124 results match your criteria targeting nonessential

A highly sensitive and group-targeting aptasensor for total phthalate determination in the environment.

J Hazard Mater 2021 Jun 19;412:125174. Epub 2021 Jan 19.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Tongji Hospital, School of Chemical Science and Engineering, Tongji University, Shanghai 200092, China. Electronic address:

As the most widely used and typical kind of plasticizers, phthalate esters (PAEs) have become one of the most common environmental pollutants in the world. Therefore, it is necessary to develop a rapid and convenient method for determining the total amount of PAEs. Herein, a molecularly tailored broad-spectrum aptamer that can recognize multiple similarly structured total amounts of PAEs (TP) and bind them with high affinity has been successfully fabricated. Read More

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Investigational Studies on a Hit Compound Cyclopropane-Carboxylic Acid Derivative Targeting -Acetylserine Sulfhydrylase as a Colistin Adjuvant.

ACS Infect Dis 2021 02 29;7(2):281-292. Epub 2021 Jan 29.

P4T Group, Department of Food and Drugs, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.

Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by Gram-positive and Gram-negative pathogens. A compound that binds OASS with a nM dissociation constant was tested as an adjuvant of colistin against six critical pathogens responsible for infections spreading worldwide, , serovar Typhimurium, , , methicillin-resistant , and . Read More

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February 2021

Signal Recognition Particle Suppressor Screening Reveals the Regulation of Membrane Protein Targeting by the Translation Rate.

mBio 2021 01 12;12(1). Epub 2021 Jan 12.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China

The signal recognition particle (SRP) is conserved in all living organisms, and it cotranslationally delivers proteins to the inner membrane or endoplasmic reticulum. Recently, SRP loss was found not to be lethal in either the eukaryote or the prokaryote In , the role of SRP in mediating inner membrane protein (IMP) targeting has long been studied. However, the essentiality of SRP remains a controversial topic, partly hindered by the lack of strains in which SRP is completely absent. Read More

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January 2021

Genome-wide identification of Streptococcus sanguinis fitness genes in human serum and discovery of potential selective drug targets.

Mol Microbiol 2021 Apr 30;115(4):658-671. Epub 2020 Nov 30.

Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA, USA.

Streptococcus sanguinis is a primary colonizer of teeth and is associated with oral health. When it enters the bloodstream, however, this bacterium may cause the serious illness infective endocarditis. The genes required for survival and proliferation in blood have not been identified. Read More

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The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to Pharmacotherapy.

Int J Mol Sci 2020 Oct 9;21(20). Epub 2020 Oct 9.

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Alzheimer's disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Read More

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October 2020

Serine restriction alters sphingolipid diversity to constrain tumour growth.

Nature 2020 10 12;586(7831):790-795. Epub 2020 Aug 12.

Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.

Serine, glycine and other nonessential amino acids are critical for tumour progression, and strategies to limit their availability are emerging as potential therapies for cancer. However, the molecular mechanisms driving this response remain unclear and the effects on lipid metabolism are relatively unexplored. Serine palmitoyltransferase (SPT) catalyses the de novo biosynthesis of sphingolipids but also produces noncanonical 1-deoxysphingolipids when using alanine as a substrate. Read More

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October 2020

Reprogramming of serine, glycine and one-carbon metabolism in cancer.

Biochim Biophys Acta Mol Basis Dis 2020 10 19;1866(10):165841. Epub 2020 May 19.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Metabolic pathways leading to the synthesis, uptake, and usage of the nonessential amino acid serine are frequently amplified in cancer. Serine encounters diverse fates in cancer cells, including being charged onto tRNAs for protein synthesis, providing head groups for sphingolipid and phospholipid synthesis, and serving as a precursor for cellular glycine and one-carbon units, which are necessary for nucleotide synthesis and methionine cycle reloading. This review will focus on the participation of serine and glycine in the mitochondrial one-carbon (SGOC) pathway during cancer progression, with an emphasis on the genetic and epigenetic determinants that drive SGOC gene expression. Read More

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October 2020

A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity.

Cell Death Discov 2020 16;6:20. Epub 2020 Apr 16.

1Neurosurgery Department, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.

Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Read More

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Identification of Drug Resistance Determinants in a Clinical Isolate of Pseudomonas aeruginosa by High-Density Transposon Mutagenesis.

