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Flexibility of equine bioenergetics and muscle plasticity in response to different types of training: An integrative approach, questioning existing paradigms.

PLoS One 2021 13;16(4):e0249922. Epub 2021 Apr 13.

Department of Virology, Parasitology and Immunology, Research Group of Comparative Physiology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Equine bioenergetics have predominantly been studied focusing on glycogen and fatty acids. Combining omics with conventional techniques allows for an integrative approach to broadly explore and identify important biomolecules. Friesian horses were aquatrained (n = 5) or dry treadmill trained (n = 7) (8 weeks) and monitored for: evolution of muscle diameter in response to aquatraining and dry treadmill training, fiber type composition and fiber cross-sectional area of the M. Read More

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Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS.

BMC Complement Med Ther 2021 Apr 12;21(1):120. Epub 2021 Apr 12.

College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China.

Background: The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.

Methods: Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Read More

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Label-Free Method Development for Hydroxyproline PTM Mapping in Human Plasma Proteome.

Protein J 2021 Apr 11. Epub 2021 Apr 11.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.

Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse components in blood. Here, we report a label-free method for identifying and mapping hydroxylated proteins using tandem mass spectrometry (MS/MS) in the human plasma sample. Read More

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Structure-guided protein engineering of human cathepsin L for efficient collagenolytic activity.

Protein Eng Des Sel 2021 Feb;34

Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064, India.

Engineering precise substrate specificity of proteases advances the potential to use them in biotechnological and therapeutic applications. Collagen degradation, a physiological process mediated by collagenases, is an integral part of extracellular matrix remodeling and when uncontrolled, implicated in different pathological conditions. Lysosomal cathepsin-K cleaves triple helical collagen fiber, whereas cathepsin-L cannot do so. Read More

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February 2021

Metabolite Analysis of Jerusalem Artichoke ( L.) Seedlings in Response to Polyethylene Glycol-Simulated Drought Stress.

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

State Key Laboratory of Crop Stress Biology for Arid Area, College of Horticulture, Northwest A&F University, Yangling 712100, China.

Jerusalem artichokes are a perennial crop with high drought tolerance and high value as a raw material to produce biofuels, functional feed, and food. However, there are few comprehensive metabolomic studies on Jerusalem artichokes under drought conditions.

Methods: Ultra-performance liquid chromatography and tandem mass spectrometry were used to identify differential metabolites in Jerusalem artichoke seedling leaves under polyethylene glycol (PEG) 6000-simulated drought stress at 0, 18, 24, and 36 h. Read More

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A highly conserved mechanism for the detoxification and assimilation of the toxic phytoproduct L-azetidine-2-carboxylic acid in Aspergillus nidulans.

Sci Rep 2021 Apr 1;11(1):7391. Epub 2021 Apr 1.

Microbial Molecular Genetics Laboratory, Institute of Biosciences and Applications, National Centre for Scientific Research, Demokritos (NCSRD), Athens, Greece.

Plants produce toxic secondary metabolites as defense mechanisms against phytopathogenic microorganisms and predators. L-azetidine-2-carboxylic acid (AZC), a toxic proline analogue produced by members of the Liliaceae and Agavaciae families, is part of such a mechanism. AZC causes a broad range of toxic, inflammatory and degenerative abnormalities in human and animal cells, while it is known that some microorganisms have evolved specialized strategies for AZC resistance. Read More

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The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection.

bioRxiv 2021 Mar 26. Epub 2021 Mar 26.

We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Read More

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Synergy and allostery in ligand binding by HIV-1 Nef.

Biochem J 2021 Mar 31. Epub 2021 Mar 31.

King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.

The Nef protein of human and simian immunodeficiency viruses boosts viral pathogenicity through its interactions with host cell proteins. By combining the polyvalency of its large unstructured regions with the binding selectivity and strength of its folded core domain, Nef can associate with many different host cell proteins, thereby disrupting their functions. For example, the combination of a linear proline-rich motif and hydrophobic core domain surface allows Nef to bind tightly and specifically to SH3 domains of Src family kinases. Read More

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Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study.

Endocr Pract 2021 Apr 14;27(4):326-333. Epub 2020 Dec 14.

Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Objective: The saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. Read More

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A plasma metabolomics study suggests alteration of multiple metabolic pathways in patients with bipolar disorder.

Psychiatry Res 2021 Mar 18;299:113880. Epub 2021 Mar 18.

