993 results match your criteria perturbed absence

Deciphering the Proteotoxic Stress Responses Triggered by the Perturbed Thylakoid Proteostasis in Arabidopsis.

Plants (Basel) 2021 Mar 10;10(3). Epub 2021 Mar 10.

Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda 669-1337, Hyogo, Japan.

Here, we explored heat dependent thylakoid FtsH protease substrates and investigated proteotoxicity induced by thermal damage and processive protease dysfunction on the thylakoid membrane. Through our thylakoid enriched proteome analysis and biochemical experiments, carbonylated stromal proteins were suggested as possible FtsH targets. Furthermore, we observed in the thylakoid fractions in the absence of FtsH stromal reactive oxygen species-detoxifying enzymes, as well as heat shock proteins and chaperones, which are known to be upregulated at the transcriptional level when this protease is absent, which is called the damaged protein response, resembling unfolded protein response in eukaryotic cells. Read More

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Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection.

Front Genet 2021 16;12:599261. Epub 2021 Mar 16.

Bioinformatics and Computational Biology Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Analyzing host cells' transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help delineate biological processes underlying viral pathogenesis. First, analysis of expression profiles of lung cell lines A549 and Calu3 revealed upregulation of antiviral interferon signaling genes in response to all three SARS-CoV-2, MERS-CoV, or influenza A virus (IAV) infections. However, perturbations in expression of genes involved in inflammatory, mitochondrial, and autophagy processes were specifically observed in SARS-CoV-2-infected cells. Read More

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Molecular Mechanisms of the Genetic Predisposition to Acute Megakaryoblastic Leukemia in Infants With Down Syndrome.

Front Oncol 2021 11;11:636633. Epub 2021 Mar 11.

Pediatric Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.

Individuals with Down syndrome are genetically predisposed to developing acute megakaryoblastic leukemia. This myeloid leukemia associated with Down syndrome (ML-DS) demonstrates a model of step-wise leukemogenesis with perturbed hematopoiesis already presenting , facilitating the acquisition of additional driver mutations such as truncating variants, which are pathognomonic to the disease. Consequently, the affected individuals suffer from a transient abnormal myelopoiesis (TAM)-a pre-leukemic state preceding the progression to ML-DS. Read More

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Diet-Dependent Changes of the DNA Methylome Using a Göttingen Minipig Model for Obesity.

Front Genet 2021 11;12:632859. Epub 2021 Mar 11.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Environmental factors can influence obesity by epigenetic mechanisms. The aim of this study was to investigate obesity-related epigenetic changes and the potential for reversal of these changes in the liver of Göttingen minipigs subjected to diet interventions. High-throughput liquid hybridization capture-based bisulfite sequencing (LHC-BS) was used to quantify the methylation status of gene promotor regions in liver tissue in three groups of male castrated Göttingen minipigs: a standard chow group (SD, = 7); a group fed high fat/fructose/cholesterol diet (FFC, = 10) and a group fed high fat/fructose/cholesterol diet during 7 months and reversed to standard diet for 6 months (FFC/SD, = 12). Read More

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Update on Calcium Signaling in Cystic Fibrosis Lung Disease.

Front Pharmacol 2021 11;12:581645. Epub 2021 Mar 11.

Department of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyperinflammation, and lung tissue damage compose the classical pathological manifestation referred to as CF lung disease. Among the multifunctional defects associated with defective CFTR, increasing evidence supports the relevant role of perturbed calcium (Ca) signaling in the pathophysiology of CF lung disease. Read More

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An early-morning gene network controlled by phytochromes and cryptochromes regulates photomorphogenesis pathways in Arabidopsis.

Mol Plant 2021 Mar 22. Epub 2021 Mar 22.

Alan Turing Institute, London, United Kingdom; Department of Biology, University of York.

Light perception at dawn plays a key role in coordinating multiple molecular processes and in entraining the plant circadian clock. An Arabidopsis mutant lacking the main photoreceptors however still shows clock entrainment, indicating that the integration of light into the morning transcriptome is not well understood. We performed a high-resolution RNA-seq time series experiment, sampling every two-minutes from dawn. Read More

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3D-FV-FE Aeroacoustic Larynx Model for Investigation of Functional Based Voice Disorders.

Front Physiol 2021 8;12:616985. Epub 2021 Mar 8.

Division of Phoniatrics and Pediatric Audiology, Department of Otorhinolaryngology, Head & Neck Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

For the clinical analysis of underlying mechanisms of voice disorders, we developed a numerical aeroacoustic larynx model, called , that mimics commonly observed functional laryngeal disorders as glottal insufficiency and vibrational left-right asymmetries. The model is a combination of the Finite Volume (FV) CFD solver Star-CCM+ and the Finite Element (FE) aeroacoustic solver CFS++. models turbulence using Large Eddy Simulations (LES) and the acoustic wave propagation with the perturbed convective wave equation (PCWE). Read More

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Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat.

