المؤلفون: Rebeca Illescas-Montes, Manuel Rueda-Fernández, Anabel González-Acedo, Lucía Melguizo-Rodríguez, Enrique García-Recio, Javier Ramos-Torrecillas, Olga García-Martínez

المصدر: Nutrients, Vol 16, Iss 1, p 23 (2023)

مصطلحات موضوعية: pomegranate, phenolic compounds, punicalagin, ellagic acid, fibroblasts, Nutrition. Foods and food supply, TX341-641

الوصف: Background: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. Objective: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10−5 to 10−9 M. Results: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10−9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10−6 M or 10−7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. Conclusions: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6643/16/1/23Test; https://doaj.org/toc/2072-6643Test

الوصول الحر: https://doaj.org/article/dc41f5fc6a854bb8861d118d2bcad877Test

المؤلفون: Heidi L. Rehm, Angela J.H. Page, Lindsay Smith, Jeremy B. Adams, Gil Alterovitz, Lawrence J. Babb, Maxmillian P. Barkley, Michael Baudis, Michael J.S. Beauvais, Tim Beck, Jacques S. Beckmann, Sergi Beltran, David Bernick, Alexander Bernier, James K. Bonfield, Tiffany F. Boughtwood, Guillaume Bourque, Sarion R. Bowers, Anthony J. Brookes, Michael Brudno, Matthew H. Brush, David Bujold, Tony Burdett, Orion J. Buske, Moran N. Cabili, Daniel L. Cameron, Robert J. Carroll, Esmeralda Casas-Silva, Debyani Chakravarty, Bimal P. Chaudhari, Shu Hui Chen, J. Michael Cherry, Justina Chung, Melissa Cline, Hayley L. Clissold, Robert M. Cook-Deegan, Mélanie Courtot, Fiona Cunningham, Miro Cupak, Robert M. Davies, Danielle Denisko, Megan J. Doerr, Lena I. Dolman, Edward S. Dove, L. Jonathan Dursi, Stephanie O.M. Dyke, James A. Eddy, Karen Eilbeck, Kyle P. Ellrott, Susan Fairley, Khalid A. Fakhro, Helen V. Firth, Michael S. Fitzsimons, Marc Fiume, Paul Flicek, Ian M. Fore, Mallory A. Freeberg, Robert R. Freimuth, Lauren A. Fromont, Jonathan Fuerth, Clara L. Gaff, Weiniu Gan, Elena M. Ghanaim, David Glazer, Robert C. Green, Malachi Griffith, Obi L. Griffith, Robert L. Grossman, Tudor Groza, Jaime M. Guidry Auvil, Roderic Guigó, Dipayan Gupta, Melissa A. Haendel, Ada Hamosh, David P. Hansen, Reece K. Hart, Dean Mitchell Hartley, David Haussler, Rachele M. Hendricks-Sturrup, Calvin W.L. Ho, Ashley E. Hobb, Michael M. Hoffman, Oliver M. Hofmann, Petr Holub, Jacob Shujui Hsu, Jean-Pierre Hubaux, Sarah E. Hunt, Ammar Husami, Julius O. Jacobsen, Saumya S. Jamuar, Elizabeth L. Janes, Francis Jeanson, Aina Jené, Amber L. Johns, Yann Joly, Steven J.M. Jones, Alexander Kanitz, Kazuto Kato, Thomas M. Keane, Kristina Kekesi-Lafrance, Jerome Kelleher, Giselle Kerry, Seik-Soon Khor, Bartha M. Knoppers, Melissa A. Konopko, Kenjiro Kosaki, Martin Kuba, Jonathan Lawson, Rasko Leinonen, Stephanie Li, Michael F. Lin, Mikael Linden, Xianglin Liu, Isuru Udara Liyanage, Javier Lopez, Anneke M. Lucassen, Michael Lukowski, Alice L. Mann, John Marshall, Michele Mattioni, Alejandro Metke-Jimenez, Anna Middleton, Richard J. Milne, Fruzsina Molnár-Gábor, Nicola Mulder, Monica C. Munoz-Torres, Rishi Nag, Hidewaki Nakagawa, Jamal Nasir, Arcadi Navarro, Tristan H. Nelson, Ania Niewielska, Amy Nisselle, Jeffrey Niu, Tommi H. Nyrönen, Brian D. O’Connor, Sabine Oesterle, Soichi Ogishima, Vivian Ota Wang, Laura A.D. Paglione, Emilio Palumbo, Helen E. Parkinson, Anthony A. Philippakis, Angel D. Pizarro, Andreas Prlic, Jordi Rambla, Augusto Rendon, Renee A. Rider, Peter N. Robinson, Kurt W. Rodarmer, Laura Lyman Rodriguez, Alan F. Rubin, Manuel Rueda, Gregory A. Rushton, Rosalyn S. Ryan, Gary I. Saunders, Helen Schuilenburg, Torsten Schwede, Serena Scollen, Alexander Senf, Nathan C. Sheffield, Neerjah Skantharajah, Albert V. Smith, Heidi J. Sofia, Dylan Spalding, Amanda B. Spurdle, Zornitza Stark, Lincoln D. Stein, Makoto Suematsu, Patrick Tan, Jonathan A. Tedds, Alastair A. Thomson, Adrian Thorogood, Timothy L. Tickle, Katsushi Tokunaga, Juha Törnroos, David Torrents, Sean Upchurch, Alfonso Valencia, Roman Valls Guimera, Jessica Vamathevan, Susheel Varma, Danya F. Vears, Coby Viner, Craig Voisin, Alex H. Wagner, Susan E. Wallace, Brian P. Walsh, Marc S. Williams, Eva C. Winkler, Barbara J. Wold, Grant M. Wood, J. Patrick Woolley, Chisato Yamasaki, Andrew D. Yates, Christina K. Yung, Lyndon J. Zass, Ksenia Zaytseva, Junjun Zhang, Peter Goodhand, Kathryn North, Ewan Birney

