108,027 results match your criteria substrates protein

Elucidation of familial relationships using hair shaft proteomics.

Forensic Sci Int Genet 2021 Jul 17;54:102564. Epub 2021 Jul 17.

Department of Environmental Toxicology, University of California, Davis, USA; Forensic Science Program, University of California, Davis, USA.

This study examines the potential of hair shaft proteomic analysis to delineate genetic relatedness. Proteomic profiling and amino acid sequence analysis provide information for quantitative and statistically-based analysis of individualization and sample similarity. Protein expression levels are a function of cell-specific transcriptional and translational programs. Read More

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A hypothesis: Fructosamine-3-Kinase-Related-Protein (FN3KRP) catalyzes deglycation of Maillard intermediates directly downstream from fructosamines.

Rejuvenation Res 2021 Jul 27. Epub 2021 Jul 27.

SeroClear, Research, Englewood, New Jersey, United States;

Non-enzymatic glycation (a.k.a. Read More

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HDAC6 Substrate Discovery Using Proteomics-Based Substrate Trapping: HDAC6 Deacetylates PRMT5 to Influence Methyltransferase Activity.

ACS Chem Biol 2021 Jul 27. Epub 2021 Jul 27.

Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.

Histone deacetylase 6 (HDAC6) is upregulated in a variety of tumor cell lines and has been linked to many cellular processes, such as cell signaling, protein degradation, cell survival, and cell motility. HDAC6 is an enzyme that deacetylates the acetyllysine residues of protein substrates, and the discovery of HDAC6 substrates, including tubulin, has revealed many roles of HDAC6 in cell biology. Unfortunately, among the wide variety of acetylated proteins in the cell, only a few are verified as HDAC6 substrates, which limits the full characterization of HDAC6 cellular functions. Read More

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All cells are created equal in the sight of autophagy: selective autophagy maintains homeostasis in senescent cells.

Autophagy 2021 Jul 27:1-2. Epub 2021 Jul 27.

School of Biological Sciences, Seoul National University, Seoul, South Korea.

Macroautophagy/autophagy is a sophisticated quality control program that limits cellular damage and maintains homeostasis, being an essential part of several lifespan-promoting interventions. However, autophagy is also necessary for full establishment of cellular senescence, a causal factor for many age-related diseases and aging. What lies ahead of us to unravel such a paradoxical role of autophagy in senescence is to identify specific targets degraded by autophagy during senescence and determine their importance in the senescence regulatory network. Read More

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Rational Multitargeted Drug Design Strategy from the Perspective of a Medicinal Chemist.

J Med Chem 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, Shandong, P. R. China.

The development of multitarget-directed ligands (MTDLs) has become a widely focused research topic, but rational design remains as an enormous challenge. This paper reviews and discusses the design strategy of incorporating the second activity into an existing single-active ligand. If the binding sites of both targets share similar endogenous substrates, MTDLs can be designed by merging two lead compounds with similar functional groups. Read More

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Electrochemical Potential Driven High-Throughput Molecular Electronic and Spintronic devices: From Molecules to Applications.

Angew Chem Int Ed Engl 2021 Jul 27. Epub 2021 Jul 27.

Universite de Bordeaux, MRGM, 33400, Talence, FRANCE.

Molecules are fascinating candidates for constructing tunable and electrically conducting devices by assembling either single or ensemble of molecules between two electrical contacts followed by current-voltage (I-V) analysis which is often termed 'molecular electronics'. Recently, there has been also an upsurge of interest in spin-based electronics or spintronics across the molecules offering an additional scope to create ultra-fast responsive devices with less power consumption and lower heat generation using the intrinsic spin property rather than electronic charge. Researchers have been exploring this idea of utilizing organic molecules, organometallics, coordination complexes, polymers, and biomolecules (proteins, enzymes, oligopeptides, DNA) in integrating molecular electronics and spintronics devices. Read More

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Precise regulation of presenilin expression is required for sea urchin early development.

J Cell Sci 2021 07 12;134(13). Epub 2021 Jul 12.

Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Sud, Université Paris-Saclay, 91405 Orsay, France.

Presenilins (PSENs) are widely expressed across eukaryotes. Two PSENs are expressed in humans, where they play a crucial role in Alzheimer's disease (AD). Each PSEN can be part of the γ-secretase complex, which has multiple substrates, including Notch and amyloid-β precursor protein (AβPP) - the source of amyloid-β (Aβ) peptides that compose the senile plaques during AD. Read More

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Assessment of SENP3-interacting proteins in hepatocytes treated with diethylnitrosamine by BioID assay.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul 27. Epub 2021 Jul 27.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

SUMOylation of proteins regulates cell behaviors and is reversibly removed by small ubiquitin-like modifier (SUMO)-specific proteases (SENPs). The SENP family member SENP3 is involved in SUMO2/3 deconjugation and has been reported to sense cell stress and accumulate in several human cancer cells and macrophages. We previously reported that Senp3-knockout heterozygous mice showed smaller liver, but the pertinent mechanisms of SENP3 and SUMOylated substrates remain unclear. Read More

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Role of cholesterol in substrate recognition by [Formula: see text]-secretase.

