bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative stress‐induced protein packaging in Enterotoxigenic Escherichia coli outer membrane vesicles and its functional impact on host‐pathogen interactions
Authors: Orench‐Rivera Nichole , Kuehn Meta 
Published: June 2021

Enterotoxigenic Escherichia coli is the leading cause of traveler's diarrhea worldwide and it remains an important causal agent of diarrheal disease, especially among children of lower income countries. Because it must adjust to different ecological niches such as fruit and vegetable surfaces, water, and its animal or human host; its cell envelope must undergo remodeling. In Gram‐negative bacteria, the cell envelope is the first barrier against environmental stress and studies have shown that the process of outer membrane vesiculation is essential for bacterial growth and survival during stressful conditions. Recent studies in our lab revealed that outer membrane vesicles (OMVs) can contain varying ratios of lipopolysaccharide (LPS) types during cell envelope remodeling under stress in Salmonella enterica, suggesting a role for vesicles in membrane remodeling. In this study, outer membrane vesicles and outer membrane fractions from ETEC were isolated from bacterial cultures, purified via density centrifugation, and submitted for proteomic analysis using quantitative one‐dimensional liquid chromatography, tandem mass spectrometry (1D‐LC‐MS/MS) to quantify differences in protein expression in vesicles and membranes during oxidizing and non‐oxidizing conditions (plus or minus Hydrogen Peroxide). Protein packaging into vesicles was determined by calculating the log‐2 of the ratio of protein expression in OMVs/outer membranes for both treatment conditions. Results indicated that two distinct sets of proteins were shown to be differentially packaged into OMVs as a function of peroxide treatment. Upon further analysis implementing a Bayesian hierarchical model, lipoproteins were observed to be preferentially exported during stress, in contrast to integral proteins, which were preferentially retained in the outer membrane. Additionally, OMVs derived from stressed cultures showed less cytotoxicity towards Y‐1 adrenal cells in a cell rounding assay. These results allow us to speculate about potential roles for OMVs in membrane remodeling of pathogenic bacteria undergoing environmental shifts both outside and inside the human host.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intestinal epithelial O‐GlcNAc signaling is indispensable for anti‐helminth type 2 immunity
Authors: Zhao Ming , Ren Kaiqun , Ruan Hai‐Bin 
Published: June 2021

More than 1 billion people worldwide are infected with helminths, which may nutritionally and physically impair infected people, particularly children. Tuft cells lying in the intestinal epithelium have been recently proposed to sense parasitic worms in the lumen and initiate type 2 immunity, which in turn remodels the intestinal epithelium and expulses parasites. However, little is known regarding the molecular mechanisms underlying tuft cell hyperplasia. O‐linked N‐Acetylglucosamine (O‐GlcNAc), a posttranslational modification that decorates a single sugar moiety onto intracellular proteins at serine and threonine residues, plays a central role in many biological processes such as gene transcription, protein stability, and cell signaling. Dysregulated O‐GlcNAc signaling has been associated with a plethora of human diseases including cardiovascular disease, diabetes, neurodegeneration, and inflammation; however, the role of O‐GlcNAcylation in intestinal homeostasis has not been fully elucidated. Here, we found that O‐GlcNAc transferase (OGT), the enzyme catalyzing O‐GlcNAcylation, was essential for homeostatic tuft cell development in mice. The deficiency in intestinal epithelial O‐GlcNAcylation impaired tuft cell hyperplasia and type 2 responses to H. polygyrus and N. brasiliensis infections. Intriguingly, such defects were not observed in mice where OGT was specifically deleted in committed tuft cells, suggesting that OGT is required for the differentiation of intestinal progenitors toward the tuft cell lineage. Indeed, STAT6, a type 2 cytokine‐responsive transcriptional factor essential for tuft cell development, is O‐GlcNAcylated. O‐GlcNAcylation of STAT6 enhances its tyrosine phosphorylation and transcriptional activity, while O‐GlcNAc‐deficient STAT6 blunted tuft cell differentiation. Taken together, our data demonstrate that protein O‐GlcNAcylation, by modifying STAT6 signaling, is indispensable for epithelial remodeling and tuft cell‐initiated type 2 immune responses to helminth infections.Support or Funding InformationAmerican Diabetes Association (18‐IBS‐167)NIAID (R21AI140109)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Parasite‐Derived Vesicular‐Mediated Protein Export by the Human Pathogen Babesia microti
Authors: Ben Mamoun Choukri , Thekkiniath Jose , Kilian Nicole , Lawres Lauren , Gewirtz Meital , Abraham Amanah , Graham Morven , Liu Xinran , Ledizet Michel 
Published: June 2021

