16 results on '"Amundarain A"'
Search Results
2. IDP Force Fields Applied to Model PPII-Rich 33-mer Gliadin Peptides
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Amundarain, María J., Vietri, Agustín, Dodero, Verónica I., and Costabel, Marcelo D.
- Abstract
The 33-mer gliadin peptide and its deamidated metabolite, 33-mer DGP, are the immunodominant peptides responsible for the adaptive immune response in celiac disease (CD). CD is a complex autoimmune chronic disorder triggered by gluten ingestion that affects the small intestine and affects ∼1% of the global population. The 33-mers are polyproline II-rich (PPII) and intrinsically disordered peptides (IDPs), whose structures remain elusive. We sampled the conformational ensembles of both 33-mer peptides via molecular dynamics simulations employing two force fields (FFs) (Amber ff03wsand Amber ff99SB-disp) specifically validated for other IDPs. Our results show that both FFs allow the extensive exploration of the conformational landscape, which was not possible with the standard FF GROMOS53A6reported before. Clustering analysis of the trajectories showed that the five largest clusters (78–88% of the total structures) present elongated, semielongated, and curved conformations in both FFs. Large average radius of gyration and solvent-exposed surfaces characterized these structures. While the structures sampled are similar, the Amber ff99SB-disptrajectories explored folded conformations with a higher probability. In addition, PPII secondary structure was preserved throughout the trajectories (58–73%) together with a non-negligible content of β structures (11–23%), in agreement with previous experimental results. This work represents the initial step in studying further the interaction of these peptides with other biologically relevant molecules, which could lead to finally disclose the molecular events that lead to CD.
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- 2023
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3. Virtual reality simulation of human-robot coexistence for an aircraft final assembly line: process evaluation and ergonomics assessment
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Ottogalli, Kiara, Rosquete, Daniel, Rojo, Javier, Amundarain, Aiert, María Rodríguez, José, and Borro, Diego
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ABSTRACTAeronautics, in the context of industry 4.0, is continuously evolving to respond to the market dynamics and has incorporated automation to many stages of aircraft manufacturing. However, most of the final assembly line processes are still done manually and remain a challenge. Virtual Reality (VR) technologies can be leveraged to study the incorporation of automation systems involving Human-Robot Coexistence (HRC) in assembly processes before the physical system is available, which is beneficial for increasing the productivity and identifying issues beforehand, thus, preventing unexpected costs. In this context, a VR simulation environment was developed with two innovative factors: (1) The possibility to evaluate multiple new automated and semi-automated cabin and cargo processes and select the best one in terms of specific Key Performance Indicators (KPIs) for a future implementation in the physical system and (2) the capability to study the ergonomics of the human worker inside the narrow space of the fuselage while assembling the parts and coexisting with robots, without compromising the worker’s safety. The results show that most of the new proposed strategies improve the assembly time, worker cost, or ergonomics of the process, with an investment varying between 100 K and 200 K euros and ROI of 1–2 years.
