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Molecular and cellular events linking variants in the histone demethylase KDM5C to the intellectual disability disorder Claes-Jensen syndrome.

FEBS J 2021 Sep 18. Epub 2021 Sep 18.

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY, 10461, United States.

The widespread availability of genetic testing for those with neurodevelopmental disorders has highlighted the importance of many genes necessary for the proper development and function of the nervous system. One gene found to be genetically altered in the X-linked intellectual disability disorder Claes-Jensen syndrome is KDM5C, which encodes a histone demethylase that regulates transcription by altering chromatin. While the genetic link between KDM5C and cognitive (dys)function is clear, how KDM5C functions to control transcriptional programs within neurons to impact their growth and activity remains the subject of ongoing research. Read More

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September 2021

Effect of an arbuscular mycorrhizal fungus on maize growth and cadmium migration in a sand column.

Ecotoxicol Environ Saf 2021 Sep 15;225:112782. Epub 2021 Sep 15.

College of Resources and Environment, Yunnan Agricultural University, Kunming 650201, Yunnan, China. Electronic address:

The ecological role of arbuscular mycorrhizal fungi (AMF) on altering cadmium (Cd) migration in polluted soil is still unresolved. The present experiment aimed to clarify whether AMF can reduce Cd loss due to leaching at different Cd concentrations (0, 5, 10, and 15 mg L) with maize as a host plant cultured in a sand column. The effects of the arbuscular mycorrhizal fungus Funneliformis mosseae on the root morphology, exudate content, and Cd uptake by maize and Cd loss due to leaching were investigated. Read More

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September 2021

Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids.

Cell Stem Cell 2021 Sep 16. Epub 2021 Sep 16.

Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. Electronic address:

Microglia are resident macrophages in the brain that emerge in early development and respond to the local environment by altering their molecular and phenotypic states. Fundamental questions about microglia diversity and function during development remain unanswered because we lack experimental strategies to interrogate their interactions with other cell types and responses to perturbations ex vivo. We compared human microglia states across culture models, including cultured primary and pluripotent stem cell-derived microglia. Read More

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September 2021

High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis.

Biol Chem 2021 Sep 20. Epub 2021 Sep 20.

Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangzhou510282, China.

It is widely accepted dietary fiber intimately linked to inflammatory and nervous diseases, which often been described with altered gastrointestinal (GI) motility. However, how dose dietary fiber modulate inflammation and crosstalk influence GI function has not been explained in detail. We found fiber-free diet reduced intestinal motility, accompanied by upregulated proinflammatory immunocytes and inflammatory cytokines in colon of mice. Read More

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September 2021

Endocannabinoid system contributions to sex-specific adolescent neurodevelopment.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Sep 14:110438. Epub 2021 Sep 14.

Department of Biological Sciences, 1812 Sir Isaac Brock Way, Brock University, St. Catharines, ON L2S 3A1, Canada; Centre for Neuroscience, 1812 Sir Isaac Brock Way, Brock University, St. Catharines, ON L2S 3A1, Canada; Department of Psychology, 1812 Sir Isaac Brock Way, Brock University, St. Catharines, ON L2S 3A1, Canada. Electronic address:

With an increasing number of countries and states adopting legislation permitting the use of cannabis for medical purposes, there is a growing interest among health and research professionals into the system through which cannabinoids principally act, the endocannabinoid system (ECS). Much of the seminal research into the ECS dates back only 30 years and, although there has been tremendous development within the field during this time, many questions remain. More recently, investigations have emerged examining the contributions of the ECS to normative development and the effect of altering this system during important critical periods. Read More

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September 2021

Insm1, Neurod1, and Pax6 promote murine pancreatic endocrine cell development through overlapping yet distinct RNA transcription and splicing programs.

G3 (Bethesda) 2021 Aug 26. Epub 2021 Aug 26.

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.

Insm1, Neurod1, and Pax6 are essential for the formation and function of pancreatic endocrine cells. Here, we report comparative immunohistochemical, transcriptomic, functional enrichment, and RNA splicing analyses of these genes using gene knock-out mice. Quantitative immunohistochemical analysis confirmed that elimination of each of these three factors variably impairs the proliferation, survival, and differentiation of endocrine cells. Read More

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Interactome screening of C9orf72 dipeptide repeats reveals VCP sequestration and functional impairment by polyGA.

