The UlaG protein family defines novel structural and functional motifs grafted on an ancient RNase fold

Background: Bacterial populations are highly successful at colonizing new habitats and adapting to changing environmental conditions, partly due to their capacity to evolve novel virulence and metabolic pathways in response to stress conditions and to shuffle them by horizontal gene transfer (HGT). A common theme in the evolution of new functions consists of gene duplication followed by functional divergence. UlaG, a unique manganese-dependent metallo-b-lactamase (MBL) enzyme involved in L-ascorbate metabolism by commensal and symbiotic enterobacteria, provides a model for the study of the emergence of new catalytic activities from the modification of an ancient fold. Furthermore, UlaG is the founding member of the so-called UlaG-like (UlaGL) protein family, a recently established and poorly characterized family comprising divalent (and perhaps trivalent)metal-binding MBLs that catalyze transformations on phosphorylated sugars and nucleotides. Results: Here we combined protein structure-guided and sequence-only molecular phylogenetic analyses to dissect the molecular evolution of UlaG and to study its phylogenomic distribution, its relatedness with present-day UlaGL protein sequences and functional conservation. Phylogenetic analyses indicate that UlaGL sequences are present in Bacteria and Archaea, with bona fide orthologs found mainly in mammalian and plant-associated Gramnegative and Gram-positive bacteria. The incongruence between the UlaGL tree and known species trees indicates exchange by HGT and suggests that the UlaGL-encoding genes provided a growth advantage under changing conditions. Our search for more distantly related protein sequences aided by structural homology has uncovered that UlaGL sequences have a common evolutionary origin with present-day RNA processing and metabolizing MBL enzymes widespread in Bacteria, Archaea, and Eukarya. This observation suggests an ancient origin for the UlaGL family within the broader trunk of the MBL superfamily by duplication, neofunctionalization and fixation. Conclusions: Our results suggest that the forerunner of UlaG was present as an RNA metabolizing enzyme in the last common ancestor, and that the modern descendants of that ancestral gene have a wide phylogenetic distribution and functional roles. We propose that the UlaGL family evolved new metabolic roles among bacterial and possibly archeal phyla in the setting of a close association with metazoans, such as in the mammalian gastrointestinal tract or in animal and plant pathogens, as well as in environmental settings. Accordingly, the major evolutionary forces shaping the UlaGL family include vertical inheritance and lineage-specific duplication and acquisition of novel metabolic functions, followed by HGT and numerous lineage-specific gene loss events

Assessing tension metrics with dark energy survey and Planck data

Lemos, P. et al.Quantifying tensions – inconsistencies amongst measurements of cosmological parameters by different experiments – has emerged as a crucial part of modern cosmological data analysis. Statistically significant tensions between two experiments or cosmological probes may indicate new physics extending beyond the standard cosmological model and need to be promptly identified. We apply several tension estimators proposed in the literature to the dark energy survey (DES) large-scale structure measurement and Planck cosmic microwave background data. We first evaluate the responsiveness of these metrics to an input tension artificially introduced between the two, using synthetic DES data. We then apply the metrics to the comparison of Planck and actual DES Year 1 data. We find that the parameter differences, Eigentension, and Suspiciousness metrics all yield similar results on both simulated and real data, while the Bayes ratio is inconsistent with the rest due to its dependence on the prior volume. Using these metrics, we calculate the tension between DES Year 1 3 × 2pt and Planck, finding the surveys to be in ∼2.3σ tension under the ΔCDM paradigm. This suite of metrics provides a toolset for robustly testing tensions in the DES Year 3 data and beyond.The DES data management system is supported by the National Science Foundation under grant numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by Ministerio de Ciencia e Innovación (MICINN) under grants ESP2017-89838, PGC2018-094773, PGC2018-102021, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the Centres de Recerca de Catalunya (CERCA) program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) do e-Universo (CNPq grant 465376/2014-2). This manuscript has been authored by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the U.S. Department of Energy, Office of Science, Office of High Energy Physics

The mechanism of the transpersulfuration reaction in a cysteine desulfurase-sulfur acceptor model system

Trabajo presentado en las 1as Jornadas Españolas de Biocatálisis, celebradas en Madrid (España) del 02 al 03 de julio de 2015.Escherichia coli CsdA cysteine desulfurase (the sulfur donor) and the CsdE sulfur acceptor are involved in biological sulfur trafficking, in iron-sulfur cluster assembly, and tRNA hypermodification [1] in the model bacterium Escherichia coli. CsdA and CsdE form a stable complex through a polar interface. Although mechanisms for the transfer of a sulfur moiety across protein-protein interfaces have been proposed based on the IscS-IscU and IscS-TusA structures [2,3], the flexibility of the catalytic Cys loops involved has precluded a high resolution view of the active-site geometry and chemical environment responsible to facilitate sulfur transfer. Here, we have used a combination of X-ray crystallography, solution NMR, biophysical and computational chemistry methods to unravel how CsdA provides a specific recognition platform for CsdE and how their complex organizes a composite functional reaction environment. A mechanistic view of sulfur transfer across protein-protein interfaces emerges from the structural analysis of the CSD system

