bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Role of Trehalose‐6‐phosphate Synthase in Oxidative Stress Tolerance of Fusarium verticillioides
Authors: McMillan Sarah D. , Oberlie Nicole R. , Brown Daren W. , McQuade Kristi L. 
Published: June 2021

Fusarium verticillioides is a filamentous fungus that infects maize and synthesizes fumonisins, a family of toxic and carcinogenic secondary metabolites. We are studying the role of trehalose in stress response in F. verticillioides. Trehalose‐6‐phosphate (T6P) synthase catalyzes the first step in trehalose synthesis, and a mutant lacking the gene that codes for T6P synthase does not produce trehalose or fumonisins. We report here that treatment with menadione or hydrogen peroxide inhibits germination of the mutant strain (Δtps1) more than the wild‐type strain. Whereas hydrogen peroxide delays germination, menadione reduces both the rate and percent germination, and significantly inhibits hyphal branching of both strains. To explore whether the sensitivity of Δtps1 to oxidative stress is caused by the lack of trehalose or the absence of a secondary function of the T6P synthase protein, we are studying mutants that express a catalytically inactive T6P synthase.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dynamic Actin Reorganization and Vav/Cdc42‐dependent Actin Polymerization Promote Macrophage Aggregated LDL Uptake and Catabolism
Authors: Singh Rajesh K. , Haka Abigail S. , Bhardwaj Priya , Maxfield Frederick R. 
Published: June 2021

During atherosclerosis, low density lipoproteins (LDL) accumulate in the arteries, where they become modified, aggregated and retained. Such deposits of aggregated LDL (agLDL) can be recognized by macrophages, which attempt to digest and clear them. AgLDL catabolism promotes internalization of cholesterol and foam cell formation, which is an important component of atherosclerosis. Characterization and therapeutic blockade of this process will likely delay disease progression. When macrophages interact with agLDL in vitro, they form a novel extracellular, hydrolytic compartment, the lysosomal synapse, aided by local actin polymerization to digest agLDL. Here, we demonstrate in vivo that atherosclerotic plaque macrophages contacting cholesterol rich LDL deposits polymerize actin and form a strikingly similar compartment. Live cell imaging revealed macrophage cortical F‐actin depolymerization driven by PIP2 hydrolysis occurs in parallel to actin polymerization at the lysosomal synapse and is required for its formation. Using siRNA‐mediated silencing, pharmacological inhibition, genetic knockout and stable overexpression, we elucidate key roles for Cdc42 Rho GTPase and guanine nucleotide exchange factor Vav in promoting actin polymerization at the lysosomal synapse, and we rule out roles for Rac1 and Rac2. These data indicate that dynamic actin rearrangement and polymerization via Vav and Cdc42 aids compartment formation, catabolism of agLDL and promotes foam cell formation.Support or Funding InformationThe project described was supported by National Institutes of Health grants R37‐DK27083 and R01‐HL093324. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.K.S. is an American Heart Association Stanley Stahl Postdoctoral Fellow (ID: 15POST22990022).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The PhoP/PhoQ two‐component regulatory system influences on Escherichia coli headgroup‐acylated glycerophospholipids
Authors: DiNardo Acadia S. , Garrett Teresa A. 
Published: June 2021

