The trypanosomal transferrin receptor of trypanosoma brucei : a review

Iron is an essential element for life. Its uptake and utility requires a careful balancing with its toxic capacity, with mammals evolving a safe and bio-viable means of its transport and storage. This transport and storage is also utilized as part of the iron-sequestration arsenal employed by the mammalian hosts’ ‘nutritional immunity’ against parasites. Interestingly, a key element of iron transport, i.e., serum transferrin (Tf), is an essential growth factor for parasitic haemo-protozoans of the genus Trypanosoma. These are major mammalian parasites causing the diseases human African trypanosomosis (HAT) and animal trypanosomosis (AT). Using components of their well-characterized immune evasion system, bloodstream Trypanosoma brucei parasites adapt and scavenge for the mammalian host serum transferrin within their broad host range. The expression site associated genes (ESAG6 and 7) are utilized to construct a heterodimeric serum Tf binding complex which, within its niche in the flagellar pocket, and coupled to the trypanosomes’ fast endocytic rate, allows receptor-mediated acquisition of essential iron from their environment. This review summarizes current knowledge of the trypanosomal transferrin receptor (TfR), with emphasis on the structure and function of the receptor, both in physiological conditions as well as in conditions where the iron supply to parasites is being limited. Potential applications using current knowledge of the parasite receptor are also briefly discussed, primarily focused on potential therapeutic interventions

Monetary Transmission in the Euro Area: Does the Interest Rate Channel Explain it All?

Drawing on recent Eurosystem research that uses a range of econometric techniques and a number of new data sets, we propose a comprehensive description of how monetary policy affects the euro area economy. We focus mainly on three questions: (1) what are the stylized facts concerning the transmission of monetary policy for the area as a whole and for individual countries? (2) can the classic' interest rate channel (IRC) alone, without capital market imperfections, explain these facts? (3) if not, is the bank lending channel a likely candidate to complete the story? We find plausible euro-area wide monetary policy responses for prices and output that are similar to those generally reported for the U.S. However, investment (relative to consumption) seems to play a larger role in euro area monetary policy transmission than in the U.S. We cannot reject the hypothesis that the IRC completely characterizes transmission in a few countries, and estimate it to be substantial in almost all. Where the IRC is not dominant, there is normally some direct evidence supporting the presence of a bank lending channel (or other financial transmission channel). The cases where financial effects appear important can be further split according to whether they primarily relate to consumption or investment.

The Output Composition Puzzle: A Difference in the Monetary Transmission Mechanism in the Euro Area and U.S.

We revisit recent evidence on how monetary policy affects output and prices in the U.S. and in the euro area. The response patterns to a shift in monetary policy are similar in most respects, but differ noticeably as to the composition of output changes. In the euro area investment is the predominant driver of output changes, while in the U.S. consumption shifts are significantly more important. We dub this difference the output composition puzzle and explore its implications and several potential explanations for it. While the evidence seems to point at differences in consumption responses, rather than investment, as the proximate cause for this fact, the source of the consumption difference remains a puzzle.

Understanding of matrix embedding: a theoretical spectroscopic study of CO interacting with Ar clusters, surfaces and matrices

Through benchmark studies, we explore the performance of PBE density functional theory, with and without Grimme's dispersion correction (DFT-D3), in predicting spectroscopic properties for molecules interacting with rare gas matrices. Here, a periodic-dispersion corrected model of matrix embedding is used for the first time. We use PBE-D3 to determine the equilibrium structures and harmonic vibrational frequencies of carbon monoxide in interaction with small Ar clusters (CO–Arn, n = 1, 2, 3), with an Ar surface and embedded in an Ar matrix. Our results show a converging trend for both the vibrational frequencies and binding energies when going from the gas-phase to a fully periodic approach describing CO embedding in Ar. This trend is explained in terms of solvation effects, as CO is expected to alter the structure of the Ar matrix. Due to a competition between CO–Ar interactions and Ar–Ar interactions, perturbations caused by the presence of CO are found to extend over several Å in the matrix. Accordingly, it is mandatory to fully relax rare gas matrices when studying their interaction with embedded molecules. Moreover, we show that the binding energy per Ar is almost constant (∼−130 cm−1 atom−1) regardless of the environment of the CO molecule. Finally, we show that the concentration of the solute into the cold matrix influences the spectroscopic parameters of molecules embedded into cold matrices. We suggest hence that several cautions should be taken before comparing these parameters to gas phase measurements and to theoretical data of isolated species

