Constrained parsimonious model-based clustering

A new methodology for constrained parsimonious model-based clustering is introduced, where some tuning parameter allows to control the strength of these constraints. The methodology includes the 14 parsimonious models that are often applied in model-based clustering when assuming normal components as limit cases. This is done in a natural way by filling the gap among models and providing a smooth transition among them. The methodology provides mathematically well-defined problems and is also useful to prevent us from obtaining spurious solutions. Novel information criteria are proposed to help the user in choosing parameters. The interest of the proposed methodology is illustrated through simulation studies and a real-data application on COVID data

Monitoring Tools in Robust CWM for the Analysis of Crime Data

Robust inference for the Cluster Weighted Model requires the specification of a few hyper-parameters. Their role is crucial for increasing the quality of the estimators, while arbitrary decisions about their value could severely hamper inferential results. To guide the user in the delicate choice of such parameters, a monitoring approach has been introduced in the recent literature, yielding an adaptive method. The approach is here exemplified, via the analysis of a dataset on the effect of punishment regimes on crime rates

Specific gene correction of the AGXT gene and direct cell reprogramming for the treatment of Primary Hyperoxaluria Type 1

P428 Primary Hyperoxaluria Type 1 (PH1) is an inherited rare metabolic liver disease caused by the deficiency in the alanine: glyoxylate aminotransferase enzyme (AGXT), involved in the glyoxylate metabolism. The only potentially curative treatment is organ transplantation. Thus, the development of new therapeutic approaches for the treatment of these patients appears as a priority.We propose the combination of site-specific gene correction and direct cell reprogramming for the generation of autologous phenotypically healthy induced hepatocytes (iHeps) from skin-derived fibroblast of PH1 patients. For the correction of AGXT mutations, we have designed specific gene editing tools to address gene correction by two different strategies, assisted by CRISPR/Cas9 system. Accurate specific point mutation correction (c.853T-C) has been achieved by homologydirected repair (HDR) with ssODN harbouring wild-type sequence. In the second strategy, an enhanced version ofAGXTcDNAhas been inserted near the transcription start codon of the endogenous gene, constituting an almost universal correction strategy for PH1 mutations. Direct reprogramming of fibroblasts has been conducted by overexpression of hepatic transcription factors and in vitro culture in defined media. In vitro characterization of healthy induced hepatocytes (iHeps) has demonstrated hepatic function of the reprogrammed cells. PH1 patient fibroblasts and , ,

SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

Suppressed-scattering spectral windows for radiative cooling applications

The scattering of light by resonant nanoparticles is a key process for enhancing the solar reflectance in daylight radiative cooling. Here, we investigate the impact of material dispersion on the scattering performance of popular nanoparticles for radiative cooling applications. We show that, due to material dispersion, nanoparticles with a qualitatively similar response at visible frequencies exhibit fundamentally different scattering properties at infrared frequencies. It is found that dispersive nanoparticles exhibit suppressed-scattering windows, allowing for selective thermal emission within a highly reflective sample. The existence of suppressed-scattering windows solely depends on material dispersion, and they appear pinned to the same wavelength even in random composite materials and periodic metasurfaces. Finally, we investigate calcium-silicate-hydrate (CSH), the main phase of concrete, as an example of a dispersive host, illustrating that the co-design of nanoparticles and host allows for tuning of the suppressed-scattering windows. Our results indicate that controlled nanoporosities would enable concrete with daylight passive radiative cooling capabilities

Response of two Citrullus amarus accessions to isolates of three species of Meloidogyne and their graft compatibility with watermelon