Headgroup‐acylated glycerophospholipids (GPLs) are a class of low abundance membrane lipids that are thought to play a roll in cell division and membrane integrity in Gram‐negative bacteria, such as Escherichia coli. The PhoP/PhoQ two‐component regulatory system is known to aid in virulence of pathogenic E. coli and responds to low Mg2+ concentrations. Previous research has suggested a protein activated by the PhoP/PhoQ system increases synthesis of acyl phosphatidylglycerol (acyl PG), a type of headgroup‐acylated GPL. Currently, though, the synthase of another headgroup‐acylated GPL, N‐acyl phosphatidylethanolamines (N‐acyl PE), is unknown. In order to determine if the PhoP/PhoQ system affects levels of acyl PGs, as well as N‐acyl PEs, wild‐type MG1655 E. coli with an empty pBAD 33.1 plasmid were grown in N‐minimal media with Mg2+ concentrations of either 8μM or 10mM. To confirm the activation of the PhoP/PhoQ system when cells are grown in 8μM Mg2+ media a reporter strain of E. coli, pNL3, was used. A β‐galactosidase assay of the pNL3 stain confirmed the activation of the PhoP/PhoQ system in low Mg2+ conditions through a 3.8 fold increase of activity in 8μM Mg2+ conditions compared to growths in 10mM Mg2+. In the MG1655 wild‐type strain, three normalized N‐acyl PE and four normalized acyl PG species were measured, utilizing reverse phase column mass spectrometry, and summed in each Mg2+ condition. N‐acyl PE and acyl PG levels in the 8μM Mg2+ growth was double that of the MG1655 grown in 10mM Mg2+. These data suggest that the PhoP/PhoQ system may be implicated in the synthesis of N‐acyl PEs and acyl PGs. Further research is required to verify the correlation between the activated PhoP/PhoQ system in N‐acyl PE and acyl PG synthase, as well as identify the protein specifically responsible for the synthesis of N‐acyl PEs.Support or Funding InformationSupported by National Science Foundation Major Research Instrumentation grant #1039659 and Research at Undergraduate Institution grant #1516805.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Native Gel Electrophoresis Reveals Partial Physical Association of band 3 and aquaporins on the Erythrocyte Membrane
Authors: Hsu Kate , Li Ying‐Syuan , Lin Hui‐Ju 
Published: June 2021

Band 3 is the most abundant membrane protein in human red cells. Band 3 primarily functions as a bi‐directional anion transporter for Cl− and HCO3− to support blood CO2 exchange. Because CO2 mainly exists in the form of HCO3− (aq) in the human body, the rate of CO2 blood respiration is dependent on the intraerythrocytic reaction CO2(g) + H2O □ HCO3− (aq) + H+ (aq). By FLIM‐FRET, we recently uncovered the existence of mobile interaction between band 3 and water channel AQP1. Their interaction could be disrupted when red cell vesicles were put in a hypotonic milieu, suggesting AQP1 bearing a functional role in the band 3‐central CO2 transport metabolon.ObjectiveAs there are at least two types of band 3 protein complexes on the erythrocyte membrane, the goal of this study was to probe the physical associations between aquaporins and different band 3 complexes.MethodWe utilized semi‐native and native gel electrophoresis to identify aquaporin complexes and to differentiate their associations with the different band 3 complexes.ResultsWater channel AQP1 and aquaglyceroporin AQP3 complexes were both identified in red cell ghosts by semi‐native gel electrophoresis. Some of the aquaporin complexes were found to be structurally linked to band 3 protein complexes.ConclusionThe physical association between AQP1 and band 3 and that between AQP3 and band 3 can be differentiated by semi‐native gel electrophoresis. Erythrocyte aquaporins also appear physically linked to other membrane‐associated proteins in the human red cells.Support or Funding InformationMOST 106‐2320‐B‐195‐002 from Taiwan Ministry of Science & TechnologyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Spices on Cancer Incidence in Peru
Authors: Perez Patricia , Solomon Rahia 
Published: June 2021

Breast and cervical cancer are a major concern for women all throughout the globe. Statistically over the last 30 years, there have been an increased incidence of breast (3.1%) and cervical cancer (0.6%) worldwide (WHO). Nutrition, natural remedies, and lifestyles of the Peruvian women were explored in an attempt to understand the effect nutrition and natural remedies have on women's health. It can be argued that nutrition plays a large role in the overall health of a person, therefore supplements, food, and spices may affect the frequency of cancer amongst Peruvian women. Patients and community members around Cusco, Peru were interviewed about their health, diets, and cooking habits. Using survey methods, we focused mainly on spices since they have been known to contain medicinal compounds. In analyzing the data from the responses about spice usage, it is clear that most spices used in the tested population are derived from meat (protein), which means that the protein was processed to be made into a broth or a dried additive. Seventeen people mentioned vegetables such as garlic, onions, parsley, tomatoes, olives, and peppers. Eight people discussed oregano as one of their most useful spice. Based on the collected survey results, oregano and other commonly used spices will undergo extraction and be tested for their effect on mammalian cells. Following, MTT and cytotoxicity assays will be conducted to help us understand the role these compounds play on mammalian cell viability.Support or Funding InformationMount Saint Mary's UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired Insulin‐like Growth Factor‐1 function in X‐linked Adrenoleukodystrophy patients
Authors: DHAUNSI GURSEV S. 
Published: June 2021

