• Notably, reduction of the intracellular K⁺ concentration was sufficient to activate NLRP3, whereas an increase in intracellular Na⁺ modulated but was not strictly required for inflammasome activation. (nih.gov)
  • Upon prolonged high intracellular rises in Ca 2+ , platelets develop a procoagulant phenotype that is characterized by the surface membrane exposure of phosphatidylserine and by the inactivation of integrin α IIb β 3 (procoagulant platelet population) ( 5 ). (frontiersin.org)
  • In addition, phosphorus plays key roles in regulation of gene transcription, activation of enzymes, maintenance of normal pH in extracellular fluid, and intracellular energy storage. (nih.gov)
  • It was confirmed in vitro by observing the lack of insulin receptor autophosphorylation, and also the impairment of insulin-induced intracellular enzyme activations and the glucose Transporter 4 translocation to the membrane. (ibecbarcelona.eu)
  • These compounds are believed to act as pro-drugs that require intracellular enzymatic activation for antimicrobial activity. (bl.uk)
  • Both extracellular and intracellular calcium concentrations are tightly regulated by bidirectional calcium transport across the plasma membrane of cells and intracellular organelles, such as the endoplasmic reticulum, the sarcoplasmic reticulum of muscle cells, and the mitochondria. (msdmanuals.com)
  • A distinctive feature of the early stages of apoptosis is the collapse of the mitochondrial membrane potential. (bitesizebio.com)
  • Shift of fluorescence emission from red to green of the JC-1 Fluorescent Probe indicating loss of mitochondrial membrane potential associated with apoptosis in treated cells compared to untreated cells. (bitesizebio.com)
  • In the intrinsic pathway, several adverse factors act upon mitochondria to cause loss of the mitochondrial membrane potential, resulting in leakage into the cytosol of cytochrome C (Cyto C), which together with apoptotic protease activating factor 1 forms the apoptosome that activates caspase-9. (cdc.gov)
  • LPE is present as a minor phospholipid in the cell membrane. (wikipedia.org)
  • These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylethanolamine synthesis by inhibiting choline-ethanolaminophosphotransferase activity. (jneurosci.org)
  • It is generally assumed that enzymatic hydrolysis of phospholipids leads to phospholipid degradation and membrane damage. (jneurosci.org)
  • Enhancement of phosphoinositide 3-kinase (PI 3-kinase) activity by membrane curvature and inositol-phospholipid-binding peptides. (tamu.edu)
  • Preferential activation of microsomal diacylglycerol/protein kinase C signaling during glucose treatment (De Novo phospholipid synthesis) of rat adipocytes. (jci.org)
  • We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. (jneurosci.org)
  • Enzymatic hydrolysis of membrane phospholipids by phospholipases produces these lipid second messengers, as well as soluble second messengers such as inositol 1,4,5-trisphosphate, and also other molecules such as choline (Cho) that are released to the extracellular medium. (jneurosci.org)
  • In the form of phospholipids, phosphorus is also a component of cell membrane structure and of the body's key energy source, ATP. (nih.gov)
  • LKB1 itself is a constitutively active kinase, which is regulated by posttranslational modifications and direct binding to phospholipids of the plasma membrane. (sdbonline.org)
  • Phosphoinositide 3-kinases (PI3Ks) are a family of lipid-modifying enzymes that phosphorylate the 3′-OH group of inositol phospholipids and play key roles in physiology ranging from cell growth and metabolism to organismal development. (nature.com)
  • Plasma obtained and RBC membrane prepared from blood collected over EDTA post-treatment were assayed for total cholesterol (TC), phospholipids and fatty acid profile using spectrophotometry and Gas chromatography while heparinized blood was subjected to fragility test. (bvsalud.org)
  • In addition, when platelets are activated, negatively charged phospholipids move from the inner to the outer leaflet of the membrane bilayer. (medscape.com)
  • Transforming growth factor-alpha (TGF-alpha) is synthesized and transported to the cell surface as a membrane-anchored precursor (proTGF-alpha) that is converted to the soluble form by proteolytic cleavage. (nih.gov)