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Interfakultäres Institut für Mikrobiologie und Infektionsmedizin Tübingen (IMIT), Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany

With the aim to identify potential new targets to restore antimicrobial susceptibility of multidrug-resistant (MDR) isolates, we generated a high-density transposon (Tn) insertion mutant library in an MDR bloodstream isolate (isolate ID40). The depletion of Tn insertion mutants upon exposure to cefepime or meropenem was measured in order to determine the common resistome for these clinically important antipseudomonal β-lactam antibiotics. The approach was validated by clean deletions of genes involved in peptidoglycan synthesis/recycling, such as the genes for the lytic transglycosylase MltG, the murein (Mur) endopeptidase MepM1, the MurNAc/GlcNAc kinase AmgK, and the uncharacterized protein YgfB, all of which were identified in our screen as playing a decisive role in survival after treatment with cefepime or meropenem. Read More

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February 2020

MicroRNA-155 and microRNA-181a, via HO-1, participate in regulating the immunotoxicity of cadmium in the kidneys of exposed Cyprinus carpio.

Fish Shellfish Immunol 2019 Dec 3;95:473-480. Epub 2019 Nov 3.

College of Fisheries, Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Henan province, PR China. Electronic address:

Cadmium (Cd) is a nonessential metal that is a contaminant in aquatic ecosystems. Cd can accumulate in aquatic animals, leading to detrimental effects in tissues, and Cd exposure can induce immunotoxicity in fish. MicroRNAs (miRNAs) play critical roles in immune responses, yet the participation of miRNAs in Cd-induced immunotoxicity remains poorly understood. Read More

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December 2019

A Novel Tool for the Generation of Conditional Knockouts To Study Gene Function across the Plasmodium falciparum Life Cycle.

mBio 2019 09 17;10(5). Epub 2019 Sep 17.

Signalling in Apicomplexan Parasites Laboratory, The Francis Crick Institute, London, United Kingdom

has a complex life cycle that involves interaction with multiple tissues inside the human and mosquito hosts. Identification of essential genes at all different stages of the life cycle is urgently required for clinical development of tools for malaria control and eradication. However, the study of is limited by the inability to genetically modify the parasite throughout its life cycle with the currently available genetic tools. Read More

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September 2019

Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle of for Antibiotic Therapy.

ACS Cent Sci 2019 Jul 26;5(7):1278-1288. Epub 2019 Jun 26.

Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.

The type 3 secretion system (T3SS) found as cell-surface appendages of many pathogenic Gram-negative bacteria, although nonessential for bacterial survival, is an important therapeutic target for drug discovery and development aimed at inhibiting bacterial virulence without inducing antibiotic resistance. We designed a fluorescence-polarization-based assay for high-throughput screening as a mechanistically well-defined general strategy for antibiotic discovery targeting the T3SS and made a serendipitous discovery of a subset of tanshinones-natural herbal compounds in traditional Chinese medicine widely used for the treatment of cardiovascular and cerebrovascular diseases-as effective inhibitors of the biogenesis of the T3SS needle of multi-drug-resistant . By inhibiting the T3SS needle assembly and, thus, cytotoxicity and pathogenicity, selected tanshinones reduced the secretion of bacterial virulence factors toxic to macrophages , and rescued experimental animals challenged with lethal doses of in a murine model of acute pneumonia. Read More

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Distinct effects of etoposide on glutamine-addicted neuroblastoma.

Cell Mol Life Sci 2020 Mar 7;77(6):1197-1207. Epub 2019 Aug 7.

Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.

The majority of anticancer drugs are DNA-damaging agents, and whether or not they may directly target mitochondria remains unclear. In addition, tumors such as neuroblastoma exhibit addiction to glutamine in spite of it being a nonessential amino acid. Our aim was to evaluate the direct effect of widely used anticancer drugs on mitochondrial activity in combination with glutamine withdrawal, and possible apoptotic effects of such interaction. Read More

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Harnessing Biological Insight to Accelerate Tuberculosis Drug Discovery.

Acc Chem Res 2019 08 30;52(8):2340-2348. Epub 2019 Jul 30.

SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit and DST/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology and Institute of Infectious Disease and Molecular Medicine , University of Cape Town , Observatory, Cape Town 7925 , South Africa.