Psychiatric Laboratory and Mental Health Center, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

Previous omics studies have greatly contributed to our knowledge of bipolar disorder. Metabolomics is a relatively new field of omics science that can provide complementary insight into data obtained from genomics, transcriptomics or proteomics analyses. In this study, we aimed to identify metabolic pathways associated with bipolar disorder. Read More

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MINI OPCAB Operation: Surgical Technique.

Surg Technol Int 2021 03 23;38. Epub 2021 Mar 23.

Invita Science Corp, Port St. Lucie, FL, USA.

Introduction: We describe how to perform left internal mammary artery (LIMA) bypass to the left anterior descending (LAD) artery, the so-called MINI Off-pump Coronary Artery Bypass (MINI OPCAB).

Materials And Methods: We included patients with a demonstrated predominant ischemia related to the LAD territory. Of 70 patients who were operated upon at the Benetti Foundation, 10 received hybrid revascularization. Read More

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Design of mutants of GH11 xylanase from for enhanced stability by amino acid substitutions in the N-terminal region: an in silico analysis.

J Biomol Struct Dyn 2021 Mar 22:1-14. Epub 2021 Mar 22.

Kaypeeyes Biotech Pvt. Ltd., Mysuru, Karnataka, India.

GH11 xylanases are versatile small-molecular-weight single-polypeptide chain monofunctional enzymes. This family of glycoside hydrolases has important applications in food, feed and chemical industries. We designed mutants for improved thermal stability with substitutions in the first six residues of the N-terminal region and evaluated the stability in silico. Read More

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Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.

Commun Biol 2021 Mar 19;4(1):367. Epub 2021 Mar 19.

Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, Nijmegen, the Netherlands.

The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. Read More

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Distinct metabolic features in the plasma of patients with silicosis and dust-exposed workers in China: a case-control study.

BMC Pulm Med 2021 Mar 17;21(1):91. Epub 2021 Mar 17.

Department of Occupational Medicine and Toxicology, Clinical Centre for Interstitial Lung Diseases, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Workers' Stadium South Road, Chao-Yang District, Beijing, 100020, China.

Background: Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. Read More

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ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ.

Hum Mol Genet 2021 Mar 17. Epub 2021 Mar 17.

Department of Biomedical Sciences, Centre for Motor Neuron Disease Research, Faculty of Medicine and Health Sciences, Macquarie University, 2 Technology Place, North Ryde, NSW 2109, Australia.

Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalisation of proteins such as TDP-43. In recent years, the dysregulation of SFPQ has also emerged as a pathological hallmark of ALS/FTD. Read More

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Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawai'i Reveals the Worldwide Emerging P681H Mutation.

Hawaii J Health Soc Welf 2021 03;80(3):52-61

Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI (DPM, LLC, CMS, VRN).

The COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in its first year, and severely affected the global economy. Hawai'i has not been spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Read More

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High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer's Disease.

Front Cell Dev Biol 2021 25;9:602887. Epub 2021 Feb 25.

National Key Disciplines of Nutrition and Food Hygiene, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.

Alzheimer's disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Read More

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February 2021

A gain-of-function mutation in CITED2 is associated with congenital heart disease.

Mutat Res 2021 Mar 1;822:111741. Epub 2021 Mar 1.

Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India. Electronic address:

CITED2 is a transcription co-activator that interacts with TFAP2 and CBP/ P300 transcription factors to regulate the proliferation and differentiation of the cardiac progenitor cells. It acts upstream to NODAL-PITX2 pathways and regulates the left-right asymmetry. Both human genetic and model organism studies have shown that altered expression of CITED2 causes various forms of congenital heart disease. Read More

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A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ.

mBio 2021 03 9;12(2). Epub 2021 Mar 9.

Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

The lifelong relationship between the Hawaiian bobtail squid and its microbial symbiont represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the host in a process termed counterillumination. The squid host hatches without its symbionts, which must be acquired from the ocean amidst a diversity of nonbeneficial bacteria, such that precise molecular communication is required for initiation of the specific relationship. Read More

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Recapitulating the Binding Affinity of Nrf2 for KEAP1 in a Cyclic Heptapeptide, Guided by NMR, X-ray Crystallography, and Machine Learning.

J Am Chem Soc 2021 Mar 8;143(10):3779-3793. Epub 2021 Mar 8.

Macrocycles, including macrocyclic peptides, have shown promise for targeting challenging protein-protein interactions (PPIs). One PPI of high interest is between Kelch-like ECH-Associated Protein-1 (KEAP1) and Nuclear Factor (Erythroid-derived 2)-like 2 (Nrf2). Guided by X-ray crystallography, NMR, modeling, and machine learning, we show that the full 20 nM binding affinity of Nrf2 for KEAP1 can be recapitulated in a cyclic 7-mer peptide, c[()-β-homoAla-DPETGE]. Read More

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Transcriptomic Responses of the Honey Bee Brain to Infection with Deformed Wing Virus.

