Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter

<p>Abstract</p> <p>Background</p> <p>DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene <it>Dlk2 </it>is coordinated with that of <it>Dlk1 </it>in several tissues and cell lines. Unlike <it>Dlk1</it>, the mouse <it>Dlk2 </it>gene and its locus at chromosome 17 are not fully characterized.</p> <p>Results</p> <p>The goal of this work was the characterization of <it>Dlk2 </it>mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the <it>Dlk2 </it>transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. <it>In silico </it>analysis revealed that <it>Dlk2 </it>possesses a TATA-less promoter containing minimal promoter elements associated with a CpG island, and sequences for Inr and DPE elements. Besides, it possesses six GC-boxes, considered as consensus sites for the transcription factor Sp1. Indeed, we report that Sp1 directly binds to the <it>Dlk2 </it>promoter, activates its transcription, and regulates its level of expression.</p> <p>Conclusions</p> <p>Our results provide the first characterization of <it>Dlk2 </it>transcripts, map the location of the <it>Dlk2 </it>core promoter, and show the role of Sp1 as a key regulator of <it>Dlk2 </it>transcription, providing new insights into the molecular mechanisms that contribute to the expression of the <it>Dlk2 </it>gene.</p

Social innovation laboratories for the social construction of knowledge

Social innovation laboratories (SIL) are spaces for the construction of knowledge where UNESCO’s Sustainable Development Goals can be met. The objective of the research was to identify the most relevant studies about the social construction of knowledge, within the framework of the SIL, related to environmental problems and to analyze them in order to propose solutions for sustainability. The method used to locate the articles published in open access, from 2010 to 2020, in Scopus, Web of Science and Google Academic, was the Systematic Literature Review. The findings show that the working groups are multidisciplinary and originate proposals from different areas of science. The products are built with an open approach. Universities are the spaces that most promote participation in the laboratories to generate sustainability actions applicable in real life and work is done to scale up the prototypes to local, national and international levels

Measurement of the social construction of knowledge: validation and reliability of the K-Social-C instrument

[EN] The social construction of knowledge developed in social innovation laboratories occurs through the open innovation approach, which is the focus of the present study. The study variables were measured with the K-Social-C questionnaire. It was necessary to consider the indicators of each of these variables reported in the literature and the characteristics of construct, content, and criterion validity and reliability to demonstrate solidly that the instrument measures what it is intended to measure. This document confrms the conceptualization and measurement of three variables: social construction of knowledge (SCK), open innovation (OI), and social innovation laboratories (SIL). The K-Social-C questionnaire is a selfadministered instrument that can measure the three variables and their indicators. The questionnaire's validity and reliability were demonstrated through statistical procedures; the content validation and expert agreement were through Kendall's concordance coefcient and the content validity coefcient. We also calculated the internal consistency with Cronbach's alpha as the reliability coefcient. We extended the calculation with exploratory factor analysis and convergent and discriminant validity. However, to study the SCK, OI and SIL variables, we still had to consider the needs and social implications of innovation in each context.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

Design and Implementation of a Pressure Monitoring System Based on IoT for Water Supply Networks

Increasing the efficiency of water supply networks is essential in arid and semi-arid regions to ensure the supply of drinking water to the inhabitants. The cost of renovating these systems is high. However, customized management models can facilitate the maintenance and rehabilitation of hydraulic infrastructures by optimizing the use of resources. The implementation of current Internet of Things (IoT) monitoring systems allows decisions to be based on objective data. In water supply systems, IoT helps to monitor the key elements to improve system efficiency. To implement IoT in a water distribution system requires sensors that are suitable for measuring the main hydraulic variables, a communication system that is adaptable to the water service companies and a friendly system for data analysis and visualization. A smart pressure monitoring and alert system was developed using low-cost hardware and open-source software. An Arduino family microcontroller transfers pressure gauge signals using Sigfox communication, a low-power wide-area network (LPWAN). The IoT ThingSpeak platform is used for data analysis and visualization. Additionally, the system can send alarms via SMS/email in real time using the If This, Then That (IFTTT) web service when anomalous pressure data are detected. The pressure monitoring system was successfully implemented in a real water distribution network in Spain. It was able to detect both breakdowns and leaks in real time

Cystoid Macular Edema: Causes, Diagnosis and Treatment

The purpose of this paper is to conduct a review of studies on cystoid macular edema published in the last seven years. Cystoid macular edema is a major cause of loss of visual acuity. It is the final common pathway of many diseases and can be caused by numerous processes including inflammatory, vascular, adverse drug reactions, retinal dystrophy or intraocular tumors. These processes disrupt the blood-retinal barrier, with fluid extravasation to the macular parenchyma. Imaging tests are essential for both detection and monitoring of this pathology. Fluorescein angiography and autofluorescence show the leakage of liquid from perifoveal vessels into the tissue where it forms cystic spaces. Optical coherence tomography is currently the gold standard technique for diagnosis and monitoring. This allows objective measurement of retinal thickness, which correlates with visual acuity and provides more complete morphological information. Based on the underlying etiology, the therapeutic approach can be either surgical or medical with anti-inflammatory drugs. We found that disruption of the blood-retinal barrier for various reasons is the key point in the pathogenesis of cystoid macular edema, therefore we believe that studies on its treatment should proceed on this path