المصدر: Cell Genomics, Vol 1, Iss 2, Pp 100029- (2021)

مصطلحات موضوعية: data sharing, data access, precision medicine, learning health system, genomics, standards, Genetics, QH426-470, Internal medicine, RC31-1245

الوصف: Summary: The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666979X21000367Test; https://doaj.org/toc/2666-979XTest

الوصول الحر: https://doaj.org/article/8843ca96b8394774b7bfa2e49aa0584aTest

المؤلفون: Elias L. Salfati, Emily G. Spencer, Sarah E. Topol, Evan D. Muse, Manuel Rueda, Jonathan R. Lucas, Glenn N. Wagner, Steven Campman, Eric J. Topol, Ali Torkamani

المصدر: Genome Medicine, Vol 11, Iss 1, Pp 1-8 (2019)

مصطلحات موضوعية: Whole-exome sequencing, Medical genetics, Molecular autopsy, Rare and undiagnosed diseases, Sudden death, Automated periodic re-analysis, Medicine, Genetics, QH426-470

الوصف: Abstract Background Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis. Methods Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem “molecular autopsy” cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest. Results Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively. Conclusions The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-994XTest

الوصول الحر: https://doaj.org/article/812335bb8de34937bace0faee446502aTest

المؤلفون: Begoña Díaz de la Noval, Iris Porcel Llaneza, Manuel Rueda Sepúlveda, Francisco Javier Ferrer Barriendos, Carmen Fernández Blanco

المصدر: Clinical Case Reports, Vol 7, Iss 11, Pp 2242-2244 (2019)

مصطلحات موضوعية: cesarean section, delivery, fetal distress, umbilical cord, Medicine, Medicine (General), R5-920

الوصف: Abstract An umbilical cord knot is an unexpected event that should not change obstetric approach for delivery.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2050-0904Test

الوصول الحر: https://doaj.org/article/3ca74aa831fb49f4a08f62d6b7fb0c6fTest

المؤلفون: Manuel Rueda, Ali Torkamani

المصدر: BMC Bioinformatics, Vol 18, Iss 1, Pp 1-10 (2017)

مصطلحات موضوعية: Mitochondrial DNA, Annotation, Healthy aging, Heteroplasmy, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5

الوصف: Abstract Background Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians. Results We have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115–3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002–1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes. Conclusions SG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdnaTest .

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12859-017-1778-6Test; https://doaj.org/toc/1471-2105Test

الوصول الحر: https://doaj.org/article/6522624108dd4675aea39cf4628f89caTest

المؤلفون: Manuel Rueda, Jennifer L. Wagner, Tierney C. Phillips, Sarah E. Topol, Evan D. Muse, Jonathan R. Lucas, Glenn N. Wagner, Eric J. Topol, Ali Torkamani

المصدر: Frontiers in Cardiovascular Medicine, Vol 4 (2018)

مصطلحات موضوعية: molecular autopsy, sudden cardiac death, whole exome sequencing, gene panel, mitochondrial DNA, Diseases of the circulatory (Cardiovascular) system, RC666-701

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/article/10.3389/fcvm.2017.00090/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/ee1f41b4d6f74388a77f351c3f69be3fTest

المؤلفون: Manuel Rueda, Jennifer L. Wagner, Tierney C. Phillips, Sarah E. Topol, Evan D. Muse, Jonathan R. Lucas, Glenn N. Wagner, Eric J. Topol, Ali Torkamani