Viruses 2021 02 12;13(2). Epub 2021 Feb 12.

Department of Biology, Bucknell University, Lewisburg, PA 17837, USA.

Managed colonies of European honey bees () are under threat from mite infestation and infection with viruses vectored by mites. In particular, deformed wing virus (DWV) is a common viral pathogen infecting honey bees worldwide that has been shown to induce behavioral changes including precocious foraging and reduced associative learning. We investigated how DWV infection of bees affects the transcriptomic response of the brain. Read More

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February 2021

Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway.

Onco Targets Ther 2021 26;14:1453-1463. Epub 2021 Feb 26.

Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China.

Background: The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression. Read More

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February 2021

Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan;

HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. Read More

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Potential of H NMR fingerprinting and a model system approach to study non-enzymatic browning in shelf-stable orange juice during storage.

Food Res Int 2021 Feb 24;140:110062. Epub 2020 Dec 24.

KU Leuven, Department of Microbial and Molecular Systems (M(2)S), Laboratory of Food Technology, Kasteelpark Arenberg 22 Box 2457, 3001 Heverlee, Belgium. Electronic address:

For the first time, a model system approach was combined with H NMR fingerprinting in studying non-enzymatic browning (NEB) of pasteurized shelf-stable orange juice during storage. Various NEB precursors were used individually or in combinations to formulate simple or complex model systems, respectively, in citric acid buffer. Based on orange juice composition, ascorbic acid, sugars (sucrose, glucose and fructose) and amino acids (proline, arginine, asparagine, aspartic acid, serine and glutamic acid) were selected as the precursors for the model systems. Read More

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February 2021

SPRR2C, DEFB4A, WIF1, CRY2, and KRT19 are correlated with the development of atopic eczema.

Eur Rev Med Pharmacol Sci 2021 Feb;25(3):1436-1446

Department of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: Atopic eczema (AE) is a chronic relapsing inflammatory skin disease. This study aims to identify key genes related to the development of AE.

Materials And Methods: The GSE6012 dataset was obtained from the Gene Expression Omnibus (GEO) database. Read More

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February 2021

Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO.

J Cancer Res Clin Oncol 2021 Feb 23. Epub 2021 Feb 23.

Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.

Purpose: Transport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC.

Methods: In this study, microarray analysis compared gene expression between control and TANGO-repressed HSC3 cells. Read More

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February 2021

Circulating metabolites and lipids are associated with glycaemic measures in South Asians.

Diabet Med 2021 Feb 25;38(2):e14494. Epub 2020 Dec 25.

Section on Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.

Background: South Asians are at higher risk for diabetes (DM) than many other racial/ethnic groups. Circulating metabolites are measurable products of metabolic processes that may explain the aetiology of elevated risk. We characterized metabolites associated with prevalent DM and glycaemic measures in South Asians. Read More

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February 2021

Serum Metabolomics Study of Papillary Thyroid Carcinoma Based on HPLC-Q-TOF-MS/MS.

Front Cell Dev Biol 2021 1;9:593510. Epub 2021 Feb 1.

Department of Breast and Thyroid Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China.

This study examined metabolite profile differences between serum samples of thyroid papillary carcinoma (PTC) patients and healthy controls, aiming to identify candidate biomarkers and pathogenesis pathways in this cancer type. Serum samples were collected from PTC patients ( = 80) and healthy controls ( = 80). Using principal component analysis (PCA), partial least squares discrimination analysis(PLS-DA), orthogonal partial least square discriminant analysis (OPLS-DA), -tests, and the volcano plot, a model of abnormal metabolic pathways in PTC was constructed. Read More

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February 2021

Construction and comprehensive characterization of an EcLDCc-CatIB set-varying linkers and aggregation inducing tags.

Microb Cell Fact 2021 Feb 17;20(1):49. Epub 2021 Feb 17.

Institute of Bio- and Geosciences IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.

Background: In recent years, the production of inclusion bodies that retained substantial catalytic activity was demonstrated. These catalytically active inclusion bodies (CatIBs) were formed by genetic fusion of an aggregation inducing tag to a gene of interest via short linker polypeptides and overproduction of the resulting gene fusion in Escherichia coli. The resulting CatIBs are known for their high stability, easy and cost efficient production, and recyclability and thus provide an interesting alternative to conventionally immobilized enzymes. Read More

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February 2021