Brain 2021 Sep 17. Epub 2021 Sep 17.

Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.

Repeat expansions in the C9orf72 gene are a common cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, two devastating neurodegenerative disorders. One of the proposed mechanisms of GGGGCC repeat expansion is their translation into non-canonical dipeptide repeats, which can then accumulate as aggregates and contribute to these pathologies. There are five different dipeptide repeat proteins (polyGA, polyGR, polyPR, polyPA and polyGP), some of which are known to be neurotoxic. Read More

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September 2021

CREB regulates the expression of Type 1 Inositol 1,4,5-trisphosphate receptors.

J Cell Sci 2021 Sep 17. Epub 2021 Sep 17.

Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, 14642, USA.

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) play a central role in regulating intracellular calcium signals in response to a variety of internal/external cues. Dysregulation of IP3R signaling is the underlying cause for numerous pathological conditions. It is well established that the activities of IP3Rs are governed by several post-translational modifications including phosphorylation by protein kinase A (PKA). Read More

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September 2021

MicroRNA and diabetic retinopathy-biomarkers and novel therapeutics.

Ann Transl Med 2021 Aug;9(15):1280

Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, USA.

Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. Read More

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Letrozole, an aromatase inhibitor, improves seminal parameters and hormonal profile in aged endangered Markhoz bucks.

Anim Biosci 2021 Aug 25. Epub 2021 Aug 25.

Department of Animal Science, Faculty of Agriculture, University of Kurdistan, Sanandaj 661715175, Iran.

Objective: Letrozole, a potent aromatase inhibitor, is known to have the potential to modify male reproductive function by altering sex hormone levels. This study aimed to evaluate the semen and testicular characteristics and hormonal profile of aged Mrakhoz bucks (Capra hircus) treated with letrozole.

Methods: Twelve Markhoz male goats, aged between 4. Read More

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Dynamin-related protein 1 regulates substrate oxidation in skeletal muscle by stabilizing cellular and mitochondrial calcium dynamics.

J Biol Chem 2021 Sep 13:101196. Epub 2021 Sep 13.

Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808; Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106. Electronic address:

Mitochondria undergo continuous cycles of fission and fusion to promote inheritance, regulate quality control, and mitigate organelle stress. More recently, this process of mitochondrial dynamics has been demonstrated to be highly sensitive to nutrient supply, ultimately conferring bioenergetic plasticity to the organelle. However, whether regulators of mitochondrial dynamics play a causative role in nutrient regulation remains unclear. Read More

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September 2021

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment.

Front Cell Dev Biol 2021 30;9:698532. Epub 2021 Aug 30.

Immunotherapy Laboratory, College of Pharmacology, Southwest Minzu University, Chengdu, China.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells generated in various pathologic conditions, which have been known to be key components of the tumor microenvironment (TME) involving in tumor immune tolerance. So MDSCs have been extensively researched recently. As its name suggests, immunosuppression is the widely accepted function of MDSCs. Read More

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Biological Functions Driven by mRNAs Carried by Extracellular Vesicles in Cancer.

Front Cell Dev Biol 2021 30;9:620498. Epub 2021 Aug 30.

Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.

Extracellular vesicles (EVs), including exosomes and microvesicles, are extracellular nanovesicles released by most cells. EVs play essential roles in intercellular communication the transport of a large variety of lipids, proteins, and nucleic acids to recipient cells. Nucleic acids are the most commonly found molecules inside EVs, and due to their small size, microRNAs and other small RNAs are the most abundant nucleic acids. Read More

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Understanding the gut microbiota and sarcopenia: a systematic review.

J Cachexia Sarcopenia Muscle 2021 Sep 14. Epub 2021 Sep 14.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia. Read More

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September 2021

Plasticity of the gastrocnemius elastic system in response to decreased work and power demand during growth.

J Exp Biol 2021 Sep 15. Epub 2021 Sep 15.

Biomechanics Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA.

Elastic energy storage and release can enhance performance that would otherwise be limited by the force-velocity constraints of muscle. While functional influence of a biological spring depends on tuning between components of an elastic system (the muscle, spring, driven mass, and lever system), we do not know whether elastic systems systematically adapt to functional demand. To test whether altering work and power generation during maturation alters the morphology of an elastic system, we prevented growing guinea fowl (Numida Meleagris) from jumping. Read More

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September 2021

Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains.

