242 results match your criteria: "Institute for Biocomputation and Physics of Complex Systems (BIFI)[Affiliation]"

A collection of magnetic nanoparticles with average particle sizes in the range between 9 and 78 nm were prepared using several synthetic approaches that also provided different particle morphologies (spherical, octahedral and flowers). Some of these particles were also subsequently coated with different molecules in order to generate a set of materials that allowed us to evaluate the impact that the particle size, shape and coating had on the heating capacity of the nanoparticles when exposed to near infrared (NIR) laser light. Moreover, one of the prepared materials (octahedral particles of ∌32 nm coated with dextran) was used to perform an assay to study the possible use of this material in the frame of photothermal treatments to trigger cell death.

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On social media platforms, priority users (e.g., verified profiles on X) are users whose posts are promoted by recommendation algorithms.

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infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase in multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide. By using a high-throughput screening strategy, in combination with in vitro DNA binding assays and antibacterial activity testing, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.

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Although aminergic GPCRs are the target for ~25% of approved drugs, developing subtype selective drugs is a major challenge due to the high sequence conservation at their orthosteric binding site. Bitopic ligands are covalently joined orthosteric and allosteric pharmacophores with the potential to boost receptor selectivity and improve current medications by reducing off-target side effects. However, the lack of structural information on their binding mode impedes rational design.

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A statistical-physics approach for codon usage optimisation.

Comput Struct Biotechnol J

December 2024

Department of Theoretical Physics, Faculty of Science, University of Zaragoza, c/ Pedro Cerbuna s/n, Zaragoza, 50009, Spain.

The concept of "codon optimisation" involves adjusting the coding sequence of a target protein to account for the inherent codon preferences of a host species and maximise protein expression in that species. However, there is still a lack of consensus on the most effective approach to achieve optimal results. Existing methods typically depend on heuristic combinations of different variables, leaving the user with the final choice of the sequence hit.

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BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses.

Immunity

September 2024

Committee on Immunology, University of Chicago, Chicago, IL, USA; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA; Department of Human Genetics, University of Chicago, Chicago, IL, USA; Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA. Electronic address:

Although the Bacille-Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, it also offers protection against a diverse range of non-mycobacterial infections. However, the underlying protective mechanisms in humans are not yet fully understood. Here, we surveyed at single-cell resolution the gene expression and chromatin landscape of human bone marrow, aspirated before and 90 days after BCG vaccination or placebo.

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Dynamics of CRISPR-mediated virus-host interactions in the human gut microbiome.

ISME J

January 2024

Centro de AstrobiologĂ­a (CAB), CSIC-INTA, Ctra. de TorrejĂłn a Ajalvir Km 4, 28850, TorrejĂłn de Ardoz, Madrid, Spain.

Article Synopsis
  • Arms races between mobile genetic elements and prokaryotic hosts significantly influence microbial community evolution and ecology.
  • Prokaryotic defense mechanisms, like CRISPR-Cas, can regulate gut microbiome composition by affecting interactions among bacteria, plasmids, and phages.
  • Our findings indicate that CRISPR-Cas immunity primarily reduces lytic phage abundance, while having lesser effects on lysogenic phages and plasmids, and highlights the role of phage interactions in promoting bacterial diversity in the human gut.
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From unbiased to maximal-entropy random walks on hypergraphs.

Phys Rev E

May 2024

Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain.

Random walks have been intensively studied on regular and complex networks, which are used to represent pairwise interactions. Nonetheless, recent works have demonstrated that many real-world processes are better captured by higher-order relationships, which are naturally represented by hypergraphs. Here we study random walks on hypergraphs.

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ISR pathway contribution to tissue specificity of mitochondrial diseases.

Trends Endocrinol Metab

October 2024

Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza 50009 and 50013, Spain; Instituto de Investigación Sanitaria (IIS) de Aragón, Zaragoza 50009, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain. Electronic address:

Mitochondrial genetic defects caused by whole-body mutations typically affect different tissues in different ways. Elucidating the molecular determinants that cause certain cell types to be primarily affected has become a critical research target within the field. We propose a differential activation of the integrated stress response as a potential contributor to this tissue specificity.

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Clostridioides (formerly Clostridium) difficile is a leading cause of infectious diarrhea associated with antibiotic therapy. The ability of this anaerobic pathogen to acquire enough iron to proliferate under iron limitation conditions imposed by the host largely determines its pathogenicity. However, since high intracellular iron catalyzes formation of deleterious reactive hydroxyl radicals, iron uptake is tightly regulated at the transcriptional level by the ferric uptake regulator Fur.

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Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers.

PLoS Comput Biol

April 2024

Centro de AstrobiologĂ­a (CAB) CSIC-INTA, TorrejĂłn de Ardoz, Madrid, Spain.

Epistasis among driver mutations is pervasive and explains relevant features of cancer, such as differential therapy response and convergence towards well-characterized molecular subtypes. Furthermore, a growing body of evidence suggests that tumor development could be hampered by the accumulation of slightly deleterious passenger mutations. In this work, we combined empirical epistasis networks, computer simulations, and mathematical models to explore how synergistic interactions among driver mutations affect cancer progression under the burden of slightly deleterious passengers.

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Comparison of the function of two novel human dopamine D2 receptor variants identifies a likely mechanism for their pathogenicity.

Biochem Pharmacol

October 2024

Research Service, Veterans Affairs Portland Health Care System, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:

Two recently discovered DRD2 mutations, c.634A > T, p.Ile212Phe and c.

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Pyridoxal 5'-Phosphate Biosynthesis by Pyridox-(am)-ine 5'-Phosphate Oxidase: Species-Specific Features.

