard gene sets, and to all Genbank sequences. A total of 13,286 of these contigs were annotated based on similarity to known genes or Genbank sequences. We used gene ontology (GO) assignments to characterize the types of genes in this transcriptome resource. The raw data, transcript contig assembly, and transcript annotations are made available online for use by the broader research community.</p> <p>Conclusion</p> <p>These data should facilitate future studies using pythons and snakes in general, helping to further contribute to the utilization of snakes as a model evolutionary and physiological system. This sequence collection represents a major genomic resource for the Burmese python, and the large number of transcript sequences characterized should contribute to future research in this and other snake species.</p

Toward Detecting Polycyclic Aromatic Hydrocarbons on Planetary Objects with ORIGIN

Polycyclic aromatic hydrocarbons (PAHs) are found on various planetary surfaces in the solar system. They are proposed to play a role in the emergence of life, as molecules that are important for biological processes could be derived from them. In this work, four PAHs (pyrene, perylene, anthracene, and coronene) were measured using the ORganics Information Gathering INstrument system (ORIGIN), a lightweight laser desorption ionization-mass spectrometer designed for space exploration missions. In this contribution, we demonstrate the current measurement capabilities of ORIGIN in detecting PAHs at different concentrations and applied laser pulse energies. Furthermore, we show that chemical processing of the PAHs during measurement is limited and that the parent mass can be detected in the majority of cases. The instrument achieves a 3σ detection limit in the order of femtomol mm−2 for all four PAHs, with the possibility of further increasing this sensitivity. This work illustrates the potential of ORIGIN as an instrument for the detection of molecules important for the emergence or presence of life, especially when viewed in combination with previous results by the instrument, such as the identification of amino acids. ORIGIN could be used on a lander or rover platform for future in situ missions to targets in the solar system, such as the icy moons of Jupiter or Saturn

Genetical genomics: spotlight on QTL hotspots

No abstract available

Functional analysis of drug resistance-associated mutations in the Trypanosoma brucei Adenosine Transporter 1 (TbAT1) and the proposal of a structural model for the protein

The Trypanosoma brucei aminopurine transporter P2/TbAT1 has long been implicated in the transport of, and resistance to, the diamidine and melaminophenyl arsenical classes of drugs that form the backbone of the pharmacopoeia against African trypanosomiasis. Genetic alterations including deletions and single nucleotide polymorphisms (SNPs) have been observed in numerous strains and clinical isolates. Here, we systematically investigate each reported mutation and assess their effects on transporter function after expression in a tbat1 -/- T. brucei line. Out of a set of six reported SNPs from a reported ‘resistance allele’, none significantly impaired sensitivity to pentamidine, diminazene or melarsoprol, relative to the TbAT1-WT allele, although several combinations, and the deletion of the codon for residue F316, resulted in highly significant impairment. These combinations of SNPs, and ΔF316, also strongly impaired the uptake of [3H]-adenosine and [3H]-diminazene, identical to the tbat1-/- control. The TbAT1 protein model predicted that residues F19, D140 and F316 interact with the substrate of the transporter. Mutation of D140 to alanine resulted in an inactive transporter, whereas the mutation F19A produced a transporter with a slightly increased affinity for [3H]-diminazene, but reduced the uptake rate. The results presented here validate earlier hypotheses of drug binding motifs for TbAT1