24 research outputs found

    Transcriptional Regulation of zma-MIR528a by Action of Nitrate and Auxin in Maize

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    In recent years, miR528, a monocot-specific miRNA, has been assigned multifaceted roles during development and stress response in several plant species. However, the transcription regulation and the molecular mechanisms controlling MIR528 expression in maize are still poorly explored. Here we analyzed the zma-MIR528a promoter region and found conserved transcription factor binding sites related to diverse signaling pathways, including the nitrate (TGA1/4) and auxin (AuxRE) response networks. Accumulation of both pre-miR528a and mature miR528 was up-regulated by exogenous nitrate and auxin treatments during imbibition, germination, and maize seedling establishment. Functional promoter analyses demonstrated that TGA1/4 and AuxRE sites are required for transcriptional induction by both stimuli. Overall, our findings of the nitrogen- and auxin-induced zma-MIR528a expression through cis-regulatory elements in its promoter contribute to the knowledge of miR528 regulome

    An experimental DUAL model of advanced liver damage

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    Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice. C57BL/6 mice received 10% vol/vol alcohol in sweetened drinking water in combination with a Western diet for 10, 23, and 52 weeks (DUAL model). Animals fed with DUAL diet elicited a significant increase in body mass index accompanied by a pronounced hypertrophy of adipocytes, hypercholesterolemia, and hyperglycemia. Significant liver damage was characterized by elevated plasma alanine aminotransferase and lactate dehydrogenase levels, extensive hepatomegaly, hepatocyte enlargement, ballooning, steatosis, hepatic cell death, and compensatory proliferation. Notably, DUAL animals developed lobular inflammation and advanced hepatic fibrosis. Sequentially, bridging cirrhotic changes were frequently observed after 12 months. Bulk RNA-sequencing analysis indicated that dysregulated molecular pathways in DUAL mice were similar to those of patients with steatohepatitis. Conclusion: Our DUAL model is characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue. Altogether, the DUAL model mimics all histological, metabolic, and transcriptomic gene signatures of human advanced steatohepatitis, and therefore serves as a preclinical tool for the development of therapeutic targets

    Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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    Contains fulltext : 172380.pdf (publisher's version ) (Open Access

    Leptin signaling and circuits in puberty and fertility

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    Preliminary interpretation of the REMS pressure data from the first 100 sols of the MSL mission

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    We provide a preliminary interpretation of the Rover Environmental Monitoring Station (REMS) pressure data from the first 100 Martian solar days (sols) of the Mars Science Laboratory mission. The pressure sensor is performing well and has revealed the existence of phenomena undetected by previous missions that include possible gravity waves excited by evening downslope flows, relatively dust-free convective vortices analogous in structure to dust devils, and signatures indicative of the circulation induced by Gale Crater and its central mound. Other more familiar phenomena are also present including the thermal tides, generated by daily insolation variations, and the CO2 cycle, driven by the condensation and sublimation of CO2 in the polar regions. The amplitude of the thermal tides is several times larger than those seen by other landers primarily because Curiosity is located where eastward and westward tidal modes constructively interfere and also because the crater circulation amplifies the tides to some extent. During the first 100 sols tidal amplitudes generally decline, which we attribute to the waning influence of the Kelvin wave. Toward the end of the 100 sol period, tidal amplitudes abruptly increased in response to a nearby regional dust storm that did not expand to global scales. Tidal phases changed abruptly during the onset of this storm suggesting a change in the interaction between eastward and westward modes. When compared to Viking Lander 2 data, the REMS daily average pressures show no evidence yet for the 1–20 Pa increase expected from the possible loss of CO2 from the south polar residual cap.Peer reviewe

    Midkine Interaction with Chondroitin Sulfate Model Synthetic Tetrasaccharides and Their Mimetics: The Role of Aromatic Interactions

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    Midkine (MK) is a neurotrophic factor that participates in the embryonic central nervous system (CNS) development and neural stem cell regulation, interacting with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. In this work, we describe the interactions between a library of synthetic models of CS‐types and mimics. We did a structural study of this library by NMR and MD (Molecular Dynamics), concluding that the basic shape is controlled by similar geometry of the glycosidic linkages. Their 3D structures are a helix with four residues per turn, almost linear. We have studied the tetrasaccharide‐midkine complexes by ligand observed NMR techniques and concluded that the shape of the ligands does not change upon binding. The ligand orientation into the complex is very variable. It is placed inside the central cavity of MK formed by the two structured beta‐sheets domains linked by an intrinsically disordered region (IDR). Docking analysis confirmed the participation of aromatics residues from MK completed with electrostatic interactions. Finally, we test the biological activity by increasing the MK expression using CS tetrasaccharides and their capacity in enhancing the growth stimulation effect of MK in NIH3T3 cells
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