Nat Commun 2021 Sep 14;12(1):5435. Epub 2021 Sep 14.

Department of Biochemistry University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.

Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat (LRR) domains. Despite their known molecular architecture, the mechanism of activation and the role of the LRR domains in this process has remained elusive. Read More

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September 2021

A C-terminus-dependent conformational change is required for HDAC3 activation by nuclear receptor corepressors.

J Biol Chem 2021 Sep 11:101192. Epub 2021 Sep 11.

Department of Pharmacology & Physiology, Saint Louis University School of Medicine, St. Louis, MO 63104. Electronic address:

Histone deacetylase 3 (HDAC3) plays an important role in signal-dependent transcription and is dysregulated in diseases such as cancer. Previous studies have shown that the function of HDAC3 requires an activation step, which is mediated by the interactions of HDAC3 with the deacetylase-activation domain (DAD) of nuclear receptor corepressors and inositol tetraphosphate (IP4). However, the role of the unique HDAC3 C-terminal region in HDAC3 activation is elusive. Read More

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September 2021

The biological approaches of altering the growth and biochemical properties of medicinal plants under salinity stress.

Appl Microbiol Biotechnol 2021 Sep 14. Epub 2021 Sep 14.

Department of Plant Science, MacDonald College of McGill University, Ste-Anne-de-Bellevue, QC, Canada.

Due to their interesting properties for human health, medicinal plants are of worldwide interest, including Iran. More has yet to be investigated and analyzed on the use of methods affecting medicinal plant growth and biochemical properties under stress. The important question about medicinal plants is the purpose of their plantation, determining their growth conditions. Read More

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September 2021

Near Complete Repair After Myocardial Infarction in Adult Mice by Altering the Inflammatory Response With Intramyocardial Injection of α-Gal Nanoparticles.

Front Cardiovasc Med 2021 25;8:719160. Epub 2021 Aug 25.

Department of Medicine, Rush University Medical Center, Chicago, IL, United States.

Neonatal mice, but not older mice, can regenerate their hearts after myocardial-infarction (MI), a process mediated by pro-reparative macrophages. α-Gal nanoparticles applied to skin wounds in adult-mice bind the anti-Gal antibody, activate the complement cascade and generate complement chemotactic peptides that recruit pro-reparative macrophages which are further activated by these nanoparticles. The recruited macrophages decrease wound healing time by ~50%, restore the normal skin structure and prevent fibrosis and scar formation in mice. Read More

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Dietary Betaine Addition Alters Carcass Traits, Meat Quality, and Nitrogen Metabolism of Bama Mini-Pigs.

Front Nutr 2021 27;8:728477. Epub 2021 Aug 27.

Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.

Betaine is widely used as feed additives in animal husbandry as it can cause many benefits such as improving antioxidant ability, growth performance, and carcass traits. However, there are limited studies about the effects of betaine on the Bama mini-pigs. The present study was conducted to evaluate the effects of dietary betaine on carcass traits, meat quality, and nitrogen metabolism of pigs. Read More

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Fungal social influencers: secondary metabolites as a platform for shaping the plant-associated community.

Plant J 2021 Sep 12. Epub 2021 Sep 12.

Northern Crop Science Laboratory, U.S. Dept. Agriculture, Fargo, North Dakota, USA.

Fungal secondary metabolites (FSMs) are capable of manipulating plant community dynamics by inhibiting or facilitating the establishment of co-habitating organisms. Although production of FSMs is not crucial for survival of the producer, their absence can indirectly impair growth and/or niche competition of these fungi on the plant. Presence of FSMs with no obvious consequence on the fitness of the producer leaves questions regarding ecological impact. Read More

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September 2021

Signal Filtering Enabled by Spike Voltage-Dependent Plasticity in Metalloporphyrin-Based Memristors.

Adv Mater 2021 Sep 12:e2104370. Epub 2021 Sep 12.

Center for Molecular Systems & Organic Devices (CMSOD), Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.

Neural systems can selectively filter and memorize spatiotemporal information, thus enabling high-efficient information processing. Emulating such an exquisite biological process in electronic devices is of fundamental importance for developing neuromorphic architectures with efficient in situ edge/parallel computing, and probabilistic inference. Here a novel multifunctional memristor is proposed and demonstrated based on metalloporphyrin/oxide hybrid heterojunction, in which the metalloporphyrin layer allows for dual electronic/ionic transport. Read More

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September 2021

A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy.