Front Pharmacol 2021 8;12:586715. Epub 2021 Mar 8.

School of Medical Science, Griffith University, Gold Coast, QLD, Australia.

Circulating bilirubin is associated with reduced adiposity in human and animal studies. A possible explanation is provided by data that demonstrates that bilirubin inhibits mitochondrial function and decreases efficient energy production. However, it remains unclear whether hyperbilirubinemic animals have similar perturbed mitochondrial function and whether this is important for regulation of energy homeostasis. Read More

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Developmental Accumulation of Gene Body and Transposon Non-CpG Methylation in the Zebrafish Brain.

Front Cell Dev Biol 2021 4;9:643603. Epub 2021 Mar 4.

Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.

DNA methylation predominantly occurs at CG dinucleotides in vertebrate genomes; however, non-CG methylation (mCH) is also detectable in vertebrate tissues, most notably in the nervous system. In mammals it is well established that mCH is targeted to CAC trinucleotides by DNMT3A during nervous system development where it is enriched in gene bodies and associated with transcriptional repression. Nevertheless, the conservation of developmental mCH accumulation and its deposition by DNMT3A is largely unexplored and has yet to be functionally demonstrated in other vertebrates. Read More

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Characterisation of a glycerol ABC transporter of involved in pathogenicity.

Appl Environ Microbiol 2021 Mar 19. Epub 2021 Mar 19.

Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Australia.

MalF has been shown to be required for virulence in the important avian pathogen To characterise the function of MalF, predicted to be part of putative ABC transporter, we compared metabolite profiles of a mutant with a transposon inserted in (MalF-deficient ST mutant 04-1; Δ) with those of wild type bacteria using GC/MS and LC/MS. Of those substrates likely to be transported by an ABC transport system, glycerol was detected at significantly lower abundance in the Δ mutant, when compared to the wild type. Stable isotope labelling using [U-C] glycerol and RT-qPCR analysis indicated that MalF was responsible for import of glycerol into and that, in the absence of MalF, the transcription of which encodes a second transporter, GtsA, was upregulated, potentially to increase import of glycerol-3-phosphate into the cell to compensate for the loss of MalF. Read More

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Metabolomic Analysis of Aqueous Humor Identifies Aberrant Amino Acid and Fatty Acid Metabolism in Vogt-Koyanagi-Harada and Behcet's Disease.

Front Immunol 2021 22;12:587393. Epub 2021 Feb 22.

The First Affiliated Hospital of Chongqing Medical University, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. Read More

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February 2021

Phosphorylation of ERK and dystrophin S3059 protect against inflammation-associated C2C12 myotube atrophy.

Am J Physiol Cell Physiol 2021 Mar 17. Epub 2021 Mar 17.

Centre for Muscle Research, Department of Anatomy and Physiology, The University of Melbourne, Victoria, 3010, Australia.

The dystrophin-glycoprotein complex (DGC) is a multi-protein structure required to maintain muscle fiber membrane integrity, transmit force by linking the actin cytoskeleton with the extracellular matrix, and maintain muscle homeostasis. Membrane localization of dystrophin is perturbed in muscles wasting as a consequence of cancer cachexia, tenotomy and advanced ageing, which are all associated with low level, chronic inflammation. Strategies to preserve dystrophin expression at the sarcolemma might therefore combat muscle wasting. Read More

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A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange.

Front Neurosci 2020 18;14:619279. Epub 2021 Feb 18.

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States.

Wild-type human SOD1 forms a highly conserved intra-molecular disulfide bond between C57-C146, and in its native state is greatly stabilized by binding one copper and one zinc atom per monomer rendering the protein dimeric. Loss of copper extinguishes dismutase activity and destabilizes the protein, increasing accessibility of the disulfide with monomerization accompanying disulfide reduction. A further pair of free thiols exist at C6 and C111 distant from metal binding sites, raising the question of their function. Read More

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February 2021

BLOC1S1/GCN5L1/BORCS1 is a critical mediator for the initiation of autolysosomal tubulation.

Autophagy 2021 Mar 11:1-18. Epub 2021 Mar 11.

Laboratory of Mitochondrial Biology and Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland.

The mechanisms orchestrating recycling of lysosomes through autophagic lysosome reformation (ALR) is incompletely understood. Previous data show that genetic depletion of BLOC1S1/GCN5L1/BORCS1 increases autolysosome (AL) accumulation. We postulated that this phenotype may manifest due to perturbed ALR. Read More

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Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.

