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Open AccessArticle
Bioactivities of Centaurium erythraea (Gentianaceae) Decoctions: Antioxidant Activity, Enzyme Inhibition and Docking Studies
Molecules 2019, 24(20), 3795; https://doi.org/10.3390/molecules24203795 (registering DOI) - 22 Oct 2019
Abstract
Centaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the [...] Read more.
Centaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the compounds were identified by liquid chromatography-high resolution tandem mass spectrometry (LC–MS/MS). Secoiridoids glycosides, like gentiopicroside and sweroside, and several xanthones, such as di-hydroxy-dimethoxyxanthone, were identified. Following some of the bioactivities previously ascribed to C. erythraea, we have studied its antioxidant capacity and the ability to inhibit acetylcholinesterase (AChE) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Significant antioxidant activities were observed, following three assays: free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction; lipoperoxidation; and NO radical scavenging capacity. The AChE and HMGR inhibitory activities for the decoction were also measured (56% at 500 μg/mL and 48% at 10 μg/mL, respectively). Molecular docking studies indicated that xanthones are better AChE inhibitors than gentiopicroside, while this compound exhibits a better shape complementarity with the HMGR active site than xanthones. To the extent of our knowledge, this is the first report on AChE and HMGR activities by C. erythraea decoctions, in a top-down analysis, complemented with in silico molecular docking, which aims to understand, at the molecular level, some of the biological effects ascribed to infusions from this plant. Full article
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Open AccessEditorial
Tubulin: Structure, Functions and Roles in Disease
Cells 2019, 8(10), 1294; https://doi.org/10.3390/cells8101294 (registering DOI) - 22 Oct 2019
Abstract
Highly conserved α- and β-tubulin heterodimers assemble into dynamic microtubules and perform multiple important cellular functions such as structural support, pathway for transport and force generation in cell division. Tubulin exists in different forms of isotypes expressed by specific genes with spatially- and [...] Read more.
Highly conserved α- and β-tubulin heterodimers assemble into dynamic microtubules and perform multiple important cellular functions such as structural support, pathway for transport and force generation in cell division. Tubulin exists in different forms of isotypes expressed by specific genes with spatially- and temporally-regulated expression levels. Some tubulin isotypes are differentially expressed in normal and neoplastic cells, providing a basis for cancer chemotherapy drug development. Moreover, specific tubulin isotypes are overexpressed and localized in the nuclei of cancer cells and/or show bioenergetic functions through the regulation of the permeability of mitochondrial ion channels. It has also become clear that tubulin isotypes are involved in multiple cellular functions without being incorporated into microtubule structures. Understanding the mutations of tubulin isotypes specifically expressed in tumors and their post-translational modifications might help to identify precise molecular targets for the design of novel anti-microtubular drugs. Knowledge of tubulin mutations present in tubulinopathies brings into focus cellular functions of tubulin in brain pathologies such as Alzheimer’s disease. Uncovering signaling pathways which affect tubulin functions during antigen-mediated activation of mast cells presents a major challenge in developing new strategies for the treatment of inflammatory and allergic diseases. γ-tubulin, a conserved member of the eukaryotic tubulin superfamily specialized for microtubule nucleation is a target of cell cycle and stress signaling. Besides its microtubule nucleation role, γ-tubulin functions in nuclear and cell cycle related processes. This special issue “Tubulin: Structure, Functions and Roles in Disease” contains eight articles, five of which are original research papers and three are review papers that cover diverse areas of tubulin biology and functions under normal and pathological conditions. Full article
(This article belongs to the Special Issue Tubulin: Structure, Functions and Roles in Disease)
Open AccessReview
What Do Microglia Really Do in Healthy Adult Brain?
Cells 2019, 8(10), 1293; https://doi.org/10.3390/cells8101293 (registering DOI) - 22 Oct 2019
Abstract
Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. [...] Read more.
Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease. Full article
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Open AccessArticle
Effects of Laser Beam Parameters on Bendability and Microstructure of Stainless Steel in Three-Dimensional Laser Forming
Appl. Sci. 2019, 9(20), 4463; https://doi.org/10.3390/app9204463 (registering DOI) - 22 Oct 2019
Abstract
In this study, the effects of beam diameter and hatch spacing between the scanning paths on the bendability and microstructural behavior of an AISI 316 stainless-steel sheet in three-dimensional laser forming were investigated. The strain on the heating lines and that between the [...] Read more.