المصدر: Frontiers in Cardiovascular Medicine, Vol 4 (2017)

مصطلحات موضوعية: molecular autopsy, sudden cardiac death, whole exome sequencing, gene panel, mitochondrial DNA, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: The Scripps molecular autopsy study seeks to incorporate genetic testing into the postmortem examination of cases of sudden death in the young (

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/article/10.3389/fcvm.2017.00072/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/8f39e99ab52142fdb2cd94a215ebc6b8Test

المؤلفون: Michela Candotti, Alberto Pérez, Carles Ferrer-Costa, Manuel Rueda, Tim Meyer, Josep Lluís Gelpí, Modesto Orozco

المصدر: PLoS Computational Biology, Vol 9, Iss 12, p e1003393 (2013)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: After decades of using urea as denaturant, the kinetic role of this molecule in the unfolding process is still undefined: does urea actively induce protein unfolding or passively stabilize the unfolded state? By analyzing a set of 30 proteins (representative of all native folds) through extensive molecular dynamics simulations in denaturant (using a range of force-fields), we derived robust rules for urea unfolding that are valid at the proteome level. Irrespective of the protein fold, presence or absence of disulphide bridges, and secondary structure composition, urea concentrates in the first solvation shell of quasi-native proteins, but with a density lower than that of the fully unfolded state. The presence of urea does not alter the spontaneous vibration pattern of proteins. In fact, it reduces the magnitude of such vibrations, leading to a counterintuitive slow down of the atomic-motions that opposes unfolding. Urea stickiness and slow diffusion is, however, crucial for unfolding. Long residence urea molecules placed around the hydrophobic core are crucial to stabilize partially open structures generated by thermal fluctuations. Our simulations indicate that although urea does not favor the formation of partially open microstates, it is not a mere spectator of unfolding that simply displaces to the right of the folded ←→ unfolded equilibrium. On the contrary, urea actively favors unfolding: it selects and stabilizes partially unfolded microstates, slowly driving the protein conformational ensemble far from the native one and also from the conformations sampled during thermal unfolding.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3861036?pdf=renderTest; https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test

الوصول الحر: https://doaj.org/article/ab704e69288b457eb30afe1d6e652e32Test

المؤلفون: Giovanni Bottegoni, Walter Rocchia, Manuel Rueda, Ruben Abagyan, Andrea Cavalli

المصدر: PLoS ONE, Vol 6, Iss 5, p e18845 (2011)

مصطلحات موضوعية: Medicine, Science

الوصف: The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3098722?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/94f12c65bb8a49d5b277e07ddf1d2687Test

المؤلفون: Abel Cabrera-Martínez, Andrea Conchado Peiró, Juan Manuel Rueda-Vázquez

المصدر: AIMS Mathematics, Vol 8, Iss 5, Pp 10654-10664 (2023)

مصطلحات موضوعية: total italian domination number, double domination number, domination number, trees, Mathematics, QA1-939

الوصف: Let $ f:V(G)\rightarrow \{0, 1, 2\} $ be a function defined from a connected graph $ G $. Let $ W_i = \{x\in V(G): f(x) = i\} $ for every $ i\in \{0, 1, 2\} $. The function $ f $ is called a total Italian dominating function on $ G $ if $ \sum_{v\in N(x)}f(v)\geq 2 $ for every vertex $ x\in W_0 $ and if $ \sum_{v\in N(x)}f(v)\geq 1 $ for every vertex $ x\in W_1\cup W_2 $. The total Italian domination number of $ G $, denoted by $ \gamma_{tI}(G) $, is the minimum weight $ \omega(f) = \sum_{x\in V(G)}f(x) $ among all total Italian dominating functions $ f $ on $ G $. In this paper, we provide new lower and upper bounds on the total Italian domination number of trees. In particular, we show that if $ T $ is a tree of order $ n(T)\geq 2 $, then the following inequality chains are satisfied. (ⅰ) $ 2\gamma(T)\leq \gamma_{tI}(T)\leq n(T)-\gamma(T)+s(T) $, (ⅱ) $ \frac{n(T)+\gamma(T)+s(T)-l(T)+1}{2}\leq \gamma_{tI}(T)\leq \frac{n(T)+\gamma(T)+l(T)}{2}, $ where $ \gamma(T) $, $ s(T) $ and $ l(T) $ represent the classical domination number, the number of support vertices and the number of leaves of $ T $, respectively. The upper bounds are derived from results obtained for the double domination number of a tree.

العلاقة: https://doaj.org/toc/2473-6988Test; https://doaj.org/article/1658ac6328f44e37bfec8d951caf6737Test

الإتاحة: https://doi.org/10.3934/math.2023540Test
https://doaj.org/article/1658ac6328f44e37bfec8d951caf6737Test