Babesia microti is the primary agent of human babesiosis, a potentially fatal malaria‐like illness with worldwide geographic distribution. Like its Plasmodium relatives, B. microti intraerythrocytic development is heavily dependent on its successful interaction with the host. While available data indicate that the parasite exports a large number of proteins into the host, the mechanism by which these proteins are exported remains completely unknown. Unlike malaria parasites, B. microti lacks a parasitophorous vacuole, and its secreted proteins are devoid of canonical motifs for trafficking into the erythrocyte cytoplasm or cell environment. Here we show that following invasion of the host erythrocyte, B. microti undergoes a major morphogenetic change during which it produces an interlacement of vesicles (the IOV system) that extends from the plasma membrane of the parasite into the cytoplasm of the infected erythrocyte. Using cell fractionation and confocal and immunoelectron microscopy analyses, we demonstrate that the IOV system serves as a major export system of the major immunodominant antigens of the parasite. The IOV system of B. microti represents a new mechanism for delivery of parasite factors into the host in the phylum Apicomplexa.Support or Funding InformationThis work was funded by NIH grants AI123321 and R43AI136118 and in part supported by the NIH grant S10 OD020142.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence for the Novel Metabolic Pathway of Ralstonia eutropha H16 to Metabolize L‐ascorbate Ryan Joyce, Tyler Stack, Michael Carter
Authors: Joyce Ryan Patrick 
Published: June 2021

L‐Ascorbate is an antioxidant produced by many eukaryotes and is available for microbial organisms in eukaryotic detritus. Ralstonia eutropha H16, a soil bacterium that is studied due to its extensive metabolism and bioplastic producing capabilities, can use L‐ascorbate via a metabolic pathway that is different from the known pathways of Escherichia coli and plants. Transcript levels were measured in L‐ascorbate‐grown Ralstonia eutropha H16 and compared to transcript levels of succinate‐ and fructose‐grown Ralstonia eutropha H16. Genes with a larger than 50‐fold upregulation during L‐ascorbate growth were investigated. A BLAST search suggested that the proteins encoded by the genes of interest in Ralstonia eutropha H16 differ from enzymes of the Escherichia coli L‐ascorbate metabolic pathway. Ralstonia eutropha H16 does not convert L‐ascorbate into L‐threonate and oxalate, as plants do. Genes of interest, h16_rs15015 and h16_rs19815, were deleted. The resultant mutants do not grow with L‐ascorbate. The deletion of specific metabolic genes allows us to better understand their function and importance to the cell's metabolism, furthering our understanding of how different enzymatic metabolic pathways function in nature.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Supplementation of multi‐vitamins, not glutamine alleviate erythrocyte oxidative status in rats with trauma‐hemorrhagic shock and resuscitation
Authors: Lo Hui‐chen , Lin Yu‐Hsin , Lee Chien‐Hsing 
Published: June 2021

