The cumulative impact of chaperone mediated protein- folding during evolution

Molecular chaperones support protein folding and unfolding along with assembly and translocation of protein complexes. Chaperones have been recognized as important mediators between organismal genotype and phenotype as well as important maintainers of cellular fitness under environmental conditions that induce high mutational loads. This thesis presents recent studies revealing that the folding assistance supplied by chaperones is evident in genomic sequences, thus implicating chaperone-mediated folding as an influential factor during protein evolution. Furthermore the evolution and the symbiogenic origin of the eukaryotic chaperone repertoire are elucidated. Protein interaction with chaperones ensures a proper folding and function, yet an adaptation to obligatory dependence on such assistance may be irreversible, representing an evolutionary trap. Correlation between chaperone requirement and protein expression level indicate that the evolution of substrate-chaperone interaction is bounded by the required substrate abundance within the cell. Accumulating evidence suggests that the utility of chaperones is governed by a delicate balance between their help in mitigating the risks of protein misfolding and aggregate formation on the one hand, and the slower rate of protein maturation and the energetic cost of chaperone synthesis on the other

Parallel Computing in Water Network Analysis and Leakage Minimization

[EN] In this paper a parallel computing based software demonstrator for the simulation and leakage minimization of water networks is presented. This demonstrator, based on the EPANET package, tackles three different types of problems making use of parallel computing. First, the solution of the hydraulic problem is treated by means of the gradient method. The key point in the parallelization of the method is the solution of the underlying linear systems, which is carried out by means of a multifrontal Choleski method. Second, the water quality simulation problem is approached by using the discrete volume element method. The application of parallel computing is based on dividing the water network in several parts using the multilevel recursive bisection graph partitioning algorithm. Finally, the problem of leakage minimization using pressure reducing valves is approached. This results in the formulation of an optimization problem for each time step, which is solved by means of sequential quadratic programming. Because these subproblems are independent of each other, they can be solved in parallel.The writers wish to acknowledge the financial support provided by the ESPRIT program of the European Commission (HIPERWATER, ESPRIT project 24003), by the CICYT TIC96-1062-C03-01 project, and also by research staff training grants from the Spanish government and the autonomous government of the Comunidad Valenciana in Spain.Alonso Ábalos, JM.; Alvarruiz Bermejo, F.; Guerrero López, D.; Hernández García, V.; Ruiz Martínez, PA.; Vidal Maciá, AM.; Martínez Alzamora, F.... (2000). Parallel Computing in Water Network Analysis and Leakage Minimization. Journal of Water Resources Planning and Management. 126(4):251-260. https://doi.org/10.1061/(ASCE)0733-9496(2000)126:4(251)S251260126

Fanny Copeland and the geographical imagination

Raised in Scotland, married and divorced in the English south, an adopted Slovene, Fanny Copeland (1872 – 1970) occupied the intersection of a number of complex spatial and temporal conjunctures. A Slavophile, she played a part in the formation of what subsequently became the Kingdom of Yugoslavia that emerged from the First World War. Living in Ljubljana, she facilitated the first ‘foreign visit’ (in 1932) of the newly formed Le Play Society (a precursor of the Institute of British Geographers) and guided its studies of Solčava (a then ‘remote’ Alpine valley system) which, led by Dudley Stamp and commended by Halford Mackinder, were subsequently hailed as a model for regional studies elsewhere. Arrested by the Gestapo and interned in Italy during the Second World War, she eventually returned to a socialist Yugoslavia, a celebrated figure. An accomplished musician, linguist, and mountaineer, she became an authority on (and populist for) the Julian Alps and was instrumental in the establishment of the Triglav National Park. Copeland’s role as participant observer (and protagonist) enriches our understanding of the particularities of her time and place and illuminates some inter-war relationships within G/geography, inside and outside the academy, suggesting their relative autonomy in the production of geographical knowledge

The Human Urine Metabolome

Urine has long been a “favored” biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca

