Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

PubMed

Ruano-Gallego, David; Álvarez, Beatriz; Fernández, Luis Ángel

2015-09-18

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these "molecular syringes" for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells.

Pathogenicity Island O-122 in enteropathogenic Escherichia coli strains is associated with diarrhea severity in children from Lima Peru

PubMed Central

Mercado, Erik H.; Piscoche, Cristian; Contreras, Carmen; Durand, David; Riveros, Maribel; Ruiz, Joaquim; Ochoa, Theresa J.

2016-01-01

EPEC is an attaching and effacing diarrheal pathogen that carries a large pathogenicity island, locus for enterocyte effacement (LEE). Recently, the pathogenicity island PAI O-122 was described among non-LEE effectors and found to be associated with diarrhea among atypical EPEC strains. It is unknown if incomplete PAI O-122 could be associated with diarrhea duration and severity. To identify these virulence determinants we analyzed 379 EPEC strains isolated from Peruvian children. EPEC was diagnosed by PCR(eae+, stx−) and classified as typical(t-EPEC) or atypical(a-EPEC). To characterize PAI O-122 we amplified three modules by PCR: Module 1(pagC), Module 2(senA, nleB and nleE) and Module 3(lifA/efa-1). To characterize the large ORF lifA/efa-1 we amplified the regions known as efa-N, efa-M and efa-C. Clinical information was obtained from the cohort study. A total of 379 EPEC strains were able to analyze PAI O-122 genes, 128 (10.4%) EPEC strains were isolated from 1235 diarrhea episodes and 251(9.2%) from 2734 healthy controls. t-EPEC strains were isolated from 14.8% (19/128) of children with diarrhea and 25/251(10.0%) from healthy controls. The most frequent PAI O-122 genes were nleE(37.7%), senA(34.6%) and nleB(37.5%), with similar prevalence among diarrhea and control samples. However, lifA/efa-1 was more common among diarrhea cases than healthy control cases (30.5% vs. 21.1%, p<0.05). The presence of complete PAI O-122 was associated with diarrhea episodes of higher severity among single pathogen infection (33.3% vs. 1.8%, p<0.05) mainly due to the presence of a complete lifA/efa-1 gene. In summary, the gene lifA/efa-1 is significantly associated with diarrheal episodes of higher severity, suggesting to be an important virulent factor. PMID:27236730

A Family of Indoles Regulate Virulence and Shiga Toxin Production in Pathogenic E. coli

PubMed Central

Izrayelit, Yevgeniy; Bhatt, Shantanu; Cartwright, Emily; Wang, Wei; Swimm, Alyson I.; Benian, Guy M.; Schroeder, Frank C.; Kalman, Daniel

2013-01-01

Enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC) and enteroaggregative E. coli (EAEC) are intestinal pathogens that cause food and water-borne disease in humans. Using biochemical methods and NMR-based comparative metabolomics in conjunction with the nematode Caenorhabditis elegans, we developed a bioassay to identify secreted small molecules produced by these pathogens. We identified indole, indole-3-carboxaldehyde (ICA), and indole-3-acetic acid (IAA), as factors that only in combination are sufficient to kill C. elegans. Importantly, although lethal to C. elegans, these molecules downregulate several bacterial processes important for pathogenesis in mammals. These include motility, biofilm formation and production of Shiga toxins. Some pathogenic E. coli strains are known to contain a Locus of Enterocyte Effacement (LEE), which encodes virulence factors that cause “attaching and effacing” (A/E) lesions in mammals, including formation of actin pedestals. We found that these indole derivatives also downregulate production of LEE virulence factors and inhibit pedestal formation on mammalian cells. Finally, upon oral administration, ICA inhibited virulence and promoted survival in a lethal mouse infection model. In summary, the C. elegans model in conjunction with metabolomics has facilitated identification of a family of indole derivatives that broadly regulate physiology in E. coli, and virulence in pathogenic strains. These molecules may enable development of new therapeutics that interfere with bacterial small-molecule signaling. PMID:23372726

A secretome view of colonisation factors in Shiga toxin-encoding Escherichia coli (STEC): from enterohaemorrhagic E. coli (EHEC) to related enteropathotypes.

PubMed

Monteiro, Ricardo; Ageorges, Valentin; Rojas-Lopez, Maricarmen; Schmidt, Herbert; Weiss, Agnes; Bertin, Yolande; Forano, Evelyne; Jubelin, Grégory; Henderson, Ian R; Livrelli, Valérie; Gobert, Alain P; Rosini, Roberto; Soriani, Marco; Desvaux, Mickaël

2016-08-01

Shiga toxin-encoding Escherichia coli (STEC) regroup strains that carry genes encoding Shiga toxin (Stx). Among intestinal pathogenic E. coli, enterohaemorrhagic E. coli (EHEC) constitute the major subgroup of virulent STEC. EHEC cause serious human disease such as haemorrhagic colitis and haemolytic-uremic syndrome. While EHEC have evolved from enteropathogenic E. coli, hybrids with enteroaggregative E. coli have recently emerged. Of note, some enteroinvasive E. coli also belong to the STEC group. While the LEE (locus of enterocyte effacement) is a key and prominent molecular determinant in the pathogenicity, neither all EHEC nor STEC contain the LEE, suggesting that they possess additional virulence and colonisation factors. Currently, nine protein secretion systems have been described in diderm-lipopolysaccharide bacteria (archetypal Gram-negative) and can be involved in the secretion of extracellular effectors, cell-surface proteins or assembly of cell-surface organelles, such as flagella or pili. In this review, we focus on the secretome of STEC and related enteropathotypes, which are relevant to the colonisation of biotic and abiotic surfaces. Considering the wealth of potential protein trafficking mechanisms, the different combinations of colonisation factors and modulation of their expression is further emphasised with regard to the ecophysiology of STEC. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of the impact of quorum sensing transcriptional regulator SdiA on long-term persistence and fecal shedding of Escherichia coli O157:H7 in weaned calves.

PubMed

Sharma, V K; Bearson, S M D

2013-04-01

Escherichia coli O157:H7 (O157) colonization of bovine intestine is mediated through the locus of enterocyte effacement (LEE)-encoded type III secretion system and secreted virulence proteins that promote colonization of the recto-anal junction (RAJ) of the large intestine of cattle. The quorum sensing transcriptional regulator SdiA, a homolog of LuxR, has been shown in vitro to repress LEE strongly when overexpressed from a multi-copy recombinant plasmid or when its activity is enhanced by the binding of N-acyl-L-homoserine lactones (AHLs), the quorum sensing signals that are detected by SdiA. Since LEE has been shown to be essential for colonization and persistence of O157 in bovine intestine, we examined whether a mutation in sdiA, which normally represses LEE in vitro, would also exert negative effect on colonization and long-term persistence of O157 in weaned calves. Ten-week old weaned calves (n = 4/group) were inoculated orally with 10(10) cfu of either the wild-type or sdiA mutant strain. Initial fecal shedding of the sdiA mutant and the wild-type strain were similar in magnitude and declined during the first 2 weeks post-inoculation. The sdiA mutant was detected in feces of only one of the four calves at low levels (≥10(2) cfu/g feces) from days 19 - 27 post-inoculation, whereas, the fecal shedding of the wild-type strain persisted at approximately 4-logs in all four calves from days 19 - 27. We also confirmed that SdiA represses ler, which encodes a positive transcriptional regulator of LEE, in response to AHLs, and reduces adherence of O157 to HEp-2 cells. In conclusion, this study demonstrates that although in vitro the sdiA gene represses LEE and LEE-mediated adherence to cultured cells, the presence of sdiA is necessary for colonization of bovine large intestine that in turn promotes persistent fecal shedding of O157 by these animals. Published by Elsevier Ltd.

Evaluation of hha and hha sepB mutant strains of Escherichia coli O157:H7 as bacterins for reducing E. coli O157:H7 shedding in cattle.

PubMed

Sharma, Vijay K; Dean-Nystrom, Evelyn A; Casey, Thomas A

2011-07-12

Escherichia coli O157:H7 colonizes cattle intestines by using the locus of enterocyte effacement (LEE)-encoded proteins. The induction of systemic immune response against LEE-encoded proteins, therefore, will prove effective in reducing E. coli O157:H7 colonization in cattle. The previous studies have demonstrated that a hha (encodes for a hemolysin expression modulating protein) deletion enhances expression of LEE-encoded proteins and a sepB (encodes an ATPase required for the secretion of LEE-encoded proteins) deletion results in intracellular accumulation of LEE proteins. In this study, we demonstrate the efficacy of the hha and hha sepB deletion mutants as bacterins for reducing fecal shedding of E. coli O157:H7 in experimentally inoculated weaned calves. The weaned calves were injected intramuscularly with the bacterins containing 10(9) heat-killed cells of the hha(+) wild-type or hha or hha sepB isogenic mutants, and boosted with the same doses 2- and 4-weeks later. The evaluation of the immune response two weeks after the last booster immunization revealed that the calves vaccinated with the hha mutant bacterin had higher antibody titers against LEE proteins compared to the titers for these antibodies in the calves vaccinated with the hha sepB mutant or hha(+) wild-type bacterins. Following oral inoculations with 10(10) CFU of the wild-type E. coli O157:H7, the greater numbers of calves in the group vaccinated with the hha or hha sepB mutant bacterins stopped shedding the inoculum strain within a few days after the inoculations compared to the group of calves vaccinated with the hha(+) wild-type bacterin or PBS sham vaccine. Thus, the use of bacterins prepared from the hha and hha sepB mutants for reducing colonization of E. coli O157:H7 in cattle could represent a potentially important pre-harvest strategy to enhance post-harvest safety of bovine food products, water and produce. Copyright © 2011 Elsevier Ltd. All rights reserved.

