Capturing coevolutionary signals in repeat proteins

The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural ensembles. Here we introduce a statistical coupling analysis for repeat proteins -- natural systems for which the identification of domains remains challenging. We show that the inherent translational symmetry of repeat protein sequences introduces a strong bias in the pair correlations at precisely the length scale of the repeat-unit. Equalizing for this bias reveals true co-evolutionary signals from which local native-contacts can be identified. Importantly, parameter values obtained for all other interactions are not significantly affected by the equalization. We quantify the robustness of the procedure and assign confidence levels to the interactions, identifying the minimum number of sequences needed to extract evolutionary information in several repeat protein families. The overall procedure can be used to reconstruct the interactions at long distances, identifying the characteristics of the strongest couplings in each family, and can be applied to any system that appears translationally symmetric

The use of the ACC deaminase producing bacterium Pseudomonas putida UW4 as a biocontrol agent for pine wilt disease

Pine wilt disease, caused by the nematode Bursaphelenchus xylophilus, is responsible for the devastation of worldwide pine forestlands. Until today, the only effective solution to this serious threat resides on the destruction of infected trees, which is both economic and ecologically unacceptable. The use of ACC deaminase-producing plant growth promoting bacteria has been shown to be a useful strategy in order to reduce biotic and abiotic constraints that affect plant health and development. In this sense, we report the use of the ACC deaminase-producing bacterium Pseudomonas putida UW4 as a potential biological control agent for pine wilt disease. An inoculation assay was performed in 3-4 months Pinus pinaster (maritime pine) seedlings obtained from a nursery in Portugal. The bacteria P. putida UW4 wild-type and ACC deaminase mutant strains were inoculated in the roots of pine seedlings followed by stem inoculation of B. xylophilus. The inoculation of the P. putida UW4 wild-type strain lead to a significant reduction of B. xylophilus induced symptoms. Moreover, regardless the inoculation with B. xylophilus, seedlings inoculated with P. putida UW4 also demonstrated an increased root and shoot development. In addition, P. putida UW4 ACC deaminase knockout mutant was unable to promote pine seedling growth or to decrease B. xylophilus induced symptoms. The results obtained indicate that the inoculation of ACC deaminase-producing bacteria in pine seedlings growing in a nursery system might constitute a novel strategy to obtain B. xylophilus resistant pine trees. This is the first report on the use of ACC deaminase-producing bacteria as potential biological control agents for tree diseases

Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space

The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal Frustration" when the folded structure is symmetric (Wolynes, P. G. Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14249-14255). Similarly, repeats and structural mosaics may be fundamentally related to landscapes with multiple embedded funnels. Here we present analytical tools to detect and compare structural repetitions in protein molecules. By an exhaustive analysis of the distribution of structural repeats using a robust metric we define those portions of a protein molecule that best describe the overall structure as a tessellation of basic units. The patterns produced by such tessellations provide intuitive representations of the repeating regions and their association towards higher order arrangements. We find that some protein architectures can be described as nearly periodic, while in others clear separations between repetitions exist. Since the method is independent of amino acid sequence information we can identify structural units that can be encoded by a variety of distinct amino acid sequences

La declaración unilateral de independencia de Kosovo a la luz de la Opinión Consultiva de la Corte Internacional de Justicia, de 22 de julio de 2010 y de las declaraciones, opiniones individuales y disidentes a la misma

The Opinion of the International Court of Justice on the unilateral declaration of independence of Kosovo is an example of what the Court should not do. Saying only that international law does not prohibit declarations of independence and refusing to answer the matters related to this claim, the Court's opinion adopts a vacuum of legal terms and irresponsible

Tests of star formation metrics in the low metallicity galaxy NGC 5253 using ALMA observations of H30α\alpha line emission

We use Atacama Large Millimeter/submillimeter Array (ALMA) observations of H30$\alpha$ (231.90 GHz) emission from the low metallicity dwarf galaxy NGC 5253 to measure the star formation rate (SFR) within the galaxy and to test the reliability of SFRs derived from other commonly-used metrics. The H30$\alpha$ emission, which originates mainly from the central starburst, yields a photoionizing photon production rate of (1.9$\pm$0.3)$\times$10$^{52}$ s$^{-1}$ and an SFR of 0.087$\pm$0.013 M$_\odot$ yr$^{-1}$ based on conversions that account for the low metallicity of the galaxy and for stellar rotation. Among the other star formation metrics we examined, the SFR calculated from the total infrared flux was statistically equivalent to the values from the H30$\alpha$ data. The SFR based on previously-published versions of the H$\alpha$ flux that were extinction corrected using Pa$\alpha$ and Pa$\beta$ lines were lower than but also statistically similar to the H30$\alpha$ value. The mid-infrared (22 $\mu$m) flux density and the composite star formation tracer based on H$\alpha$ and mid-infrared emission give SFRs that were significantly higher because the dust emission appears unusually hot compared to typical spiral galaxies. Conversely, the 70 and 160 $\mu$m flux densities yielded SFR lower than the H30$\alpha$ value, although the SFRs from the 70 $\mu$m and H30$\alpha$ data were within 1-2$\sigma$ of each other. While further analysis on a broader range of galaxies are needed, these results are instructive of the best and worst methods to use when measuring SFR in low metallicity dwarf galaxies like NGC 5253.Comment: 14 pages, 5 figures, accepted for publication in MNRA