Formulas for Continued Fractions. An Automated Guess and Prove Approach

We describe a simple method that produces automatically closed forms for the coefficients of continued fractions expansions of a large number of special functions. The function is specified by a non-linear differential equation and initial conditions. This is used to generate the first few coefficients and from there a conjectured formula. This formula is then proved automatically thanks to a linear recurrence satisfied by some remainder terms. Extensive experiments show that this simple approach and its straightforward generalization to difference and $q$-difference equations capture a large part of the formulas in the literature on continued fractions.Comment: Maple worksheet attache

NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes.

BackgroundThe molecular pathway that controls cardiogenesis is temporally and spatially regulated by master transcriptional regulators such as NKX2-5, Isl1, MEF2C, GATA4, and beta-catenin. The interplay between these factors and their downstream targets are not completely understood. Here, we studied regulation of beta-catenin and GATA4 by NKX2-5 in human fetal cardiac myocytes.Methodology/principal findingsUsing antisense inhibition we disrupted the expression of NKX2-5 and studied changes in expression of cardiac-associated genes. Down-regulation of NKX2-5 resulted in increased beta-catenin while GATA4 was decreased. We demonstrated that this regulation was conferred by binding of NKX2-5 to specific elements (NKEs) in the promoter region of the beta-catenin and GATA4 genes. Using promoter-luciferase reporter assay combined with mutational analysis of the NKEs we demonstrated that the identified NKX2-5 binding sites were essential for the suppression of beta-catenin, and upregulation of GATA4 by NKX2-5.ConclusionsThis study suggests that NKX2-5 modulates the beta-catenin and GATA4 transcriptional activities in developing human cardiac myocytes

Relationship between habitat area and the distribution of tidal marsh birds

To assess the relationship between marsh area and relative abundance of tidal marsh bird species, we surveyed birds on 86 circular plots in 40 salt and brackish tidal marshes in Connecticut. We measured marsh area in two ways: the amount of contiguous marsh vegetation not interrupted by broad barriers (\u3e500 m of open water or \u3e50 m of upland habitat) and by narrow barriers (\u3e30 m of open water or \u3e10 m upland). We determined the relationship between marsh area and the relative abundance of particular species (mean number of individuals per survey plot) with linear or logistic regression. When the broad barrier definition was used, we found that all three species of short grass meadow specialists, Willets (Catoptrophorus semipalmatus), Seaside Sparrows (Ammodramus maritimus), and Saltmarsh Sharp-tailed Sparrows (A. caudacutus), were less abundant or absent in survey plots in smaller marshes. The Seaside Sparrow and Willet also showed a significant tendency to be less frequent in smaller marshes when the narrow barrier definition was used. In contrast, species that used a wider range of wetland types, as in the Virginia Rail (Rallus limicola), Marsh Wren (Cistothorus palustris), and Swamp Sparrow (Melospiza georgiana), were equally frequent on plots in marshes of different areas. Our results are consistent with the hypothesis that fragmentation of marsh systems with artificial habitat causes a decline in the density of short grass meadow specialists in the remaining patches of appropriate habitat

Efficient checkpoint/verification patterns

International audienceErrors have become a critical problem for high performance computing. Checkpointing protocols are often used for error recovery after fail-stop failures. However, silent errors cannot be ignored, and their peculiarity is that such errors are identified only when the corrupted data is activated. To cope with silent errors, we need a verification mechanism to check whether the application state is correct. Checkpoints should be supplemented with verifications to detect silent errors. When a verification is successful, only the last checkpoint needs to be kept in memory because it is known to be correct. In this paper, we analytically determine the best balance of verifications and checkpoints so as to optimize platform throughput. We introduce a balanced algorithm using a pattern with p checkpoints and q verifica-tions, which regularly interleaves both checkpoints and verifications across same-size computational chunks. We show how to compute the waste of an arbitrary pattern, and we prove that the balanced algorithm is optimal when the platform MTBF (Mean Time Between Failures) is large in front of the other parameters (checkpointing, verification and recovery costs). We conduct several simulations to show the gain achieved by this balanced algorithm for well-chosen values of p and q, compared to the base algorithm that always perform a verification just before taking a checkpoint (p = q = 1), and we exhibit gains of up to 19%