IntroductionX‐linked Adrenoleukodystrophy (X‐ALD), a common peroxisomal disorder is characterized by elevated very long chain fatty acids (VLCFA) levels in tissues and body fluids of patients. X‐ALD patients present with adrenal insufficiency, demyelination and progressive mental retardation and IGF‐1 has been reported to alleviate demyelination and neurodegeneration in an animal model of X‐ALD. We examined the effect of VLCFA on IGF‐1 function in human skin fibroblasts.MethodsHuman skin fibroblasts grown from skin explants were cultured in growth medium. Cell cultures were treated with varying concentrations of IGF‐1 and/or VLCFA (Lignoceric acid; C24:0, hexadecanoic acid; C26:0 ) for 24–72 hrs. DNA synthesis into cultured fibroblasts was measured and total RNA was extracted for RT‐PCR analysis of IGF‐1 receptor and GAPDH. Cell homogenates were prepared for western blotting and protein measurements. Levels of IGF‐1 and VLCFA were measured in blood samples of 10 patients with confirmed diagnosis of X‐ALD.ResultsBoth VLCFAs used in this study significantly (p <0.01) reduced the IGF‐1–induced DNA synthesis in cultured skin fibroblasts. Lignoceric acid as well as hexadecanoic acid markedly reduced the gene expression of IGF‐1 receptor. IGF‐1 receptor protein was also significantly reduced following 48 hrs of treatment with VLCFAs. X‐ALD patients were observed to have significantly lower levels of plasma IGF‐1 as compared to healthy controls.ConclusionsThis study suggests that abnormally elevated VLCFA in X‐ALD patients might impair IGF‐1 function through downregulation of IGF‐1 receptor thereby providing a new insight into molecular mechanisms of X‐ALD pathogenesis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Zinc on Mitochondrial Morphology
Authors: Knies Katherine , Lu Qiping , Li Yang 
Published: June 2021

Zinc (Zn2+) is involved in normal and abnormal cellular physiology. Cellular insults may cause zinc overload, which may affect mitochondrial functioning. Mitochondrial functioning influences mitochondrial morphology. Normal mitochondrial morphology has a tubular appearance, while abnormal mitochondrial morphology has a blob or donut appearance. In this study, it was addressed whether mitochondrial stress and insults caused by zinc resulted in abnormal mitochondrial morphology. To indicate mitochondrial morphology, live HeLa cells were stained with either MitoFluor Red 589 or MitoTracker Red. The two different treatments applied to the cells were zinc chloride pyrithione or pyrithione. Zinc chloride pyrithione was the experimental treatment and pyrithione was the vehicle in this study. These treatments were applied for 30 minutes. Images were taken before and after treatment to assess different parameters of morphology. The parameters examined were the length, diameter, surface area, mitochondrial morphology, and the number of mitochondria per area. Pyrithione did not have a significant effect on the measured parameters. In the zinc chloride pyrithione treated cells, the morphology changed from the tubular shape to donut and blob shape. This indicated that there was a rise in mitochondrial stress. There was also a reduction in mitochondrial number within zinc chloride pyrithione treated cells. This finding indicated that there was a higher amount of mitophagy, which is a form of autophagy that removes defective mitochondria, in these cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Theasinensins A Against Methylglyoxal‐Induced Neurotoxicity via Autophagy in SH‐SY5Y Cells
Authors: Cheng An‐Chin , Lee Ming‐Fen , Huang Tzu‐Li , Cai Kuan‐Ci , Pan Min‐Hsiung 
Published: June 2021