Tuberculosis (TB) is the leading cause of mortality globally resulting from an infectious disease, killing almost 1.6 million people annually and accounting for approximately 30% of deaths attributed to antimicrobial resistance (AMR). This despite the widespread administration of a neonatal vaccine, and the availability of an effective combination drug therapy against the causative agent, (Mtb). Read More

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Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?

Cancers (Basel) 2019 Jun 11;11(6). Epub 2019 Jun 11.

Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Distinct from normal differentiated tissues, cancer cells reprogram nutrient uptake and utilization to accommodate their elevated demands for biosynthesis and energy production. A hallmark of these types of reprogramming is the increased utilization of, and dependency on glutamine, a nonessential amino acid, for cancer cell growth and survival. It is well-accepted that glutamine is a versatile biosynthetic substrate in cancer cells beyond its role as a proteinogenic amino acid. Read More

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A Genome-Wide Helicobacter pylori Morphology Screen Uncovers a Membrane-Spanning Helical Cell Shape Complex.

J Bacteriol 2019 07 21;201(14). Epub 2019 Jun 21.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Evident in its name, the gastric pathogen has a helical cell morphology which facilitates efficient colonization of the human stomach. An improved light-focusing strategy allowed us to robustly distinguish even subtle perturbations of cell morphology by deviations in light-scattering properties measured by flow cytometry. Profiling of an arrayed genome-wide deletion library identified 28 genes that influence different aspects of cell shape, including properties of the helix, cell length or width, cell filament formation, cell shape heterogeneity, and cell branching. Read More

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Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection.

Mol Med Rep 2019 May 21;19(5):4057-4066. Epub 2019 Mar 21.

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Burn‑site infections, commonly due to Pseudomonas aeruginosa, have been associated with deranged intestinal integrity, allowing bacteria and their products to translocate from the gut to the circulatory system. The P. aeruginosa quorum sensing (QS) transcription factor MvfR (PqsR) controls the expression of numerous virulence factors, and the synthesis of several toxic products. Read More

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Development of drug-inducible CRISPR-Cas9 systems for large-scale functional screening.

BMC Genomics 2019 Mar 19;20(1):225. Epub 2019 Mar 19.

AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL, 60064, USA.

Background: Large-scale genetic screening using CRISPR-Cas9 technology has emerged as a powerful approach to uncover and validate gene functions. The ability to control the timing of genetic perturbation during CRISPR screens will facilitate precise dissection of dynamic and complex biological processes. Here, we report the optimization of a drug-inducible CRISPR-Cas9 system that allows high-throughput gene interrogation with a temporal control. Read More

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Group I Metabotropic Glutamate Receptors (mGluRs): Ins and Outs.

Adv Exp Med Biol 2018;1112:163-175

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, SAS Nagar, Punjab, India.

Glutamate is a nonessential amino acid, known to act as a major excitatory neurotransmitter in the central nervous system. Glutamate transduces its signal by activating two types of receptors, viz., ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Read More

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Murine Cytomegalovirus Glycoprotein O Promotes Epithelial Cell Infection .

J Virol 2019 02 17;93(3). Epub 2019 Jan 17.

School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia

Cytomegaloviruses (CMVs) establish systemic infections across diverse cell types. Glycoproteins that alter tropism can potentially guide their spread. Glycoprotein O (gO) is a nonessential fusion complex component of both human CMV (HCMV) and murine CMV (MCMV). Read More

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February 2019

Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca in bovine mammary epithelial cells.

J Dairy Sci 2018 Dec 27;101(12):11354-11363. Epub 2018 Sep 27.

Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801. Electronic address:

Amino acids play a key role in regulating milk protein synthesis partly through activation of the mammalian target of rapamycin (mTOR) signaling pathway. However, the involvement of extracellular AA sensing receptors in this process is not well understood. In nonruminants, it is well established that the AA taste 1 receptor member 1/3 (TAS1R1/TAS1R3) heterodimer contributes to the sensing of most l-AA. Read More

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December 2018

Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Antibody MEDI3902, Are Conserved Among Diverse Global Clinical Isolates.

J Infect Dis 2018 11;218(12):1983-1994

Microbial Sciences, Gaithersburg, Maryland.

Background: Bispecific antibody MEDI3902, targeting the Pseudomonas aeruginosa type 3 secretion system (PcrV) and Psl exopolysaccharide, is currently in phase 2b development for prevention of nosocomial pneumonia in patients undergoing mechanical ventilation. We surveyed a diverse collection of isolates to study MEDI3902 epitope conservation and protective activity.