In this study, the effects of beam diameter and hatch spacing between the scanning paths on the bendability and microstructural behavior of an AISI 316 stainless-steel sheet in three-dimensional laser forming were investigated. The strain on the heating lines and that between the scanning tracks were numerically investigated to elucidate the effects of process parameters. The strain on heating lines and that between scanning tracks were numerically investigated. The increase in hatch spacing caused a larger amount of counter bending to be retained in the unaffected areas between the tracks through a process dominated by a temperature gradient mechanism (TGM), and also caused a lower deformation. The formation of small equiaxed dendrite grains instead of coarse and inhomogeneous austenite grains occurred during the process at a larger beam diameter and smaller hatch spacing, which increased the bendability of the material, owing to the decrease in anisotropy in the microstructure. Moreover, the increase in the grain size of the reheated overlap region of the deformed sample led to a higher bendability. Under these conditions, the microhardness was also increased owing to the grain boundary strengthening effect. Full article
(This article belongs to the Section Mechanical Engineering)
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Open AccessArticle
An Exploratory Study of ASL Demonstratives
Languages 2019, 4(4), 80; https://doi.org/10.3390/languages4040080 (registering DOI) - 22 Oct 2019
Abstract
American Sign Language (ASL) makes extensive use of pointing signs, but there has been only limited documentation of how pointing signs are used for demonstrative functions. We elicited demonstratives from four adult Deaf signers of ASL in a puzzle completion task. Our preliminary [...] Read more.
American Sign Language (ASL) makes extensive use of pointing signs, but there has been only limited documentation of how pointing signs are used for demonstrative functions. We elicited demonstratives from four adult Deaf signers of ASL in a puzzle completion task. Our preliminary analysis of the demonstratives produced by these signers supports three important conclusions in need of further investigation. First, despite descriptions of four demonstrative signs in the literature, participants expressed demonstrative function 95% of the time through pointing signs. Second, proximal and distal demonstrative referents were not distinguished categorically on the basis of different demonstrative signs, nor on the basis of pointing handshape or trajectory. Third, non-manual features including eye gaze and facial markers were essential to assigning meaning to demonstratives. Our results identify new avenues for investigation of demonstratives in ASL. Full article
(This article belongs to the Special Issue HDLS 13: Challenges to Common Beliefs in Linguistic Research)
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Open AccessArticle
Simultaneous Determination and Quantification of Triterpene Saponins from Camellia sinensis Seeds Using UPLC-PDA-QTOF-MS/MS
Molecules 2019, 24(20), 3794; https://doi.org/10.3390/molecules24203794 (registering DOI) - 22 Oct 2019
Abstract
Saponins in the Camellia sinensis seeds have a broad spectrum of biological properties and application potentials. However, up to now, no chromatographic methods have been developed to provide full fingerprinting and quality assurance for these saponins. This research aimed to develop a novel [...] Read more.
Saponins in the Camellia sinensis seeds have a broad spectrum of biological properties and application potentials. However, up to now, no chromatographic methods have been developed to provide full fingerprinting and quality assurance for these saponins. This research aimed to develop a novel method to tentatively identify and quantify saponins in C. sinensis seeds by ultra-high-performance liquid chromatography coupled with photo-diode array detector and quadrupole time-of-flight mass spectrometry (UPLC-PDA-QTOF-MS/MS), and compare it with the classic vanillin-sulfuric acid assay. Fifty-one triterpene saponins, including six potentially new compounds, were simultaneously detected by UPLC-PDA-MS/MS, and their chemical structures were speculated according to the retention behavior and fragmentation pattern. The total saponin content in the crude extract and the purified saponin fraction of C. sinensis seeds were quantified to be 19.57 ± 0.05% (wt %) and 41.68 ± 0.09% (wt %) respectively by UPLC-PDA at 210 nm, while the corresponding values were determined to be 43.11 ± 3.17% (wt %) and 56.60 ± 5.79% (wt %) respectively by the vanillin-sulfuric acid assay. The developed UPLC-PDA -MS/MS method could determine specified saponins, and is more reliable for quantifying the C. sinensis seed saponins than the classic spectrophotometric method. It is of great significance for the future investigations and applications of these saponins. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessReview
Bioengineered Scaffolds as Substitutes for Grafts for Urethra Reconstruction
Materials 2019, 12(20), 3449; https://doi.org/10.3390/ma12203449 (registering DOI) - 22 Oct 2019
Abstract
Urethral defects originating from congenital malformations, trauma, inflammation or carcinoma still pose a great challenge to modern urology. Recent therapies have failed many times and have not provided the expected results. This negatively affects patients’ quality of life. By combining cells, bioactive molecules, [...] Read more.