Chemistry in isolation: High CCH/HCO+ line ratio in the AMIGA galaxy CIG 638

Multi-molecule observations towards an increasing variety of galaxies have been showing that the relative molecular abundances are affected by the type of activity. However, these studies are biased towards bright active galaxies, which are typically in interaction. We study the molecular composition of one of the most isolated galaxies in the local Universe where the physical and chemical properties of their molecular clouds have been determined by intrinsic mechanisms. We present 3 mm broad band observations of the galaxy CIG 638, extracted from the AMIGA sample of isolated galaxies. The emission of the J=1-0 transitions of CCH, HCN, HCO+, and HNC are detected. Integrated intensity ratios between these line are compared with similar observations from the literature towards active galaxies including starburst galaxies (SB), active galactic nuclei (AGN), luminous infrared galaxies (LIRG), and GMCs in M33. A significantly high ratio of CCH with respect to HCN, HCO+, and HNC is found towards CIG 638 when compared with all other galaxies where these species have been detected. This points to either an overabundance of CCH or to a relative lack of dense molecular gas as supported by the low HCN/CO ratio, or both. The data suggest that the CIG 638 is naturally a less perturbed galaxy where a lower fraction of dense molecular gas, as well as a more even distribution could explain the measured ratios. In this scenario the dense gas tracers would be naturally dimmer, while the UV enhanced CCH, would be overproduced in a less shielded medium.Comment: Letter accepted for publication in A&

Comunicación corta. Exportación de los macroelementos mayoritarios por los frutos de diferentes cultivares de almendro

The amount of the major macroelements required to produce a given crop has been determined for a set of 11 almond (Prunus amygdalus Batsch) cultivars growing in the Middle Ebro Valley (NE Spain). A wide diversity of nutrient exports was found among the different cultivars. Although the production of kernels is the main objective when growing almonds, all the different fruit components: the mesocarp (hull), the endocarp (shell) and the seed (kernel), were taken into account. The different fruit components showed a great variation among cultivars, and the amount of fruit dry matter required for producing 1 kg of kernel ranged from 4.32 kg in ‘Guara’ to 10.56 kg in ‘Desmayo Largueta’. Similarly, the macroelement requirements to produce a given amount of kernels varied among the different cultivars. ‘Guara’ has proved to be the most effective cultivar in taking advantage of the mineral elements for producing a crop, showing that this efficiency is independent of the shell type. Se determinó la cantidad de macroelementos mayoritarios necesarios para producir una determinada cantidad de cosecha en un grupo de 11 cultivares de almendro (Prunus amygdalus Batsch) cultivados en el Valle Medio del Ebro (NE de España). Se encontró una gran diversidad de requerimientos entre los diferentes cultivares. Aunque la producción de pepitas es el objetivo principal en el cultivo del almendro, todos los componentes del fruto se han de tener en cuenta en este cálculo: el mesocarpo (la piel), el endocarpo (la cáscara) y la semilla (la pepita). Estos tres componentes del fruto mostraron una gran variabilidad entre los cultivares y la cantidad de materia seca necesaria para producir 1 kg de pepita osciló entre 4,32 kg en ‘Guara’ y 10,56 kg en ‘Desmayo Largueta’. Igualmente, los requisitos en macroelementos para producir una cantidad determinada de pepita varió entre los diferentes cultivares. ‘Guara’ mostró ser el cultivar más eficiente en la utilización de los elementos minerales para la producción de una cosecha, mostrando que esta eficiencia es independiente del tipo de cáscara

Investigation of the pathways related to intrinsic miltefosine tolerance in Leishmania (Viannia) braziliensis clinical isolates reveals differences in drug uptake

In Brazil, cutaneous leishmaniasis is caused predominantly by L. (V.) braziliensis. The few therapeutic drugs available exhibit several limitations, mainly related to drug toxicity and reduced efficacy in some regions. Miltefosine (MF), the only oral drug available for leishmaniasis treatment, is not widely available and has not yet been approved for human use in Brazil. Our group previously reported the existence of differential susceptibility among L. (V.) braziliensis clinical isolates. In this work, we further characterized three of these isolates of L. (V.) braziliensis chosen because they exhibited the lowest and the highest MF half maximal inhibitory concentrations and were therefore considered less tolerant or more tolerant, respectively. Uptake of MF, and also of phosphocholine, were found to be significantly different in more tolerant parasites compared to the less sensitive isolate, which raised the hypothesis of differences in the MF transport complex Miltefosine Transporter (MT)-Ros3. Although some polymorphisms in those genes were found, they did not correlate with the drug susceptibility phenotype. Drug efflux and compartmentalization were similar in the isolates tested, and amphotericin B susceptibility was retained in MF tolerant parasites, suggesting that increased fitness was also not the basis of observed differences. Transcriptomic analysis revealed that Ros3 mRNA levels were upregulated in the sensitive strain compared to the tolerant ones. Increased mRNA abundance in more tolerant isolates was validated by quantitative PCR. Our results suggest that differential gene expression of the MT transporter complex is the basis of the differential susceptibility in these unselected, naturally occurring parasites