[EN] The response of two Citrullus amarus accessions, BGV0005164 and BGV0005167, was assessed against different Meloidogyne arenaria, Meloidogyne incognita, and Meloidogyne javanica isolates in pot experiments and against M. incognita in plastic greenhouse. In the pot experiments, plants were inoculated with a second-stage juvenile per cm(3) of sterile sand and maintained in a growth chamber at 25 degrees C for 50 days. The watermelon cv. Sugar Baby was included as a susceptible control for comparison. At the end of the experiments, the number of egg masses and eggs per plant was determined, and the reproduction index was calculated as the percentage of the number of eggs produced in the C. amarus accessions with regard to that produced in the susceptible cv. Sugar Baby. In the plastic greenhouse experiment, the ungrafted watermelon cv. Sugar Baby and watermelons grafted onto each of the C. amarus accessions and onto the watermelon rootstock cv. Robusta were cultivated from May to August 2016 in plots with nematode densities from 46 to 1392 J2 per 250 cm(3) of soil at transplantation. At the end of the experiment, the galling index and the number of eggs per plant were determined, and the reproduction index was calculated. Additionally, the compatibility of the two accessions with the watermelon cv. Sugar Baby and the effect on fruit quality (weight, size, shape, firmness, pH, total soluble solids, and flesh color) were assessed under a hydroponic system in a greenhouse. The commercial rootstocks cv. Cobalt and cv. Robusta were also included. All the Meloidogyne isolates produced less egg masses and eggs per plant on the accessions than on Sugar Baby. Both accessions performed as resistant against M. arenaria, and from highly to moderately resistant to M. incognita and M. javanica in pot experiments. In the plastic greenhouse experiment, both C. amarus accessions performed as resistant to M. incognita. Both C. amarus accessions were compatible with the watermelon cv. Sugar Baby, but only the BGV0005167 accession did not influence the fruit quality. Then, the BGV0005167 accession is a promising rootstock for managing the three tropical root-knot nematode species without influencing watermelon fruit quality.The authors thank MINECO and FEDER for funding projects AGL2013-49040-C2-1-R, AGL2014-53398-C2-2-R-AR, AGL2017-89785-R, and AGL2017-85563-C2-1-R-AR. H. A. Garcia-Mendivil acknowledges CONACYT for suport through a pre-doctoral grant.Garcia-Mendivil, HA.; Munera, M.; Giné, A.; Escudero, N.; Picó Sirvent, MB.; Gisbert Domenech, MC.; Sorribas, FJ. (2019). Response of two Citrullus amarus accessions to isolates of three species of Meloidogyne and their graft compatibility with watermelon. Crop Protection. 119:208-213. https://doi.org/10.1016/j.cropro.2019.02.005S20821311

Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation

Bile acid; Inflammation; Oncostatin MÀcid biliar; Inflamació; Oncostatina MÁcido biliar; Inflamación; Oncostatina MBile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.This study was supported by the CIBERehd (EHD15PI05/2016) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819, PI20/00189, and PI20/01663 co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Junta de Castilla y Leon (SA074P20); Fundació Marato TV3 (Ref. 201916/31), Spain; AECC Scientific Foundation (2017/2020), Spain; Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of Wuerzburg, Germany (Project A-E-384 to H.M.H.); grants PID2019-111669-RB-I00, PID2020-115055RB-I00 from Agencia Estatal de Investigación (AEI), Spain; the AGAUR of the Generalidad de Cataluña SGR-2017-1112, Spain; and European Cooperation in Science & Technology (COST) Action CA17112. R.E.E was recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). J.A. was recipient of a grant from Fundación Echebano (2020–2022)

Improving our own knowledge through analysing an episode from teachers’ practice – different focuses of analysis

Una de las formas esenciales para lograr una mejor comprensión del contenido del conocimiento del profesor está ligada al análisis de su práctica. Esa práctica puede ser encarada de una forma amplia que no se limite sólo a la práctica de clase. Por otro lado, una discusión y reflexión sobre una misma situación de la práctica desde diferentes perspectivas teóricas y metodológicas puede contribuir también a una mejor comprensión no solo de la práctica sino también de los instrumentos metodológicos y teóricos en los que se sustenta el análisis. En esta comunicación presentamos y discutimos parte del trabajo desarrollado en la reunión intermedia del grupo de investigación sobre el conocimiento y desarrollo profesional del profesor de la SEIEM y cuyo foco de atención fue la discusión de las potencialidades del análisis de un mismo episodio desde cinco focos teóricos distintos.One of the core ways allowing obtain an ampler and deeper understanding on the content of teachers’ knowledge concerns analysing teachers’ practices. Such practice can be perceived in a broader way, not limited to classroom practice. On the other side, discussing and reflecting on the same situation with different theoretical and methodological approaches seems to contribute also for obtaining a deeper understanding not only on such practice but also on the used approaches for such analysis. In this paper we present and discuss part of the work developed in the intermeeting of the group research teachers’ knowledge and development of SEIEM concerning the potentialities of analyzing one episode using five different theoretical approaches