Urethral defects originating from congenital malformations, trauma, inflammation or carcinoma still pose a great challenge to modern urology. Recent therapies have failed many times and have not provided the expected results. This negatively affects patients’ quality of life. By combining cells, bioactive molecules, and biomaterials, tissue engineering can provide promising treatment options. This review focused on scaffold systems for urethra reconstruction. We also discussed different technologies, such as electrospinning and 3D bioprinting which provide great possibility for the preparation of a hollow structure with well-defined architecture. Full article
(This article belongs to the Section Biomaterials)
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Open AccessArticle
Workforce Ageing and Labour Productivity in Europe
Sustainability 2019, 11(20), 5851; https://doi.org/10.3390/su11205851 (registering DOI) - 22 Oct 2019
Abstract
This article analyses the influence of workforce ageing on labour productivity in Europe. This question is relevant because of the impact it may have on economic activity, social security systems sustainability and the wellbeing of the population. The method applied is a quantitative [...] Read more.
This article analyses the influence of workforce ageing on labour productivity in Europe. This question is relevant because of the impact it may have on economic activity, social security systems sustainability and the wellbeing of the population. The method applied is a quantitative contrast using the panel data technique for 24 countries in the period 1983–2014. This research is framed in the open conversation in the literature on the possible impact of ageing on productivity and takes as reference the seminal work of James Feyrer and the contrast model developed by Shekhar Aiyar, Christian Ebeke, and Xiaobo Shao. The results obtained show how a 1% increase in the workforce between the ages of 55 and 64 is related to a decrease of the annual increase in productivity between −0.106% and −0.479%. The main contribution of the article is to provide, as far as the authors are aware, the first evidence of this negative relationship for the period 1983–2014, in addition to suggesting that the influence of ageing on productivity may be reduced by the evolution of the economies in question toward capital and/or knowledge-intensive sectors. Full article
(This article belongs to the Special Issue Aging: Healthcare, Inequalities, Challenges and Trends)
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Open AccessFeature PaperArticle
Integrated Battery Charger for Electric Vehicles Based on a Dual-Inverter Drive and a Three-Phase Current Rectifier
Electronics 2019, 8(10), 1199; https://doi.org/10.3390/electronics8101199 (registering DOI) - 22 Oct 2019
Abstract
This paper presents a new three-phase battery charger integrated with the propulsion system of an electric vehicle. The propulsion system consists of a dual-inverter topology connected to an induction motor via open windings. The electrical vehicles (EV) batteries are divided by two inverters. [...] Read more.
This paper presents a new three-phase battery charger integrated with the propulsion system of an electric vehicle. The propulsion system consists of a dual-inverter topology connected to an induction motor via open windings. The electrical vehicles (EV) batteries are divided by two inverters. This will result in a drive with multilevel characteristics reducing the total harmonic distortion (THD) of the voltage applied to the motor. The modularity of the multilevel inverter will be maintained since two classical three-phase inverters are used. The charger will be fed by a three-phase high power factor current source rectifier. The motor windings will take the role of the DC-inductor required by the rectifier. In this way, an intermediate storage element between the grid and the batteries of the vehicle exist. For the control system of the battery charger, we propose the use of the instantaneous power theory and a sliding mode controller for the three-phase charger input currents. Finally, to verify the behavior and characteristics of the proposed integrated battery charger and control system, several tests are be presented. Full article
(This article belongs to the Section Electrical and Autonomous Vehicles)
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Open AccessArticle
Parental Declaration of Adverse Event Following Immunization in a Cross-Sectional Study in Poland
Int. J. Environ. Res. Public Health 2019, 16(20), 4038; https://doi.org/10.3390/ijerph16204038 (registering DOI) - 22 Oct 2019
Abstract
Vaccines are a well-known and effective preventive measure in communicable diseases. However, like any medical product, vaccines can cause some adverse effects. With increasing population awareness, the number of reported events related to vaccination has increased. Aim: The aim of the study was [...] Read more.