Methylglyoxal (MG) is a highly reactive dicarbonyl aldehyde. MG has been proved to be toxic to neuron and may be the reason of many neurodegenerative diseases. Tea polyphenols have notable effects against various types of cancers, blood pressure, cardiovascular problems, arthritis, and atherosclerosis without inducing major toxicity consequences. Tea polyphenols have a role in the reversal of age‐related loss of neuronal plasticity and recovery after neuronal lesions. Theasinensins are a group of tea polyphenols different from green tea catechins, and they are considered as bioactive compounds in Oolong tea. During enzymatic oxidation, EGCG is fermentated and several B‐ring homodimers: theasinensins A (TSA) intermediates generated. TSA had been found to have many bioactivities, such as anti‐oxidation. However, the effect of the neuroprotective effect of this tea polyphenol remains unclear. The aim of this study is to investigate the neuroprotective effects and the molecular mechanism of TSA against MG‐induced toxicity in SH‐SY5Y cell model. The cell viability assay demonstrated that TSA treatment protected cells from MG‐induced neurotoxicity. The result of acridine orange (AO) stain, detecting AO fluoresce intensity and the level of LC3, showed that TSA could increase intracellular AVO value and induce autophagy in MG‐treated neuron cell. We expect that TSA could be reagents to protect neurodegenerative diseases.Support or Funding InformationThis study was supported by NSC 100‐2313‐B‐309‐003 to A‐C ChengThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
β‐Catenin Deficiency in Hepatocytes Aggravates Hepatocarcinogenesis Driven by Oncogenic β‐Catenin and MET
Authors: Liang Yan , Feng Yun , Zong Min , Wei Xu‐Fu , Lee Jin , Feng Yukuan , Li Hairi , Yang Guang‐Shun , Wu Zhong‐Jun , Fu Xiang‐Dong , Feng Gen‐Sheng 
Published: June 2021

Both activating and inactivating mutations in ctnnb1, encoding β‐catenin, have been implicated in liver tumorigenesis in humans and mice, although the underlying mechanisms are not fully understood. Herein we show that deletion of endogenous β‐catenin in hepatocytes aggravated hepatocellular carcinoma (HCC) development driven by an oncogenic version of β‐catenin (CAT) in combination with HGF receptor MET. Although the mitogenic signaling and cell cycle progression was modestly impaired after CAT/MET transfection, the β‐catenin‐deficient livers displayed changes in transcriptomes, increased DNA damage response, expanded Sox9+ cells, and upregulation of pro‐tumorigenic cytokines including IL‐6 and TGF‐β1. These events eventually exacerbated CAT/MET‐driven hepatocarcinogenesis in β‐catenin‐deficient livers, featured by upregulation of Erk, Akt and Wnt/β‐catenin signaling and cyclin D1 expression. The resultant mouse tumors showed similar transcriptomes to human HCC samples with concomitant CTNNB1 mutations and MET overexpression. These data argue that while dominantly activating mutants of β‐catenin are oncogenic, inhibiting the oncogenic signaling pathway generates a prooncogenic microenvironment, which may facilitate HCC recurrence following a targeted therapy of the primary tumor. Therefore, an effective therapeutic strategy must require disruption of the oncogenic signaling in tumor cells and also suppression of the secondary tumor‐promoting stromal effects in the liver microenvironment.Support or Funding InformationThis project was supported by NIHR01CA176012 and R01CA188506 (to G.S.F.). Yan Liang was supported by a pre‐doctoral fellowship of FISP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Putative MicroRNA Regulatory Networks in Hepatic Stellate Cells Underlying Chronic Ethanol‐Mediated Impairment of Liver Regeneration after Partial Hepatectomy
Authors: Parrish Austin , Juskeviciute Egle , Hoek Jan , Vadigepalli Rajanikanth 
Published: June 2021