Resuscitation fluid replacement is the major life saving strategy for patients with hemorrhagic shock; however, resuscitation‐induced oxidative stress may lead to systemic inflammation, multiple organ failure (MOF), and even death. Studies showed that reduction of oxidative stress and preservation of ATP production may improve MOF in animals with trauma‐hemorrhagic shock and resuscitation (THR). In addition, glutamine has been considered as a cellular fuel and is the source of glutathione and multi‐vitamins possess antioxidant activity and play important roles in energy metabolism. Therefore, we investigated the effects of single or simultaneous administration of multi‐vitamins and glutamine on antioxidant defense systems, including enzymatic and non‐enzymatic, in the plasma and erythrocytes of THR. Male SD rats were suffered with THR, including a 5 cm midline laparotomy and mean arterial pressure 30 to 35 mmHg for 60 min followed by resuscitation lactate Ringer's (LR) solution with or without L‐alanyl‐L‐glutamine and/or multi‐vitamins. The sham‐operated, parenterally fed rats were included. After infused with continuous, slow rate of LR solutions for 42 hours, the THR rats had significantly decreased red blood cells and hematocrit and increased erythrocyte glutathione (one‐way ANOVA, p<0.05). Intravenous glutamine significantly increased erythrocyte total and protein‐bound thiol groups and plasma TBARS; intravenous multi‐vitamins significantly decreased erythrocyte TBARS; and combination of glutamine and multi‐vitamins significantly decreased erythrocyte TBARS and the ratio of plasma reduced to oxidized glutathione and increased plasma TBARS. In addition, multi‐vitamins was the main factor to decrease plasma total and protein‐bound thiol groups and plasma and erythrocyte TBARS and to increase the ratio of plasma reduced to oxidized glutathione (two‐way ANOVA, p < 0.05). In conclusion, multi‐vitamins, not glutamine, may alleviate erythrocyte oxidative status in trauma‐hemorrhagic shock and resuscitation.Support or Funding InformationNSC 102‐2320‐B‐030‐005‐MY3This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selenium Reduces Lectin‐Like Oxidized LDL Receptor‐1 (LOX‐1)‐ Mediated Vascular Oxidative Stress Induced by Inhalation of Pyrolysis Oil Vapors
Authors: Moustafa Mohamed El‐Sayed , Fawaz Youssef B. 
Published: June 2021

Pyrolysis oil (PO) is a renewable fuel produced from municipal solid waste and there is a concern about the adverse effects of its vapors on vascular oxidative stress. In this study, we investigated the effects of exposing mice to PO vapors on lectin‐like oxidized LDL receptor‐1 (LOX‐1)‐mediated vascular oxidative stress. We also examined the effects of selenium supplementation in these mice. Our results showed that the exposure of mice to PO vapors increased aortic levels of malondialdehyde, LOX‐1 and its soluble form sLOX‐1, NADPH oxidase 4 (NOX‐4), NF‐kB (p65) and endothelial NOS (eNOS). The administration of 1.78 μg selenium/kg body weight into these mice 15 minutes before the exposure to PO vapors reduced the increased levels of the above parameters. In conclusion, the exposure to pyrolysis oil vapors contributes to the increased LOX‐1–mediated vascular oxidative stress which can be reduced with selenium supplementation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In‐vivo evaluation of ethanolic seed extract of Walnut (Tetracarpidium Conophorum) on N‐acetyl‐ 1,4‐benzoquinone imine‐induced oxidative stress in albino rats
Authors: Nosiri Chidi Ijeoma , Anyanwu Chukwuma , Benedict Sandra 
Published: June 2021

This study evaluated the liver integrity and antioxidant effects of ethanolic seed extract of Walnut (Tetracarpidium Conophorum) on paracetamol (PCM) induced hepatotoxicity via its reactive intermediate metabolite N‐acetyl‐1,4‐benzoquinone imine (NAPQI) in albino rats. PCM is an over the counter drug and commonly abused. Overdose of NAPQI causes oxidative stress to the liver and other tissues as the endogenous enzymes will not be able to handle the toxicity. Tetracarpidium conophorum (TC) nutritionally contains a lot of vitamins C and E. The rats were divided into five groups of five rats each. (Gp1: n‐saline, Gp2: PCM alone, Gp3: PCM + 250mg/kg Extr., Gp4: PCM +500mg/kg Extr. and Gp5: PCM + 750mg/kg Extr.) All the animals were starved for 24hrs before the administration of PCM to groups 2 – 5. After 48hrs, Gps 3 – 5 were given 250, 500 and 750mg/kg of TC extract respectively for 7 days and then the animals were sacrificed. The levels of the transaminase enzymes were used to assess the intergrity of the liver. The antioxidant status in the liver was determined by measuring the activity of Glutathione (GSH), Superoxide dismutase (SOD) and Catalase (CAT). The oral treatment of rats with different doses of the extract showed significant (P≤ 0.05) hepatoprotective activity against NAPQI induced hepatotoxicity by decreasing the activities of transaminases (U/L) (ALT from 53.00 ± 2.10 – 31.40 ± 1.33, AST from 127.20 ± 1.16 – 106.00 ± 2.21, ALP 67.80 ± 0.86 – 57.60 ± 0.93), Total Cholesterol from 87.40 ± 0.61 – 67.68 ± 1.27, Total Bilirubin (g/dl) from 1.50 ± 0.05 – 1.24 ± 0.08 and significantly (P≤ 0.05) increasing the liver homogenate (U/L) of GSH from 28.80 ± 0.73 – 35.80 ±.86, CAT from 17.80 ± 0.28 – 18.5 ± 0.16 and SOD from 15.80 ± 0.37 – 19.60 ± 0.68 activities compared with the negative control. These findings showed that the walnut seed may have cytoprotective and antioxidant properties.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neuromuscular function during aging is protected in baicalein‐treated C57BL/6 mice
Authors: Bhattacharya Arunabh , Walsh Michael , Hamilton Ryan , Singh Rashmi , Rahman Mizanur , Rodriguez Karl , Chaudhuri Asish , Sharma Ramaswamy 
Published: June 2021