Front Pharmacol 2020 18;11:620724. Epub 2021 Jan 18.

Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. Read More

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January 2021

A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease.

Mov Disord 2021 Feb 22. Epub 2021 Feb 22.

Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.

Background: The SNCA gene encoding α-synuclein (αSyn) is the first gene identified to cause autosomal-dominant Parkinson's disease (PD).

Objective: We report the identification of a novel heterozygous A30G mutation of the SNCA gene in familial PD and describe clinical features of affected patients, genetic findings, and functional consequences.

Methods: Whole exome sequencing was performed in the discovery family proband. Read More

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February 2021

Regulation of the Switchable Luminescence of Tridentate Platinum(II) Complexes by Photoisomerization.

Front Chem 2020 5;8:622256. Epub 2021 Feb 5.

College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, China.

Organoplatinum (II) complexes are promising candidates for the construction of smart supramolecular materials due to their unique flat structures. This accompanied by intriguing luminescent properties, prompts the molecules to aggregate after external stimuli. Nevertheless, the utilization of photo-responsive subunits to modulate their assemble behaviors and functions are still rarely explored. Read More

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February 2021

Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation.

Front Endocrinol (Lausanne) 2020 4;11:621944. Epub 2021 Feb 4.

Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan.

Perturbed Nicotinamide adenine dinucleotide (NAD) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Read More

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February 2021

Nicotinamide Mononucleotide Restores the Meiotic Competency of Porcine Oocytes Exposed to Ethylene Glycol Butyl Ether.

Front Cell Dev Biol 2021 2;9:628580. Epub 2021 Feb 2.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Ethylene glycol butyl ether (EGBE), a type of glycol ethers, is a common chemical used in both industrial and household products. Increasing animal studies have indicated that it produces reproductive problems, such as testicular damage, reduced female fertility, death of embryos, and birth defects. However, how it influences the female germ cells has not yet determined. Read More

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February 2021

HLA Class I Knockout Converts Allogeneic Primary NK Cells Into Suitable Effectors for "Off-the-Shelf" Immunotherapy.

Front Immunol 2020 29;11:586168. Epub 2021 Jan 29.

Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Cellular immunotherapy using chimeric antigen receptors (CARs) so far has almost exclusively used autologous peripheral blood-derived T cells as immune effector cells. However, harvesting sufficient numbers of T cells is often challenging in heavily pre-treated patients with malignancies and perturbed hematopoiesis and perturbed hematopoiesis. Also, such a CAR product will always be specific for the individual patient. Read More

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January 2021

Neuromechanics of Dynamic Balance Tasks in the Presence of Perturbations.

Front Hum Neurosci 2020 20;14:560630. Epub 2021 Jan 20.

Department of Training and Movement Sciences, Humboldt-Universität zu Berlin, Berlin, Germany.

Understanding the neuromechanical responses to perturbations in humans may help to explain the reported improvements in stability performance and muscle strength after perturbation-based training. In this study, we investigated the effects of perturbations, induced by unstable surfaces, on the mechanical loading and the modular organization of motor control in the lower limb muscles during lunging forward and backward. Fifteen healthy adults performed 50 forward and 50 backward lunges on stable and unstable ground. Read More

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January 2021

Inactivation of cytosolic FUMARASE2 enhances growth and photosynthesis under simultaneous copper and iron deprivation in Arabidopsis.

Plant J 2021 Feb 14. Epub 2021 Feb 14.

Faculty of Biology, Plant Molecular Biology, Ludwig-Maximilians-University Munich, Großhadernerstr. 2-4, Planegg-Martinsried, D-82152, Germany.

Copper (Cu) and iron (Fe) are essential for plant growth and are often in short supply under natural conditions. Molecular responses to simultaneous lack of both metals (-Cu-Fe) differ from those seen in the absence of either alone. Metabolome profiling of plant leaves previously revealed that fumarate levels fall under -Cu-Fe conditions. Read More

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February 2021

Acute Changes in Carotid-Femoral Pulse-Wave Velocity Are Tracked by Heart-Femoral Pulse-Wave Velocity.

Front Cardiovasc Med 2020 20;7:592834. Epub 2021 Jan 20.

Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Carotid-femoral pulse-wave velocity (cfPWV) is the reference standard measure of central arterial stiffness. However, it requires assessment of the carotid artery, which is technically challenging, and subject-level factors, including carotid artery plaque, may confound measurements. A promising alternative that overcomes these limitations is heart-femoral PWV (hfPWV), but it is not known to what extent changes in cfPWV and hfPWV are associated. Read More

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January 2021

Evolutionary Rescue of an Environmental in Response to Anthropogenic Perturbation.