Correlating levels of type III secretion and secreted proteins with fecal shedding of Escherichia coli O157:H7 in cattle.

PubMed

Sharma, V K; Sacco, R E; Kunkle, R A; Bearson, S M D; Palmquist, D E

2012-04-01

The locus of enterocyte effacement (LEE) of Escherichia coli O157:H7 (O157) encodes a type III secretion system (T3SS) for secreting LEE-encoded and non-LEE-encoded virulence proteins that promote the adherence of O157 to intestinal epithelial cells and the persistence of this food-borne human pathogen in bovine intestines. In this study, we compared hha sepB and hha mutants of O157 for LEE transcription, T3SS activity, adherence to HEp-2 cells, persistence in bovine intestines, and the ability to induce changes in the expression of proinflammatory cytokines. LEE transcription was upregulated in the hha sepB and hha mutant strains compared to that in the wild-type strain, but the secretion of virulence proteins in the hha sepB mutant was severely compromised. This reduced secretion resulted in reduced adherence of the hha sepB mutant to Hep-2 cells, correlating with a significantly shorter duration and lower magnitude of fecal shedding in feces of weaned (n = 4 per group) calves inoculated with this mutant strain. The levels of LEE transcription, T3SS activity, and adherence to HEp-2 cells were much lower in the wild-type strain than in the hha mutant, but no significant differences were observed in the duration or the magnitude of fecal shedding in calves inoculated with these strains. Examination of the rectoanal junction (RAJ) tissues from three groups of calves showed no adherent O157 bacteria and similar proinflammatory cytokine gene expression, irrespective of the inoculated strain, with the exception that interleukin-1β was upregulated in calves inoculated with the hha sepB mutant. These results indicate that the T3SS is essential for intestinal colonization and prolonged shedding, but increased secretion of virulence proteins did not enhance the duration and magnitude of fecal shedding of O157 in cattle or have any significant impact on the cytokine gene expression in RAJ tissue compared with that in small intestinal tissue from the same calves.

Pathogenicity Island O-122 in enteropathogenic Escherichia coli strains is associated with diarrhea severity in children from Lima Peru.

PubMed

Mercado, Erik H; Piscoche, Cristian; Contreras, Carmen; Durand, David; Riveros, Maribel; Ruiz, Joaquim; Ochoa, Theresa J

2016-06-01

EPEC is an attaching and effacing diarrheal pathogen that carries a large pathogenicity island, locus for enterocyte effacement (LEE). Recently, the pathogenicity island PAI O-122 was described among non-LEE effectors and found to be associated with diarrhea among atypical EPEC strains. It is unknown if incomplete PAI O-122 could be associated with diarrhea duration and severity. To identify these virulence determinants we analyzed 379 EPEC strains isolated from Peruvian children. EPEC was diagnosed by PCR(eae+, stx-) and classified as typical(t-EPEC) or atypical(a-EPEC). To characterize PAI O-122 we amplified three modules by PCR: Module 1(pagC), Module 2(senA, nleB and nleE) and Module 3(lifA/efa-1). To characterize the large ORF lifA/efa-1 we amplified the regions known as efa-N, efa-M and efa-C. Clinical information was obtained from the cohort study. A total of 379 EPEC strains were able to analyze PAI O-122 genes, 128 (10.4%) EPEC strains were isolated from 1235 diarrhea episodes and 251(9.2%) from 2734 healthy controls. t-EPEC strains were isolated from 14.8% (19/128) of children with diarrhea and 25/251(10.0%) from healthy controls. The most frequent PAI O-122 genes were nleE(37.7%), senA(34.6%) and nleB(37.5%), with similar prevalence among diarrhea and control samples. However, lifA/efa-1 was more common among diarrhea cases than healthy control cases (30.5% vs. 21.1%, p<0.05). The presence of complete PAI O-122 was associated with diarrhea episodes of higher severity among single pathogen infection (33.3% vs. 1.8%, p<0.05) mainly due to the presence of a complete lifA/efa-1 gene. In summary, the gene lifA/efa-1 is significantly associated with diarrheal episodes of higher severity, suggesting to be an important virulent factor. Copyright © 2016 Elsevier GmbH. All rights reserved.

Curli modulates adherence of Escherichia coli O157 to bovine recto-anal junction squamous epithelial cells

USDA-ARS?s Scientific Manuscript database

Our recent studies have shown that Intimin and the Locus of Enterocyte Effacement-encoded proteins do not play a role in Escherichia coli O157 (O157) adherence to the bovine recto-anal junction squamous epithelial cells (RSE) cells. Hence, to define factors that play a contributory role, we investi...

Curli temper adherence of Escherichia coli O157:H7 to squamous epithelial cells from the bovine recto-anal junction in a strain-dependent manner

USDA-ARS?s Scientific Manuscript database

Our recent studies have shown that Intimin and the Locus of Enterocyte Effacement-encoded proteins do not play a role in Escherichia coli O157 (O157) adherence to the bovine recto-anal junction squamous epithelial cells (RSE) cells. Hence, to define factors that play a contributory role, we investi...

RNA-Seq analysis of isolate- and growth phase-specific differences in the global transcriptomes of enteropathogenic Escherichia coli prototype isolates

PubMed Central

Hazen, Tracy H.; Daugherty, Sean C.; Shetty, Amol; Mahurkar, Anup A.; White, Owen; Kaper, James B.; Rasko, David A.

2015-01-01

Enteropathogenic Escherichia coli (EPEC) are a leading cause of diarrheal illness among infants in developing countries. E. coli isolates classified as typical EPEC are identified by the presence of the locus of enterocyte effacement (LEE) and the bundle-forming pilus (BFP), and absence of the Shiga-toxin genes, while the atypical EPEC also encode LEE but do not encode BFP or Shiga-toxin. Comparative genomic analyses have demonstrated that EPEC isolates belong to diverse evolutionary lineages and possess lineage- and isolate-specific genomic content. To investigate whether this genomic diversity results in significant differences in global gene expression, we used an RNA sequencing (RNA-Seq) approach to characterize the global transcriptomes of the prototype typical EPEC isolates E2348/69, B171, C581-05, and the prototype atypical EPEC isolate E110019. The global transcriptomes were characterized during laboratory growth in two different media and three different growth phases, as well as during adherence of the EPEC isolates to human cells using in vitro tissue culture assays. Comparison of the global transcriptomes during these conditions was used to identify isolate- and growth phase-specific differences in EPEC gene expression. These analyses resulted in the identification of genes that encode proteins involved in survival and metabolism that were coordinately expressed with virulence factors. These findings demonstrate there are isolate- and growth phase-specific differences in the global transcriptomes of EPEC prototype isolates, and highlight the utility of comparative transcriptomics for identifying additional factors that are directly or indirectly involved in EPEC pathogenesis. PMID:26124752

Vaccination with killed whole-cells of Escherichia coli O157:H7 hha mutant emulsified with an adjuvant induced vaccine strain-specific serum antibodies and reduced E. coli O157:H7 fecal shedding in cattle.

PubMed

Sharma, Vijay K; Schaut, Robert G; Loving, Crystal L

2018-06-01

Escherichia coli O157:H7 (O157) can cause from a mild diarrheal illness to hemorrhagic colitis and hemolytic uremic syndrome in humans. Cattle are the primary reservoir for O157 and fecal shedding of O157 by these animals is a major risk factor in contamination of cattle hides and carcasses at slaughter. Vaccination is an important strategy to reduce fecal shedding of O157 in cattle. In this study, we evaluated the immunogenicity and efficacy of an inactivated vaccine strain of O157 formulated with an adjuvant. This vaccine strain was deleted of the hha gene enabling high level expression of the locus of enterocyte effacement (LEE) encoded proteins required for O157 colonization in cattle. The inactivated vaccine strain emulsified with the adjuvant or suspended in the phosphate-buffered saline (PBS) was injected in the neck muscles of two groups of weaned calves followed by a booster three weeks later with the corresponding formulation. Animals in groups 3 and 4 were injected similarly with the adjuvant and PBS, respectively. All animals were orally inoculated three weeks post-booster vaccination with a live culture of O157. The animals vaccinated with the adjuvanted vaccine showed higher serum antibody titers to the vaccine strain and shed O157 for a shorter duration and at lower numbers compared to the animals vaccinated with the non-adjuvanted vaccine, adjuvant-only, or PBS. Western blotting of the vaccine strain lysates showed higher immunoreactivity of serum IgG in vaccinated animals to several O157-specific proteins and lipopolysaccharides (LPS). The vaccination induced IgG showed specificity to LEE-encoded proteins and outer membrane LPS as LEE and waaL deletion mutants, unable to produce LEE proteins and synthesize high molecular weight LPS, respectively, yielded significantly lower antibody titers compared to the parent vaccine strain. The positive reactivity of the immune serum was also observed for purified LEE-encoded proteins EspA and EspB. In conclusion, the results of this animal study showed that a two-dose regimen of an adjuvanted vaccine is capable of inducing O157-specific immune response that directly or indirectly reduced fecal shedding of O157 in cattle. Published by Elsevier B.V.

