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Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called "haptosecretagogue" signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.
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Glândulas Suprarrenais , Aldosterona , Pressão Sanguínea , Células Endoteliais , Macrófagos , Animais , Macrófagos/metabolismo , Aldosterona/metabolismo , Células Endoteliais/metabolismo , Camundongos , Humanos , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zona Glomerulosa/metabolismo , Zona Glomerulosa/patologia , Masculino , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Hiperaldosteronismo/genética , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Glucocorticoids, also known as corticosteroids or steroids, are drugs derived from cholesterol. They are synthesized by the adrenal cortex, along with other hormones, such as cortisol and aldosterone. Glucocorticoids are drugs recommended for patients undergoing surgery on the oral cavity, facial skeleton, and related cervical structures due to their high efficacy against inflammatory and immune processes. However, these drugs are restricted due to their multiple and serious adverse effects. The objective of this study was to verify the efficacy of corticosteroids administered in major surgeries of the oral cavity, as well as of the cervical and facial structures, based on the characteristics of the patient so as to select the best therapeutic strategy. METHODS: Articles in the databases of PubMed, Nature Portfolio, Medline, Cochrane Library, and Google Scholar were thoroughly examined. RESULTS: A total of 54 articles were selected to address the proposed objectives. The results obtained show that it is effective and safe to use glucocorticoids as pre- or postsurgical therapy in oral and maxillofacial surgery to control the processes of inflammation, pain, lockjaw, and edema. However, when referring to the use of these drugs, one must proceed with caution and pay particular attention when handling them. The concentration of the glucocorticoids used must be individualized, as well as the selection of the route of administration. Various studies show that, although the oral route is the most used route, the most effective route is the intramuscular route due to its easy absorption. However, for patients who have recurrent inflammatory and vesiculobullous ulcerative lesions, the topical route should be chosen to mitigate side effects, considering that recurrent applications must be made to prevent the worsening of the lesion and to avoid having to use medications enterally. In patients with cervicofacial infections, antibiotics continue to be the main drugs used to manage the condition in conjunction with corticosteroids. It is important to know the possible interactions of glucocorticoids with other medicines or food: it has been described that the interaction between Ritonavir, an antiretroviral drug that inhibits human immunodeficiency virus (HIV) proteases, and prednisone causes an increase in the concentration of prednisone, leading to possible toxicity in normally safe doses and, in many cases, iatrogenic Cushing's syndrome. It is also important to know the systemic or topical adverse effects of the chronic or high-dose use of glucocorticoids. CONCLUSIONS: It can be concluded that by making adequate use of glucocorticoid therapy in oral and maxillofacial surgery to manage clinical manifestations, it is possible to attenuate the morbidities of treatment and intervention.
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Plasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism, growth and response to stress or drugs. In Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that provides a model to dissect the molecular details underlying cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence revealing novel roles of the cytosolic N- and C-termini of Jen1 in its biogenesis, PM stability and transport activity, using functional analyses of Jen1 truncations and chimeric constructs with UapA, an endocytosis-insensitive transporter of Aspergillus nidulans. Our results show that both N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. Importantly, we provide evidence that Jen1 N- and C-termini undergo transport-dependent dynamic intramolecular interactions, which affect the transport activity and turnover of Jen1. Our results support an emerging concept where the cytoplasmic termini of PM transporters control transporter cell surface stability and function through flexible intramolecular interactions with each other. These findings might be extended to other MFS members to understand conserved and evolving mechanisms underlying transporter structure-function relationships. This article has an associated First Person interview with the first authors of the paper.
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Proteínas de Saccharomyces cerevisiae , Simportadores , Endocitose/fisiologia , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Simportadores/metabolismoRESUMO
Clinicians should appreciate the effectiveness of virtual reality (VR) headsets for managing both the anxiety and the behaviour of non-cooperative paediatric patients who require treatment over several dental appointments. The aim of this study was to assess the effectiveness of using a VR headset as a distraction for managing the anxiety and behaviour of paediatric patients during their dental treatment. Eighty patients, aged between five and ten years old and who required dental treatment over three or more appointments, were randomly allocated into two groups. One group used a VR headset during all their appointments, and the other one did not use any distraction technique. The patients were asked to take a Facial Image Scale Test during their first and last appointments to assess their level of anxiety. Additionally, the dentist completed the Frankl Test to quantify the child's behaviour at the beginning and the end of their treatment. The results obtained, both from the group using the VR headset and from the control group, were compared using the chi-square test. The use of a VR headset during dental treatment significantly reduced anxiety (95% of the children were happy) and improved behaviour (100% positive behaviour) as compared with the control group (40% and 57.5%, respectively). A VR headset can effectively distract a paediatric patient, helping to reduce anxiety and manage behaviour during dental treatment.
