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  1. Article ; Online: Exponential consensus ranking improves the outcome in docking and receptor ensemble docking

    Karen Palacio-Rodríguez / Isaias Lans / Claudio N. Cavasotto / Pilar Cossio

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: Abstract Consensus-scoring methods are commonly used with molecular docking in virtual screening campaigns to filter potential ligands for a protein target. Traditional consensus methods combine results from different docking programs by averaging the ... ...

    Abstract Abstract Consensus-scoring methods are commonly used with molecular docking in virtual screening campaigns to filter potential ligands for a protein target. Traditional consensus methods combine results from different docking programs by averaging the score or rank of each molecule obtained from individual programs. Unfortunately, these methods fail if one of the docking programs has poor performance, which is likely to occur due to training-set dependencies and scoring-function parameterization. In this work, we introduce a novel consensus method that overcomes these limitations. We combine the results from individual docking programs using a sum of exponential distributions as a function of the molecule rank for each program. We test the method over several benchmark systems using individual and ensembles of target structures from diverse protein families with challenging decoy/ligand datasets. The results demonstrate that the novel method outperforms the best traditional consensus strategies over a wide range of systems. Moreover, because the novel method is based on the rank rather than the score, it is independent of the score units, scales and offsets, which can hinder the combination of results from different structures or programs. Our method is simple and robust, providing a theoretical basis not only for molecular docking but also for any consensus strategy in general.
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The SARS-CoV-2 crisis and its impact on neglected tropical diseases

    Claire Chaumont / Kimberly Kamara / Elisa Baring / Karen Palacio / Ana Power / Warren Lancaster

    PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e

    Threat or opportunity?

    2020  Volume 0008680

    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270 ; covid19
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments

    Julian Giraldo-Barreto / Sebastian Ortiz / Erik H. Thiede / Karen Palacio-Rodriguez / Bob Carpenter / Alex H. Barnett / Pilar Cossio

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: Abstract Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information ... ...

    Abstract Abstract Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule’s conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of $$k_BT$$ k B T . We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Towards a shared understanding of sustainability for neglected tropical disease programs.

    Jeffrey Glenn / Aparna Barua Adams / Girija Sankar / Carolyn Henry / Karen Palacio / Wangeci Thuo / Katherine Williams

    PLoS Neglected Tropical Diseases, Vol 15, Iss 8, p e

    2021  Volume 0009595

    Abstract: Background Sustainability within neglected tropical disease (NTD) programs is a complex and challenging issue. The need for a shared understanding about what sustainability means for NTD programs is more important than ever as stakeholders are currently ... ...

    Abstract Background Sustainability within neglected tropical disease (NTD) programs is a complex and challenging issue. The need for a shared understanding about what sustainability means for NTD programs is more important than ever as stakeholders are currently realigning for the next decade of NTD programming with the launch of WHO's new NTD roadmap for 2012-2030. The aim of this paper is to assess different perspectives to generate a working definition of sustainability for NTD programs. Methodology/principal findings This study surveyed affiliates of the NTD NGO Network (NNN) about their definitions of sustainability and then analyzed the data using an inductive and deductive process. The research team drafted a sustainability statement based on the survey findings and then solicited and incorporated feedback on the statement from a diverse group of expert reviewers. The final statement includes a working definition of sustainability for NTD programs that highlights three key essential components to sustainability: domestic commitment, responsive resource mobilization, and accountability. Conclusions/significance This research resulted in a sustainability statement, based on a survey and extensive consultation with stakeholders, that represents a starting point for shared understanding around the concept of sustainability for NTD programs. Future collaborative work should build off this definition and seek to incorporate indicators for sustainability into programmatic decision-making.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 720
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: In silico discovery and biological validation of ligands of FAD synthase, a promising new antimicrobial target.

    Isaias Lans / Ernesto Anoz-Carbonell / Karen Palacio-Rodríguez / José Antonio Aínsa / Milagros Medina / Pilar Cossio

    PLoS Computational Biology, Vol 16, Iss 8, p e

    2020  Volume 1007898

    Abstract: New treatments for diseases caused by antimicrobial-resistant microorganisms can be developed by identifying unexplored therapeutic targets and by designing efficient drug screening protocols. In this study, we have screened a library of compounds to ... ...

    Abstract New treatments for diseases caused by antimicrobial-resistant microorganisms can be developed by identifying unexplored therapeutic targets and by designing efficient drug screening protocols. In this study, we have screened a library of compounds to find ligands for the flavin-adenine dinucleotide synthase (FADS) -a potential target for drug design against tuberculosis and pneumonia- by implementing a new and efficient virtual screening protocol. The protocol has been developed for the in silico search of ligands of unexplored therapeutic targets, for which limited information about ligands or ligand-receptor structures is available. It implements an integrative funnel-like strategy with filtering layers that increase in computational accuracy. The protocol starts with a pharmacophore-based virtual screening strategy that uses ligand-free receptor conformations from molecular dynamics (MD) simulations. Then, it performs a molecular docking stage using several docking programs and an exponential consensus ranking strategy. The last filter, samples the conformations of compounds bound to the target using MD simulations. The MD conformations are scored using several traditional scoring functions in combination with a newly-proposed score that takes into account the fluctuations of the molecule with a Morse-based potential. The protocol was optimized and validated using a compound library with known ligands of the Corynebacterium ammoniagenes FADS. Then, it was used to find new FADS ligands from a compound library of 14,000 molecules. A small set of 17 in silico filtered molecules were tested experimentally. We identified five inhibitors of the activity of the flavin adenylyl transferase module of the FADS, and some of them were able to inhibit growth of three bacterial species: C. ammoniagenes, Mycobacterium tuberculosis, and Streptococcus pneumoniae, where the last two are human pathogens. Overall, the results show that the integrative VS protocol is a cost-effective solution for the discovery of ligands of ...
    Keywords Biology (General) ; QH301-705.5
    Subject code 540 ; 500
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Características morfológicas de las cianobacterias y fitoplancton dominante en tres embalses de Antioquia