Front Microbiol 2020 18;11:563885. Epub 2021 Jan 18.

Departamento de Ecología Evolutiva, Instituto de Ecología, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.

Anthropogenic perturbations introduce novel selective pressures to natural environments, impacting the genomic variability of organisms and thus altering the evolutionary trajectory of populations. Water overexploitation for agricultural purposes and defective policies in Cuatro Cienegas, Coahuila, Mexico, have strongly impacted its water reservoir, pushing entire hydrological systems to the brink of extinction along with their native populations. Here, we studied the effects of continuous water overexploitation on an environmental aquatic lineage of over a 13-year period which encompasses three desiccation events. Read More

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January 2021

Vascular Adhesion Protein-1 Determines the Cellular Properties of Endometrial Pericytes.

Front Cell Dev Biol 2020 18;8:621016. Epub 2021 Jan 18.

Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule and a primary amine oxidase involved in immune cell trafficking. Leukocyte extravasation into tissues is mediated by adhesion molecules expressed on endothelial cells and pericytes. Pericytes play a major role in the angiogenesis and vascularization of cycling endometrium. Read More

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January 2021

The Bruton's Tyrosine Kinase Inhibitor Ibrutinib Impairs the Vascular Development of Zebrafish Larvae.

Front Pharmacol 2020 13;11:625498. Epub 2021 Jan 13.

Department of Biology, Southern University of Science and Technology, Shenzhen, China.

Ibrutinib is an orally bioavailable, irreversible selective Bruton's tyrosine kinase inhibitor that has demonstrated impressive therapeutic effects in patients with B cell malignancies. However, adverse effects, such as bleeding and hypertension, are also reported, implying that studies on the toxicological effect of ibrutinib on living organisms are needed. Here, we have used zebrafish, a successful model organism for studying toxicology, to investigate the influence of ibrutinib during embryogenesis. Read More

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January 2021

Dissecting Efficacy and Metabolic Characteristic Mechanism of on Renal Fibrosis by Multivariate Approach and Ultra-Performance Liquid Chromatography Coupled With Mass Spectrometry-Based Metabolomics Strategy.

Front Pharmacol 2020 14;11:608511. Epub 2021 Jan 14.

Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guangxi, China.

Taxifolin (TFN) is an important natural compound with antifibrotic activity; however, its pharmacological mechanism is not clear. In this study, our aim is to gain insight into the effects of TFN and its potential mechanisms in unilateral ureteral obstruction (UUO) animal model using metabolomics approach to identify the metabolic biomarkers and perturbed pathways. Serum metabolomics analysis by UPLC-Q-TOF/MS was carried out to discover the changes in the metabolic profile. Read More

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January 2021

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation.

Front Neurol 2020 7;11:595532. Epub 2021 Jan 7.

Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, United States.

Post-translational modifications (PTMs) on tau have long been recognized as affecting protein function and contributing to neurodegeneration. The explosion of information on potential and observed PTMs on tau provides an opportunity to better understand these modifications in the context of tau homeostasis, which becomes perturbed with aging and disease. Prevailing views regard tau as a protein that undergoes abnormal phosphorylation prior to its accumulation into the toxic aggregates implicated in Alzheimer's disease (AD) and other tauopathies. Read More

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January 2021

The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism.

Mol Biol Cell 2021 03 21;32(6):475-491. Epub 2021 Jan 21.

Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute.

Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations in cause Sengers syndrome, an autosomal recessive condition characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis. We mapped the proteomic changes in Sengers patient fibroblasts and AGK cell lines to understand the effects of AGK dysfunction on mitochondria. Read More

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Circulating IL-10 is compromised in patients predisposed to developing and in patients with severe knee osteoarthritis.

Sci Rep 2021 Jan 19;11(1):1812. Epub 2021 Jan 19.

The Orthopedic Specialty Hospital, Murray, UT, 84107, USA.

The purpose of this investigation was to identify if serum interleukin (IL)-10 and tumor necrosis factor (TNF)-α concentrations and their ratio (IL-10/TNF-α) are altered in subjects predisposed to developing knee osteoarthritis following ligamentous injury and in those with severe knee osteoarthritis. Serum IL-10 and TNF-α concentrations were measured in four groups of subjects (n = 218): (1) reportedly-healthy and non-injured control subjects (CON; n = 92), (2) subjects scheduled to undergo anterior cruciate ligament surgery (ACL; n = 42), (3) non-surgical subjects with knee osteoarthritis (OA; n = 60), and (4) subjects with knee osteoarthritis scheduled to undergo total knee arthroplasty (TKA; n = 24). X-ray images were used to grade the severity of knee osteoarthritis. Read More

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January 2021