Distribution of putative adhesins in different seropathotypes of Shiga toxin-producing Escherichia coli.

PubMed

Toma, Claudia; Martínez Espinosa, Estela; Song, Tianyan; Miliwebsky, Elizabeth; Chinen, Isabel; Iyoda, Sunao; Iwanaga, Masaaki; Rivas, Marta

2004-11-01

The distribution of eight putative adhesins that are not encoded in the locus for enterocyte effacement (LEE) in 139 Shiga toxin-producing Escherichia coli (STEC) of different serotypes was investigated by PCR. Five of the adhesins (Iha, Efa1, LPF(O157/OI-141), LPF(O157/OI-154), and LPF(O113)) are encoded in regions corresponding to genomic O islands of E. coli EDL933, while the other three adhesins have been reported to be encoded in the STEC megaplasmid of various serotypes (ToxB [O157:H7], Saa [O113:H21], and Sfp [O157:NM]). STEC strains were isolated from humans (n = 54), animals (n = 52), and food (n = 33). They were classified into five seropathotypes (A through E) based on the reported occurrence of STEC serotypes in human disease, in outbreaks, and in the hemolytic-uremic syndrome (M. A. Karmali, M. Mascarenhas, S. Shen, K. Ziebell, S. Johnson, R. Reid-Smith, J. Isaac-Renton, C. Clark, K. Rahn, and J. B. Kaper, J. Clin. Microbiol. 41:4930-4940, 2003). The most prevalent adhesin was that encoded by the iha gene (91%; 127 of 139 strains), which was distributed in all seropathotypes. toxB and efa1 were present mainly in strains of seropathotypes A and B, which were LEE positive. saa was present only in strains of seropathotypes C, D, and E, which were LEE negative. Two fimbrial genes, lpfA(O157/OI-141) and lpfA(O157/OI-154), were strongly associated with seropathotype A. The fimbrial gene lpfA(O113) was present in all seropathotypes except for seropathotype A, while sfpA was not present in any of the strains studied. The distribution of STEC adhesins depends mainly on serotypes and not on the source of isolation. Seropathotype A, which is associated with severe disease and frequently is involved in outbreaks, possesses a unique adhesin profile which is not present in the other seropathotypes. The wide distribution of iha in STEC strains suggested that it could be a candidate for vaccine development.

Kefiran protects Caco-2 cells from cytopathic effects induced by Bacillus cereus infection.

PubMed

Medrano, Micaela; Hamet, Maria F; Abraham, Analía G; Pérez, Pablo F

2009-11-01

The aim of this work was to evaluate the ability of kefiran to antagonize cytopathic effects triggered by Bacillus cereus strain B10502 on cultured human enterocytes (Caco-2 cells). Cell damage was evaluated by F-actin labelling, scanning electron microscopy and determination of ratios of necrotic and detached cells. To assess the interaction between kefiran and bacteria or eukaryotic cells, flow cytometric analysis was conducted with FITC-labelled kefiran. Kefiran significantly protected infected cells from cytopathic effects induced by B. cereus such as cell necrosis, F-actin disorganisation and microvilli effacement, although presence of kefiran did not modify the adhesion of microorganisms to cultured human enterocytes. Results could be ascribed to the ability of kefiran to interact with both bacteria and eukaryotic cells thus antagonizing interactions necessary for maximal biological effects. Our findings encourage further research on the use of bacterial exopolysaccharides to antagonize virulence factors associated to direct bacteria-cell interactions.

Surface Structures Involved in Plant Stomata and Leaf Colonization by Shiga-Toxigenic Escherichia Coli O157:H7

PubMed Central

Saldaña, Zeus; Sánchez, Ethel; Xicohtencatl-Cortes, Juan; Puente, Jose Luis; Girón, Jorge A.

2011-01-01

Shiga-toxigenic Escherichia coli (STEC) O157:H7 uses a myriad of surface adhesive appendages including pili, flagella, and the type 3 secretion system (T3SS) to adhere to and inflict damage to the human gut mucosa. Consumption of contaminated ground beef, milk, juices, water, or leafy greens has been associated with outbreaks of diarrheal disease in humans due to STEC. The aim of this study was to investigate which of the known STEC O157:H7 adherence factors mediate colonization of baby spinach leaves and where the bacteria reside within tainted leaves. We found that STEC O157:H7 colonizes baby spinach leaves through the coordinated production of curli, the E. coli common pilus, hemorrhagic coli type 4 pilus, flagella, and T3SS. Electron microscopy analysis of tainted leaves revealed STEC bacteria in the internal cavity of the stomata, in intercellular spaces, and within vascular tissue (xylem and phloem), where the bacteria were protected from the bactericidal effect of gentamicin, sodium hypochlorite or ozonated water treatments. We confirmed that the T3S escN mutant showed a reduced number of bacteria within the stomata suggesting that T3S is required for the successful colonization of leaves. In agreement, non-pathogenic E. coli K-12 strain DH5α transformed with a plasmid carrying the locus of enterocyte effacement (LEE) pathogenicity island, harboring the T3SS and effector genes, internalized into stomata more efficiently than without the LEE. This study highlights a role for pili, flagella, and T3SS in the interaction of STEC with spinach leaves. Colonization of plant stomata and internal tissues may constitute a strategy by which STEC survives in a nutrient-rich microenvironment protected from external foes and may be a potential source for human infection. PMID:21887151

LEE-encoded regulator (Ler) mutants elicit serotype-specific protection, but not cross protection, against attaching and effacing E. coli strains.

PubMed

Zhu, C; Feng, S; Yang, Z; Davis, K; Rios, H; Kaper, J B; Boedeker, E C

2007-02-26

We previously showed that single dose orogastric immunization with an attenuated regulatory Lee-encoded regulator (ler) mutant of the rabbit enteropathogenic Escherichia coli (REPEC) strain E22 (O103:H2) protected rabbits from fatal infection with the highly virulent parent strain. In the current study we assessed the degree of homologous (serotype-specific) and heterologous (cross-serotype) protection induced by immunization with REPEC ler mutant strains of differing serotypes, or with a prototype strain RDEC-1 (O15:H-) which expresses a full array of ler up-regulated proteins. We constructed an additional ler mutant using RDEC-1 thus, permitting immunization with a ler mutant of either serotype, O15 or O103, followed by challenge with a virulent REPEC strain of the same or different serotypes. Consistent with our previous data, the current study demonstrated that rabbits immunized with a RDEC-1 ler mutant were protected from challenge with virulent RDEC-H19A (RDEC-1 transduced with Shiga toxin-producing phage H19A) of the same serotype. Rabbits immunized with RDEC-1 or E22 derivative ler mutants demonstrated significant increase in serum antibody titers to the respective whole bacterial cells expressing O antigen but not to the LEE-encoded proteins. However, immunization with the ler mutants of either E22 or RDEC-1 failed to protect rabbits from infections with virulent organisms belonging to different serotypes. In contrast, rabbits immunized with the prototype RDEC-1 were cross protected against challenge with the heterologous E22 strain as shown by normal weight gain, and the absence of clinical signs of disease or characteristic attaching and effacing (A/E) lesions. Immunization with RDEC-1 induced significantly elevated serum IgG titers to LEE-encoded proteins. We thus, demonstrated homologous protection induced by the REPEC ler mutants and heterologous protection by RDEC-1. The observed correlation between elevated immune responses to the LEE-encoded proteins and the protection against challenge with heterologous virulent REPEC strain suggests that serotype-non-specific cross protection requires the expression of, and induction of antibody to, LEE-encoded virulence factors.

Evaluation of the effects of sdiA, a luxR homologue, on adherence and motility of Escherichia coli O157 : H7.