  • hence, the activity probably locates on the outer surface of the cell membrane. (nih.gov)
  • In the cell-free reconstitution system, the membrane-bound Suc-Ala-Ala-Ala-MCA-hydrolyzing enzyme from CHO cells was also activated by phorbol ester in the presence of the soluble fraction, ATP, and vanadate. (nih.gov)
  • Furthermore, reactive oxygen species generation or a change in cell volume was not necessary for NLRP3 activation. (nih.gov)
  • A lysophosphatidylethanolamine (LPE) is a chemical compound derived from a phosphatidylethanolamine, which is typical of cell membranes. (wikipedia.org)
  • Lysophosphatidylethanolamine (LPE also, lisophos ) is a minor constituent of cell membranes(natural compound). (wikipedia.org)
  • LPE plays a role in cell-mediated cell signaling and activation of other enzymes. (wikipedia.org)
  • At term, programmed cell death and activation of catabolic enzymes, such as collagenase and mechanical forces, result in ruptured membranes. (medscape.com)
  • Furthermore, activation of autophagy allows to extend cell survival when exposed to different types of stressors such as starvation or cytotoxic drugs. (hindawi.com)
  • Notably, Bacillus thuringiensis israelensis ( Bti ) produces four highly specific and potent toxins in the form of nanocrystals, which upon ingestion by mosquito larvae will dissolve in their gut, oligomerize upon proteolytic activation by digestive enzymes and perforate intestinal cell membranes, leading to larvae death. (cea.fr)
  • Denaturation of plant cell enzymes by autoclaving, arrested the enzymatic activity resulting in a 10% deactivation of the compounds. (astm.org)
  • This effect was observed well before any significant membrane damage and cell death. (jneurosci.org)
  • Secretory granules move towards the periphery of the cell and upon stimulation, their membranes fuse with the cell membrane, and their protein load is exteriorized. (slideserve.com)
  • Activation of AMPK by low energy supply and phosphorylation of LKB1 results in an inhibition of mTOR , thus decreasing energy-consuming processes, in particular translation and, thus, cell growth. (sdbonline.org)
  • When a neuron is stimulated, the NaV1.7 channel opens and allows positively charged sodium ions to cross the cell membrane and enter the previously negatively charged cell. (scitechdaily.com)
  • The change in charge across the cell membrane generates an electrical current, which increases the excitability of the neuron and sets in motion a cascade of events that leads to pain. (scitechdaily.com)
  • CRMP2 is a protein that binds to NaV1.7 and transports it to the cell membrane, where sodium ions are then transferred into the cell. (scitechdaily.com)
  • In the new study, Joseph Friedman and colleagues at the Weizmann Institute of Science in Rehovot exposed rat and human cell cultures, and also isolated cell membranes, to low-level electromagnetic radiation at 875 megahertz - a similar frequency to those of GSM phone signals. (emfacts.com)
  • The power of the signal was far lower than the intensity of the typical cellphone, yet after just 10 minutes of exposure, the team identified activation of the pathway for ERK1/2, an enzyme that regulates cell differentiation and division. (emfacts.com)
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane protein which exhibits biological activities on the cell surface. (ox.ac.uk)
  • One of the characteristic functions of this enzyme is activation of proMMP-2 on the cell surface (1). (ox.ac.uk)
  • Hormones often cause a cell to elicit multiple responses because during protein kinase activation, enzymes phosphorylate many other enzymes. (proprofs.com)
  • Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. (mdpi.com)
  • BACKGROUND: Deformability and fluidity function of the red blood cell membrane are properties defined by the lipid composition. (bvsalud.org)
  • This study therefore investigated the effect of exposure to toxic copper level for 30 days on red blood cell membrane deformability and fluidity in female Wistar rats. (bvsalud.org)
  • Cell-membrane-coated biomimetic nanoparticles (NPs) have attracted great attention due to their prolonged circulation time, immune escape mechanisms and homotypic targeting properties. (bvsalud.org)
