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International Journal of Molecular... Aug 2021The biology and chemistry of proteins and peptides are inextricably linked with water as the solvent. The reason for the high stability of some proteins or uncontrolled...
The biology and chemistry of proteins and peptides are inextricably linked with water as the solvent. The reason for the high stability of some proteins or uncontrolled aggregation of others may be hidden in the properties of their hydration water. In this study, we investigated the effect of stabilizing osmolyte-TMAO (trimethylamine -oxide) and destabilizing osmolyte-urea on hydration shells of two short peptides, NAGMA (-acetyl-glycine-methylamide) and diglycine, by means of FTIR spectroscopy and molecular dynamics simulations. We isolated the spectroscopic share of water molecules that are simultaneously under the influence of peptide and osmolyte and determined the structural and energetic properties of these water molecules. Our experimental and computational results revealed that the changes in the structure of water around peptides, caused by the presence of stabilizing or destabilizing osmolyte, are significantly different for both NAGMA and diglycine. The main factor determining the influence of osmolytes on peptides is the structural-energetic similarity of their hydration spheres. We showed that the chosen peptides can serve as models for various fragments of the protein surface: NAGMA for the protein backbone and diglycine for the protein surface with polar side chains.
Topics: Chemical Phenomena; Glycine; Glycylglycine; Methylamines; Molecular Dynamics Simulation; Osmotic Pressure; Peptides; Solutions; Spectroscopy, Fourier Transform Infrared; Urea; Water
PubMed: 34502252
DOI: 10.3390/ijms22179350 -
Food and Chemical Toxicology : An... Jun 2019Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely... (Review)
Review
Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.
Topics: Amines; Ecosystem; Glycine; Herbicides; Quaternary Ammonium Compounds; Risk Assessment; Surface-Active Agents; Glyphosate
PubMed: 30951798
DOI: 10.1016/j.fct.2019.03.053 -
Oxidative Medicine and Cellular... 2019Oxidative stress plays a crucial role in the pathogenesis of diabetic vascular complications. It is known that the accumulation of advanced glycation end products (AGEs)...
Oxidative stress plays a crucial role in the pathogenesis of diabetic vascular complications. It is known that the accumulation of advanced glycation end products (AGEs) and the activation of the receptor of AGEs (RAGE) induce sustained oxidative stress in the vascular tissue. Growing evidence indicates that glycine, the simplest amino acid, exerts antioxidant and antiglycation effects and also improves vascular function. However, the mechanism whereby glycine protects vascular tissue against oxidative stress in models with diabetes has not been investigated. In the present study, we evaluated whether glycine can attenuate oxidative stress by suppressing the AGE/RAGE signaling pathway in the aorta of streptozotocin-induced diabetic rats and in human umbilical vascular endothelial cells (HUVECs). Our results showed that oral glycine administration increased NO content and ameliorated oxidative stress in the serum and aorta of diabetic rats. The AGE/RAGE signaling pathway in the aorta of diabetic rats was significantly attenuated by glycine treatment as manifested by decreases in levels of AGEs, RAGE, Nox4, and NF-B p65. The suppressive effect of glycine on the formation of AGEs was associated with increased activity and expression of aortic glyoxalase-1 (Glo1), a crucial enzyme that degrades methylglyoxal (MG), the major precursor of AGEs. In MG-treated HUVECs, glycine restored the function of Glo1, suppressed the AGE/RAGE signaling pathway, and inhibited the generation of reactive oxygen species. In addition, the reduction in the formation of AGEs in HUVECs caused by glycine treatment was inhibited by Glo1 inhibition. Taken together, our study provides evidence that glycine might inhibit the AGE/RAGE pathway and subsequent oxidative stress by improving Glo1 function, thus protecting against diabetic macrovascular complications.
Topics: Animals; Aorta; Glycation End Products, Advanced; Glycine; Humans; Lactoylglutathione Lyase; Male; Oxidative Stress; Rats; Signal Transduction
PubMed: 30944692
DOI: 10.1155/2019/4628962 -
Environmental Toxicology and Chemistry Oct 2022Herbicides are the most widely used pesticides globally. Although used to control weeds, they may also pose a risk to bee health. A key knowledge gap is how bees could...