PubMed

Sharma, Vijay K; Bearson, Shawn M D; Bearson, Bradley L

2010-05-01

Quorum-sensing (QS) signalling pathways are important regulatory networks for controlling the expression of genes promoting adherence of enterohaemorrhagic Escherichia coli (EHEC) O157 : H7 to epithelial cells. A recent study has shown that EHEC O157 : H7 encodes a luxR homologue, called sdiA, which upon overexpression reduces the expression of genes encoding flagellar and locus of enterocyte effacement (LEE) proteins, thus negatively impacting on the motility and intimate adherence phenotypes, respectively. Here, we show that the deletion of sdiA from EHEC O157 : H7 strain 86-24, and from a hha (a negative regulator of ler) mutant of this strain, enhanced bacterial adherence to HEp-2 epithelial cells of the sdiA mutant strains relative to the strains containing a wild-type copy of sdiA. Quantitative reverse transcription PCR showed that the expression of LEE-encoded genes ler, espA and eae in strains with the sdiA deletions was not significantly different from that of the strains wild-type for sdiA. Similarly, no additional increases in the expression of LEE genes were observed in a sdiA hha double mutant strain relative to that observed in the hha deletion mutant. While the expression of fliC, which encodes flagellin, was enhanced in the sdiA mutant strain, the expression of fliC was reduced by several fold in the hha mutant strain, irrespective of the presence or absence of sdiA, indicating that the genes sdiA and hha exert opposing effects on the expression of fliC. The strains with deletions in sdiA or hha showed enhanced expression of csgA, encoding curlin of the curli fimbriae, with the expression of csgA highest in the sdiA hha double mutant, suggesting an additive effect of these two gene deletions on the expression of csgA. No significant differences were observed in the expression of the genes lpfA and fimA of the operons encoding long polar and type 1 fimbriae in the sdiA mutant strain. These data indicate that SdiA has no significant effect on the expression of LEE genes, but that it appears to act as a strong repressor of genes encoding flagella and curli fimbriae, and the alleviation of the SdiA-mediated repression of these genes in an EHEC O157 : H7 sdiA mutant strain contributes to enhanced bacterial motility and increased adherence to HEp-2 epithelial cells.

Emerging types of Shiga toxin-producing E. coli (STEC) O178 present in cattle, deer, and humans from Argentina and Germany

PubMed Central

Miko, Angelika; Rivas, Marta; Bentancor, Adriana; Delannoy, Sabine; Fach, Patrick; Beutin, Lothar

2014-01-01

More than 400 serotypes of Shiga toxin-producing Escherichia coli (STEC) have been implicated in outbreaks and sporadic human diseases. In recent years STEC strains belonging to serogroup O178 have been commonly isolated from cattle and food of bovine origin in South America and Europe. In order to explore the significance of these STEC strains as potential human pathogens, 74 German and Argentinean E. coli O178 strains from animals, food and humans were characterized phenotypically and investigated for their serotypes, stx-genotypes and 43 virulence-associated markers by a real-time PCR-microarray. The majority (n = 66) of the O178 strains belonged to serotype O178:H19. The remaining strains divided into O178:H7 (n = 6), O178:H10 (n = 1), and O178:H16 (n = 1). STEC O178:H19 strains were mainly isolated from cattle and food of bovine origin, but one strain was from a patient with hemolytic uremic syndrome (HUS). Genotyping of the STEC O178:H19 strains by pulsed-field gel electrophoresis revealed two major clusters of genetically highly related strains which differ in their stx-genotypes and non-Stx putative virulence traits, including adhesins, toxins, and serine-proteases. Cluster A-strains including the HUS-strain (n = 35) carried genes associated with severe disease in humans (stx2a, stx2d, ehxA, saa, subAB1, lpfAO113, terE combined with stx1a, espP, iha). Cluster B-strains (n = 26) showed a limited repertoire of virulence genes (stx2c, pagC, lpfAO113, espP, iha). Among O178:H7 strains isolated from deer meat and patients with uncomplicated disease a new STEC variant was detected that is associated with the genotype stx1c/stx2b/ehxA/subAB2/espI/[terE]/espP/iha. None of the STEC O178 strains was positive for locus of enterocyte effacement (LEE)- and nle-genes. Results indicate that STEC O178:H19 strains belong to the growing group of LEE-negative STEC that should be considered with respect to their potential to cause diseases in humans. PMID:24987616

Role of Tir and Intimin in the Virulence of Rabbit Enteropathogenic Escherichia coli Serotype O103:H2

PubMed Central

Marchès, Olivier; Nougayrède, Jean-Philippe; Boullier, Séverine; Mainil, Jacques; Charlier, Gérard; Raymond, Isabelle; Pohl, Pierre; Boury, Michèle; De Rycke, Jean; Milon, Alain; Oswald, Eric

2000-01-01

Attaching and effacing (A/E) rabbit enteropathogenic Escherichia coli (REPEC) strains belonging to serogroup O103 are an important cause of diarrhea in weaned rabbits. Like human EPEC strains, they possess the locus of enterocyte effacement clustering the genes involved in the formation of the A/E lesions. In addition, pathogenic REPEC O103 strains produce an Esp-dependent but Eae (intimin)-independent alteration of the host cell cytoskeleton characterized by the formation of focal adhesion complexes and the reorganization of the actin cytoskeleton into bundles of stress fibers. To investigate the role of intimin and its translocated coreceptor (Tir) in the pathogenicity of REPEC, we have used a newly constructed isogenic tir null mutant together with a previously described eae null mutant. When human HeLa epithelial cells were infected, the tir mutant was still able to induce the formation of stress fibers as previously reported for the eae null mutant. When the rabbit epithelial cell line RK13 was used, REPEC O103 produced a classical fluorescent actin staining (FAS) effect, whereas both the eae and tir mutants were FAS negative. In a rabbit ligated ileal loop model, neither mutant was able to induce A/E lesions. In contrast to the parental strain, which intimately adhered to the enterocytes and destroyed the brush border microvilli, bacteria of both mutants were clustered in the mucus without reaching and damaging the microvilli. The role of intimin and Tir was then analyzed in vivo by oral inoculation of weaned rabbits. Although both mutants were still present in the intestinal flora of the rabbits 3 weeks after oral inoculation, neither mutant strain induced any clinical signs or significant weight loss in the inoculated rabbits whereas the parental strain caused the death of 90% of the inoculated rabbits. Nevertheless, an inflammatory infiltrate was present in the lamina propria of the rabbits infected with both mutants, with an inflammatory response greater for the eae null mutant. In conclusion, we have confirmed the role of intimin in virulence, and we have shown, for the first time, that Tir is also a key factor in vivo for pathogenicity. PMID:10722617

Role of tir and intimin in the virulence of rabbit enteropathogenic Escherichia coli serotype O103:H2.

PubMed

Marchès, O; Nougayrède, J P; Boullier, S; Mainil, J; Charlier, G; Raymond, I; Pohl, P; Boury, M; De Rycke, J; Milon, A; Oswald, E

2000-04-01

Attaching and effacing (A/E) rabbit enteropathogenic Escherichia coli (REPEC) strains belonging to serogroup O103 are an important cause of diarrhea in weaned rabbits. Like human EPEC strains, they possess the locus of enterocyte effacement clustering the genes involved in the formation of the A/E lesions. In addition, pathogenic REPEC O103 strains produce an Esp-dependent but Eae (intimin)-independent alteration of the host cell cytoskeleton characterized by the formation of focal adhesion complexes and the reorganization of the actin cytoskeleton into bundles of stress fibers. To investigate the role of intimin and its translocated coreceptor (Tir) in the pathogenicity of REPEC, we have used a newly constructed isogenic tir null mutant together with a previously described eae null mutant. When human HeLa epithelial cells were infected, the tir mutant was still able to induce the formation of stress fibers as previously reported for the eae null mutant. When the rabbit epithelial cell line RK13 was used, REPEC O103 produced a classical fluorescent actin staining (FAS) effect, whereas both the eae and tir mutants were FAS negative. In a rabbit ligated ileal loop model, neither mutant was able to induce A/E lesions. In contrast to the parental strain, which intimately adhered to the enterocytes and destroyed the brush border microvilli, bacteria of both mutants were clustered in the mucus without reaching and damaging the microvilli. The role of intimin and Tir was then analyzed in vivo by oral inoculation of weaned rabbits. Although both mutants were still present in the intestinal flora of the rabbits 3 weeks after oral inoculation, neither mutant strain induced any clinical signs or significant weight loss in the inoculated rabbits whereas the parental strain caused the death of 90% of the inoculated rabbits. Nevertheless, an inflammatory infiltrate was present in the lamina propria of the rabbits infected with both mutants, with an inflammatory response greater for the eae null mutant. In conclusion, we have confirmed the role of intimin in virulence, and we have shown, for the first time, that Tir is also a key factor in vivo for pathogenicity.

Association of Cell-adhesion Activities with Virulence in Shiga toxin-producing Escherichia coli O103：H2.