  • Biomimetic nanosystems from different types of cell -membranes (CMs) can perform increasingly complex tasks in dynamic biological environments thanks to specific proteins and other properties inherited from the source cells. (bvsalud.org)
  • Herein, we coated doxorubicin (DOX)-loaded reduction-sensitive chitosan (CS) NPs with 4T1 cancer cell -membranes (CCMs), red blood cell -membranes (RBCMs) and hybrid erythrocyte-cancer membranes (RBC-4T1CMs) to enhance the delivery of DOX to breast cancer cells. (bvsalud.org)
  • The authors suggest the need to characterize the enzyme and inhibiting effects of Hg on tissue, examine the interaction of Hg with cell membranes of the renal tubules, develop epidemiologic investigations of working populations, and to pursue the effects of Hg exposure on reproduction. (cdc.gov)
  • Mutations in the MMP14 gene alter matrix metallopeptidase 14 so that less of the enzyme is able to reach the cell surface. (medlineplus.gov)
  • Seems to be directly involved in T-cell activation. (lu.se)
  • A very natural place to study gene detecting and metabolizing lactose, it is known that the overall regulation is in the metabolism of the cell, and then specifically in effect of expressing the lac genes in vain is a drop in the growth rate the regulation of genes that code for enzymes and transporter of as much as 5% [1,6]. (lu.se)
  • Excessive Ca 2 + entry through glutamate receptors activates a large array of potential neurotoxic mechanisms, which include activation of enzymes such as phospholipases, calpains and other proteases, protein kinases, nitric oxide synthetase, endonucleases, as well as reactive oxygen species (for review, see Sattler and Tymianski, 2000 ). (jneurosci.org)
  • The activation of protein kinases and the subsequent phosphorylation of enzymes allow for the amplification and coordination of cellular responses to hormonal signals. (proprofs.com)
  • it is involved in skeletal muscle contraction, excitation-contraction coupling in cardiac and smooth muscle, and activation of protein kinases and enzyme phosphorylation. (msdmanuals.com)
  • Interestingly, recent data suggest a function for ULK1 not only during autophagy activation but also during elongation and closure of the autophagosomal membrane via binding to ATG8 proteins [ 8 ]. (hindawi.com)
  • Highly specific proteins catalysts, "enzymes" can be used to control the "fire" in useful ways. (slideserve.com)
  • Used in the manufacture of all proteins and enzymes. (slideserve.com)
  • The second major membrane system that breaks down proteins and lipids. (slideserve.com)
  • Platelet activation allows binding of these proteins, which bridges adjacent platelets. (medscape.com)
  • Using the fluorogenic substrate succinyl-Ala-Ala-Ala-4-methylcoumaryl-7-amide (Suc-Ala-Ala-Ala-MCA), containing the sequence similar to the cleavage sites for proTGF-alpha processing, we identified a putative candidate proTGF-alpha-converting enzyme in the membrane fractions of Chinese hamster ovary (CHO) cells. (nih.gov)
  • 4) Secretory granules: A small subcellular vesicle, surrounded by a membrane, that is formed from the Golgi apparatus and contains a highly concentrated protein destined for secretion. (slideserve.com)
  • The plasma membrane-enriched fraction isolated from smooth muscle of rat gastric fundus was found to contain a substantial level of potassium-stimulated p-nitrophenylphosphatase activity (K-pNPPase), and its subcellular distribution closely resembled that of other plasma membrane enzyme markers. (mcmaster.ca)
  • Presently, we examined the major subcellular site of PKC translocation/activation in response to glucose-induced DAG. (jci.org)
  • These results provide a unifying model for the activation of the NLRP3 inflammasome in which a drop in cytosolic K⁺ is the common step that is necessary and sufficient for caspase-1 activation. (nih.gov)
  • Inhibitors of apoptosis (IAPs) can prevent caspase activation under certain conditions. (cdc.gov)
  • Requirement of vanadate, an inhibitor for protein phosphatases, for activation of the enzyme in this system suggests that phosphorylation-dephosphorylation probably plays a key role in the regulated cleavage of proTGF-alpha. (nih.gov)
