Double Diffusion Encoding Prevents Degeneracy in Parameter Estimation of Biophysical Models in Diffusion MRI

Purpose: Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, the general Standard Model has recently shown that model parameter estimation from dMRI data is ill-posed unless very strong magnetic gradients are used. We analyse this issue for the Neurite Orientation Dispersion and Density Imaging with Diffusivity Assessment (NODDIDA) model and demonstrate that its extension from Single Diffusion Encoding (SDE) to Double Diffusion Encoding (DDE) solves the ill-posedness and increases the accuracy of the parameter estimation. Methods: We analyse theoretically the cumulant expansion up to fourth order in b of SDE and DDE signals. Additionally, we perform in silico experiments to compare SDE and DDE capabilities under similar noise conditions. Results: We prove analytically that DDE provides invariant information non-accessible from SDE, which makes the NODDIDA parameter estimation injective. The in silico experiments show that DDE reduces the bias and mean square error of the estimation along the whole feasible region of 5D model parameter space. Conclusions: DDE adds additional information for estimating the model parameters, unexplored by SDE, which is enough to solve the degeneracy in the NODDIDA model parameter estimation.Comment: 22 pages, 7 figure

Single-cell RNA sequencing of human blood eosinophils reveals plasticity and absence of canonical cell subsets

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMPI21/0089

zoolog R package: Zooarchaeological analysis with log-ratios

Log Size Indexes (LSI) allow the increase of the number of data and have been used in a number of zooarchaeological studies since 1950. However, some standards to calculate the log ratios remain unpublished, the calculation of the indexes can be tedious, and it is further hindered by the diversity of data recording practices. The R package ‘zoolog’ enables calculation of thousands of log-ratios in seconds, with the advantage that the users can choose between different public references, which increases the repeatability and comparability of the results, allowing the smooth integration of references and databases with heterogeneous nomenclatures. Alternatively, the users may use their own references. This paper presents the main functionalities and procedures enabled by the package ‘zoolog’, together with some examples of use. A real dataset and several examples with R code are provided with the aim of facilitating osteometrical analyses in zooarchaeology.This work was developed as part of the ERC-Starting Grant ZooMWest (Grant agreement 716298)

Positivity and conservation of superenergy tensors

Two essential properties of energy-momentum tensors T_{\mu\nu} are their positivity and conservation. This is mathematically formalized by, respectively, an energy condition, as the dominant energy condition, and the vanishing of their divergence \nabla^\mu T_{\mu\nu}=0. The classical Bel and Bel-Robinson superenergy tensors, generated from the Riemann and Weyl tensors, respectively, are rank-4 tensors. But they share these two properties with energy momentum tensors: the Dominant Property (DP) and the divergence-free property in the absence of sources (vacuum). Senovilla defined a universal algebraic construction which generates a basic superenergy tensor T{A} from any arbitrary tensor A. In this construction the seed tensor A is structured as an r-fold multivector, which can always be done. The most important feature of the basic superenergy tensors is that they satisfy automatically the DP, independently of the generating tensor A. In a previous paper we presented a more compact definition of T{A} using the r-fold Clifford algebra. This form for the superenergy tensors allowed to obtain an easy proof of the DP valid for any dimension. In this paper we include this proof. We explain which new elements appear when we consider the tensor T{A} generated by a non-degree-defined r-fold multivector A and how orthogonal Lorentz transformations and bilinear observables of spinor fields are included as particular cases of superenergy tensors. We find some sufficient conditions for the seed tensor A, which guarantee that the generated tensor T{A} is divergence-free. These sufficient conditions are satisfied by some physical fields, which are presented as examples.Comment: 19 pages, no figures. Language and minor changes. Published versio

New Red-Emitting Chloride-Sensitive Fluorescent Protein with Biological Uses

This work was financially supported by CTQ2017-85685-R, CTQ2017-85454-C2-1-P, and CTQ2017-86125-P (MICIU/AEI/ERDF). J.M.P. and J.D.V. thank UEQ for funding. J.V.P. is supported by an FPU fellowship (FPU17/04749). D.A. was supported by the Italian Cystic Fibrosis Foundation (grant FFC#3/2019) and by Fondazione Cassa Rurale Trento Rovereto (ref 2018.256). The authors acknowledge the Universidad of Granada (Spain) cell culture and microscopy central facilities (CIC-UGR).A new chloride-sensitive red fluorescent protein derived from Entacmaea quadricolor is described. We found that mBeRFP exhibited moderate sensitivity to chloride and, via sitedirected mutagenesis (S94V and R205Y), we increased the chloride affinity by more than an order of magnitude (kd = 106 ± 6 mM) at physiological pH. In addition, cis−trans isomerization of the chromophore produces a dual emission band with different chloride sensitivities, which allowed us to develop a ratiometric methodology to measure intracellular chloride concentrations.MICIU/AEI/ERDF CTQ2017-85685-R CTQ2017-85454-C2-1-P CTQ2017-86125-PUEQSpanish Government FPU17/04749Ministry of Health, ItalyItalian Cystic Fibrosis Research Foundation 3/2019Fondazione Cassa Rurale Trento Rovereto 2018.25