Int J Mol Sci

March 2024

Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences, University of Zaragoza, 50009 Zaragoza, Spain.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx).

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Introduction: The slow descent in TB burden, the COVID-19 pandemic, along with the rise of multidrug-resistant strains of , seriously threaten TB control and the goals of the End TB strategy. To fight back, several vaccine candidates are under development, with some of them undergoing the phases 2B and 3 of the development pipeline. The impact of these vaccines on the general population needs to be addressed using disease-transmission models, and, in a country like China, which last year ranked third in number of cases worldwide, and where the population is aging at a fast pace, the impact of TB vaccination campaigns may depend heavily upon the age of targeted populations, the mechanistic descriptions of the TB vaccines and the coupling between TB dynamics and demographic evolution.

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Objective: To identify new parameters predicting fetal acidemia.

Methods: A retrospective case-control study in a cohort of deliveries from a tertiary referral hospital-based cohort deliveries in Zaragoza, Spain between 2018 and 2021 was performed. To predict fetal acidemia, the NICHD categorizations and non-NICHD parameters were analyzed in the electronic fetal monitoring (EFM).

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In this work, we analyze how reputation-based interactions influence the emergence of innovations. To do so, we make use of a dynamic model that mimics the discovery process by which, at each time step, a pair of individuals meet and merge their knowledge to eventually result in a novel technology of higher value. The way in which these pairs are brought together is found to be crucial for achieving the highest technological level.

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Article Synopsis
  • Mitochondrial alterations are linked to various cancers, including multiple myeloma (MM), and natural flavonoids like Hesperetin and Naringenin are studied for their potential to target mitochondrial dynamics by affecting the protein Drp1.
  • The study involved multiple methods such as molecular docking, cell viability tests, and transcriptomic analyses to explore how Hes and Nar influence MM cells, including effects on cell growth and apoptosis.
  • Results showed that Hes and Nar inhibit Drp1, leading to changes in mitochondrial structure, reduced cancer cell survival and growth, and altered cellular metabolism by down-regulating key transcription factors involved in lipogenesis.
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Background And Objectives: The variability in the number of donations together with a growing demand for platelet concentrates and plasma-derived medicines make us seek solutions aimed at optimizing the processing of blood. Some mathematical models to improve efficiencies in blood banking have been published. The goal of this work is to validate and evaluate an algorithm's impact in the production of blood components in the Blood and Tissues Bank of Aragon (BTBA).

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Structure of the dopamine D3 receptor bound to a bitopic agonist reveals a new specificity site in an expanded allosteric pocket.

Res Sq

December 2023

Institute for Biocomputation and Physics of Complex Systems (BIFI) and Laboratorio de MicroscopĂ­as Avanzadas (LMA), University of Zaragoza, 50018, Zaragoza, Spain.

Although aminergic GPCRs are the target for ~25% of approved drugs, developing subtype selective drugs is a major challenge due to the high sequence conservation at their orthosteric binding site. Bitopic ligands are covalently joined orthosteric and allosteric pharmacophores with the potential to boost receptor selectivity, driven by the binding of the secondary pharmacophore to non-conserved regions of the receptor. Although bitopic ligands have great potential to improve current medications by reducing off-target side effects, the lack of structural information on their binding mode impedes rational design.

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The role of complexity for digital twins of cities.

Nat Comput Sci

May 2023

Technologies for Smart Communities, DG CNECT, European Commission, Brussels, Belgium.

We argue that theories and methods drawn from complexity science are urgently needed to guide the development and use of digital twins for cities. The theoretical framework from complexity science takes into account both the short-term and the long-term dynamics of cities and their interactions. This is the foundation for a new approach that treats cities not as large machines or logistic systems but as mutually interwoven self-organizing phenomena, which evolve, to an extent, like living systems.

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Determining the key elements of interconnected infrastructure and complex systems is paramount to ensure system functionality and integrity. This work quantifies the dominance of the networks' nodes in their respective neighborhoods, introducing a centrality metric, DomiRank, that integrates local and global topological information via a tunable parameter. We present an analytical formula and an efficient parallelizable algorithm for DomiRank centrality, making it applicable to massive networks.

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While the Bacille-Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, it also offers protection against a diverse range of non-mycobacterial infections. However, the underlying protective mechanisms in humans are not yet fully understood. Here, we surveyed at single-cell resolution the gene expression and chromatin landscape of human bone marrow, aspirated before and 90 days after BCG vaccination or placebo administration.

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The neuronal calcium sensor 1 (NCS-1), an EF-hand Ca binding protein, and Ric-8A coregulate synapse number and probability of neurotransmitter release. Recently, the structures of Ric-8A bound to Gα have revealed how Ric-8A phosphorylation promotes Gα recognition and activity as a chaperone and guanine nucleotide exchange factor. However, the molecular mechanism by which NCS-1 regulates Ric-8A activity and its interaction with Gα subunits is not well understood.

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Mitochondrial carrier homologs 1 (MTCH1) and 2 (MTCH2) are orphan members of the mitochondrial transporter family SLC25. Human MTCH1 is also known as presenilin 1-associated protein, PSAP. MTCH2 is a receptor for tBid and is related to lipid metabolism.

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Robustness and Complexity of Directed and Weighted Metabolic Hypergraphs.

Entropy (Basel)

November 2023

Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain.

Metabolic networks are probably among the most challenging and important biological networks. Their study provides insight into how biological pathways work and how robust a specific organism is against an environment or therapy. Here, we propose a directed hypergraph with edge-dependent vertex weight as a novel framework to represent metabolic networks.

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