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- 2021
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4. Characterization of complete lncRNAs transcriptome reveals the functional and clinical impact of lncRNAs in multiple myeloma
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Carrasco-Leon, Arantxa, Ezponda, Teresa, Meydan, Cem, Valcárcel, Luis V., Ordoñez, Raquel, Kulis, Marta, Garate, Leire, Miranda, Estíbaliz, Segura, Victor, Guruceaga, Elisabeth, Vilas-Zornoza, Amaia, Alignani, Diego, Pascual, Marién, Amundarain, Ane, Castro-Labrador, Laura, Martín-Uriz, Patxi San, El-Omri, Halima, Taha, Ruba Y., Calasanz, Maria J., Planes, Francisco J., Paiva, Bruno, Mason, Christopher E., San Miguel, Jesús F., Martin-Subero, José I., Melnick, Ari, Prosper, Felipe, and Agirre, Xabier
- Abstract
Multiple myeloma (MM) is an incurable disease, whose clinical heterogeneity makes its management challenging, highlighting the need for biological features to guide improved therapies. Deregulation of specific long non-coding RNAs (lncRNAs) has been shown in MM, nevertheless, the complete lncRNA transcriptome has not yet been elucidated. In this work, we identified 40,511 novel lncRNAs in MM samples. lncRNAs accounted for 82% of the MM transcriptome and were more heterogeneously expressed than coding genes. A total of 10,351 overexpressed and 9,535 downregulated lncRNAs were identified in MM patients when compared with normal bone-marrow plasma cells. Transcriptional dynamics study of lncRNAs in the context of normal B-cell maturation revealed 989 lncRNAs with exclusive expression in MM, among which 89 showed de novo epigenomic activation. Knockdown studies on one of these lncRNAs, SMILO(specific myeloma intergenic long non-coding RNA), resulted in reduced proliferation and induction of apoptosis of MM cells, and activation of the interferon pathway. We also showed that the expression of lncRNAs, together with clinical and genetic risk alterations, stratified MM patients into several progression-free survival and overall survival groups. In summary, our global analysis of the lncRNAs transcriptome reveals the presence of specific lncRNAs associated with the biological and clinical behavior of the disease.
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- 2021
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5. Gene expression derived from alternative promoters improves prognostic stratification in multiple myeloma
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Valcárcel, Luis V., Amundarain, Ane, Kulis, Marta, Charalampopoulou, Stella, Melnick, Ari, San Miguel, Jesús, Martín-Subero, José I., Planes, Francisco J., Agirre, Xabier, and Prosper, Felipe
- Abstract
Clinical and genetic risk factors are currently used in multiple myeloma (MM) to stratify patients and to design specific therapies. However, these systems do not capture the heterogeneity of the disease supporting the development of new prognostic factors. In this study, we identified active promoters and alternative active promoters in 6 different B cell subpopulations, including bone-marrow plasma cells, and 32 MM patient samples, using RNA-seq data. We find that expression initiated at both regular and alternative promoters was specific of each B cell subpopulation or MM plasma cells, showing a remarkable level of consistency with chromatin-based promoter definition. Interestingly, using 595 MM patient samples from the CoMMpass dataset, we observed that the expression derived from some alternative promoters was associated with lower progression-free and overall survival in MM patients independently of genetic alterations. Altogether, our results define cancer-specific alternative active promoters as new transcriptomic features that can provide a new avenue for prognostic stratification possibilities in patients with MM.
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- 2021
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6. Oleic Acid Could Act as a Channel Blocker in the Inhibition of nAChR: Insights from Molecular Dynamics Simulations
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Obiol, Diego J., Amundarain, María J., Zamarreño, Fernando, Vietri, Agustín, Antollini, Silvia S., and Costabel, Marcelo D.
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The activation of the muscular nicotinic acetylcholine receptor (nAChR) produces the opening of the channel, with the consequent increase in the permeability of cations, triggering an excitatory signal. Free fatty acids (FFA) are known to modulate the activity of the receptor as noncompetitive antagonists, acting at the membrane–AChR interface. We present molecular dynamics simulations of a model of nAChR in a desensitized closed state embedded in a lipid bilayer in which distinct membrane phospholipids were replaced by two different monounsaturated FFA that differ in the position of a double bond. This allowed us to detect and describe that the cis-18:1ω-9 FFA were located at the interface between the transmembrane segments of α2and γ subunits diffused into the channel lumen with the consequent potential ability to block the channel to the passage of ions.
