| 1. |
- Duran-Ferrer, Marti, et al.
(författare)
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The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
- 2020
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Ingår i: NATURE CANCER. - : Springer Nature. - 2662-1347. ; 1:11, s. 1066-1081
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Tidskriftsartikel (refereegranskat)abstract
- We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.
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| 2. |
- Martínez-Sánchez, Noelia, et al.
(författare)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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| 3. |
- Blennow, Mattias, 1980-, et al.
(författare)
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Bounds on lepton non-unitarity and heavy neutrino mixing
- 2023
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Ingår i: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479. ; 2023:8
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Tidskriftsartikel (refereegranskat)abstract
- We present an updated and improved global fit analysis of current flavour and electroweak precision observables to derive bounds on unitarity deviations of the leptonic mixing matrix and on the mixing of heavy neutrinos with the active flavours. This new analysis is motivated by new and updated experimental results on key observables such as V-ud, the invisible decay width of the Z boson and the W boson mass. It also improves upon previous studies by considering the full correlations among the different observables and explicitly calibrating the test statistic, which may present significant deviations from a & chi;(2) distribution. The results are provided for three different Type-I seesaw scenarios: the minimal scenario with only two additional right-handed neutrinos, the next to minimal one with three extra neutrinos, and the most general one with an arbitrary number of heavy neutrinos that we parametrise via a generic deviation from a unitary leptonic mixing matrix. Additionally, we also analyze the case of generic deviations from unitarity of the leptonic mixing matrix, not necessarily induced by the presence of additional neutrinos. This last case relaxes some correlations among the parameters and is able to provide a better fit to the data. Nevertheless, inducing only leptonic unitarity deviations avoiding both the correlations implied by the right-handed neutrino extension as well as more strongly constrained operators is challenging and would imply significantly more complex UV completions.
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| 4. |
- Blennow, Mattias, 1980-, et al.
(författare)
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Updated global bounds on non-unitarity and heavy neutrinos
- 2024
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Ingår i: European Physical Society Conference on High Energy Physics, EPS-HEP 2023. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- We present an updated and improved global fit analysis of current flavor and electroweak precision observables to derive bounds on unitarity deviations of the leptonic mixing matrix and on the mixing of heavy neutrinos with the active flavours, which is motivated by the latest experimental updates on key observables such as Vud, the Z invisible width and the W mass.
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| 5. |
- Matxain, Jon M, et al.
(författare)
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New solids based on B12N12 fullerenes
- 2007
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Ingår i: The Journal of Physical Chemistry C. - Washington, DC : American Chemical Society. - 1932-7447 .- 1932-7455. ; 111:36, s. 13354-60
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, BN fullerenes have been synthesized experimentally. As their carbon counterparts, these BN fullerenes could be assembled in molecular solids, but this possibility has been studied little in the literature. In this work, we focus on the smallest synthesized BN fullerene, B12N12, which is built by squares and hexagons. First, the interaction between two of these fullerenes has been analyzed, using the hybrid B3LYP and MPW1PW91 density functional methods. Two different interactions have been studied in the dimer, a square facing a square (S−S) and a hexagon facing a hexagon (H−H). In both cases, a B is facing a N. The most stable dimer was found to be S−S facing, with covalent interactions between the monomers, but other dimers with weak interactions have been found as well, which opens possibilities of new systems, as in the case of fullerene dimers and solids. The solids resulting from the infinite repetition of the characterized dimers were optimized, finding two different solids, with covalent and weak interactions between monomers, respectively. The solid with covalent interactions is a nanoporous material that is more stable by around 12 eV. Because of the nanoporous character of this solid, it could be used for heterogeneous catalysis, molecular transport, and so forth. The SIESTA code with the GGA-PBE density functional method has been used for the solid-state calculations.
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| 6. |
- Sebastian, Eider San, et al.
(författare)
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Metal ion dependent adhesion sites in integrins : A Combined DFT and QMC Study on Mn2
- 2007
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Ingår i: Journal of Physical Chemistry B. - Washington, DC : American Chemical Society. - 1520-6106 .- 1520-5207. ; 111:30, s. 9099-9103
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Tidskriftsartikel (refereegranskat)abstract
- The theoretical study of relative energies of different spin states of Mn2+ has been carried out for the isolated cation and for structures in which the cation is coordinated to ligands that represent the first coordination shell in a protein environment that contains a metal ion dependent adhesion site (MIDAS, found in the ligand binding domain of protein LFA-1). The calculations determine whether the ligand field generated by a prototype protein environment affects the relative energies between high, intermediate, and low spin states. Geometry optimizations and vibrational frequency calculations were carried out at the B3LYP/SKBJ+* level of theory. Single point calculations were performed at the B3LYP/6-311++G(2df,2p) and diffusion monte carlo (DMC) levels for the refinement of the electronic energies. These calculations reveal important differences in the relative energies between high/low spin complexes obtained by B3LYP and DMC and show that although both DFT and DMC show similar trends, a higher level method such as DMC is necessary for a quantitative description of the interactions between Mn2+ and its natural ligands. (G)s of acetate-type ligand binding reactions were calculated that show that the higher the spin of the manganese complex, the lower the affinity for the ligand.
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