Neurobiol Dis 2021 Sep 9:105507. Epub 2021 Sep 9.

Neuroscience Discovery, Merck & Co., Inc., West Point, PA 19486, United States. Electronic address:

Mutations in the lysosomal enzyme glucocerebrosidase (GCase, GBA1 gene) are the most common genetic risk factor for developing Parkinson's disease (PD). GCase metabolizes the glycosphingolipids glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Mutations in GBA1 reduce enzyme activity and the resulting accumulation of glycosphingolipids may contribute to the underlying pathology of PD, possibly via altering lysosomal function. Read More

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September 2021

The role of neck muscle co-contraction and postural changes in head kinematics after safe head impacts: Investigation of head/neck injury reduction.

J Biomech 2021 Sep 1;128:110732. Epub 2021 Sep 1.

Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA. Electronic address:

Concerns surrounding concussions from impacts to the head necessitate research to generate new knowledge about ways to prevent them and reduce risk. In this paper, we report the relative temporal characteristics of the head resulting from neck muscle co-contraction and postural changes following a sudden force applied to the head in four different directions. In the two "prepared" conditions (i. Read More

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September 2021

The Dietary Fiber Pectin: Health Benefits and Potential for the Treatment of Allergies by Modulation of Gut Microbiota.

Curr Allergy Asthma Rep 2021 Sep 10;21(10):43. Epub 2021 Sep 10.

Molecular Allergology, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Langen, Germany.

Purpose Of Review: The incidence of allergies is increasing and has been associated with several environmental factors including westernized diets. Changes in environment and nutrition can result in dysbiosis of the skin, gut, and lung microbiota altering the production of microbial metabolites, which may in turn generate epigenetic modifications. The present review addresses studies on pectin-mediated effects on allergies, including the immune modulating mechanisms by bacterial metabolites. Read More

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September 2021

Parameter Identification from Normal and Pathological Middle Ears Using a Tailored Parameter Identification Algorithm.

J Biomech Eng 2021 Sep 10. Epub 2021 Sep 10.

Reutlingen University, 72762 Reutlingen, Germany.

Current clinical practice is often unable to identify the causes of conductive hearing loss in the middle ear with sufficient certainty without exploratory surgery. Besides the large uncertainties due to interindividual variances, only partially understood cause-effect principles are a major reason for the hesitant use of objective methods such as wideband tympanometry in diagnosis, despite their high sensitivity to pathological changes. For a better understanding of objective metrics of the middle ear, this study presents a model that can be used to reproduce characteristic changes in metrics of the middle ear by altering local physical model parameters linked to the anatomical causes of a pathology. Read More

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September 2021

Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease.

Front Med (Lausanne) 2021 24;8:708453. Epub 2021 Aug 24.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Read More

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Riceberry rice ( L.) slows gastric emptying and improves the postprandial glycemic response.

Br J Nutr 2021 Sep 10:1-22. Epub 2021 Sep 10.

Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Rd., Bangkoknoi, Bangkok, 10700, Thailand.

Postprandial glycemia is a key determinant of overall glycemic control. One mechanism by which dietary strategies can reduce postprandial glycemic excursions is by slowing gastric emptying. This study aimed to evaluate the acute effect of ingesting riceberry rice (RR) compared to that of ingesting white rice (WR) on gastric emptying rate (GER), plasma glucose, and glucose-regulating hormones, including insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1), in healthy subjects. Read More

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September 2021

The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin.

Int J Mol Sci 2021 Sep 2;22(17). Epub 2021 Sep 2.

Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-000, Brazil.

Cancer development is associated with abnormal proliferation, genetic instability, cell death resistance, metabolic reprogramming, immunity evasion, and metastasis. These alterations are triggered by genetic and epigenetic alterations in genes that control cell homeostasis. Increased reactive oxygen and nitrogen species (ROS, RNS) induced by different enzymes and reactions with distinct molecules contribute to malignant transformation and tumor progression by modifying DNA, proteins, and lipids, altering their activities. Read More

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September 2021

Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics.

Int J Mol Sci 2021 Aug 25;22(17). Epub 2021 Aug 25.

Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Location VUmc, 1081 HZ Amsterdam, The Netherlands.

The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. has been implicated in a novel congenital myopathy, and in distal arthrogryposis (DA), and and in nemaline myopathy (NEM). Read More

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