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In the last decades, 3-bromopyruvate (3BP) has been intensively studied as a promising anticancer and antimicrobial agent. The transport of this drug inside the cell is a critical step for its toxicity in cancer and microorganisms. The Cryptococcus neoformans is the most sensitive species of microorganisms toward 3BP. Its cells exhibit the highest uptake rate of 3BP among all tested fungal strains. In Saccharomyces cerevisiae cells, the Jen1 transporter was found to be responsible for 3BP sensitivity. The deletion of Jen1 resulted in the abolishment of 3BP mediated transport. We functionally characterized the Jen4 protein, a Jen1 homologue of C. neoformans, and its role in the phenotypic 3BP sensitivity. The deletion of the CNAG_04704 gene, which encodes Jen4, was found to impair the mediated transport of 3BP and decrease 3BP sensitivity. Further heterologous expression of Jen4 in the S. cerevisiae jen1Δ ady2Δ strain restored the mediated transport of 3BP. The application of a green fluorescent protein fusion tag with the CNAG_04704, revealed the Jen4 labeled on the plasma membrane. The identification of 3BP transporters in pathogen cells is of great importance for understanding the mechanisms of 3BP action and to anticipate the application of this compound as an antimicrobial drug.
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Cryptococcus neoformans/metabolismo , Proteínas Fúngicas/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Piruvatos/metabolismo , Transporte Biológico , Membrana Celular/metabolismo , Cryptococcus neoformans/genética , Proteínas Fúngicas/genética , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Proteínas de Fluorescência Verde , Transportadores de Ácidos Monocarboxílicos/genética , Saccharomyces cerevisiae/genéticaRESUMO
Organic acids are recognized as one of the most prevalent compounds in ecosystems, thus the transport and assimilation of these molecules represent an adaptive advantage for organisms. The AceTr family members are associated with the active transport of organic acids, namely acetate and succinate. The phylogenetic analysis shows this family is dispersed in the tree of life. However, in eukaryotes, it is almost limited to microbes, though reaching a prevalence close to 100% in fungi, with an essential role in spore development. Aiming at deepening the knowledge in this family, we studied the acetate permease AceP from Methanosarcina acetivorans, as the first functionally characterized archaeal member of this family. Furthermore, we demonstrate that the yeast Gpr1 from Yarrowia lipolytica is an acetate permease, whereas the Ady2 closest homologue in Saccharomyces cerevisiae, Fun34, has no role in acetate uptake. In this work, we describe the functional role of the AceTr conserved motif NPAPLGL(M/S). We further unveiled the role of the amino acid residues R122 and Q125 of SatP as essential for protein activity.
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Transporte Biológico/genética , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Methanosarcina/enzimologia , Ácido Acético/química , Ácido Acético/metabolismo , Motivos de Aminoácidos/genética , Sequência de Aminoácidos , Proteínas de Membrana/química , Proteínas de Membrana Transportadoras/química , Methanosarcina/genética , Filogenia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Ácido Succínico/química , Ácido Succínico/metabolismo , Yarrowia/genéticaRESUMO
Pulpal necrosis in permanent teeth that have not completed their root development leads to teeth with a very short root, roots with very thin walls, and an inadequate crown-root ratio, which overshadows their survival prognosis. Currently, there are various therapies to treat immature permanent teeth with pulpal pathology such as the case of apexification. An electronic search was performed in the PubMed database (www.ncbi.nlm.nih.gov), Scopus (www.scopus.com), Cochrane (www.cochrane.org) to identify the clinical investigations related to evolution of the cases. The search of the literature of clinical studies on permanent teeth with open apex that present pulpar pathology and that need treatment, have been found 11 clinical studies of treatments with apexification. The apexification by calcium hydroxide has been applied for many years back to the present as a valid therapy to perform the treatment of apexification.
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Nowadays, research in autonomous underwater manipulation has demonstrated simple applications like picking an object from the sea floor, turning a valve or plugging and unplugging a connector. These are fairly simple tasks compared with those already demonstrated by the mobile robotics community, which include, among others, safe arm motion within areas populated with a priori unknown obstacles or the recognition and location of objects based on their 3D model to grasp them. Kinect-like 3D sensors have contributed significantly to the advance of mobile manipulation providing 3D sensing capabilities in real-time at low cost. Unfortunately, the underwater robotics community is lacking a 3D sensor with similar capabilities to provide rich 3D information of the work space. In this paper, we present a new underwater 3D laser scanner and demonstrate its capabilities for underwater manipulation. In order to use this sensor in conjunction with manipulators, a calibration method to find the relative position between the manipulator and the 3D laser scanner is presented. Then, two different advanced underwater manipulation tasks beyond the state of the art are demonstrated using two different manipulation systems. First, an eight Degrees of Freedom (DoF) fixed-base manipulator system is used to demonstrate arm motion within a work space populated with a priori unknown fixed obstacles. Next, an eight DoF free floating Underwater Vehicle-Manipulator System (UVMS) is used to autonomously grasp an object from the bottom of a water tank.