  • Our results confirm that monomeric amyloid beta-peptide 1-40 activates insulin receptor autophosphorylation, triggering downstream enzyme phosphorylarions and the glucose Transporter 4 translocation to the membrane. (ibecbarcelona.eu)
  • Glucose-induced activation of DAG/PKC signaling in microsomes was not associated with a change in the translocation of Glut-4 transporters from microsomes to the plasma membrane, a biological response that is known to be stimulated by agonists, e.g., phorbol esters, which increase DAG/PKC signaling in plasma membranes, as well as in microsomes. (jci.org)
  • We have therefore used isolated rat adipocytes to examine the mechanisms, including membrane translocation, whereby insulin and the insulin-mimicking agents vanadate and peroxovanadate control PKB. (lu.se)
  • Significant translocation of PKB to membranes could not be demonstrated after insulin stimulation, but peroxovanadate, which appeared to activate PI 3-kinase to a higher extent than insulin, induced substantial translocation. (lu.se)
  • The translocation was prevented by wortmannin, suggesting that PI 3-kinase and/or the 3-phosphorylated phosphoinositides generated by PI 3-kinase are indeed involved in the membrane targeting of PKB. (lu.se)
  • It has a membrane peripheral V1 sector for ATP hydrolysis and an integral V0 for proton translocation. (lu.se)
  • To assess the role of cytosol and cytosolic membrane-bound enzymes in the activation and detoxification of the PAH, the coincubation assay was performed with a S12 supernatant from sonicated cells. (astm.org)
  • Although these platelet activation processes are relatively well-studied as a function of the platelet environment, only since recently it is becoming clear that a multitude of proteases present in plasma or produced by platelets themselves are important for the distinct properties of platelet populations, often by cleaving specific receptors. (frontiersin.org)
  • The major membrane system extends from the nucleus to the external surface of the plasma membrane. (slideserve.com)
  • 5) Endosomes are granular membranes that contains endolithic material pinched off from the inside surface of the plasma membrane for transport to the lysosomes for degradation. (slideserve.com)
  • Glucose rapidly increased DAG content and PKC enzyme activity in microsomes, but not in plasma membranes or other membranes, during a 30-min treatment of rat adipocytes. (jci.org)
  • RESULTS AND CONCLUSION: Plasma TC increased by 4.33% while RBC membrane TC decreased by 20.32% in copper-toxic group compared to control. (bvsalud.org)
  • Number of cis- and saturated fatty acids increased in copper-treated plasma and RBC membrane compared to control. (bvsalud.org)
  • It is known that the activities of Na+/K+- and Ca2+-ATPases in the plasma membrane with an excess of cholesterol are compromised. (bvsalud.org)
  • Furthermore, we observed that CysLT1R is located in the plasma membrane and in the outer nuclei membrane. (lu.se)
  • The enzyme activity was about 5-6-fold increased by exposure of the cells with phorbol ester or with calcium ionophore. (nih.gov)
  • These findings suggest that the enzyme is a processing protease involved in the cleavage of proTGF-alpha and that induction of proTGF-alpha conversion by phorbol ester or by calcium ionophore can be attributed to activation of the processing protease. (nih.gov)
  • Phosphatidylserine-exposing platelets, usually located around a thrombus, provide a negatively charged membrane surface, which supports coagulation factor binding and the formation of tenase and prothrombinase complexes ( 6 , 7 ). (frontiersin.org)
  • The enzyme was partially purified from membranes of phorbol ester-treated CHO cells. (nih.gov)
  • Inhibitor profile of the enzyme, including inhibition by serine protease inhibitors and no inhibition by elastatinal, coincides with that previously reported for proTGF-alpha cleavage activity on CHO cells. (nih.gov)
  • Using a compound they designed and dubbed 194, the team successfully regulated NaV1.7 activation in the laboratory using nerve cells from four different species , including humans. (scitechdaily.com)
  • The activation of a series of cytosolic proteases, called caspases, is a hallmark of apoptosis. (bitesizebio.com)