Sci Rep 2021 Jul 26;11(1):15213. Epub 2021 Jul 26.

Department of Physical Chemistry, Gdansk University of Technology, Gdansk, 80-233, Poland.

[Formula: see text]-Secretase is an enzyme known to cleave multiple substrates within their transmembrane domains, with the amyloid precursor protein of Alzheimer's Disease among the most prominent examples. The activity of [Formula: see text]-secretase strictly depends on the membrane cholesterol content, yet the mechanistic role of cholesterol in the substrate binding and cleavage remains unclear. In this work, we used all-atom molecular dynamics simulations to examine the role of cholesterol in the initial binding of a direct precursor of [Formula: see text]-amyloid polypeptides by [Formula: see text]-secretase. Read More

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Molecular insights into the human ABCB6 transporter.

Cell Discov 2021 Jul 27;7(1):55. Epub 2021 Jul 27.

Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.

ABCB6 plays a crucial role in energy-dependent porphyrin transport, drug resistance, toxic metal resistance, porphyrin biosynthesis, protection against stress, and encoding a blood group system Langereis antigen. However, the mechanism underlying porphyrin transport is still unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structures of nanodisc-reconstituted human ABCB6 trapped in an apo-state and an ATP-bound state at resolutions of 3. Read More

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Mol Pharmacol 2021 Jul 26. Epub 2021 Jul 26.

Pharmacology, University of Texas Southwestern Medical Center, United States

The WNK (with-no lysine (K)) kinases and their downstream effector kinases, OSR1 (oxidative stress responsive 1) and SPAK (SPS/STE20-related proline-alanine rich kinase), have well-established functions in the maintenance of cell volume and ion homeostasis. Mutations in these kinases have been linked to an inherited form of hypertension, neurological defects, and other pathologies. A rapidly expanding body of evidence points to the involvement of WNKs in regulating multiple diverse cellular processes as well as the progression of some forms of cancer. Read More

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Assessment of EGFP-Q74 degradation for the measurement of autophagic flux.

Methods Cell Biol 2021 27;165:31-38. Epub 2021 Apr 27.

Centre de Recherche des Cordeliers, Équipe 11 Labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address:

Autophagy plays a major role in physiological and pathological processes. The quantitation of the abundance of autophagy-specific substrates constitutes an efficient strategy for assessing autophagic activity. Here, we provide a detailed protocol for quantifying the decay of a fusion protein composed by enhanced green fluorescent protein (EGFP) and glutamine repeats (Q74) using regular or high-throughput fluorescence microscopy. Read More

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Turnover of Variant Surface Glycoprotein in Trypanosoma brucei Is a Bimodal Process.

mBio 2021 Jul 27:e0172521. Epub 2021 Jul 27.

Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), Buffalo, New York, USA.

African trypanosomes utilize glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) to evade the host immune system. VSG turnover is thought to be mediated via cleavage of the GPI anchor by endogenous GPI-specific phospholipase C (GPI-PLC). However, GPI-PLC is topologically sequestered from VSG substrates in intact cells. Read More

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Requirement of CRMP2 Phosphorylation in Neuronal Migration of Developing Mouse Cerebral Cortex and Hippocampus and Redundant Roles of CRMP1 and CRMP4.

Cereb Cortex 2021 Jul 23. Epub 2021 Jul 23.

Laboratory for Molecular Brain Science, Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan.

The mammalian cerebral cortex is characterized by a 6-layer structure, and proper neuronal migration is critical for its formation. Cyclin-dependent kinase 5 (Cdk5) has been shown to be a critical kinase for neuronal migration. Several Cdk5 substrates have been suggested to be involved in ordered neuronal migration. Read More

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HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.

Nat Chem Biol 2021 Jul 22. Epub 2021 Jul 22.

Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.

HUWE1 is a universal quality-control E3 ligase that marks diverse client proteins for proteasomal degradation. Although the giant HECT enzyme is an essential component of the ubiquitin-proteasome system closely linked with severe human diseases, its molecular mechanism is little understood. Here, we present the crystal structure of Nematocida HUWE1, revealing how a single E3 enzyme has specificity for a multitude of unrelated substrates. Read More

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An on-demand, drop-on-drop method for studying enzyme catalysis by serial crystallography.

Nat Commun 2021 07 22;12(1):4461. Epub 2021 Jul 22.

Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

Serial femtosecond crystallography has opened up many new opportunities in structural biology. In recent years, several approaches employing light-inducible systems have emerged to enable time-resolved experiments that reveal protein dynamics at high atomic and temporal resolutions. However, very few enzymes are light-dependent, whereas macromolecules requiring ligand diffusion into an active site are ubiquitous. Read More

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Developmental validation of a multiplex proteomic assay for the identification of forensically relevant biological fluids.

Forensic Sci Int 2021 Jul 17;326:110908. Epub 2021 Jul 17.

The Center for Forensic Science Research & Education, Willow Grove, PA 19090, USA. Electronic address:

The aim of this study was to validate a multiplex proteomic assay for the identification of high-specificity protein biomarkers by multiple reaction monitoring mass spectrometry on a triple quadrupole mass spectrometer for the accurate, reliable, and confirmatory identification of bodily fluids commonly encountered in a forensic context. This includes the identification of peripheral blood, semen, saliva, urine, and vaginal/menstrual fluid. The assay is able to efficiently identify pure or mixed stains through the identification of target peptide fragments originating from tissue-specific proteins including: uromodulin from urine; prostatic acid phosphatase, prostate specific antigen and semenogelin-II for semen; statherin, submaxillary gland androgen-regulated protein 3B and amylase for saliva; cornulin, martrigel-induced gene C4 protein, suprabasin and neutrophil gelatinase-associated lipocalin for vaginal/menstrual fluid; and alpha-1 antitrypsin, hemopexin, and hemoglobin subunit beta for peripheral blood. Read More

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Pre-incubation with OATP1B1 and OATP1B3 inhibitors potentiates inhibitory effects in physiologically relevant sandwich-cultured primary human hepatocytes.

Eur J Pharm Sci 2021 Jul 23:105951. Epub 2021 Jul 23.

Department of Pharmaceutical Sciences. Electronic address:

Organic anion transporting polypeptides (OATP)1B1 and OATP1B3 are liver-specific transport proteins that express on the basolateral membrane of human hepatocytes and mediate hepatic uptake of many drugs, including statins. They are important determinants of transporter-mediated drug-drug interactions (DDIs). It has been reported that pre-incubation with some OATP1B1 and OATP1B3 inhibitors potentiates the inhibitory effects, yielding reduced IC values. Read More

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Single Molecule Fluorescence Energy Transfer Study of Ribosome Protein Synthesis.

Yuhong Wang

J Vis Exp 2021 Jul 6(173). Epub 2021 Jul 6.

Department of Biology and Biochemistry, University of Houston;

The ribosome is a large ribonucleoprotein complex that assembles proteins processively along mRNA templates. The diameter of the ribosome is approximately 20 nm to accommodate large tRNA substrates at the A-, P- and E-sites. Consequently, the ribosome dynamics are naturally de-phased quickly. Read More

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Modulation of the enzymatic activity of the flagellar lytic transglycosylase SltF by rod components, and the scaffolding protein FlgJ in .

J Bacteriol 2021 Jul 26:JB0037221. Epub 2021 Jul 26.

Instituto de Fisiología Celular and Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México.

Macromolecular cell-envelope-spanning structures such as the bacterial flagellum must traverse the cell wall. Lytic transglycosylases enzymes are capable of enlarging gaps in the peptidoglycan meshwork to allow the efficient assembly of supramolecular complexes. In the periplasmic space, the assembly of the flagellar rod requires the scaffold protein FlgJ, which includes a muramidase domain in the canonical models and . Read More

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Importance of Substrate-Particle Repulsion for Protein-Templated Assembly of Metal Nanoparticles.

Langmuir 2021 Jul 26. Epub 2021 Jul 26.

Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.

We study the protein-directed assembly of colloidal gold nanoparticles on designed protein nanofiber templates. Using sequential assembly on glass substrates, we attach positively charged gold nanoparticles to protein nanofibers engineered to have a high density of negatively charged surface residues. Using a combination of electron and optical microscopy, we measure the density of particle attachment and characterize binding specificity. Read More

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Chiral Plasmonic Triangular Nanorings with SERS Activity for Ultrasensitive Detection of Amyloid Proteins in Alzheimer's Disease.

Adv Mater 2021 Jul 26:e2102337. Epub 2021 Jul 26.

International Joint Research Laboratory for Biointerface and Biodetection, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.

Chiral plasmonic nanomaterials have attracted unprecedented attention due to their broad applications in biomedicine, negative refractive index, and chiral sensing. Here, using a wet-chemistry process, chiral triangular Au nanorings are fabricated with a platinum (Pt) framework (l/[email protected] triangular nanorings, named l/[email protected] TNRs). The l/[email protected] TNRs exhibit strong optical activity with a g-factor of 0. Read More

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Single-step Replacement of an Unreactive C-H Bond by a C-S Bond Using Polysulfide as the Direct Sulfur Source in Anaerobic Ergothioneine Biosynthesis.