Methods: P. Read More

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November 2018

Evaluation of Current and Emerging Antimalarial Medicines for Inhibition of Toxoplasma gondii Growth in Vitro.

ACS Infect Dis 2018 08 25;4(8):1264-1274. Epub 2018 Jul 25.

Department of Molecular Microbiology , Washington University School of Medicine in St. Louis , 600 S. Euclid Avenue , St. Louis , Missouri 63110 , United States.

Toxoplasma gondii is a common zoonotic infection of humans, and estimates indicate that 1-2 billion people are chronically infected. Although largely asymptomatic, chronic infection poses risk of serious disease due to reactivation should immunity decline. Current therapies for toxoplasmosis only control acute infection caused by actively proliferating tachyzoites but do not eradicate the chronic tissue cyst stages. Read More

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Antibiotic Combinations That Enable One-Step, Targeted Mutagenesis of Chromosomal Genes.

ACS Infect Dis 2018 06 23;4(6):1007-1018. Epub 2018 Mar 23.

Department of Microbiology and Immunobiology , Harvard Medical School , 4 Blackfan Circle , Boston , Massachusetts 02115 , United States.

Targeted modification of bacterial chromosomes is necessary to understand new drug targets, investigate virulence factors, elucidate cell physiology, and validate results of -omics-based approaches. For some bacteria, reverse genetics remains a major bottleneck to progress in research. Here, we describe a compound-centric strategy that combines new negative selection markers with known positive selection markers to achieve simple, efficient one-step genome engineering of bacterial chromosomes. Read More

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The Impact of GFP Reporter Gene Transduction and Expression on Metabolomics of Placental Mesenchymal Stem Cells Determined by UHPLC-Q/TOF-MS.

Stem Cells Int 2017 5;2017:3167985. Epub 2017 Nov 5.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Introduction: Green fluorescent protein (GFP) is widely used as a reporter gene in regenerative medicine research to label and track stem cells. Here, we examined whether expressing GFP gene may impact the metabolism of human placental mesenchymal stem cells (hPMSCs).

Methods: The GFP gene was transduced into hPMSCs using lentiviral-based infection to establish GFPhPMSCs. Read More

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November 2017

Protocol for Construction of a Tunable CRISPR Interference (tCRISPRi) Strain for .

Bio Protoc 2017 Oct;7(19)

UC San Diego, Department of Physics and Section of Molecular Biology, Division of Biology, La Jolla, CA, USA.

We present a protocol for construction of tunable CRISPR interference (tCRISPRi) strains for . The tCRISPRi system alleviates most of the known problems of plasmid-based expression methods, and can be immediately used to construct libraries of sgRNAs that can complement the Keio collection by targeting both essential and nonessential genes. Most importantly from a practical perspective, construction of tCRISPRi to target a new gene requires only one-step oligo recombineering. Read More

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October 2017

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex.

Cell 2017 Nov 12;171(4):904-917.e19. Epub 2017 Oct 12.

Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich, Otto-Stern-Weg 3, CH-8093 Zurich, Switzerland. Electronic address:

Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. Read More

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November 2017

Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens.

G3 (Bethesda) 2017 08 7;7(8):2719-2727. Epub 2017 Aug 7.

Donnelly Centre, University of Toronto, Ontario M5S3E1, Canada.

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled-library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. Read More

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Construction of a Gene Knockdown System Based on Catalytically Inactive ("Dead") Cas9 (dCas9) in Staphylococcus aureus.

Appl Environ Microbiol 2017 06 31;83(12). Epub 2017 May 31.

CAS Key Laboratory of Innate Immunity and Chronic Disease and School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, China

There has been an absence of an efficient method of gene knockdown in the important human pathogen like RNA interference in eukaryotes. The previously developed antisense RNA technology is mainly applied for forward genetic screening but is rather limited in specific gene knockdown because of the lack of rational antisense RNA design strategies. Here we report an efficient and specific system for gene knockdown in based on the type II clustered regularly interspaced short palindromic repeat (CRISPR) system from We can achieve gene silencing with the coexpression of dCas9, an RNA-guided DNA binding protein, and a small guide RNA complementary to the target gene. Read More

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Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes.

Wolfgang Maret

Prev Nutr Food Sci 2017 Mar 31;22(1):1-8. Epub 2017 Mar 31.

Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9NH, UK.

About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Read More

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