PubMed

Kobayashi, Naoki; Maeda, Eriko; Saito, Shioko; Furukawa, Ichiro; Ohnishi, Takahiro; Watanabe, Maiko; Terajima, Jun; Hara-Kudo, Yukiko

2016-01-01

The characteristics of 11 strains of Stx1-producing and Stx2-non-producing STEC O103：H2 were analyzed to investigate the differences in virulence in a single serotype of Shiga toxin (Stx) -producing Escherichia coli (STEC). Differences in the cell-adhesion activity to Caco-2 cells were observed among the strains. The activity of the one strain, isolated from a patient with hemolytic uremic syndrome was 4-20-fold higher than those of the other strains. Although the strains with high cell-adhesion activity showed high expressions of eae, espB, espD, and tir in the locus of enterocyte effacement related with cell-adhesion, those were not specific for this strain. In addition, the Stx1 production level of the strain was not particularly high. It was indicated that the high adhesion activity might be a potential factor to associate serious symptom.

Effect of Zinc in Enteropathogenic Escherichia coli Infection▿ †

PubMed Central

Crane, John K.; Naeher, Tonniele M.; Shulgina, Irina; Zhu, Chengru; Boedeker, Edgar C.

2007-01-01

Enteropathogenic Escherichia coli (EPEC) infection triggers the release of ATP from host intestinal cells, and the ATP is broken down to ADP, AMP, and adenosine in the lumen of the intestine. Ecto-5′-nucleotidase (CD73) is the main enzyme responsible for the conversion of 5′-AMP to adenosine, which triggers fluid secretion from host intestinal cells and also has growth-promoting effects on EPEC bacteria. In a recent study, we examined the role of the host enzyme CD73 in EPEC infection by testing the effect of ecto-5′-nucleotidase inhibitors. Zinc was a less potent inhibitor of ecto-5′-nucleotidase in vitro than the nucleotide analog α,β-methylene-ADP, but in vivo, zinc was much more efficacious in preventing EPEC-induced fluid secretion in rabbit ileal loops than α,β-methylene-ADP. This discrepancy between the in vitro and in vivo potencies of the two inhibitors prompted us to search for potential targets of zinc other than ecto-5′-nucleotidase. Zinc, at concentrations that produced little or no inhibition of EPEC growth, caused a decrease in the expression of EPEC protein virulence factors, such as bundle-forming pilus (BFP), EPEC secreted protein A, and other EPEC secreted proteins, and reduced EPEC adherence to cells in tissue culture. The effects of zinc were not mimicked by other transition metals, such as manganese, iron, copper, or nickel, and the effects were not reversed by an excess of iron. Quantitative real-time PCR showed that zinc reduced the abundance of the RNAs encoded by the bfp gene, by the plasmid-encoded regulator (per) gene, by the locus for the enterocyte effacement (LEE)-encoded regulator (ler) gene, and by several of the esp genes. In vivo, zinc reduced EPEC-induced fluid secretion into ligated rabbit ileal loops, decreased the adherence of EPEC to rabbit ileum, and reduced histopathological damage such as villus blunting. Some of the beneficial effects of zinc on EPEC infection appear to be due to the action of the metal on EPEC bacteria as well as on the host. PMID:17875638

Genetic diversity and virulence potential of shiga toxin-producing Escherichia coli O113:H21 strains isolated from clinical, environmental, and food sources.

PubMed

Feng, Peter C H; Delannoy, Sabine; Lacher, David W; Dos Santos, Luis Fernando; Beutin, Lothar; Fach, Patrick; Rivas, Marta; Hartland, Elizabeth L; Paton, Adrienne W; Guth, Beatriz E C

2014-08-01

Shiga toxin-producing Escherichia coli strains of serotype O113:H21 have caused severe human diseases, but they are unusual in that they do not produce adherence factors coded by the locus of enterocyte effacement. Here, a PCR microarray was used to characterize 65 O113:H21 strains isolated from the environment, food, and clinical infections from various countries. In comparison to the pathogenic strains that were implicated in hemolytic-uremic syndrome in Australia, there were no clear differences between the pathogens and the environmental strains with respect to the 41 genetic markers tested. Furthermore, all of the strains carried only Shiga toxin subtypes associated with human infections, suggesting that the environmental strains have the potential to cause disease. Most of the O113:H21 strains were closely related and belonged in the same clonal group (ST-223), but CRISPR analysis showed a great degree of genetic diversity among the O113:H21 strains. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Serotypes, virulence markers and cell invasion ability of Shiga toxin-producing Escherichia coli strains isolated from healthy dairy cattle.

PubMed

Gonzalez, A G M; Cerqueira, A M F; Guth, B E C; Coutinho, C A; Liberal, M H T; Souza, R M; Andrade, J R C

2016-10-01

The occurrence of virulence markers, serotypes and invasive ability were investigated in Shiga toxin-producing Escherichia coli (STEC) isolated from faecal samples of healthy dairy cattle at Rio de Janeiro State, Brazil. From 1562 stx-positive faecal samples, 105 STEC strains were isolated by immuno-magnetic separation (IMS) or plating onto MacConkey agar (MC) followed by colony hybridisation. Fifty (47·6%) strains belonged to nine serotypes (O8:H19, O22:H8, O22:H16, O74:H42, O113:H21, O141:H21, O157:H7, O171:H2 and ONT:H21). The prevalent serotypes were O157:H7 (12·4%), O113:H21 (6·7%) and O8:H19 (5·7%). Virulence genes were identified by polymerase chain reaction (PCR). E-hlyA (77·1%) was the more prevalent virulence marker, followed by espP (64·8%), saa (39%), eae (24·8%) and astA (21·9%). All O157:H7 strains carried the γ (gamma) variant of the locus of enterocyte effacement (LEE) genes and the stx2c gene, while the stx1/stx2 genotype prevailed among the eae-negative strains. None of the eae-positive STEC produced the localized adherence (LA) phenotype in HEp-2 or Caco-2 cells. However, intimate attachment (judged by the fluorescent actin staining test) was detected in some eae-positive strains, both in HEp-2 (23·1%) and in Caco-2 cells (11·5%). Most strains (87·5%) showed 'peripheral association' (PA) adherence phenotype to undifferentiated Caco-2 cells. Twenty-five (92·6%) of 27 strains invaded Caco-2 cells. The highest average value of invasion (9·6%) was observed among the eae-negative bovine strains from serotypes described in human disease. Healthy dairy cattle is a reservoir of STEC carrying virulence genes and properties associated with human disease. Although reports of human disease associated with STEC are scarce in Brazil, the colonization of the animal reservoir by potentially pathogenic strains offers a significant risk to our population. © 2016 The Society for Applied Microbiology.

Molecular Profiling of Shiga Toxin-Producing Escherichia coli and Enteropathogenic E. coli Strains Isolated from French Coastal Environments.

PubMed

Balière, C; Rincé, A; Delannoy, S; Fach, P; Gourmelon, M

2016-07-01

Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) strains may be responsible for food-borne infections in humans. Twenty-eight STEC and 75 EPEC strains previously isolated from French shellfish-harvesting areas and their watersheds and belonging to 68 distinguishable serotypes were characterized in this study. High-throughput real-time PCR was used to search for the presence of 75 E. coli virulence-associated gene targets, and genes encoding Shiga toxin (stx) and intimin (eae) were subtyped using PCR tests and DNA sequencing, respectively. The results showed a high level of diversity between strains, with 17 unique virulence gene profiles for STEC and 56 for EPEC. Seven STEC and 15 EPEC strains were found to display a large number or a particular combination of genetic markers of virulence and the presence of stx and/or eae variants, suggesting their potential pathogenicity for humans. Among these, an O26:H11 stx1a eae-β1 strain was associated with a large number of virulence-associated genes (n = 47), including genes carried on the locus of enterocyte effacement (LEE) or other pathogenicity islands, such as OI-122, OI-71, OI-43/48, OI-50, OI-57, and the high-pathogenicity island (HPI). One O91:H21 STEC strain containing 4 stx variants (stx1a, stx2a, stx2c, and stx2d) was found to possess genes associated with pathogenicity islands OI-122, OI-43/48, and OI-15. Among EPEC strains harboring a large number of virulence genes (n, 34 to 50), eight belonged to serotype O26:H11, O103:H2, O103:H25, O145:H28, O157:H7, or O153:H2. The species E. coli includes a wide variety of strains, some of which may be responsible for severe infections. This study, a molecular risk assessment study of E. coli strains isolated from the coastal environment, was conducted to evaluate the potential risk for shellfish consumers. This report describes the characterization of virulence gene profiles and stx/eae polymorphisms of E. coli isolates and clearly highlights the finding that the majority of strains isolated from coastal environment are potentially weakly pathogenic, while some are likely to be more pathogenic. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Different Cellular Origins and Functions of Extracellular Proteins from Escherichia coli O157:H7 and O104:H4 as Determined by Comparative Proteomic Analysis