    Karen Palacio Gómez / Esnedy Hernández Atilano / Gustavo Peñuela Mesa / Néstor Aguirre Ramírez / Fabio Vélez Macías

    Revista U.D.C.A Actualidad & Divulgación Científica, Vol 22, Iss

    un enfoque basado en la forma y el biovolumen

    2019  Volume 2

    Abstract: El desarrollo masivo de cianobacterias y la contaminación por cianotoxinas constituyen una problemática ambiental de especial interés en los sistemas acuáticos, debido a los diversos impactos negativos que los florecimientos (blooms) de cianobacterias ... ...

    Abstract El desarrollo masivo de cianobacterias y la contaminación por cianotoxinas constituyen una problemática ambiental de especial interés en los sistemas acuáticos, debido a los diversos impactos negativos que los florecimientos (blooms) de cianobacterias pueden ocasionar. Dada la importancia recreacional y de abastecimiento de los embalses Abreo - Malpaso, Peñol - Guatapé y Playas, ubicados en el oriente de Antioquia - Colombia, en este estudio, se estimó la densidad de cianobacterias planctónicas y otros organismos del fitoplancton, así como el biovolumen geométrico, la relación superficie volumen (S/V) y la dimensión lineal máxima (DLM), a través de cuatro muestreos, en tres estaciones, para cada uno de los embalses. Se identificaron, dentro del phylum Cyanobacteria, con potencial de producción de cianotoxinas, el complejo Microcystis, los géneros Woronichinia, Aphanocapsa y Oscillatoria y la especie Radiocystis fernandoi. Al aplicar la prueba no parámetrica Kruskal – Wallis, no se encontraron diferencias significativas entre los embalses estudiados (p>0,05); sin embargo, el embalse El Peñol – Guatapé presentó la mayor biomasa algal y densidad de cianobacterias, por lo que, según los niveles de riesgo planteados para los embalses estudiados y de acuerdo con las características morfológicas de estos organismos, este embalse presenta un nivel de riesgo Medio Alto con relación a la presencia y morfología de las cianobacterias, mientras que los embalses Abreo – Malpaso y Playas están asociados a un riesgo Medio Bajo. Se sugiere establecer medidas de control y de prevención, con el fin de evitar un desarrollo masivo de cianobacterias, una potencial presencia de cianotoxinas y afectaciones graves a seres humanos y animales.
    Keywords morfología ; riesgo ; fitoplancton ; biovolumen ; embalse ; Agriculture (General) ; S1-972 ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Language Spanish
    Publishing date 2019-10-01T00:00:00Z
    Publisher Universidad de Ciencias Aplicadas y Ambientales
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: National mapping of schistosomiasis, soil-transmitted helminthiasis and anaemia in Yemen

    Nur Alia Johari / Dhekra Amin Annuzaili / Hani Farouk El-Talabawy / Maryam Ba-Break / Abdulsalam M Al-Mekhlafi / Samira Al-Eryani / Abdulhakim Ali Alkohlani / Albis Francesco Gabrielli / Riadh Ben-Ismail / Sami Alhaidari / Adel Muaydh / Rasheed Alshami / Magid Al Gunaid / Alaa Hamed / Nehad Kamel / Karen Palacio / Fiona Fleming / Michael Duncan French

    PLoS Neglected Tropical Diseases, Vol 16, Iss 3, p e

    Towards better national control and elimination.

    2022  Volume 0010092

    Abstract: Background Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are known to be endemic in Yemen. However, the distribution of both diseases had not previously been assessed by a well-structured national mapping study covering all governorates. ...

    Abstract Background Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are known to be endemic in Yemen. However, the distribution of both diseases had not previously been assessed by a well-structured national mapping study covering all governorates. The main aim of this study was, therefore, to map the prevalence of SCH and STH in Yemen in order to better inform implementation of effective national control and elimination interventions. The assessment of the distribution of anaemia was also included as a well-known consequence of infection with both SCH and STH. Secondarily, the study aimed to provide a broad indication of the impact of large-scale treatment on the distribution of infection. Methodology and principal findings To achive these aims, 80,432 children (10-14 years old) from 2,664 schools in 332 of Yemen's 333 districts were included, in 2014, into this national cross-sectional survey. Countrywide, 63.3% (210/332) and 75.6% (251/332) of districts were found to be endemic for SCH and STH respectively. More districts were affected by intestinal than urogenital SCH (54.2% and 31.6% respectively). SCH infection was mostly mild and moderate, with no districts reporting high infection. One quarter (24.4%) of Yemeni districts had high or moderate levels of Ascaris lumbricoides infection. Infection with Trichuris trichiura was the second most common STH (44.9% of districts infected) after A. lumbricoides (68.1%). Hookworm was the least prevalent STH (9.0%). Anaemia was prevalent in 96.4% of districts; it represented a severe public health problem (prevalence ≥ 40%) in 26.5% of districts, and a mild to moderate problem in two thirds of the districts (33.7% and 36.1% respectively). Conclusion This study provided the first comprehensive mapping of SCH, STH, and anaemia across the country. This formed the basis for evaluating and continuing the national control and elimination programme for these neglected tropical diseases in Yemen.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 910
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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