Chaperonin-Dependent Accelerated Substitution Rates in Prokaryotes

Many proteins require the assistance of molecular chaperones in order to fold efficiently. Chaperones are known to mask the effects of mutations that induce misfolding because they can compensate for the deficiency in spontaneous folding. One of the best studied chaperones is the eubacterial GroEL/GroES system. In Escherichia coli, three classes of proteins have been distinguished based on their degree of dependency on GroEL for folding: 1) those that do not require GroEL, 2) those that require GroEL in a temperature-dependent manner, and 3) those that obligately require GroEL for proper folding. The buffering effects of GroEL have so far been observed in experimental regimens, but their effect on genomes during evolution has not been examined. Using 446 sequenced proteobacterial genomes, we have compared the frequency of amino acid replacements among orthologs of 236 proteins corresponding to the three categories of GroEL dependency determined for E. coli. Evolutionary rates are significantly correlated with GroEL dependency upon folding with GroEL dependency class accounting for up to 84% of the variation in amino acid substitution rates. Greater GroEL dependency entails increased evolutionary rates with GroEL obligatory proteins (Class III) evolving on average up to 15% faster than GroEL partially dependent proteins (Class II) and 35% faster than GroEL-independent proteins (Class I). Moreover, GroEL dependency class correlations are strictly conserved throughout all proteobacteria surveyed, as is a significant correlation between folding class and codon bias. The results suggest that during evolution, GroEL-dependent folding increases evolutionary rate by buffering the deleterious effects of misfolding-related mutations

Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors

Homogenization of the long-term global ozonesonde records

Póster presentado en: WMO Technical Conference on Meteorological and Environmental Instruments and Methods of Observation celebrada del 10 al 13 de octubre de 2022 en París