ACS Catal 2020 Aug 16;10(16):8981-8994. Epub 2020 Jul 16.

Department of Chemistry, Boston University, Boston, MA 02215, USA.

Ergothioneine, a natural longevity vitamin and antioxidant, is a thiol-histidine derivative. Recently, two types of biosynthetic pathways were reported. In the aerobic ergothioneine biosynthesis, a non-heme iron enzyme incorporates a sulfoxide to an sp C-H bond in trimethyl-histidine (hercynine) through oxidation reactions. Read More

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Sex-Specific Linear Polyubiquitination Is a Critical Regulator of Contextual Fear Memory Formation.

Front Behav Neurosci 2021 9;15:709392. Epub 2021 Jul 9.

School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.

Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner. Read More

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Enhanced Phytase Production by Bacillus subtilis subsp. subtilis in Solid State Fermentation and its Utility in Improving Food Nutrition.

Protein Pept Lett 2021 Jul 20. Epub 2021 Jul 20.

Department of Physics, RPS Degree College, Balana, Satnali Road, Mahendergarh-123029, Haryana, India.

Background: Phytic acid acts as anti-nutritional factor in food and feed ingredients for monogastric animals as they lack phytases.

Objective: Phytase production by Bacillus subtilis subsp. subtilis JJBS250 was studied in solid state fermentation and its applicability in dephytinization of food Methods: Bacterial culture was grown in solid state fermentation using wheat bran and various culture conditions were optimized using 'One variable at a time' (OVAT) approach. Read More

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A Common Molecular Switch for HS to Regulate Multiple Protein Targets.

Adv Exp Med Biol 2021 ;1315:1-16

Shanghai Key Laboratory of Bioactive Small Molecules and Shanghai Key Laboratory of Clinical Geriatric Medicine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Hydrogen sulfide, a small molecule, produced by endogenous enzymes, such as CTH, CBS, and MPST using L-cysteine as substrates, has been reported to have numerous protective effects. However, the key problem that the target of HS and how it can affect the structure and activity of biological molecules is still unknown. Till now, there are two main theories of its working mechanism. Read More

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Anaerobic hydrolysis of complex substrates in full-scale aerobic granular sludge: enzymatic activity determined in different sludge fractions.

Appl Microbiol Biotechnol 2021 Jul 24. Epub 2021 Jul 24.

Section Sanitary Engineering, Department of Water Management, Delft University of Technology, Stevinweg 1, Delft, 2628 CN, The Netherlands.

Complex substrates, like proteins, carbohydrates, and lipids, are major components of domestic wastewater, and yet their degradation in biofilm-based wastewater treatment technologies, such as aerobic granular sludge (AGS), is not well understood. Hydrolysis is considered the rate-limiting step in the bioconversion of complex substrates, and as such, it will impact the utilization of a large wastewater COD (chemical oxygen demand) fraction by the biofilms or granules. To study the hydrolysis of complex substrates within these types of biomass, this paper investigates the anaerobic activity of major hydrolytic enzymes in the different sludge fractions of a full-scale AGS reactor. Read More

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BACE inhibitor treatment of mice induces hyperactivity in a Seizure-related gene 6 family dependent manner without altering learning and memory.

Sci Rep 2021 Jul 23;11(1):15084. Epub 2021 Jul 23.

Department of Anatomy and Physiology, University of Melbourne, Melbourne, VIC, Australia.

BACE inhibitors, which decrease BACE1 (β-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer's disease. Clinical trials using BACE inhibitors have reported a lack of positive effect on patient symptoms and, in some cases, have led to increased adverse events, cognitive worsening and hippocampal atrophy. A potential drawback of this strategy is the effect of BACE inhibition on other BACE1 substrates such as Seizure-related gene 6 (Sez6) family proteins which are known to have a role in neuronal function. Read More

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Phenethylamine in chlorella alleviates high-fat diet-induced mouse liver damage by regulating generation of methylglyoxal.

NPJ Sci Food 2021 Jul 23;5(1):22. Epub 2021 Jul 23.

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Kyoto, Japan.

This study examined the effects of oral administration of water extract of chlorella (WEC) (100 mg/kg bodyweight) and phenethylamine (10 μg/kg bodyweight) on high-fat diet (HFD)-induced liver damage in mice. Phenethylamine significantly mitigated HFD-induced lipid oxidation (generation of malondialdehyde) and liver damage without markedly decreasing hepatic lipid accumulation. WEC exerted similar effects although with decreased efficacy. Read More

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Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests.

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy.

The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. Read More

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