PubMed Central

Islam, Nazrul; Nagy, Attila; Garrett, Wesley M.; Shelton, Dan

2016-01-01

ABSTRACT Extracellular proteins play important roles in bacterial interactions with the environmental matrices. In this study, we examined the extracellular proteins from Escherichia coli O157:H7 and O104:H4 by tandem mass spectrometry. We identified 500 and 859 proteins from the growth media of E. coli O157:H7 and O104:H4, respectively, including 371 proteins common to both strains. Among proteins that were considered specific to E. coli O157:H7 or present at higher relative abundances in O157:H7 medium, most (57 of 65) had secretion signal sequences in their encoding genes. Noticeably, the proteins included locus of enterocyte effacement (LEE) virulence factors, proteins required for peptidyl-lipoprotein accumulation, and proteins involved in iron scavenging. In contrast, a much smaller proportion of proteins (37 of 150) that were considered specific to O104:H4 or presented at higher relative abundances in O104:H4 medium had signals targeting them for secretion. These proteins included Shiga toxin 2 subunit B and O104:H4 signature proteins, including AAF/1 major fimbrial subunit and serine protease autotransporters. Most of the abundant proteins from the growth medium of E. coli O104:H4 were annotated as having functions in the cytoplasm. We provide evidence that the extensive presence of cytoplasmic proteins in E. coli O104:H4 growth medium was due to biological processes independent of cell lysis, indicating alternative mechanisms for this potent pathogen releasing cytoplasmic contents into the growth milieu, which could play a role in interaction with the environmental matrices, such as pathogenesis and biofilm formation. IMPORTANCE In this study, we compared the extracellular proteins from two of the most prominent foodborne pathogenic E. coli organisms that have caused severe outbreaks in the United States and in Europe. E. coli O157:H7 is a well-studied Shiga toxigenic foodborne pathogen of the enterohemorrhagic pathotype that has caused numerous outbreaks associated with various contaminated foods worldwide. E. coli O104:H4 is a newly emerged Shiga toxigenic foodborne pathogen of the enteroaggregative pathotype that gained notoriety for causing one of the most deadly foodborne outbreaks in Europe in 2011. Comparison of proteins in the growth medium revealed significant differences in the compositions of the extracellular proteins for these two pathogens. These differences may provide valuable information regarding the cellular responses of these pathogens to their environment, including cell survival and pathogenesis. PMID:27208096

Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of-Hospital Cardiac Arrest.

PubMed

Starling, Rebecca M; Shekdar, Karuna; Licht, Dan; Nadkarni, Vinay M; Berg, Robert A; Topjian, Alexis A

2015-07-01

Head CT after out-of-hospital cardiac arrest is often obtained to evaluate intracranial pathology. Among children admitted to the PICU following pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white matter differentiation and basilar cistern and sulcal effacement are associated with mortality and unfavorable neurologic outcome. Retrospective, cohort study. Single, tertiary-care center PICU. Seventy-eight patients less than 18 years old who survived out-of-hospital cardiac arrest to PICU admission and had a head CT within 24 hours of return of spontaneous circulation were evaluated from July 2005 through May 2012. None. Median time to head CT from return of spontaneous circulation was 3.3 hours (1.0, 6.0). Median patient age was 2.3 years (0.4, 9.5). Thirty-nine patients (50%) survived, of whom 29 (74%) had favorable neurologic outcome. Nonsurvivors were more likely than survivors to have 1) loss of gray-white matter differentiation (Hounsfield unit ratios, 0.96 [0.88, 1.07] vs 1.1 [1.07, 1.2]; p < 0.001), 2) basilar cistern effacement (93% vs 7%; p = 0.001; positive predictive value, 94%; negative predictive value, 59%), and 3) sulcal effacement (100% vs 0%; p ≤ 0.001; positive predictive value, 100%; negative predictive value, 68%). All patients with poor gray-white matter differentiation or sulcal effacement had unfavorable neurologic outcomes. Only one patient with basilar cistern effacement had favorable outcome. Loss of gray-white matter differentiation and basilar cistern effacement and sulcal effacement are associated with poor outcome after pediatric out-of-hospital cardiac arrest. Select patients may have favorable outcomes despite these findings.

Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of-Hospital Cardiac Arrest

PubMed Central

Starling, Rebecca M.; Shekdar, Karuna; Licht, Dan; Nadkarni, Vinay M.; Berg, Robert A.; Topjian, Alexis A.

2015-01-01

Objectives Head CT after out-of-hospital cardiac arrest is often obtained to evaluate intracranial pathology. Among children admitted to the PICU following pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white matter differentiation and basilar cistern and sulcal effacement are associated with mortality and unfavorable neurologic outcome. Design Retrospective, cohort study. Setting Single, tertiary-care center PICU. Patients Seventy-eight patients less than 18 years old who survived out-of-hospital cardiac arrest to PICU admission and had a head CT within 24 hours of return of spontaneous circulation were evaluated from July 2005 through May 2012. Interventions None. Measurements and Main Results Median time to head CT from return of spontaneous circulation was 3.3 hours (1.0, 6.0). Median patient age was 2.3 years (0.4, 9.5). Thirty-nine patients (50%) survived, of whom 29 (74%) had favorable neurologic outcome. Nonsurvivors were more likely than survivors to have 1) loss of gray-white matter differentiation (Hounsfield unit ratios, 0.96 [0.88, 1.07] vs 1.1 [1.07, 1.2]; p < 0.001), 2) basilar cistern effacement (93% vs 7%; p = 0.001; positive predictive value, 94%; negative predictive value, 59%), and 3) sulcal effacement (100% vs 0%; p ≤ 0.001; positive predictive value, 100%; negative predictive value, 68%). All patients with poor gray-white matter differentiation or sulcal effacement had unfavorable neurologic outcomes. Only one patient with basilar cistern effacement had favorable outcome. Conclusions Loss of gray-white matter differentiation and basilar cistern effacement and sulcal effacement are associated with poor outcome after pediatric out-of-hospital cardiac arrest. Select patients may have favorable outcomes despite these findings. PMID:25844694

Lectin histochemistry of enterocytes sugar residues in the gut of the chick embryo and of the newborn.

PubMed

Bryk, S Gheri; Gheri, G

2002-01-01

The glycoconjugates sugar residues content, distribution and changes in the enterocytes of different tracts of the developing intestine of the chick embryo and of 1-day-old chick were investigated, using a battery of seven HRP-conjugated lectins (DBA, SBA, PNA, WGA, ConA, LTA and UEAI). The results of the present research have shown the presence of a large amount of glycoconjugates sugar residues in the enterocytes of duodenal, ileal and colonic anlage, starting from the beginning of the second week of incubation. Differences were detected among the three investigated intestinal segments, as to the time of appearance of the glycoconjugates sugar residues in the enterocytes. The duodenal enterocytes showed the most precocious appearance of lectin-reactive material, followed by the ileal enterocytes and afterwards by colonic enterocytes. The duodenal enterocytes were characterised by the presence of SBA binding sites, which were not detectable in the duodenal enterocytes of the adult animal.

Vaginal Examination Simulation Using Citrus Fruit to Simulate Cervical Dilation and Effacement

PubMed Central

Shea, Kathleen L

2015-01-01

This technical report describes the creation and use of a cervical dilation and effacement model in a pre-licensure nursing course in reproductive health. Vaginal examination is typically taught in reproductive health courses; however, nursing students do not always have sufficient opportunity to practice on actual patients. This low-cost task-training model provides undergraduate nursing students the opportunity to experience performing a vaginal examination to assess for cervical dilation and effacement during the labor process. PMID:26457235

Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury.

PubMed

Nourallah, Basil; Menon, David K; Zeiler, Frederick A

2018-04-04

This study aims to determine the relationship between pupillary reactivity, midline shift and basal cistern effacement on brain computed tomography (CT) in moderate-to-severe traumatic brain injury (TBI). All are important diagnostic and prognostic measures, but their relationship is unclear. A total of 204 patients with moderate-to-severe TBI, documented pupillary reactivity, and archived neuroimaging were included. Extent of midline shift and basal cistern effacement were extracted from admission brain CT. Mean midline shift was calculated for each ordinal category of pupillary reactivity and basal cistern effacement. Sequential Chi-square analysis was used to calculate a threshold midline shift for pupillary abnormalities and basal cistern effacement. Univariable and multiple logistic regression analyses were performed. Pupils were bilaterally reactive in 163 patients, unilaterally reactive in 24, and bilaterally unreactive in 17, with mean midline shift (mm) of 1.96, 3.75, and 2.56, respectively (p = 0.14). Basal cisterns were normal in 118 patients, compressed in 45, and absent in 41, with mean midline shift (mm) of 0.64, 2.97, and 5.93, respectively (p < 0.001). Sequential Chi-square analysis identified a threshold for abnormal pupils at a midline shift of 7-7.25 mm (p = 0.032), compressed basal cisterns at 2 mm (p < 0.001), and completely effaced basal cisterns at 7.5 mm (p < 0.001). Logistic regression revealed no association between midline shift and pupillary reactivity. With effaced basal cisterns, the odds ratio for normal pupils was 0.22 (95% CI 0.08-0.56; p = 0.0016) and for at least one unreactive pupil was 0.061 (95% CI 0.012-0.24; p < 0.001). Basal cistern effacement strongly predicted midline shift (OR 1.27; 95% CI 1.17-1.40; p < 0.001). Basal cistern effacement alone is associated with pupillary reactivity and is closely associated with midline shift. It may represent a uniquely useful neuroimaging marker to guide intervention in traumatic brain injury.