microRNAs (miRNAs) are a class of small, non‐coding RNAs ~22 nucleotides in length that are involved in post‐transcriptional regulation of a wide variety of processes critical for normal cell function, such as development, cell differentiation, cell proliferation, and cell death. There remains, however, a comparative lack of knowledge on the precise role and function of miRNAs in the context of alcoholic liver disease. In this study, we sought to characterize global miRNA expression patterns in the rat liver for both control and ethanol‐fed animals before and after 70% partial hepatectomy (PHx). Chronic ethanol consumption using the Lieber‐DeCarli diet leads to a maladaptive response across multiple organ systems, and is sufficient by itself to alter normal miRNA expression dynamics in the liver. This adaptation to ethanol consumption has also been shown to alter miRNA expression in response to PHx when compared with control animals. Additionally, the regenerative capacity of the liver in response to injury is significantly decreased by chronic ethanol consumption. Previous research has identified several miRNAs that may be key regulators of liver regeneration, such as miR‐21, whose role in liver regeneration and liver disease has been well‐studied by our lab and others. By using the NanoString nCounter expression system, we obtained an un‐biased view of changes in miRNA expression. Our results show that the differentially expressed miRNAs exhibit complex expression dynamics during liver regeneration, and that many of these miRNAs appear to be strongly correlated with each other, suggesting the possibility of co‐regulatory networks. This is further supported by our results showing that alteration of the expression of a single miRNA, in this case inhibition of miR‐21, is capable of affecting the expression of multiple other miRNAs in both correlated and anti‐correlated fashions. Functional analysis of these dysregulated miRNAs suggests potential mechanisms involved in hepatic stellate cell activity, which was further supported by gene set enrichment analysis using previously published data involving stellate cell‐specific miRNAs. In conclusion, we have identified a network of miRNAs whose differential expression may regulate liver regeneration via alteration of hepatic stellate cell function.Support or Funding InformationResearch was supported by the following NIH grants from NIAAA: R01 AA018873, U01EB023224, F31 AA024969‐01, and T32 AA007463.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Translation For Portuguese And Validation Of The Questionnaire Of The Patient Neuropathy Interpretation (PIN)
Authors: Reis MM , Parisi MCR , Giannella‐Neto D 
Published: June 2021

BackgroundThe instruments that could evaluate and extend self‐care carried on are in demanding for the prevention of chronic complication of diabetes. The Patient Interpretation of Neuropathy (PIN) has been developed and validated in the USA and in the UK and comprises a questionnaire for the qualitative measurement of comprehension of the patient with diabetes at risk to develop diabetic foot due to neuropathy and micro/macrovascular diseases. By means of this instrument, the patient can self‐evaluate her/his foot and health care provided to her/him, aiming the prevention of ulcer diabetic foot.ObjectiveThe aim of the present study was to translate to Portuguese validating the PIN and to assess the degree of comprehension regarding patient awareness to her/him clinical condition.MethodsHundred patients from the outpatient Clinic of Insensitive Foot at the Institute of Orthopedics and Traumatology, University of Sao Paulo, were surveyed by the application of PIN to determine awareness and knowledge regarding risks and consequences of and prevention of diabetic foot. Score data were expressed as mean and standard deviation and statistical analysis was performed by parametric and non‐parametric tests when needed. Statistical significance was set at p<0.05.ResultThe representative values of the assessment of the level of patients' understanding are presented in Figure 1, below. ID, identity of the disease; C, concerning; CC, cure; TL, timeline; CONS, consequences; MS, emotion. There were significant statistical differences when Sao Paulo data were compared to that obtained in UK and USA centers in most of the domains. For agreement analysis, the Spearman correlation coefficient was used. The level of significance was set at P <0.05.ConclusionThe results of this study suggest that the use of the PIN provides better understanding of patients' condition regarding diabetic foot risk. Moreover, PIN can improve the awareness of the patients to carry on simple measures performed at home, such as, moisturize the feet, use appropriate shoes, visit the health service regularly, and daily monitoring and inspecting the feet. The application of a questionnaire as the PIN serves both to assess the patient's self‐care, but also allows the health professional delineates measures of effective prevention.funding source: Universidade Nove de Julho ‐ UNINOVESupport or Funding InformationUNIVERSIDADE NOVE DE JULHO ‐ UNINOVE tableThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.