The loss of muscle mass and strength during aging is a debilitating condition leading to altered metabolism and the loss of independence in older adults. The causes of this condition, known as sarcopenia, are not known. We previously reported an increase in arachidonic acid and its metabolite 12‐hydroxyeicosatetraenoic acid (12‐HETE), which is generated by 12/15‐lipoxygenase (12/15‐LO), in sciatic nerves of old (28–30 months) C57Bl/6 mice. To determine if 12/15‐LO activity contributes to the age‐related decline in muscle and nerve function, we treated middle‐aged (24 mo old) mice with the 12/15‐LO inhibitor baicalein for 14–16 weeks. Compared to baseline measurements, baicalein treatment improved hindlimb muscle force generated by electrical stimulation. Baicalein treatment partially prevented the decline in fatigue observed in vehicle‐treated old mice compared to baseline. These improvements occurred without any change in muscle mass or sciatic nerve conduction velocity. Baicalein treatment was associated with a reduction in oxidative and ubiquitin modifications to proteins in sciatic nerves from old mice, which may be due to elevated proteasome activity and altered stress response in sciatic nerves from baicalein‐treated mice. Our data suggest that lipid metabolites generated by 12/15‐LO may contribute to the age‐related loss of muscle strength observed during aging.Support or Funding InformationNational Institutes of Health (K01AG038555) and American Federation for Aging Research (AB), K99/R00 Pathway to Independence Award (AG049940‐01A1) (KR), T32 AG021890‐08 (NIA) National Service Research Award to Postdoctoral Fellow Training Grant on the Biology of Aging to Steven N. Austad for trainee (RTH)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Novel Way to Use Vitamin C? Characterizing L‐Ascorbate (Vitamin C) Catabolism in Ralstonia eutropha
Authors: Wille Brendan , Stack Tyler , Carter Michael 
Published: June 2021

L‐Ascorbate (Vitamin C) is present in the environment in plant tissues, typically at concentrations from 1–10mM, and as high as 300mM. L‐Ascorbate is also an essential radical scavenger (antioxidant) for plants and mammals and is not synthesized by bacteria. Given the ubiquity of L‐ascorbate in the environment, metabolism of L‐ascorbate necessarily contributes to ecological recycling. Ralstonia eutropha H16, a soil bacterium commonly studied for its versatile use of organic and inorganic carbon sources, can use L‐ascorbate as a carbon source via an unknown pathway. Using RNAseq, whole cell transcript levels in R. eutropha were compared between L‐ascorbate‐grown cells and succinate‐or fructose‐grown cells (controls). Putative pathway genes were identified by their increase in expression greater than 50‐fold in R. eutropha grown with L‐ascorbate. Mutant strains (lacking putative pathway genes) were generated by homologous recombination directed allelic exchange. Wild type and mutant strains were grown in liquid cultures with either L‐ascorbate or succinate as their sole carbon source and monitored by optical density to observe the phenotypic result of gene deletion. Growth studies have been performed, and L‐ascorbate no growth phenotype has been confirmed for three mutant strains. Collaborators have characterized putative pathway enzymes. Characterizing the proposed catabolic pathway of L‐ascorbate in R. eutropha will provide information regarding environmental nutrient cycling and contribute novel functions of suspected pathway enzymes to protein databases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Andrographolide alters metabolism and mitochondrial function in prostate cancer
Authors: Lopez Rivas Andres R , Sanchez Vazquez Maria R , Zuazaga Humberto Ortiz , Torres Ramos Carlos A , Ferrer Magaly Martinez 
Published: June 2021