Battle of Postdisaster Response and Restoration

[EN] The paper presents the results of the Battle of Postdisaster Response and Restoration (BPDRR) presented in a special session at the first International water distribution systems analysis & computing and control in the water industry (WDSA/CCWI) Joint Conference, held in Kingston, Ontario, Canada, in July 2018. The BPDRR problem focused on how to respond and restore water service after the occurrence of five earthquake scenarios that cause structural damage in a water distribution system. Participants were required to propose a prioritization schedule to fix the damages of each scenario while following restrictions on visibility/nonvisibility of damages. Each team/approach was evaluated against six performance criteria: (1) time without supply for hospital/firefighting, (2) rapidity of recovery, (3) resilience loss, (4) average time of no user service, (5) number of users without service for eight consecutive hours, and (6) water loss. Three main types of approaches were identified from the submissions: (1) general-purpose metaheuristic algorithms, (2) greedy algorithms, and (3) ranking-based prioritizations. All three approaches showed potential to solve the challenge efficiently. The results of the participants showed that for this network, the impact of a large-diameter pipe failure on the network is more significant than several smaller pipes failures. The location of isolation valves and the size of hydraulic segments influenced the resilience of the system during emergencies. On average, the interruptions to water supply (hospitals and firefighting) varied considerably among solutions and emergency scenarios, highlighting the importance of private water storage for emergencies. The effects of damages and repair work were more noticeable during the peak demand periods (morning and noontime) than during the low-flow periods; and tank storage helped to preserve functionality of the network in the first few hours after a simulated event. (C) 2020 American Society of Civil Engineers.Paez, D.; Filion, Y.; Castro-Gama, M.; Quintiliani, C.; Santopietro, S.; Sweetapple, C.; Meng, F.... (2020). Battle of Postdisaster Response and Restoration. Journal of Water Resources Planning and Management. 146(8):1-13. https://doi.org/10.1061/(ASCE)WR.1943-5452.0001239S1131468Balut A. R. Brodziak J. Bylka and P. Zakrzewski. 2018. “Battle of post-disaster response and restauration (BPDRR).” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Bibok A. 2018. “Near-optimal restoration scheduling of damaged drinking water distribution systems using machine learning.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Castro-Gama M. C. Quintiliani and S. Santopietro. 2018. “After earthquake post-disaster response using a many-objective approach a greedy and engineering interventions.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Cimellaro, G. P., Tinebra, A., Renschler, C., & Fragiadakis, M. (2016). New Resilience Index for Urban Water Distribution Networks. Journal of Structural Engineering, 142(8). doi:10.1061/(asce)st.1943-541x.0001433Cover, T., & Hart, P. (1967). Nearest neighbor pattern classification. IEEE Transactions on Information Theory, 13(1), 21-27. doi:10.1109/tit.1967.1053964Creaco, E., Franchini, M., & Alvisi, S. (2010). Optimal Placement of Isolation Valves in Water Distribution Systems Based on Valve Cost and Weighted Average Demand Shortfall. Water Resources Management, 24(15), 4317-4338. doi:10.1007/s11269-010-9661-5Deb, K., Mohan, M., & Mishra, S. (2005). Evaluating the ε-Domination Based Multi-Objective Evolutionary Algorithm for a Quick Computation of Pareto-Optimal Solutions. Evolutionary Computation, 13(4), 501-525. doi:10.1162/106365605774666895Deuerlein J. D. Gilbert E. Abraham and O. Piller. 2018. “A greedy scheduling of post-disaster response and restoration using pressure-driven models and graph segment analysis.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Deuerlein, J. W. (2008). Decomposition Model of a General Water Supply Network Graph. Journal of Hydraulic Engineering, 134(6), 822-832. doi:10.1061/(asce)0733-9429(2008)134:6(822)Di Nardo, A., Di Natale, M., Giudicianni, C., Santonastaso, G. F., & Savic, D. (2018). Simplified Approach to Water Distribution System Management via Identification of a Primary Network. Journal of Water Resources Planning and Management, 144(2), 04017089. doi:10.1061/(asce)wr.1943-5452.0000885Eliades D. G. M. Kyriakou S. Vrachimis and M. M. Polycarpou. 2016. “EPANET-MATLAB toolkit: An open-source software for interfacing EPANET with MATLAB.” In Proc. 14th Int. Conf. on Computing and Control for the Water Industry (CCWI) 8. The Hague The Netherlands: International Water Conferences. https://doi.org/10.5281/zenodo.831493.Fragiadakis, M., Christodoulou, S. E., & Vamvatsikos, D. (2013). Reliability Assessment of Urban Water Distribution Networks Under Seismic Loads. Water Resources Management, 27(10), 3739-3764. doi:10.1007/s11269-013-0378-0Gilbert, D., Abraham, E., Montalvo, I., & Piller, O. (2017). Iterative Multistage Method for a Large Water Network Sectorization into DMAs under Multiple Design Objectives. Journal of Water Resources Planning and Management, 143(11), 04017067. doi:10.1061/(asce)wr.1943-5452.0000835Hill, D., Kerkez, B., Rasekh, A., Ostfeld, A., Minsker, B., & Banks, M. K. (2014). Sensing and Cyberinfrastructure for Smarter Water Management: The Promise and Challenge of Ubiquity. Journal of Water Resources Planning and Management, 140(7), 01814002. doi:10.1061/(asce)wr.1943-5452.0000449Hwang, H. H. M., Lin, H., & Shinozuka, M. (1998). Seismic Performance Assessment of Water Delivery Systems. Journal of Infrastructure Systems, 4(3), 118-125. doi:10.1061/(asce)1076-0342(1998)4:3(118)Li Y. J. Gao C. Jian C. Ou and S. Hu. 2018. “A two-stage post-disaster response and restoration method for the water distribution system.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Liu, W., Zhao, Y., & Li, J. (2014). Seismic functional reliability analysis of water distribution networks. Structure and Infrastructure Engineering, 11(3), 363-375. doi:10.1080/15732479.2014.887121Luong, H. T., & Nagarur, N. N. (2005). Optimal Maintenance Policy and Fund Allocation in Water Distribution Networks. Journal of Water Resources Planning and Management, 131(4), 299-306. doi:10.1061/(asce)0733-9496(2005)131:4(299)MacQueen J. B. 1967. “Some methods for classification and analysis of multivariate observations.” In Vol. 1 of Proc. 5th Berkeley Symp. on Mathematical Statistics and Probability 281–297. Berkeley: University of California Press.Mahmoud, H. A., Kapelan, Z., & Savić, D. (2018). Real-Time Operational Response Methodology for Reducing Failure Impacts in Water Distribution Systems. Journal of Water Resources Planning and Management, 144(7), 04018029. doi:10.1061/(asce)wr.1943-5452.0000956Meng, F., Fu, G., Farmani, R., Sweetapple, C., & Butler, D. (2018). Topological attributes of network resilience: A study in water distribution systems. Water Research, 143, 376-386. doi:10.1016/j.watres.2018.06.048Ostfeld, A., Uber, J. G., Salomons, E., Berry, J. W., Hart, W. E., Phillips, C. A., … Walski, T. (2008). The Battle of the Water Sensor Networks (BWSN): A Design Challenge for Engineers and Algorithms. Journal of Water Resources Planning and Management, 134(6), 556-568. doi:10.1061/(asce)0733-9496(2008)134:6(556)Paez D. Y. Filion and M. Hulley. 2018a. “Battle of post-disaster response and restoration (BPDRR)—Problem description and rules.” Accessed June 14 2019. https://www.queensu.ca/wdsa-ccwi2018/problem-description-and-files.Paez, D., Suribabu, C. R., & Filion, Y. (2018). Method for Extended Period Simulation of Water Distribution Networks with Pressure Driven Demands. Water Resources Management, 32(8), 2837-2846. doi:10.1007/s11269-018-1961-1Salcedo C. A. Aguilar P. Cuero S. Gonzalez S. Muñoz J. Pérez A. Posada J. Robles and K. Vargas. 2018. “Determination of the hydraulic restoration capacity of b-city involving a multi-criteria decision support model.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Santonastaso G. F. E. Creaco A. Di Nardo and M. Di Natale. 2018. “Post-disaster response and restauration of B-town network based on primary network.” In Vol. 1 of Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. Kingston Canada: Open Journal Systems.Sophocleous S. E. Nikoloudi H. A. Mahmoud K. Woodward and M. Romano. 2018. “Simulation-based framework for the restoration of earthquake-damaged water distribution networks using a genetic algorithm.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Sweetapple C. F. Meng R. Farmani G. Fu and D. Butler. 2018. “A heuristic approach to water network post-disaster response and restoration.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems.Tabucchi, T., Davidson, R., & Brink, S. (2010). Simulation of post-earthquake water supply system restoration. Civil Engineering and Environmental Systems, 27(4), 263-279. doi:10.1080/10286600902862615Taormina, R., Galelli, S., Tippenhauer, N. O., Salomons, E., Ostfeld, A., Eliades, D. G., … Ohar, Z. (2018). Battle of the Attack Detection Algorithms: Disclosing Cyber Attacks on Water Distribution Networks. Journal of Water Resources Planning and Management, 144(8), 04018048. doi:10.1061/(asce)wr.1943-5452.0000969Walski, T. M. (1993). Water distribution valve topology for reliability analysis. Reliability Engineering & System Safety, 42(1), 21-27. doi:10.1016/0951-8320(93)90051-yWang, Y., Au, S.-K., & Fu, Q. (2010). Seismic Risk Assessment and Mitigation of Water Supply Systems. Earthquake Spectra, 26(1), 257-274. doi:10.1193/1.3276900Yoo, D. G., Kang, D., & Kim, J. H. (2016). Optimal design of water supply networks for enhancing seismic reliability. Reliability Engineering & System Safety, 146, 79-88. doi:10.1016/j.ress.2015.10.001Zhang Q. F. Zheng K. Diao B. Ulanicki and Y. Huang. 2018. “Solving the battle of post-disaster response and restauration (BPDRR) problem with the aid of multi-phase optimization framework.” In Proc. 1st Int. WDSA/CCWI 2018 Joint Conf. 14. Kingston Canada: Open Journal Systems

