Publications by authors named "M Mar Albà"

299 Publications

Inhibition of estrogen related receptor α blocks liver steatosis and steatohepatitis and attenuates triglyceride biosynthesis.

Am J Pathol 2021 Apr 21. Epub 2021 Apr 21.

Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033. Electronic address:

The ERR family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study is to explore the role of estrogen-related receptor α (ERRα) in lipid metabolism and explore the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, we used three experimental mouse models: high fat diet, high carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/PI3K signaling pathway. Using a recently developed small molecule inhibitor for ERRα, we demonstrate that inhibiting ERRα blocks NAFLD development induced by either HCD or HFD feeding. ERRα inhibition also diminishes lipid accumulation and attenuates NASH development in the Pten null mice. We discovered glycerolipid synthesis as an additional mechanism for ERRα regulated NAFLD/NASH development and identified glycerophosphate acyltransferase 4 (GPAT4) as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.
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http://dx.doi.org/10.1016/j.ajpath.2021.04.007DOI Listing
April 2021

Hierarchical carrier transport simulator for defected nanoparticle solids.

Sci Rep 2021 Apr 2;11(1):7458. Epub 2021 Apr 2.

Physics Department, University of California, Davis, USA.

The efficiency of nanoparticle (NP) solar cells has grown impressively in recent years, exceeding 16%. However, the carrier mobility in NP solar cells, and in other optoelectronic applications remains low, thus critically limiting their performance. Therefore, carrier transport in NP solids needs to be better understood to further improve the overall efficiency of NP solar cell technology. However, it is technically challenging to simulate experimental scale samples, as physical processes from atomic to mesoscopic scales all crucially impact transport. To rise to this challenge, here we report the development of TRIDENS: the Transport in Defected Nanoparticle Solids Simulator, that adds three more hierarchical layers to our previously developed HINTS code for nanoparticle solar cells. In TRIDENS, we first introduced planar defects, such as twin planes and grain boundaries into individual NP SLs superlattices (SLs) that comprised the order of 10 NPs. Then we used HINTS to simulate the transport across tens of thousands of defected NP SLs, and constructed the distribution of the NP SL mobilities with planar defects. Second, the defected NP SLs were assembled into a resistor network with more than 10 NP SLs, thus representing about 10 individual NPs. Finally, the TRIDENS results were analyzed by finite size scaling to explore whether the percolation transition, separating the phase where the low mobility defected NP SLs percolate, from the phase where the high mobility undefected NP SLs percolate drives a low-mobility-to-highmobility transport crossover that can be extrapolated to genuinely macroscopic length scales. For the theoretical description, we adapted the Efros-Shklovskii bimodal mobility distribution percolation model. We demonstrated that the ES bimodal theory's two-variable scaling function is an effective tool to quantitatively characterize this low-mobility-to-high-mobility transport crossover.
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http://dx.doi.org/10.1038/s41598-021-86790-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018958PMC
April 2021

Enhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10.

Stem Cell Res Ther 2021 Feb 12;12(1):124. Epub 2021 Feb 12.

Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Av. Complutense 40, 28040, Madrid, Spain.

Background: Mesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced.

Methods: Human adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs.

Results: Transfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs.

Conclusions: Our results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1186/s13287-021-02193-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881581PMC
February 2021

Occupation, occupational exposures and mammographic density in Spanish women.

Environ Res 2021 04 30;195:110816. Epub 2021 Jan 30.

Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health, CIBERESP, Madrid, Spain.

Introduction: Mammographic density (MD), the proportion of radiologically dense breast tissue, is a strong risk factor for breast cancer. Our objective is to investigate the influence of occupations and occupational exposure to physical, chemical, and microbiological agents on MD in Spanish premenopausal women.

Methods: This is a cross-sectional study based on 1362 premenopausal workers, aged 39-50, who attended a gynecological screening in a breast radiodiagnosis unit of Madrid City Council. The work history was compiled through a personal interview. Exposure to occupational agents was evaluated using the Spanish job-exposure matrix MatEmESp. MD percentage was assessed using the validated semi-automated computer tool DM-Scan. The association between occupation, occupational exposures, and MD was quantified using multiple linear regression models, adjusted for age, educational level, body mass index, parity, previous breast biopsies, family history of breast cancer, energy intake, use of oral contraceptives, smoking, and alcohol consumption.

Results: Although no occupation was statistically significantly associated with MD, a borderline significant inverse association was mainly observed in orchard, greenhouse, nursery, and garden workers (β = -6.60; 95% confidence interval (95%CI) = -14.27; 1.07) and information and communication technology technicians (β = -7.27; 95%CI = -15.37; 0.84). On the contrary, a positive association was found among technicians in art galleries, museums, and libraries (β = 8.47; 95%CI = -0.65; 17.60). Women occupationally exposed to fungicides, herbicides, and insecticides tended to have lower MD. The percentage of density decreased by almost 2% for every 5 years spent in occupations exposed to the mentioned agents.

Conclusions: Although our findings point to a lack of association with the occupations and exposures analyzed, this study supports a deeper exploration of the role of certain occupational agents in MD, such as pesticides.
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http://dx.doi.org/10.1016/j.envres.2021.110816DOI Listing
April 2021

Uncovering de novo gene birth in yeast using deep transcriptomics.

Nat Commun 2021 01 27;12(1):604. Epub 2021 Jan 27.

Evolutionary Genomics Group, Research Programme on Biomedical Informatics, Hospital del Mar Research Institute (IMIM) and Universitat Pompeu Fabra (UPF), Barcelona, Spain.

De novo gene origination has been recently established as an important mechanism for the formation of new genes. In organisms with a large genome, intergenic and intronic regions provide plenty of raw material for new transcriptional events to occur, but little is know about how de novo transcripts originate in more densely-packed genomes. Here, we identify 213 de novo originated transcripts in Saccharomyces cerevisiae using deep transcriptomics and genomic synteny information from multiple yeast species grown in two different conditions. We find that about half of the de novo transcripts are expressed from regions which already harbor other genes in the opposite orientation; these transcripts show similar expression changes in response to stress as their overlapping counterparts, and some appear to translate small proteins. Thus, a large fraction of de novo genes in yeast are likely to co-evolve with already existing genes.
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http://dx.doi.org/10.1038/s41467-021-20911-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841160PMC
January 2021