The influence of anisotropic growth and geometry on the stress of solid tumors

Solid stresses can affect tumor patho-physiology in at least two ways: directly, by compressing cancer and stromal cells, and indirectly, by deforming blood and lymphatic vessels. In this work, we model the tumor mass as a growing hyperelastic material. We enforce a multiplicative decomposition of the deformation gradient to study the role of anisotropic tumor growth on the evolution and spatial distribution of stresses. Specifically, we exploit radial symmetry and analyze the response of circumferential and radial stresses to (a) degree of anisotropy, (b) geometry of the tumor mass (cylindrical versus spherical shape), and (c) different tumor types (in terms of mechanical properties). According to our results, both radial and circumferential stresses are compressive in the tumor inner regions, whereas circumferential stresses are tensile at the periphery. Furthermore, we show that the growth rate is inversely correlated with the stresses’ magnitudes. These qualitative trends are consistent with experimental results. Our findings therefore elucidate the role of anisotropic growth on the tumor stress state. The potential of stress-alleviation strategies working together with anticancer therapies can result in better treatments

Power distribution in a 13 kW three-phase rectifier system: impact on weight, volume and efficiency

This paper addresses the power delivery strategy on an aircraft application consisting on seven isolated DC loads to be supplied from the AC grid. Distributed or centralized power processing is evaluated taking into account weight and efficiency. Additionally, the rectifier switching frequency has to be synchronized with an external frequency clock to minimize the interference of the converter harmonics with the loads

The role of malignant tissue on the thermal distribution of cancerous breast

The present work focuses on the integration of analytical and numerical strategies to investigate the thermal distribution of cancerous breasts. Coupled stationary bioheat transfer equations are considered for the glandular and heterogeneous tumor regions, which are characterized by different thermophysical properties. The cross-section of the cancerous breast is identified by a homogeneous glandular tissue that surrounds the heterogeneous tumor tissue, which is assumed to be a two-phase periodic composite with non-overlapping circular inclusions and a square lattice distribution, wherein the constituents exhibit isotropic thermal conductivity behavior. Asymptotic periodic homogenization method is used to find the effective properties in the heterogeneous region. The tissue effective thermal conductivities are computed analytically and then used in the homogenized model, which is solved numerically. Results are compared with appropriate experimental data reported in the literature. In particular, the tissue scale temperature profile agrees with experimental observations. Moreover, as a novelty result we find that the tumor volume fraction in the heterogeneous zone influences the breast surface temperature

Foveal avascular zone and choroidal thickness are decreased in subjects with hard drusen and without high genetic risk of developing Alzheimer’s disease

A family history (FH+) of Alzheimer’s disease (AD) and ɛ4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ɛ4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ɛ4−, HD+) group compared with (i) both the (FH−, ɛ4−, HD−) and the (FH+, ɛ4+, HD+) groups in the superior and inferior points at 1500 μm, and (ii) the (FH+, ɛ4−, HD+) group in the superior point at 1500 μm. There were statistically significant differences in the superficial FAZ between the (FH+, ɛ4−, HD+) group and (i) the (FH+, ɛ4−, HD−) group and (ii) the (FH+, ɛ4+, HD−) group. In conclusion, ocular vascular changes are not yet evident in participants with a genetic risk of developing AD

The Impact of the Eye in Dementia: The Eye and its Role in Diagnosis and Follow‐up

Over the last few decades, the importance of ophthalmic examination in neurodegenerative diseases of the CNS has reportedly increased. The retina is an extension of the CNS and thus should not be surprising to find abnormal results in both the test exploring visual processing and those examining the retina of patients with CNS degeneration. Current in vivo imaging techniques are allowing ophthalmologists to detect and quantify data consistent with the histopathological findings described in the retinas of Alzheimer’s disease (AD) patients and may help to reveal unsuspected retinal and optic‐nerve repercussions of other CNS diseases. In this chapter, we perform an analysis of the physiological changes in ocular and cerebral ageing. We analyse the ocular manifestations in CNS disorders such as stroke, AD and Parkinson’s disease. In addition, the pathophysiology of both the eye and the visual pathway in AD are described. The value of the visual psychophysical tests in AD diagnosis is reviewed as well as the main findings of the optical coherence tomography as a contribution to the diagnosis and monitoring of the disease. Finally, we examine the association of two neurodegenerative diseases, AD and glaucoma, as mere coincidence or possible role in the progression of the neurodegeneration