Herbicides are the most widely used pesticides globally. Although used to control weeds, they may also pose a risk to bee health. A key knowledge gap is how bees could be exposed to herbicides in the environment, including whether they may forage on treated plants before they die. We used a choice test to determine if bumblebees would forage on plants treated with glyphosate at two time periods after treatment. We also determined whether glyphosate and its degradation product aminomethylphosphonic acid were present as residues in the pollen collected by the bees while foraging. Finally, we explored if floral resources (nectar and pollen) remained present in plants after herbicide treatment. In general bees indiscriminately foraged on both plants treated with glyphosate and controls, showing no avoidance of treated plants. Although the time spent on individual flowers was slightly lower on glyphosate treated plants, this did not affect the bees' choice overall. We found that floral resources remained present in plants for at least 5 days after lethal treatment with glyphosate and that glyphosate residues were present in pollen for at least 70 h posttreatment. Our results suggest that bees could be exposed to herbicide in the environment, both topically and orally, by foraging on plants in the period between herbicide treatment and death. Identifying this route of exposure is a first step in understanding the risks of herbicides to bees. The effects of herbicides on bees themselves are uncertain and warrant further investigation to allow full risk assessment of these compounds to pollinating insects. Environ Toxicol Chem 2022;41:2603-2612. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Animals; Bees; Glycine; Herbicides; Pesticides; Plant Nectar; Plants; Glyphosate
PubMed: 35866464
DOI: 10.1002/etc.5442 -
Journal of Agricultural and Food... Jun 2011Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and... (Review)
Review
Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and cotton growers use to manage weeds. The use of GR crops continues to grow, but weeds are adapting to the common practice of using only glyphosate to control weeds. Growers using only a single mode of action to manage weeds need to change to a more diverse array of herbicidal, mechanical, and cultural practices to maintain the effectiveness of glyphosate. Unfortunately, the introduction of GR crops and the high initial efficacy of glyphosate often lead to a decline in the use of other herbicide options and less investment by industry to discover new herbicide active ingredients. With some exceptions, most growers can still manage their weed problems with currently available selective and HR crop-enabled herbicides. However, current crop management systems are in jeopardy given the pace at which weed populations are evolving glyphosate resistance. New HR crop technologies will expand the utility of currently available herbicides and enable new interim solutions for growers to manage HR weeds, but will not replace the long-term need to diversify weed management tactics and discover herbicides with new modes of action. This paper reviews the strengths and weaknesses of anticipated weed management options and the best management practices that growers need to implement in HR crops to maximize the long-term benefits of current technologies and reduce weed shifts to difficult-to-control and HR weeds.
Topics: Crops, Agricultural; Glycine; Herbicide Resistance; Herbicides; Plant Weeds; Weed Control; Glyphosate
PubMed: 20586458
DOI: 10.1021/jf101286h -
The New Phytologist Sep 2019The human-directed, global selection for glyphosate resistance in weeds has revealed a fascinating diversity of evolved resistance mechanisms, including herbicide... (Review)
Review
The human-directed, global selection for glyphosate resistance in weeds has revealed a fascinating diversity of evolved resistance mechanisms, including herbicide sequestration in the vacuole, a rapid cell death response, nucleotide polymorphisms in the herbicide target (5-enolpyruvylshikimate-3-phosphate synthase, EPSPS) and increased gene copy number of EPSPS. For this latter mechanism, two distinct molecular genetic mechanisms have been observed, a tandem duplication mechanism and a large extrachromosomal circular DNA (eccDNA) that is tethered to the chromosomes and passed to gametes at meiosis. These divergent mechanisms have a range of consequences for the spread, fitness, and inheritance of resistance traits, and, particularly in the case of the eccDNA, demonstrate how evolved herbicide resistance can generate new insights into plant adaptation to contemporary environmental stress.
Topics: Adaptation, Physiological; Biological Evolution; Gene Duplication; Glycine; Herbicide Resistance; Quantitative Trait, Heritable; Glyphosate
PubMed: 31002387
DOI: 10.1111/nph.15858 -
Environmental Research Jun 2024Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in...
BACKGROUND
Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in muscle physiology and reduced contractile strength associated with glyphosate exposure, while epidemiological studies have shown associations between glyphosate exposure and adverse health outcomes in critical biological systems affecting muscle function.
METHODS
This study used data from a nationally representative survey of the non-institutionalized U.S. general population (NHANES, n = 2132). Urine glyphosate concentrations were determined by ion chromatography with tandem mass spectrometry. Hand grip strength (HGS) was measured using a Takei Dynamometer, and relative strength estimated as the ratio between HGS in the dominant hand and the appendicular lean mass (ALM) to body mass index (ALMBMI) ratio. Low HGS and low relative HGS were defined as 1 sex-, age- and race-specific SD below the mean. Physical function limitations were identified as significant difficulty or incapacity in various activities.