  • Here, we review current knowledge how proteases act on platelet receptors and the platelet membrane surface. (frontiersin.org)
  • The psychophysics of this state clearly emphasize that the pain is evoked by the activation of low threshold mechano-receptors (Aß afferents). (asra.com)
  • The strong dependence of PI 3-kinase function on membrane curvature suggests possible localization of PI 3-kinase activity at sites where clustering of receptors, for example, may locally deform the membrane, and suggests that once PI 3-kinase is localized and activated at surface sites, the reaction may become self-accelerating. (tamu.edu)
  • Alcohol also interferes with proper inflammatory responses by disturbing the enzymatic processing of TNFα by TNFα Converting Enzyme (TACE) and abrogating TNFα/TACE function [ 11 , 12 ]. (cdc.gov)
  • In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. (mdpi.com)
  • Here we review recent advances in the study of Al in plants at physiological, biochemical and molecular levels, focusing mainly on the beneficial effect of Al in plants (stimulation of root growth, increased nutrient uptake, the increase in enzyme activity, and others). (frontiersin.org)
  • Interestingly, stimulation of CysLT1R located in the nuclei induced the activation of ERK1/2, an enzyme which have been shown to mediate LTD4 induced proliferation. (lu.se)
  • Toxic copper level induces membrane lipid peroxidation which could cause membrane instability. (bvsalud.org)
  • The natural agonist, diacylglycerol (DAG), and the natural product superagonist, phorbol dibutyrate (PDB), activate the enzyme to produce wide-ranging physiological effects. (embl-heidelberg.de)
  • The data also suggest that half of the domain, including the phorbol site and one of the zinc sites, is capable of inserting into membranes. (embl-heidelberg.de)
  • We provide a comprehensive overview of the proteases acting on the platelet membrane. (frontiersin.org)
  • The flow-dependent adhesion of platelets to those and other extracellular matrix components is stabilized by a panel of integrins, including integrin α 2 β 1 , α IIb β 3 , and α 6 β 1 (adhesive platelet population), while the initial activation of platelets is achieved by signaling via the collagen/laminin receptor, glycoprotein VI (GPVI). (frontiersin.org)
  • Independently of such activation processes, platelet heterogeneity can be achieved by aging and an accompanied inactivation ( 3 ). (frontiersin.org)
  • Platelet activation pathways. (medscape.com)
  • Following starvation-induced autophagy, nascent lysosomes are formed from autolysosomal membranes through an evolutionarily conserved cellular process, autophagic lysosome reformation (ALR), which is critical for maintaining lysosome homeostasis. (nature.com)
  • Complexes of Vps34, the sole class III PI3K member, produce PI 3-phosphate (PI(3)P) in the endolysosomal system and during autophagy to regulate vesicle-mediated sorting en route to lysosomes 1 . (nature.com)
  • Preterm PROM occurs probably due to the same mechanisms and premature activation of these pathways. (medscape.com)
  • Mechanism(s) controlling conversion of the membrane-anchored precursor to the soluble TGF-alpha are unknown, and the responsible protease has not been identified. (nih.gov)
  • However, its mechanism of activation remains largely unknown. (nih.gov)
  • Pawlowski, N. Dynamin self-assembly and the vesicle scission mechanism: how dynamin oligomers cleave the membrane neck of clathrin-coated pits during endocytosis. (nature.com)
  • We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. (nature.com)
  • In keeping with the role of TbNTR in nitrodrug activation, loss of an NTR gene copy in T. brucei was found to be one, but not the only, mechanism that may lead to nitrodrug resistance. (bl.uk)
  • Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. (medlineplus.gov)
  • This negative surface provides binding sites for enzymes and cofactors of the coagulation system, resulting in the formation of a clot (secondary hemostasis). (medscape.com)
  • Transient overexpression of UBCv1 impaired activation of NF-κB and AP-1 transcription factors induced by several agonists of these pathways. (mdpi.com)
  • Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. (cdc.gov)