Edwardsiella piscicida-like pathogen in cultured grouper.

PubMed

Ucko, Michal; Colorni, Angelo; Dubytska, Lidiya; Thune, Ronald L

2016-09-26

An Edwardsiella sp. was isolated from the kidney of diseased groupers (Epinephelus aeneus and E. marginatus) cultured in Eilat (Israel, Red Sea). Affected fish presented a severe suppurative nephritis with large abscesses occasionally spreading into the surrounding musculature. Biochemical profiles and phenotypic comparisons failed to provide a clear identification to the species level, and genetic analysis of the 16S subunit failed to discriminate between Edwardsiella piscicida, E. tarda and E. ictaluri. Analysis of the gyrB gene, however, placed the grouper isolates into the E. piscicida-like group, a newly recognized taxon which also encompasses the non-motile strains previously classified as atypical E. tarda. Initial genomic analysis revealed the presence of the Edwardsiella type 3 secretion system (T3SS) but also revealed a pathogenicity island encoding a second T3SS with homology to the locus of enterocyte effacement of Escherichia coli. Further analysis revealed 3 different type 6 secretion systems that were also present in all sequenced isolates of Edwardsiella piscicida-like strains. Based on estimated DNA-DNA hybridization values and the average nucleotide index, the grouper strain fits into the E. piscicida-like phylogroup described as E. anguillarum sp. nov. The peculiarities associated with this isolate and the association of other conspecific piscine isolates from multiple marine and brackish water species suggest a link of the entire E. piscicida-like phylogroup to the marine environment.

Impact of Infection Dose and Previous Serum Antibodies against the Locus of Enterocyte Effacement Proteins on Escherichia coli O157:H7 Shedding in Calves following Experimental Infection.

PubMed

Martorelli, L; Hovde, C J; Vilte, D A; Albanese, A; Zotta, E; Ibarra, C; Cantet, R J C; Mercado, E C; Cataldi, A

2015-01-01

Escherichia coli O157:H7 is the main causative agent of haemolytic uremic syndrome. Cattle are the main reservoir of these bacteria, and have been shown to develop immune response to colonization. Our aim was to investigate the faecal shedding pattern of E. coli O157:H7 in calves challenged intragastrically with either 10(8) or 10(10) CFU, as well as the ability of specific preexisting antibodies to reduce shedding of the pathogen. Shedding was analysed by direct counting as well as enrichment of rectoanal mucosal swabs. Statistical analysis was performed using a linear model for repeated measures with and without the inclusion of preexisting antibodies against the carboxy-terminal fraction of intimin-γ (γ-intimin C280) as a covariable. Results suggest that there is a statistical difference in the area under the shedding curves between both doses for 14 as well as 28 days after challenge (p = 0.0069 and 0.0209, resp.). This difference is increased when the prechallenge antibodies are taken into account (p = 0.0056 and 0.0185). We concluded that the bacterial dose influences shedding on calves experimentally challenged and that preexisting antibodies against E. coli O157:H7 γ-intimin C280 could partially reduce faecal excretion.

Interferon-gamma inhibits intestinal restitution by preventing gap junction communication between enterocytes.

PubMed

Leaphart, Cynthia L; Qureshi, Faisal; Cetin, Selma; Li, Jun; Dubowski, Theresa; Baty, Catherine; Batey, Catherine; Beer-Stolz, Donna; Guo, Fengli; Murray, Sandra A; Hackam, David J

2007-06-01

Necrotizing enterocolitis (NEC) is characterized by interferon-gamma (IFN-gamma) release and inadequate intestinal restitution. Because enterocytes migrate together, mucosal healing may require interenterocyte communication via connexin 43-mediated gap junctions. We hypothesize that enterocyte migration requires interenterocyte communication, that IFN impairs migration by impairing connexin 43, and that impaired healing during NEC is associated with reduced gap junctions. NEC was induced in Swiss-Webster or IFN(-/-) mice, and restitution was determined in the presence of the gap junction inhibitor oleamide, or via time-lapse microscopy of IEC-6 cells. Connexin 43 expression, trafficking, and localization were detected in cultured or primary enterocytes or mouse or human intestine by confocal microscopy and (35)S-labeling, and gap junction communication was assessed using live microscopy with oleamide or connexin 43 siRNA. Enterocytes expressed connexin 43 in vitro and in vivo, and exchanged fluorescent dye via gap junctions. Gap junction inhibition significantly reduced enterocyte migration in vitro and in vivo. NEC was associated with IFN release and loss of enterocyte connexin 43 expression. IFN inhibited enterocyte migration by reducing gap junction communication through the dephosphorylation and internalization of connexin 43. Gap junction inhibition significantly increased NEC severity, whereas reversal of the inhibitory effects of IFN on gap junction communication restored enterocyte migration after IFN exposure. Strikingly, IFN(-/-) mice were protected from the development of NEC, and showed restored connexin 43 expression and intestinal restitution. IFN inhibits enterocyte migration by preventing interenterocyte gap junction communication. Connexin 43 loss may provide insights into the development of NEC, in which restitution is impaired.

Investigation and control of an attaching and effacing Escherichia coli outbreak in a colony of captive budgerigars (Melopsittacus undulatus).

PubMed

Seeley, Kathryn E; Baitchman, Eric; Bartlett, Susan; DebRoy, Chitrita; Garner, Michael M

2014-12-01

An increase in mortality in a captive flock of budgerigars (Melopsittacus undulatus) coincided with the isolation of attaching and effacing Escherichia coli from postmortem samples. Common histologic lesions included hepatitis, enteritis, and in one case attaching and effacing lesions along the intestinal tract. Retrospective review of necropsy records and increased sampling led to the identification of several cases of E. coli with the attaching and effacing (eae) virulence gene. Factors such as environment, nutrition, and concomitant pathogens were thought to contribute to mortality in the flock. Although it is not clear whether E. coli was a primary pathogen during the period of increased mortality, the presence of the eae gene combined with associated histologic lesions supports the conclusion that this organism was a significant contributor to mortality. Manipulation of diet, environment, and the addition of probiotic supplementation resulted in a decline in mortality rate and decreased shedding of E. coli based on negative follow-up cultures of intestines, liver, and feces.

Candida species differ in their interactions with immature human gastrointestinal epithelial cells

PubMed Central

Falgier, Christina; Kegley, Sara; Podgorski, Heather; Heisel, Timothy; Storey, Kathleen; Bendel, Catherine M.; Gale, Cheryl A.

2011-01-01

Life-threatening gastrointestinal (GI) diseases of prematurity are highly associated with systemic candidiasis. This implicates the premature GI tract as an important site for invasion by Candida. Invasive interactions of Candida spp. with immature enterocytes have heretofore not been analyzed. Using a primary immature human enterocyte line, we compared the ability of multiple isolates of different Candida spp. to penetrate, injure, and induce a cytokine response from host cells. Of all the Candida spp. analyzed, C. albicans had the greatest ability to penetrate and injure immature enterocytes and to elicit interleukin-8 (IL-8) release (p < 0.01). In addition, C. albicans was the only Candida spp. to form filamentous hyphae when in contact with immature enterocytes. Similarly, a C. albicans mutant with defective hyphal morphogenesis and invasiveness had attenuated cytotoxicity for immature enterocytes (p < 0.003). Thus, hyphal morphogenesis correlates with immature enterocyte penetration, injury and inflammatory responses. Furthermore, variability in enterocyte injury was observed among hyphal-producing C. albicans strains suggesting that individual organism genotypes also influence host-pathogen interactions. Overall, the finding that Candida spp. differed in their interactions with immature enterocytes implicates that individual spp. may employ different pathogenesis mechanisms. PMID:21283049

Different Cellular Origins and Functions of Extracellular Proteins from Escherichia coli O157:H7 and O104:H4 as Determined by Comparative Proteomic Analysis.