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Somatostatin (SST) and cortistatin (CORT) regulate numerous endocrine secretions and their absence [knockout (KO)-models] causes important endocrine-metabolic alterations, including pituitary dysregulations. We have demonstrated that the metabolic phenotype of single or combined SST/CORT KO-models is not drastically altered under normal conditions. However, the biological actions of SST/CORT are conditioned by the metabolic-status (e.g. obesity). Therefore, we used male/female SST- and CORT-KO mice fed low-fat (LF) or high-fat (HF) diet to explore the interplay between SST/CORT and obesity in the control of relevant pituitary-axes and whole-body metabolism. Our results showed that the SST/CORT role in the control of GH/prolactin secretions is maintained under LF- and HF-diet conditions as SST-KOs presented higher GH/prolactin-levels, while CORT-KOs displayed higher GH- and lower prolactin-levels than controls under both diets. Moreover, the impact of lack of SST/CORT on the metabolic-function was gender- and diet-dependent. Particularly, SST-KOs were more sensitive to HF-diet, exhibiting altered growth and body-composition (fat/lean percentage) and impaired glucose/insulin-metabolism, especially in males. Conversely, only males CORT-KO under LF-diet conditions exhibited significant alterations, displaying higher glucose-levels and insulin-resistance. Altogether, these data demonstrate a tight interplay between SST/CORT-axis and the metabolic status in the control of endocrine/metabolic functions and unveil a clear dissociation of SST/CORT rolesThis work was supported by the following grants: Junta de Andalucía (CTS-1406, BIO-0139), ISCIII-FIS [PI13/00651 and PIE14/00005 (co-funded by European Regional Development Fund/European Social Fund “Investing in your future”)], MINECO (BFU2013–43282-R), “Miguel Servet” Program, CIBERobn and Ayuda Merck Serono 2013S

Oropharyngeal botryomycosis in a geriatric mare

Botryomycosis is an uncommon chronic bacterial infection that can have cutaneous and visceral involvement. This report describes an 18‐year‐old mixed‐breed mare presented with dysphagia, dyspnoea and an upper respiratory noise that developed secondary to oropharyngeal botryomycosis. Histological examination of the mass showed a granulomatous formation with Splendore–Hoeppli phenomenon surrounding Gram‐positive bacteria. This report describes the clinical signs, approach and management of an oropharyngeal Staphylococcus aureus granuloma in a geriatric mare.info:eu-repo/semantics/acceptedVersio

Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth

Glioblastomas (GBMs) are very aggressive tumors that are resistant to conventional chemo- and radiotherapy. New molecular therapeutic strategies are required to effectively eliminate the subpopulation of GBM tumor-initiating cells that are responsible for relapse. Since EGFR is altered in 50% of GBMs, it represents one of the most promising targets; however, EGFR kinase inhibitors have produced poor results in clinical assays, with no clear explanation for the observed resistance. We uncovered a fundamental role for the dual-specificity tyrosine phosphorylation-regulated kinase, DYRK1A, in regulating EGFR in GBMs. We found that DYRK1A was highly expressed in these tumors and that its expression was correlated with that of EGFR. Moreover, DYRK1A inhibition promoted EGFR degradation in primary GBM cell lines and neural progenitor cells, sharply reducing the self-renewal capacity of normal and tumorigenic cells. Most importantly, our data suggest that a subset of GBMs depends on high surface EGFR levels, as DYRK1A inhibition compromised their survival and produced a profound decrease in tumor burden. We propose that the recovery of EGFR stability is a key oncogenic event in a large proportion of gliomas and that pharmacological inhibition of DYRK1A could represent a promising therapeutic intervention for EGFR-dependent GBMs.This work was supported by grants from the Ministerio de Educación y Ciencia (MEC; SAF2008-04531), the Ministerio de Ciencia e Innovación (MICINN, PLE2009-0115), and the Ministerio de Asuntos Exteriores y Cooperación (MAEC-AECID A/023963/09; to P. Sánchez-Gómez), as well as by grants from the Fondo de Investigación Sanitaria (FIS-PS09-01977) and Fundación Mutua-madrileña grants (FMM 2007/057, to J.R. Ricoy; and FMM2011/89, to J.M. Sepúlveda).S