Prostate cancer (PCa) is the second most common diagnosed cancer and the fifth cause of cancer mortality in men worldwide. In the United States, PCa is the most common diagnosed cancer and the third cause of cancer mortality in men. PCa is often treated using radiation, chemotherapy or radical prostatectomy. However, the combination of natural products with the standard of care treatment is an emerging area of cancer therapeutics. Previous studies from our laboratory showed that Andrographolide inhibits prostate cancer progression through a DNA damage response mechanism. In this study, we investigated the role of Andrographolide in metabolic function. Tumor development was performed by using an orthotopic xenograft model in which the prostates of SCID mice were injected with the prostate cancer cell line 22RV1. These mice were treated three times per week with Andrographolide 10 or 25 mg/kg for 4 weeks. Tumor tissue was collected to evaluate the effect of Andrographolide in tumor gene expression. Microarray analysis identified carbohydrate metabolism, connective tissue development and function, and cell cycle as a major molecular and cellular function altered in tumors treated with Andrographolide. Specifically, we found that the expression profiles of SASS6, FBXL4, MYDGF, TKK, MRSP33 and ZNF766 were significantly altered, suggesting that Andrographolide may be altering tumor metabolism. To confirm this observation, bioenergetics profile was determined using an Extracellular Flux Analyzer (Seahorse XF Mito Stress assay). The results of these experiments indicate that Andrographolide treatment decreases the Maximum and Spare Respiratory Capacity of PCa cells. These data suggest that Andrographolide disrupts the bioenergetics profile of PCa cells.Support or Funding InformationWork funded by Institutional funds from the University of Puerto Rico Comprehensive Cancer Center and the School of Pharmacy. HOZ was supported in part by NIH‐NCI grant U54CA096297. MARC grant 5T34GM007821‐38.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Leucine‐rich diet changes tumor metabolism, reducing glucose consumption and metastasis in Walker 256 tumor‐bearing rats
Authors: Viana Lais ROSA , Tobar Natalia , Busanello Estela , Marques Ana Carolina , Lima Tanes , Machado Gabrielly , Castelucci Bianca , Ramos Celso Dario , Sergio  , Silveira Leonardo Reis , Vercesi Anibal Eugenio , Consonni Silvio Roberto , Gomes‐Marcondes Maria Cristina Cintra 
Published: June 2021

Leucine stimulates muscle protein synthesis and is begin used as a potential treatment for muscle wasting conditions, such as cancer cachexia. However, the effects of leucine in the tumor tissue are still unknown. We aimed to describe the effects of a leucine‐rich diet on the Walker 256 tumor tissue. For this purpose, tumor‐bearing Wistar rats were randomly distributed into a control group (normoprotein diet) and leucine group (leucine‐rich diet (18% protein + 3% leucine)). After 20 days of tumor inoculation, the animals underwent to 18F‐FDG PET‐CT and after being euthanized, fresh tumor biopsies were collected to measure the oxygen consumption rate and fixed for electron microscopy analysis. Our results showed that the leucine‐rich diet leads to a lower tumor glucose (18F‐FDG) uptake by tumor and reduced number of metastases sites. Furthermore, leucine‐rich diet changed the mitochondrial morphology and function (from a glycolytic to an oxidative phenotype), associated with a higher gene expression of oxidative phosphorylation components. In addition, tumor tissue from leucine group showed a higher number of apoptotic nuclei with an increased oxidative stress. In conclusion, leucine‐enriched diet was associated with considerable metabolic activity reduction of malignant tissue associated with mitochondrial morphology and function changes in Walker 256 tumor tissue.Support or Funding InformationThe authors are grateful for financial support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico #302863/2013‐3; #302425/2016‐9), and FAPESP [grant number #2012/06955‐0; #2014/13334‐7; #2015/21890‐0; #2017/02739‐4].This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.