Vaccines are a well-known and effective preventive measure in communicable diseases. However, like any medical product, vaccines can cause some adverse effects. With increasing population awareness, the number of reported events related to vaccination has increased. Aim: The aim of the study was to assess the frequency and type of reported adverse events following childhood immunization (AEFI), and to recognize the determinant of their occurrence related with a socio-demographic situation, parental knowledge, and/or opinions on vaccinations. Material and Methods: The self-administrated questionnaire was distributed to a group of 3000 random parents or legal guardians living in the Silesian Voivodship (the southern part of Poland) in 2016. The response rate was eventually 41.3% from 1239 participants. Both, the number of children and the percentage of vaccinations given in the studied region, was representative for Poland as a whole. Results: Approximately one-third (32%) of surveyed parents declared the occurrence of AEFI in their children. The most frequently declared AEFIs were: redness, pain, swelling at the injection site (27%), and fever (24.9%). The frequency of reported AEFI was associated with a higher level of parental education and the number of vaccinations given. A negative attitude toward vaccination and the belief that vaccination is unsafe were associated with a higher number of reported AEFI. Conclusions: The results obtained confirmed that the number of declared mild and moderate AEFI is related to a lower parental educational level and is associated with a better experience as a consequence of a higher number of vaccinations given. Frequent AEFI reporters represent negative attitudes toward vaccinations. Further investigation with the exact surveillance system is needed to improve parental trust in vaccination safety. Full article
(This article belongs to the Section Children's Health)
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Open AccessReview
The ST2/Interleukin-33 Axis in Hematologic Malignancies: The IL-33 Paradox
Int. J. Mol. Sci. 2019, 20(20), 5226; https://doi.org/10.3390/ijms20205226 (registering DOI) - 22 Oct 2019
Abstract
Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an “alarmin” able to stimulate several [...] Read more.
Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an “alarmin” able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and—less frequently—antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones. Full article
(This article belongs to the Section Molecular Immunology)
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Open AccessReview
Evasion of Innate and Intrinsic Antiviral Pathways by the Zika Virus
Viruses 2019, 11(10), 970; https://doi.org/10.3390/v11100970 (registering DOI) - 22 Oct 2019
Abstract
The Zika virus (ZIKV) is a recently emerged mosquito-borne flavivirus that, while typically asymptomatic, can cause neurological symptoms in adults and birth defects in babies born to infected mothers. The interactions of ZIKV with many different pathways in the human host ultimately determine [...] Read more.
The Zika virus (ZIKV) is a recently emerged mosquito-borne flavivirus that, while typically asymptomatic, can cause neurological symptoms in adults and birth defects in babies born to infected mothers. The interactions of ZIKV with many different pathways in the human host ultimately determine successful virus replication and ZIKV-induced pathogenesis; however, the molecular mechanisms of such host-ZIKV interactions have just begun to be elucidated. Here, we summarize the recent advances that defined the mechanisms by which ZIKV antagonizes antiviral innate immune signaling pathways, with a particular focus on evasion of the type I interferon response in the human host. Furthermore, we describe emerging evidence that indicated the contribution of several cell-intrinsic mechanisms to an effective restriction of ZIKV infection, such as nonsense-mediated mRNA decay, stress granule formation, and “reticulophagy”, a type of selective autophagy. Finally, we summarize the recent work that identified strategies by which ZIKV modulated these intrinsic antiviral responses. Full article
(This article belongs to the Special Issue Viruses Ten-Year Anniversary)
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Open AccessArticle
Association of Workplace Bullying and Workplace Vulnerability in the Psychological Distress of Chilean Workers
Int. J. Environ. Res. Public Health 2019, 16(20), 4039; https://doi.org/10.3390/ijerph16204039 (registering DOI) - 22 Oct 2019
Abstract
Workplace bullying has been identified as a global problem because of its growing magnitude and the harmful effects in victims and organizations. Workplace vulnerability is a component of job precarious1ness that reflects insecurity, fear, and labor uncertainty. This paper aims to analyze the [...] Read more.