Mechanism of sulfur transfer across protein-protein interfaces: The cysteine desulfurase model system

CsdA cysteine desulfurase (the sulfur donor) and the CsdE sulfur acceptor are involved in biological sulfur trafficking and in iron-sulfur cluster assembly in the model bacterium Escherichia coli. CsdA and CsdE form a stable complex through a polar interface that includes CsdA Cys328 and CsdE Cys61, the two residues known to be involved in the sulfur transfer reaction. Although mechanisms for the transfer of a sulfur moiety across protein-protein interfaces have been proposed based on the IscS-IscU and IscS-TusA structures, the flexibility of the catalytic cysteine loops involved has precluded a high resolution view of the active-site geometry and chemical environment for sulfur transfer. Here, we have used a combination of X-ray crystallography, solution NMR and SAXS, isothermal calorimetry, and computational chemistry methods to unravel how CsdA provides a specific recognition platform for CsdE and how their complex organizes a composite functional reaction environment. The X-ray structures of persulfurated (CsdA) and persulfurated (CsdA-CsdE) complexes reveal the crucial roles of the conserved active-site cysteine loop and additional catalytic residues in supporting the transpersulfuration reaction. A mechanistic view of sulfur transfer across protein-protein interfaces that underpins the requirement for the conserved cysteine loop to provide electrostatic stabilization for the in-transfer sulfur atom emerges from the analysis of the persulfurated (CsdA-CsdE) complex structure.BFU2008-02372/BMC, CSD 2006-23, and BFU2011-22588 to M.C., CTQ2012-36253-C03-03 and CTQ2015-66223-C2 to I.T., CTQ2015-64597-C2-1-P to J.J.B., and BFU2010-22266- C02-02 and CTQ2015-66206-C2-2-R to M.C.V. Further support for this work was obtained from the Generalitat Valenciana (ACOMP/2015/239 to I.T.) and from the European Commission FP7 ComplexINC grant (contract no. 279039) to M.C.V.Peer Reviewe

Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart

[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78 +/- 10 vs. 68 +/- 10 ms) and after atropine (76 +/- 8 vs. 67 +/- 10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53 +/- 8 vs. 42 +/- 7 ms and 50 +/- 6 vs. 40 +/- 6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5 +/- 1.5% vs. 15.1 +/- 3.8%) and, decreased after atropine (15.1 +/- 3.8% vs. 12.2 +/- 2.4%) in the control group. The trained group showed higher NE values before (0.40 +/- 0.04 vs. 0.36 +/- 0.05) and after atropine (0.37 +/- 0.04 vs. 0.34 +/- 0.06; p = 0.08). Training decreased the CV of NE both before (23.3 +/- 2% vs. 25.2 +/- 4%; p = 0.08) and after parasympathetic blockade (22.6 +/- 1% vs. 26.1 +/- 5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34 +/- 8 vs. 41 +/- 5), and increased after atropine in the control group (41 +/- 5 vs. 48 +/- 9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.This research was supported by the Spanish Ministry of Education and Science, (DEP2007-73234-C03-01 to AMA), http://www.mecd.gob.es/portada-mecd/; and the Generalitat Valenciana (PROMETEO 2010/093 to FJC, and FPI/2008/003 to MZ), http://www.gva.es/va/inicio/presentacion; jsessionid=ydprbDQZTsCTz85W1Such-Miquel, L.; Brines-Ferrando, L.; Alberola, A.; Zarzoso Muñoz, M.; Chorro Gasco, FJ.; Guerrero-Martínez, JF.; Parra-Giraldo, G.... (2018). Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart. PLoS ONE. 13(12). https://doi.org/10.1371/journal.pone.0209085S1312Billman, G. E. (2002). Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention. Journal of Applied Physiology, 92(2), 446-454. doi:10.1152/japplphysiol.00874.2001Billman, G. E. (2006). A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: Implications for future anti-arrhythmic drug development. Pharmacology & Therapeutics, 111(3), 808-835. doi:10.1016/j.pharmthera.2006.01.002Dor-Haim, H., Berenfeld, O., Horowitz, M., Lotan, C., & Swissa, M. (2013). Reduced Ventricular Arrhythmogeneity and Increased Electrical Complexity in Normal Exercised Rats. PLoS ONE, 8(6), e66658. doi:10.1371/journal.pone.0066658Hamer, M., & Stamatakis, E. (2008). Physical Activity and Cardiovascular Disease: Directions for Future Research. The Open Sports Sciences Journal, 1(1), 1-2. doi:10.2174/1875399x00801010001Powers, S. K., Smuder, A. J., Kavazis, A. N., & Quindry, J. C. (2014). Mechanisms of Exercise-Induced Cardioprotection. Physiology, 29(1), 27-38. doi:10.1152/physiol.00030.2013Hull, S. S., Vanoli, E., Adamson, P. B., Verrier, R. L., Foreman, R. D., & Schwartz, P. J. (1994). Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation, 89(2), 548-552. doi:10.1161/01.cir.89.2.548Hajnal, Á., Nagy, O., Litvai, Á., Papp, J., Parratt, J. R., & Végh, Á. (2005). Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs. Life Sciences, 77(16), 1960-1971. doi:10.1016/j.lfs.2005.02.015Such, L., Alberola, A. M., Such-Miquel, L., López, L., Trapero, I., Pelechano, F., … Chorro, F. J. (2008). Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart. Acta Physiologica, 193(4), 331-339. doi:10.1111/j.1748-1716.2008.01851.xZarzoso, M., Such-Miquel, L., Parra, G., Brines-Ferrando, L., Such, L., Chorro, F. J., … Alberola, A. (2011). The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity. European Journal of Applied Physiology, 112(6), 2185-2193. doi:10.1007/s00421-011-2189-4Billman, G. E. (2009). Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1171-H1193. doi:10.1152/ajpheart.00534.2009HAN, J., & MOE, G. K. (1964). Nonuniform Recovery of Excitability in Ventricular Muscle. Circulation Research, 14(1), 44-60. doi:10.1161/01.res.14.1.44Beaumont, E., Salavatian, S., Southerland, E. M., Vinet, A., Jacquemet, V., Armour, J. A., & Ardell, J. L. (2013). Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function. The Journal of Physiology, 591(18), 4515-4533. doi:10.1113/jphysiol.2013.259382Armour, J. 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Influence of Regulated Deficit Irrigation on Arbequina’s Crop Yield and EVOOs Quality and Sensory Profile