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BACKGROUND: Periodontitis develops through an inflammatory process caused by an infection at the microbial biofilm, followed by tissue destruction mediated by leukocytes, which cause clinically significant destruction of connective tissue and bone. Several elements derived from the bacteria cause the inflammatory response and the release of mediators involved in destruction of the periodontium. There are number of inflammatory mediators released by leukocytes, mainly neutrophils, upon bacterial challenge. Neutrophils produce and release eosinophil cationic protein (ECP) and histamine, two important inflammatory mediators; however, their role has not been characterized in periodontal inflammation. Thus, the purpose of this study is to investigate whether neutrophils from patients with periodontitis can produce ECP and histamine in response to lipopolysaccharides (LPSs). METHODS: ECP and histamine production in response to LPSs was analyzed by enzyme-linked immunosorbent assay. Expression of the histidine decarboxylase and ECP was also analyzed by flow cytometry and fluorescence microscopy in neutrophils from patients with periodontitis in response to LPS. RESULTS: It was found that neutrophils from patients with periodontitis express higher levels of histidine decarboxylase and ECP than those from healthy volunteers, and they also release higher levels of histamine. CONCLUSION: Findings described could represent new knowledge indicating neutrophils as a source of histamine and ECP in the progression of periodontitis.
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Proteína Catiônica de Eosinófilo , Periodontite , Histamina , Humanos , Leucócitos , NeutrófilosRESUMO
Sugar acids can be used as platform chemicals to generate primary building blocks of industrially relevant products. Microbial production of these organic compounds at high yields requires the engineering of the enzymatic machinery and the presence of plasma membrane transporters able to export them outside the cells. In this study, several yeast carboxylic acid transporters belonging to the Jen family were screened for the transport of biotechnologically relevant sugar acids, namely gluconic, saccharic, mucic, xylaric and xylonic acid, and functionally characterised in Saccharomyces cerevisiae. We show that Jen permeases are capable of transporting most of these sugar acids, although with different specificities. Saccharate is a substrate of the transporters ScJen1-S271Q and KlJen2, gluconate of CaJen2 and KlJen2, and xylarate and mucate of CaJen2. A molecular docking approach of these transporters identified the residues that play a major role in the substrate binding of these sugar acids, namely R188 (ScJen1), R122 (CaJen2) and R127 (KlJen2), all equivalent residues (TMS II). The identification of Jen members as sugar acid transporters can contribute to engineering efficient microbial cell factories with increased sugar acid production, as the ScJen1 is able to promote substrate efflux.
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Proteínas de Membrana Transportadoras/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/metabolismo , Açúcares Ácidos/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Especificidade por SubstratoRESUMO
This paper describes a pose-based underwater 3D Simultaneous Localization and Mapping (SLAM) using a multibeam echosounder to produce high consistency underwater maps. The proposed algorithm compounds swath profiles of the seafloor with dead reckoning localization to build surface patches (i.e., point clouds). An Iterative Closest Point (ICP) with a probabilistic implementation is then used to register the point clouds, taking into account their uncertainties. The registration process is divided in two steps: (1) point-to-point association for coarse registration and (2) point-to-plane association for fine registration. The point clouds of the surfaces to be registered are sub-sampled in order to decrease both the computation time and also the potential of falling into local minima during the registration. In addition, a heuristic is used to decrease the complexity of the association step of the ICP from O(n2) to O(n) . The performance of the SLAM framework is tested using two real world datasets: First, a 2.5D bathymetric dataset obtained with the usual down-looking multibeam sonar configuration, and second, a full 3D underwater dataset acquired with a multibeam sonar mounted on a pan and tilt unit.
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This paper presents a new tracking system for autonomous underwater vehicles (AUVs) navigating in a close formation, based on computer vision and the use of active light markers. While acoustic localization can be very effective from medium to long distances, it is not so advantageous in short distances when the safety of the vehicles requires higher accuracy and update rates. The proposed system allows the estimation of the pose of a target vehicle at short ranges, with high accuracy and execution speed. To extend the field of view, an omnidirectional camera is used. This camera provides a full coverage of the lower hemisphere and enables the concurrent tracking of multiple vehicles in different positions. The system was evaluated in real sea conditions by tracking vehicles in mapping missions, where it demonstrated robust operation during extended periods of time.