Workplace bullying has been identified as a global problem because of its growing magnitude and the harmful effects in victims and organizations. Workplace vulnerability is a component of job precarious1ness that reflects insecurity, fear, and labor uncertainty. This paper aims to analyze the associations between the exposure to workplace vulnerability and psychological distress, and to explore the associations between exposure to workplace bullying and psychological distress, by sex. A cross-sectional and probabilistic survey was applied to a randomly-selected valid sample of 1995 salaried workers in three main metropolitan areas of Chile. Chi-square test and logistic regression models controlling for confounders were tested. Female workers were more exposed to workplace vulnerability and presented a higher prevalence of psychological distress. Among women who were vulnerable, one of three reported psychological distress (30.8%), which is higher than men (16.5%). Workers exposed to workplace vulnerability had a greater chance of workplace bullying, workers who perceived high workplace vulnerability had a greater chance of psychological distress, and workers exposed to workplace violence had a greater likelihood of psychological distress in comparison to those who were not exposed. Increasing employment security can reduce the perception of job vulnerability and help prevent the existence of workplace bullying. Additionally, occupational health protection policies should prevent, protect from, and intervene in workplace bullying as a precursor to mental health problems in Chile. Full article
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Open AccessArticle
The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1
Int. J. Mol. Sci. 2019, 20(20), 5225; https://doi.org/10.3390/ijms20205225 (registering DOI) - 22 Oct 2019
Abstract
Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper [...] Read more.
Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Copper sulfate also increased the levels of apoptosis, senescence, mitochondrial dysfunction, autophagy, ROS, and the expression of several stress proteins, including ATF3, c-Fos, DEC1 (differentiated embryonic chondrocyte gene 1), p21, p53, and HIF-1α (hypoxia-inducible factor 1 alpha). The suppression of copper-induced ROS generation by the ROS scavenger N-acetyl cysteine verified copper’s functional role, while the suppression of copper’s effects by the copper chelator disulfiram, confirmed its specificity. Selective induction of HIF-1α, p53, and phosphorylated ERK proteins by copper was blocked by the knockdown of the transcription factor DEC1, suggesting copper’s effects are mediated by DEC1. In addition to HeLa cells, copper also exerted cytotoxic effects in human endometrial (HEC-1-A) and lung (A549) adenocarcinoma cells, but not in normal human kidney (HEK293) or bronchial (Beas-2B) epithelial cells. These findings shed new light on the functional roles of copper within cells. Full article
(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)
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Open AccessArticle
Autoregulation of greA Expression Relies on GraL Rather than on greA Promoter Region
Int. J. Mol. Sci. 2019, 20(20), 5224; https://doi.org/10.3390/ijms20205224 (registering DOI) - 22 Oct 2019
Abstract
GreA is a well-characterized transcriptional factor that acts primarily by rescuing stalled RNA polymerase complexes, but has also been shown to be the major transcriptional fidelity and proofreading factor, while it inhibits DNA break repair. Regulation of greA gene expression itself is still [...] Read more.
GreA is a well-characterized transcriptional factor that acts primarily by rescuing stalled RNA polymerase complexes, but has also been shown to be the major transcriptional fidelity and proofreading factor, while it inhibits DNA break repair. Regulation of greA gene expression itself is still not well understood. So far, it has been shown that its expression is driven by two overlapping promoters and that greA leader encodes a small RNA (GraL) that is acting in trans on nudE mRNA. It has been also shown that GreA autoinhibits its own expression in vivo. Here, we decided to investigate the inner workings of this autoregulatory loop. Transcriptional fusions with lacZ reporter carrying different modifications (made both to the greA promoter and leader regions) were made to pinpoint the sequences responsible for this autoregulation, while GraL levels were also monitored. Our data indicate that GreA mediated regulation of its own gene expression is dependent on GraL acting in cis (a rare example of dual-action sRNA), rather than on the promoter region. However, a yet unidentified, additional factor seems to participate in this regulation as well. Overall, the GreA/GraL regulatory loop seems to have unique but hard to classify properties. Full article
(This article belongs to the Section Molecular Microbiology)
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