Regulated deficit irrigation in super-high-density (SHD) olive orchards is a well-known strategy to save water and control plant vigor, without decreasing fruit or oil yield. As there is controversial information about its influence on virgin olive oil quality, a trial was conducted in five SHD olive orchards of Arbequina cultivar in different locations of central, east, north and northeast Spain under full irrigation (FI) and regulated deficit irrigation (RDI) treatments. RDI applied during phase II of fruit growing (40% of total needs) saves more than 20% of water on average, without reductions in olive fruit or extra virgin olive oil (EVOO) yield. No threshold of 3.5 MPa of stem water potential was crossed in any case. RDI modified sterols and the fatty acid profile of EVOOs but not phenols, quality parameters, or the sensory profile. Latitude, altitude, and yearly rainfall have a big impact on some compounds such as campesterol, oleuropein, or margaroleic or linolenic acids.info:eu-repo/semantics/publishedVersio

Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, >= 27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with >= 27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with = 27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype

The PAU Survey: A Forward Modeling Approach for Narrow-band Imaging

Weak gravitational lensing is a powerful probe of the dark sector, once measurement systematic errors can be controlled. In Refregier & Amara (2014), a calibration method based on forward modeling, called MCCL, was proposed. This relies on fast image simulations (e.g., UFig; Berge et al. 2013) that capture the key features of galaxy populations and measurement effects. The MCCL approach has been used in Herbel et al. (2017) to determine the redshift distribution of cosmological galaxy samples and, in the process, the authors derived a model for the galaxy population mainly based on broad-band photometry. Here, we test this model by forward modeling the 40 narrow-band photometry given by the novel PAU Survey (PAUS). For this purpose, we apply the same forced photometric pipeline on data and simulations using Source Extractor (Bertin & Arnouts 1996). The image simulation scheme performance is assessed at the image and at the catalogues level. We find good agreement for the distribution of pixel values, the magnitudes, in the magnitude-size relation and the interband correlations. A principal component analysis is then performed, in order to derive a global comparison of the narrow-band photometry between the data and the simulations. We use a `mixing' matrix to quantify the agreement between the observed and simulated sets of Principal Components (PCs). We find good agreement, especially for the first three most significant PCs. We also compare the coefficients of the PCs decomposition. While there are slight differences for some coefficients, we find that the distributions are in good agreement. Together, our results show that the galaxy population model derived from broad-band photometry is in good overall agreement with the PAUS data. This offers good prospect for incorporating spectral information to the galaxy model by adjusting it to the PAUS narrow-band data using forward modeling.Comment: Submitted to JCAP, 28 pages, 15 figures, 3 appendice