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- 2024
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7. Orthosteric and benzodiazepine cavities of the α1β2γ2GABAAreceptor: insights from experimentally validated in silicomethods
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Amundarain, María Julia, Viso, Juan Francisco, Zamarreño, Fernando, Giorgetti, Alejandro, and Costabel, Marcelo
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γ-aminobutyric acid-type A (GABAA) receptors mediate fast synaptic inhibition in the central nervous system of mammals. They are modulated via several sites by numerous compounds, which include GABA, benzodiazepines, ethanol, neurosteroids and anaesthetics among others. Due to their potential as targets of novel drugs, a detailed knowledge of their structure–function relationships is needed. Here, we present the model of the α1β2γ2subtype GABAAreceptor in the APO state and in complex with selected ligands, including agonists, antagonists and allosteric modulators. The model is based on the crystallographic structure of the human β3homopentamer GABAAreceptor. The complexes were refined using atomistic molecular dynamics simulations. This allowed a broad description of the binding modes and the detection of important interactions in agreement with experimental information. From the best of our knowledge, this is the only model of the α1β2γ2GABAAreceptor that represents altogether the desensitized state of the channel and comprehensively describes the interactions of ligands of the orthosteric and benzodiazepines binding sites in agreement with the available experimental data. Furthermore, it is able to explain small differences regarding the binding of a variety of chemically divergent ligands. Finally, this new model may pave the way for the design of focused experimental studies that will allow a deeper description of the receptor.
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- 2019
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8. Light Chain Amyloidosis Plasma Cells Show Specific Chromatin Accessibility and Transcriptome
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Ariceta, Beñat, Nevone, Alice, Cenzano, Itziar, Amundarain, Ane, Vilas-Zornoza, Amaia, Garate, Leire, Aguirre-Ruiz, Paula, Miranda, Estibaliz, San-Martin, Patxi, Milani, Paolo, Lecumberri Villamediana, Ramon, Alignani, Diego, Palladini, Giovanni, Paiva, Bruno, Martin-Subero, Jose Ignacio, Merlini, Giampaolo, San-Miguel, Jesus, Hernaez, Mikel, Gomez-Cabrero, David, Agirre, Xabier, Nuvolone, Mario, and Prosper, Felipe
- Abstract
Immunoglobin light chain amyloidosis (AL) is a monoclonal gammopathy characterized by the accumulation of malignant plasma cells (PC) in the bone marrow. These PCs secrete misfolded immunoglobulin light chains fibrils, which deposit in various organs, leading to organ dysfunction. Unlike other monoclonal gammopathies such as Multiple Myeloma, both its rarity and the lower BM PC burden has limited the deep study of the tumor population. The aim of this study was to analyze the transcriptome and epigenome of the PC from patients with AL amyloidosis to identify the role of chromatin modifications in the pathogenesis of the disease.
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- 2023
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9. Conserved charged amino acids are key determinants for fatty acid binding proteins (FABPs)-membrane interactions. A multi-methodological computational approach
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Zamarreño, Fernando, Giorgetti, Alejandro, Amundarain, María Julia, Viso, Juan Francisco, Córsico, Betina, and Costabel, Marcelo D.
- Abstract
Based on the analysis of the mechanism of ligand transfer to membranes employing in vitromethods, Fatty Acid Binding Protein (FABP) family has been divided in two subgroups: collisional and diffusional FABPs. Although the collisional mechanism has been well characterized employing in vitromethods, the structural features responsible for the difference between collisional and diffusional mechanisms remain uncertain. In this work, we have identified the amino acids putatively responsible for the interaction with membranes of both, collisional and diffusional, subgroups of FABPs. Moreover, we show how specific changes in FABPs’ structure could change the mechanism of interaction with membranes. We have computed protein–membrane interaction energies for members of each subgroup of the family, and performed Molecular Dynamics simulations that have shown different configurations for the initial interaction between FABPs and membranes. In order to generalize our hypothesis, we extended the electrostatic and bioinformatics analysis over FABPs of different mammalian genus. Also, our methodological approach could be used for other systems involving protein–membrane interactions.