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This chapter covers the functionally characterized plasma membrane carboxylic acids transporters Jen1, Ady2, Fps1 and Pdr12 in the yeast Saccharomyces cerevisiae, addressing also their homologues in other microorganisms, as filamentous fungi and bacteria. Carboxylic acids can either be transported into the cells, to be used as nutrients, or extruded in response to acid stress conditions. The secondary active transporters Jen1 and Ady2 can mediate the uptake of the anionic form of these substrates by a H(+)-symport mechanism. The undissociated form of carboxylic acids is lipid-soluble, crossing the plasma membrane by simple diffusion. Furthermore, acetic acid can also be transported by facilitated diffusion via Fps1 channel. At the cytoplasmic physiological pH, the anionic form of the acid prevails and it can be exported by the Pdr12 pump. This review will highlight the mechanisms involving carboxylic acids transporters, and the way they operate according to the yeast cell response to environmental changes, as carbon source availability, extracellular pH and acid stress conditions.
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Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácidos Carboxílicos/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas de Membrana/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Simportadores/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Ácido Acético/metabolismo , Adaptação Fisiológica , Transporte Biológico , Membrana Celular/química , Membrana Celular/metabolismo , Difusão , Concentração de Íons de Hidrogênio , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Moleculares , Transportadores de Ácidos Monocarboxílicos/química , Transportadores de Ácidos Monocarboxílicos/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Transdução de Sinais , Estresse Fisiológico , Simportadores/química , Simportadores/genéticaRESUMO
We have functionally characterized the four Saccharomyces cerevisiae (Sc) Jen1 homologues of Debaryomyces hansenii (Dh) by heterologous expression in S. cerevisiae. Debaryomyces hansenii cells display mediated transport for the uptake of lactate, acetate, succinate and malate. DHJEN genes expression was detected by RT-PCR in all carbon sources assayed, namely lactate, succinate, citrate, glycerol and glucose. The heterologous expression in the S. cerevisiae W303-1A jen1Δ ady2Δ strain demonstrated that the D. hansenii JEN genes encode four carboxylate transporters. DH27 gene encodes an acetate transporter (Km 0.94 ± 0.17 mM; Vmax 0.43 ± 0.03 nmol s(-1) mg(-1)), DH17 encodes a malate transporter (Km 0.27 ± 0.04 mM; Vmax 0.11 ± 0.01 nmol s(-1) mg(-1)) and both DH18 and DH24 encode succinate transporters with the following kinetic parameters, respectively, Km 0.31 ± 0.06 mM; Vmax 0.83 ± 0.04 nmol s(-1) mg(-1)and Km 0.16 ± 0.02 mM; Vmax 0.19 ± 0.02 nmol s(-1) mg(-1). Surprisingly, no lactate transporter was found, although D. hansenii presents a mediated transport for this acid. This work advanced the current knowledge on yeast carboxylate transporters by characterizing four new plasma membrane transporters in D. hansenii.
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Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Transporte Biológico , Ácidos Carboxílicos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por SubstratoRESUMO
This paper presents the development of an underwater omnidirectional multi-camera system (OMS) based on a commercially available six-camera system, originally designed for land applications. A full calibration method is presented for the estimation of both the intrinsic and extrinsic parameters, which is able to cope with wide-angle lenses and non-overlapping cameras simultaneously. This method is valid for any OMS in both land or water applications. For underwater use, a customized housing is required, which often leads to strong image distortion due to refraction among the different media. This phenomena makes the basic pinhole camera model invalid for underwater cameras, especially when using wide-angle lenses, and requires the explicit modeling of the individual optical rays. To address this problem, a ray tracing approach has been adopted to create a field-of-view (FOV) simulator for underwater cameras. The simulator allows for the testing of different housing geometries and optics for the cameras to ensure a complete hemisphere coverage in underwater operation. This paper describes the design and testing of a compact custom housing for a commercial off-the-shelf OMS camera (Ladybug 3) and presents the first results of its use. A proposed three-stage calibration process allows for the estimation of all of the relevant camera parameters. Experimental results are presented, which illustrate the performance of the calibration method and validate the approach.
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In the present paper we describe a new carboxylic acid transporter in Escherichia coli encoded by the gene yaaH. In contrast to what had been described for other YaaH family members, the E. coli transporter is highly specific for acetic acid (a monocarboxylate) and for succinic acid (a dicarboxylate), with affinity constants at pH 6.0 of 1.24±0.13 mM for acetic acid and 1.18±0.10 mM for succinic acid. In glucose-grown cells the ΔyaaH mutant is compromised for the uptake of both labelled acetic and succinic acids. YaaH, together with ActP, described previously as an acetate transporter, affect the use of acetic acid as sole carbon and energy source. Both genes have to be deleted simultaneously to abolish acetate transport. The uptake of acetate and succinate was restored when yaaH was expressed in trans in ΔyaaH ΔactP cells. We also demonstrate the critical role of YaaH amino acid residues Leu¹³¹ and Ala¹64 on the enhanced ability to transport lactate. Owing to its functional role in acetate and succinate uptake we propose its assignment as SatP: the Succinate-Acetate Transporter Protein.