  • Complement activation is known to occur in many diverse renal diseases, including glomerulonephritis, thrombotic microangiopathies and transplant rejection. (wjgnet.com)
  • In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease. (wjgnet.com)
  • It is therefore possible that inhibiting complement activation would reduce inflammation, lead to reduced fibrosis and preservation of renal function. (wjgnet.com)
  • The molecular mass of the enzyme was estimated to be about 84 kDa by gel filtration analysis. (nih.gov)
  • Researchers at our institute, leading a consortium of 11 laboratories, combined several approaches of structural biology, molecular biology, biochemistry, biophysics and toxicology to elucidate the activation cascade of Cyt1Aa, from its crystallization within the bacterium to its toxic activity in the insect. (cea.fr)
  • In other studies, LPE inhibited the activity of phospholipase D (PLD), a membrane degrading enzyme, of which active is increased during senescence. (wikipedia.org)
  • Researchers at our institute have elucidated the activation cascade of Cyt1Aa (one of the 4 Bacillus thuringiensis toxins that specifically target mosquito larvae to prevent them from becoming vectors of devastating diseases) from its crystallization within the bacterium to toxic activity in the insect. (cea.fr)
  • The specific activity of K-pNPPase and its sensitivity to ouabain was significantly increased in the presence of saponin, indicating that part of this activity is latent when assayed on native membrane preparation. (mcmaster.ca)
  • The activation status of RuBisCO, and the protein content and activity of RuBisCO activase, but not the total content and transcripts of RuBisCO were closely related to the endogenous BR levels in different genotypes. (biomedcentral.com)
  • Our main goal was to find out whether quercetin, resveratrol, or caffeic acid, in the nano- and low micromolar concentration ranges, can improve the ATPase activity in human erythrocyte membranes with excess cholesterol. (bvsalud.org)
  • This is because several of the contaminants in technical grade methoxychlor are directly estrogenic (Kupfer and Bulger 1987b), whereas pure methoxychlor is proestrogenic and requires metabolic activation before exhibiting estrogenic activity (Bulger et al. (cdc.gov)
  • In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. (mdpi.com)
  • Cloning has emphasized that there are multiple populations of voltage sensitive sodium channels (NaV), differing in their current activation properties and structure. (asra.com)
  • beta-peptide 1-40 blocks insulin receptor, impairing its activation. (ibecbarcelona.eu)
  • The decrease in electrophoretic mobility and activation of PKB induced by insulin was reversed both in vitro by treatment of the enzyme with alkaline phosphatase and in the intact adipocyte upon removal of insulin or addition of the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin. (lu.se)
  • Because human intestines lack the phytase enzyme, much phosphorus in this form is unavailable for absorption [ 1 ]. (nih.gov)
  • Here, the role of the bacterial-like nitroreductase TbNTR as a nitrodrug activating enzyme is examined through overexpression and knock-out studies in T. brucei. (bl.uk)
  • Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. (wjgnet.com)
  • The Ca2+-inhibition of K-pNNPase was accompanied by increased sensitivity of the enzyme to ouabain. (mcmaster.ca)
  • Since TB prevention and control efforts directed at preventing TB transmission are fundamentally different from efforts to prevent activation of latent TB infection, genotyping offers a powerful tool to help direct the application of appropriate efforts. (cdc.gov)
  • The V-ATPase is an heteromultimeric enzyme composed of at least thirteen different subunits. (lu.se)
  • A continuation of the nuclear membrane as a set of extensive channels. (slideserve.com)
  • It is the high energy bond of ATP that raises the substrate plus the enzyme to a higher level of activation allowing the metabolic process to go. (slideserve.com)
  • SORS:Exploring mechanistic details in enzyme catalysis through mutiscale hybrid QM/MM simulations. (bsc.es)
  • We show that maximal growth is achieved when pathway activation is a more or less steeply graded function of the nutrient concentration. (lu.se)