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- 2018
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10. Chemical recycling of monolayer PET tray waste by alkaline hydrolysis
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Barredo, Asier, Asueta, Asier, Amundarain, Izotz, Leivar, Jon, Miguel-Fernández, Rafael, Arnaiz, Sixto, Epelde, Eva, López-Fonseca, Rubén, and Gutiérrez-Ortiz, José Ignacio
- Abstract
The high demand for recycled polyethylene terephthalate (rPET) driven by an increase in environmental awareness, the application of more restrictive environmental legislations, together with the large increase in the generation of post-consumer PET plastic waste, has resulted in an urgent need for efficient recycling processes. In this work, alkaline hydrolysis is presented as a promising chemical recycling alternative for PET tray waste. PET depolymerization reactions were carried out under mild conditions (80–100 ºC and atmospheric pressure) using tributylhexadecylphosphonium bromide quaternary salt (TBHDPB) as catalyst. Several operating variables were studied based on PET conversion and terephthalic acid (TPA) yield criteria: (i) catalyst mass ratio of TBHDPB to PET (0–0.2); (ii) particle size (0.5–10 mm); (iii) stirring rate (350–700 rpm); and, (iv) temperature (80–100 °C). A good compromise between PET conversion (99.9%) and TPA yield (93.5%) was established after 4 h of reaction, under the following operating conditions: TBHDPB:PET catalyst ratio, 0.2; 100 °C; particle size, 1–1.4 mm; and, stirring rate, 525 rpm. In addition, the experimental kinetic data correctly fits to the proposed shrinking core model. Activation energy values of 60 and 57.4 kJ mol-1were established for the non-catalyzed and catalyzed reactions, respectively, which implies that TBHDPB catalyst does not apparently modify the reaction mechanism.
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- 2023
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11. Space-State Modeling and Control of Tokamak Reactors
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Garrido, I., Garrido, A.J., Sevillano, G., Alberdi, M., Amundarain, M., and Barambones, O.
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Nuclear fusion has the potential to produce unlimited, clean energy, which presents itself as a reliable energy supply but it also helps to stop the threat of climate change that faces the world nowadays. However, to sustain the pulse duration long enough to produce the necessary energy, new controls have to be developed, composing a new application area of Control Engineering, with new and interesting challenges for the control community. In this sense, this paper deals with the modeling of tokamak nuclear fusion reactors. In order to control the creation of unstable modes in fusion processes, it is necessary to derive numerical models suitable for control strategies. The model presented in this paper addresses flux and energy conservation issues, discussing the mechanisms behind the creation of uncontrollable modes. The dynamics of the system is given by means of the energy functions which are solved for the currents in the structure, plasma current and plasma position. Thus, the equations for the state variables are derived based on the Hamiltonian equation of motion. In order to solve this system numerically, this model is linearized around an operation point by taking a Newton-Raphson step. Besides, the system output is completed by considering the equations for the flux and the poloidal field. Finally, the resulting low-order linear model is modified so as to obtain the corresponding state-space model which is verified by means of numerical experiments.
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- 2009
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12. Virtual reality for aircraft engines maintainability
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Amundarain, Aiert, Borro, Diego, García-Alonso, Alex, Gil, Jorge Juan, Matey, Luis, and Savall, Joan
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REVIMA is a virtual reality system for maintainability simulation in Aeronautics. It comprises both hardware and software developments, plus system integration. REVIMA required the design of a new haptic system. It is used both to track hand movements and to return force feedback that provides the sensation of working with a physical mock-up. The main software modules are: image generation, collision detection and control. System integration is based on two LAN connected PCs that share the different tasks and data. The visualization module has been built using low-cost graphic systems, and we have thoroughly analysed this problem to achieve a drawing frame rate acceptable for simulation analysis. The models comprise more than two thousand different elements that require about two million polygons to describe their shapes. Different organization strategies have been tested in order to achieve the real simulation goal. We also present the different visualization algorithms we have used.
