Resultados de investigación

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).--, Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC., This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366) (Project of Excellence, Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). The authors are also grateful for grants 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and grant 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur), which were used to facilitate recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and wish to express their gratitude for the unrestricted funding from the Menarini Group and AstraZeneca., Peer reviewed

Supplementary Material contains: - Experimental procedures - Tables S1-S10 - Figure S1 - Figure S2 - Figure S3e, © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Caloric restriction is a non-pharmacological intervention known to ameliorate the metabolic defects associated with aging, including insulin resistance. The levels of miRNA expression may represent a predictive tool for aging-related alterations. In order to investigate the role of miRNAs underlying insulin resistance in adipose tissue during the early stages of aging, 3- and 12-month-old male animals fed ad libitum, and 12-month-old male animals fed with a 20% caloric restricted diet were used. In this work we demonstrate that specific miRNAs may contribute to the impaired insulin-stimulated glucose metabolism specifically in the subcutaneous white adipose tissue, through the regulation of target genes implicated in the insulin signaling cascade. Moreover, the expression of these miRNAs is modified by caloric restriction in middle-aged animals, in accordance with the improvement of the metabolic state. Overall, our work demonstrates that alterations in posttranscriptional gene expression because of miRNAs dysregulation might represent an endogenous mechanism by which insulin response in the subcutaneous fat depot is already affected at middle age. Importantly, caloric restriction could prevent this modulation, demonstrating that certain miRNAs could constitute potential biomarkers of age-related metabolic alterations., This work was supported by grants from Community of Madrid (Found action by the Community of Madrid in the framework of the Multiannual Agreement with the Rey Juan Carlos University in line of action 1, “Encouragement of Young PhD investigation”, A-485-EPIGENIDAD to P.C. and S2017/BMD-3684 and P2022/BMD-7227 to G.M.G.) and the Spanish Ministry of Economy and Competitiveness (BFU2013-47384-R, BFU2016-78951-R, and BFU2017-90578-REDT) and Spanish Ministry of Science and Innovation (PID2020-116875RB-I00) to G.M.G and “Ayuda a la Investigación Ignacio Hernando de Larramendi 2014” from Mapfre Foundation to G.M.G., Peer reviewed

Additional file 1. Supplementary figures., Instituto de Salud Carlos III Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Peer reviewed

The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed

The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed

The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed

pbio.3002315.t002 - Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics, Peer reviewed

pbio.3002315.t001 - Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics, Peer reviewed

Schematics showing the current working models: (A) uni- and bipotent hepatoblast contributions to hepatocytes and BECs following heterogeneous lineage decisions. (B) Hepatoblasts contribute with heterogeneous proliferation behaviours to postembryonic liver growth. Cells from the embryonic left lobe contribute to the ventral lobe, including the formation of giant clusters (magenta). (C) The liver morphology changes dramatically simultaneous to the intestinal bending occurring during postembryonic growth (green). BEC, biliary epithelial cell; dpf, day postfertilization; SL, standard length., Peer reviewed

(A) The 6 steps of ventral liver lobe formation correlate with fish standard length (SL). The numerical values that were used to generate the graph can be found in S1 Data. (B) Stage I: A small tissue extension at the tip of the left lobe is visible (n = 12 livers). (C) Stage II: a thin ventral lobe originates in the lower half of the left lobe (n = 6 livers). (D) Stage III: the thin ventral lobe shifts position towards the more anterior part of the left lobe (n = 4 livers). (E) Stage IV: the tip of the ventral lobe starts to expand (n = 7 livers). (F) Stage V: lateral-oriented expansion of the ventral lobe (n = 28 livers). (G) Stage VI: enlargement of all lobes in width (n = 6 livers). The blue areas in the schematics mark the region characteristic for the respective stage. (H) Schematic depicting the morphology of the liver in relation to the folding of the intestine in stages I-VI. A, anterior; P, posterior; R, right; L, left; RL, right lobe; LL, left lobe; VL, ventral lobe., Peer reviewed