Chance and necessity in the genome evolution of endosymbiotic bacteria of insects

[EN] An open question in evolutionary biology is how does the selection¿drift balance determine the fates of biological interactions. We searched for signatures of selection and drift in genomes of five endosymbiotic bacterial groups known to evolve under strong genetic drift. Although most genes in endosymbiotic bacteria showed evidence of relaxed purifying selection, many genes in these bacteria exhibited stronger selective constraints than their orthologs in free-living bacterial relatives. Remarkably, most of these highly constrained genes had no role in the host¿symbiont interactions but were involved in either buffering the deleterious consequences of drift or other host-unrelated functions, suggesting that they have either acquired new roles or their role became more central in endosymbiotic bacteria. Experimental evolution of Escherichia coli under strong genetic drift revealed remarkable similarities in the mutational spectrum, genome reduction patterns and gene losses to endosymbiotic bacteria of insects. Interestingly, the transcriptome of the experimentally evolved lines showed a generalized deregulation of the genome that affected genes encoding proteins involved in mutational buffering, regulation and amino acid biosynthesis, patterns identical to those found in endosymbiotic bacteria. Our results indicate that drift has shaped endosymbiotic associations through a change in the functional landscape of bacterial genes and that the host had only a small role in such a shiftThis work was supported by Science Foundation Ireland (12/IP/1637) and grants from the Spanish Ministerio de Economia y Competitividad (MINECO-FEDER; BFU2012-36346 and BFU2015-66073-P) to MAF. 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