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- 2004
13. Characterization of Complete Lncrnas Transcriptome Reveals Expression of Lncrnas As a Prognostic Factor and Linc-Smilo As a Potential Therapeutic Target in Multiple Myeloma
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Carrasco, Arantxa, Ezponda, Teresa, Meydan, Cem, Valcárcel, Luis Vitores, Ordoñez, Raquel, Kulis, Marta, Garate, Leire, Miranda, Estíbaliz, Segura, Victor, Guruceaga, Elizabeth, Vilas-Zornoza, Amaia, Alignani, Diego, Castro, Laura, Pascual, Marien, Amundarain, Ane, El Omri, Halima, Yasin, Ruba, Calasanz, Maria Jose, Planes, Francisco J, Paiva, Bruno, Mason, Christopher, San-Miguel, Jesús, Subero, Inaki Martin, Melnick, Ari M, Prosper, Felipe, and Agirre, Xabier
- Abstract
Paiva: Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Melnick:KDAc Therapeutics: Membership on an entity's Board of Directors or advisory committees; Constellation Pharmaceuticals: Consultancy; Epizyme: Consultancy; Janssenn: Research Funding.
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- 2019
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14. Lncrnas As New Partners of Novel Chimeric Transcripts in Multiple Myeloma
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Amundarain, Ane, Valcárcel, Luis Vitores, Ordoñez, Raquel, Garate, Leire, Miranda, Estíbaliz, Cendoya, Xabier, Calasanz, Maria Jose, Paiva, Bruno, San-Miguel, Jesús, Planes, Francisco J, Prósper, Felipe, and Agirre, Xabier
- Abstract
Deregulation of long non-coding RNAs (lncRNAs) is a common feature of cancer, including Multiple Myeloma (MM). In our previous studies, we detected 11,495 and 40,511 previously non-annotated lncRNAs during normal humoral immune response and MM patient samples, respectively. These results support an important role for the lncRNAs transcriptome in this hematological malignancy. lncRNAs are genes that differ from coding genes in that they do not give rise to a protein. Nevertheless, lncRNA could undergo the same genetic alterations as coding genes. In this study, we hypothesize that lncRNAs can be involved in the principal genetic alterations occurring in MM such as chromosomal translocations, affecting the Immunoglobulin loci (IG) and in the majority of which the fusion partner still remains unknown.
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- 2019
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15. Characterization of Complete Lncrnas Transcriptome Reveals Expression of Lncrnas As a Prognostic Factor and Linc-SmiloAs a Potential Therapeutic Target in Multiple Myeloma
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Carrasco, Arantxa, Ezponda, Teresa, Meydan, Cem, Valcárcel, Luis Vitores, Ordoñez, Raquel, Kulis, Marta, Garate, Leire, Miranda, Estíbaliz, Segura, Victor, Guruceaga, Elizabeth, Vilas-Zornoza, Amaia, Alignani, Diego, Castro, Laura, Pascual, Marien, Amundarain, Ane, El Omri, Halima, Yasin, Ruba, Calasanz, Maria Jose, Planes, Francisco J, Paiva, Bruno, Mason, Christopher, San-Miguel, Jesús, Subero, Inaki Martin, Melnick, Ari M, Prosper, Felipe, and Agirre, Xabier
- Abstract
Deregulation of long non-coding RNAs (lncRNAs) is emerging as a common feature of different human tumors and their investigation may uncover novel biomarkers and oncogenic mechanisms. Previous studies have suggested that the alteration of some lncRNAs may play an important role in the pathogenesis of multiple myeloma (MM); however, the complete expression landscape of lncRNAs has not been elucidated. In the present work we characterized the lncRNAs transcriptome of MM and determined the potential involvement of lncRNAs in the pathogenesis and clinical behavior of MM.
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- 2019
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16. Electrostatic Analysis of the Aggregation of TrV Viral Particles
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Costabel, Marcelo D., Amundarain, María J., Zamarreño, Fernando, Sánchez-Eugenia, Rubén, Agirre, Jon, and Guérin, Diego M.A.
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- 2011
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