RESULTS
In fully-adjusted models, the Mean Differences (MD) and 95% confidence intervals [95%CI] per doubling increase in glyphosate concentrations were -0.55 [-1.09, -0.01] kg for HGS in the dominant hand, and -0.90 [-1.58. -0.21] kg for HGS/ALMBMI. The Odds Ratios (OR) [95% CI] for low HGS, low relative HGS and functional limitations by glyphosate concentrations were 1.27 [1.03, 1.57] for low HGS; 1.43 [1.05; 1.94] for low relative HGS; 1.33 [1.08, 1.63] for stooping, crouching or kneeling difficulty; 1.17 [0.91, 1.50] for lifting or carrying items weighting up to 10 pounds difficulty; 1.21 [1.01, 1.40] for standing up from armless chair difficulty; and 1.47 [1.05, 2.29] for ascending ten steps without pause difficulty.
CONCLUSIONS
Glyphosate exposure may be a risk factor for decreased grip strength and increased physical functional limitations. More studies investigating the influence of this and other environmental pollutants on functional aging are needed.
Topics: Glyphosate; Glycine; Humans; Male; Middle Aged; Female; Aged; Herbicides; Hand Strength; Environmental Exposure; Nutrition Surveys
PubMed: 38452917
DOI: 10.1016/j.envres.2024.118547 -
JPMA. the Journal of the Pakistan... Aug 2023
Topics: Humans; Glycine; Glyphosate
PubMed: 37697797
DOI: 10.47391/JPMA.8475 -
Molecules (Basel, Switzerland) Dec 2012A peptide nucleic acid (PNA) is a synthetic nucleic acid mimic in which the sugar-phosphate backbone is replaced by a peptide backbone. PNAs hybridize to complementary... (Review)
Review
A peptide nucleic acid (PNA) is a synthetic nucleic acid mimic in which the sugar-phosphate backbone is replaced by a peptide backbone. PNAs hybridize to complementary DNA and RNA with higher affinity and superior sequence selectivity compared to DNA. PNAs are resistant to nucleases and proteases and have a low affinity for proteins. These properties make PNAs an attractive agent for biological and medical applications. To improve the antisense and antigene properties of PNAs, many backbone modifications of PNAs have been explored under the concept of preorganization. This review focuses on chiral PNAs bearing a substituent in the N-(2-aminoethyl)glycine backbone. Syntheses, properties, and applications of chiral PNAs are described.
Topics: DNA, Antisense; DNA-Binding Proteins; Glycine; Peptide Nucleic Acids; RNA; Sequence Analysis, DNA
PubMed: 23271467
DOI: 10.3390/molecules18010287 -
Clinical Pharmacology in Drug... May 2022Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor in development for treatment of anemia of chronic kidney disease. We evaluated the role of hepatic...
Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor in development for treatment of anemia of chronic kidney disease. We evaluated the role of hepatic impairment on daprodustat pharmacokinetics, pharmacodynamics, and tolerability. Participants with mild (Child-Pugh Class A, score 5-6) and moderate (Child-Pugh Class B, score 7-9) hepatic impairment and matched healthy controls were administered single 6-mg doses of daprodustat. Exposure parameters were determined for daprodustat and its six metabolites. Comparisons resulted in 1.5- and 2.0-fold higher daprodustat C and area under the curve (AUC) exposures in participants with mild and moderate hepatic impairment, respectively, versus controls; C in mild hepatic impairment was comparable to controls. Similarly, aligned with parent drug, unbound daprodustat C and AUC exposures increased 1.6- to 2.3-fold in hepatic-impaired participants versus controls, and metabolite exposures were 1.2- to 2.0-fold higher in participants with hepatic impairment. Erythropoeitin (EPO) baseline-corrected AUC exposures were between 0.3-fold lower and 2.2-fold higher in matched controls versus hepatic-impaired participants. No serious or study drug-related adverse events were reported. Daprodustat exposure was increased in participants with moderate and mild hepatic impairment compared with matched controls; however, no meaningful differences in EPO were observed and no new safety concerns were identified (ClinicalTrials.gov: NCT03223337).
Topics: Barbiturates; Female; Glycine; Humans; Liver Diseases; Male; Prolyl-Hydroxylase Inhibitors
PubMed: 35355447
DOI: 10.1002/cpdd.1090