PubMed

Islam, Nazrul; Nagy, Attila; Garrett, Wesley M; Shelton, Dan; Cooper, Bret; Nou, Xiangwu

2016-07-15

Extracellular proteins play important roles in bacterial interactions with the environmental matrices. In this study, we examined the extracellular proteins from Escherichia coli O157:H7 and O104:H4 by tandem mass spectrometry. We identified 500 and 859 proteins from the growth media of E. coli O157:H7 and O104:H4, respectively, including 371 proteins common to both strains. Among proteins that were considered specific to E. coli O157:H7 or present at higher relative abundances in O157:H7 medium, most (57 of 65) had secretion signal sequences in their encoding genes. Noticeably, the proteins included locus of enterocyte effacement (LEE) virulence factors, proteins required for peptidyl-lipoprotein accumulation, and proteins involved in iron scavenging. In contrast, a much smaller proportion of proteins (37 of 150) that were considered specific to O104:H4 or presented at higher relative abundances in O104:H4 medium had signals targeting them for secretion. These proteins included Shiga toxin 2 subunit B and O104:H4 signature proteins, including AAF/1 major fimbrial subunit and serine protease autotransporters. Most of the abundant proteins from the growth medium of E. coli O104:H4 were annotated as having functions in the cytoplasm. We provide evidence that the extensive presence of cytoplasmic proteins in E. coli O104:H4 growth medium was due to biological processes independent of cell lysis, indicating alternative mechanisms for this potent pathogen releasing cytoplasmic contents into the growth milieu, which could play a role in interaction with the environmental matrices, such as pathogenesis and biofilm formation. In this study, we compared the extracellular proteins from two of the most prominent foodborne pathogenic E. coli organisms that have caused severe outbreaks in the United States and in Europe. E. coli O157:H7 is a well-studied Shiga toxigenic foodborne pathogen of the enterohemorrhagic pathotype that has caused numerous outbreaks associated with various contaminated foods worldwide. E. coli O104:H4 is a newly emerged Shiga toxigenic foodborne pathogen of the enteroaggregative pathotype that gained notoriety for causing one of the most deadly foodborne outbreaks in Europe in 2011. Comparison of proteins in the growth medium revealed significant differences in the compositions of the extracellular proteins for these two pathogens. These differences may provide valuable information regarding the cellular responses of these pathogens to their environment, including cell survival and pathogenesis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Virulence and antimicrobial resistance determinants of verotoxigenic Escherichia coli (VTEC) and of multidrug-resistant E. coli from foods of animal origin illegally imported to the EU by flight passengers.

PubMed

Nagy, B; Szmolka, A; Smole Možina, S; Kovač, J; Strauss, A; Schlager, S; Beutlich, J; Appel, B; Lušicky, M; Aprikian, P; Pászti, J; Tóth, I; Kugler, R; Wagner, M

2015-09-16

The aim of this study was to reveal phenotype/genotype characteristics of verotoxigenic Escherichia coli (VTEC) and multidrug resistant E. coli in food products of animal origin confiscated as illegal import at Austrian, German and Slovenian airports. VTEC isolates were obtained by using ISO guidelines 16654:2001 for O157 VTEC or ISO/ TS13136:2012 for non-O157 VTEC, with additional use of the RIDASCREEN® Verotoxin immunoassay. The testing of 1526 samples resulted in 15 VTEC isolates (1.0%) primarily isolated from hard cheese from Turkey and Balkan countries. Genotyping for virulence by using a miniaturized microarray identified a wide range of virulence determinants. One VTEC isolate (O26:H46) possessing intimin (eae) and all other essential genes of Locus of Enterocyte Effacement (LEE) was designated as enterohemorrhagic E. coli (EHEC). None of the other VTEC strains belonged to serogroups O157, O145, O111, O104 or O103. VTEC strains harbored either stx(1) (variants stx1(a) or stx(1c)) or st(x2) (variants stx(2a), stx(2b), stx(2a/d) or stx(2c/d)) genes. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) demonstrated high genetic diversity and identified three new sequence types (STs): 4505, 4506 and 4507. Food samples collected from the Vienna airport were also tested for E. coli quantities using the ISO 16649:2001, and for detection of multidrug resistant phenotypes and genotypes. The resulting 113 commensal E. coli isolates were first tested in a pre-screening against 6 selected antimicrobials to demonstrate multidrug resistance. The resulting 14 multidrug resistant (MDR) E. coli isolates, representing 0.9% of the samples, were subjected to further resistance phenotyping and to microarray analyses targeting genetic markers of antimicrobial resistance and virulence. Genotyping revealed various combinations of resistance determinants as well as the presence of class 1, class 2 integrons. The isolates harbored 6 to 11 antibiotic resistance genes as well as 1 to 14 virulence genes. In this panel of 14 MDR E. coli two strains proved to carry CTX-M type ESBLs, and one single isolate was identified as enteropathogenic E. coli (EPEC). In general, isolates carrying a high number of resistance determinants had lower number of virulence genes and vice versa. In conclusion, this first pilot study on the prevalence of VTEC and of MDR/ESBL E. coli in illegally imported food products of animal origin suggests that these strains could represent reservoirs for dissemination of potentially new types of pathogenic and MDR E. coli in Europe. Copyright © 2015 Elsevier B.V. All rights reserved.

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters.

PubMed

Tetteh, Paul W; Basak, Onur; Farin, Henner F; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; de Sauvage, Frederic; van Es, Johan H; van Oudenaarden, Alexander; Clevers, Hans

2016-02-04

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate-mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth-like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Epithelial Microvilli Establish an Electrostatic Barrier to Microbial Adhesion

PubMed Central

Bennett, Kaila M.; Walker, Sharon L.

2014-01-01

Microvilli are membrane extensions on the apical surface of polarized epithelia, such as intestinal enterocytes and tubule and duct epithelia. One notable exception in mucosal epithelia is M cells, which are specialized for capturing luminal microbial particles; M cells display a unique apical membrane lacking microvilli. Based on studies of M cell uptake under different ionic conditions, we hypothesized that microvilli may augment the mucosal barrier by providing an increased surface charge density from the increased membrane surface and associated glycoproteins. Thus, electrostatic charges may repel microbes from epithelial cells bearing microvilli, while M cells are more susceptible to microbial adhesion. To test the role of microvilli in bacterial adhesion and uptake, we developed polarized intestinal epithelial cells with reduced microvilli (“microvillus-minus,” or MVM) but retaining normal tight junctions. When tested for interactions with microbial particles in suspension, MVM cells showed greatly enhanced adhesion and uptake of particles compared to microvillus-positive cells. This preference showed a linear relationship to bacterial surface charge, suggesting that microvilli resist binding of microbes by using electrostatic repulsion. Moreover, this predicts that pathogen modification of electrostatic forces may contribute directly to virulence. Accordingly, the effacement effector protein Tir from enterohemorrhagic Escherichia coli O157:H7 expressed in epithelial cells induced a loss of microvilli with consequent enhanced microbial binding. These results provide a new context for microvillus function in the host-pathogen relationship, based on electrostatic interactions. PMID:24778113

Connexin 26 facilitates gastrointestinal bacterial infection in vitro.

PubMed

Simpson, Charlotte; Kelsell, David P; Marchès, Olivier

2013-01-01

Escherichia coli, including enteropathogenic E. coli (EPEC), represents the most common cause of diarrhoea worldwide and is therefore a serious public health burden. Treatment for gastrointestinal pathogens is hindered by the emergence of multiple antibiotic resistance, leading to the requirement for the development of new therapies. A variety of mechanisms act in combination to mediate gastrointestinal-bacterial-associated diarrhoea development. For example, EPEC infection of enterocytes induces attaching and effacing lesion formation and the disruption of tight junctions. An alternative enteric pathogen, Shigella flexneri, manipulates the expression of Connexin 26 (Cx26), a gap junction protein. S. flexneri can open Cx26 hemichannels allowing the release of ATP, whereas HeLa cells expressing mutant gap-junction-associated Cx26 are less susceptible to cellular invasion by S. flexneri than cells expressing wild-type (WT) Cx26. We have investigated further the link between Cx26 expression and gastrointestinal infection by using EPEC and S. flexneri as in vitro models of infection. In this study, a significant reduction in EPEC adherence was observed in cells expressing mutant Cx26 compared with WT Cx26. Furthermore, a significant reduction in both cellular invasion by S. flexneri and adherence by EPEC was demonstrated in human intestinal cell lines following treatment with Cx26 short interfering RNA. These in vitro results suggest that the loss of functional Cx26 expression provides improved protection against gastrointestinal bacterial pathogens. Thus, Cx26 represents a potential therapeutic target for gastrointestinal bacterial infection.

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

PubMed Central

Hung, Yu-Han; Carreiro, Alicia L.; Buhman, Kimberly K.

2017-01-01

Enterocytes, the absorptive cells of the small intestine, mediate efficient absorption of dietary fat (triacylglycerol, TAG). The digestive products of dietary fat are taken up by enterocytes, re-esterified into TAG, and packaged on chylomicrons (CMs) for secretion into blood or temporarily stored within cytoplasmic lipid droplets (CLDs). Altered enterocyte TAG distribution impacts susceptibility to high fat diet associated diseases, but molecular mechanisms directing TAG toward these fates are unclear. Two enzymes, acyl CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2, catalyze the final, committed step of TAG synthesis within enterocytes. Mice with intestine-specific overexpression of Dgat1 (Dgat1Int) or Dgat2 (Dgat2Int), or lack of Dgat1 (Dgat1−/−), were previously found to have altered intestinal TAG secretion and storage. We hypothesized that varying intestinal Dgat1 and Dgat2 levels alters TAG distribution in subcellular pools for CM synthesis as well as the morphology and proteome of CLDs. To test this we used ultrastructural and proteomic methods to investigate intracellular TAG distribution and CLD-associated proteins in enterocytes from Dgat1Int, Dgat2Int, and Dgat1−/− mice 2 hours after a 200 μl oral olive oil gavage. We found that varying levels of intestinal Dgat1 and Dgat2 altered TAG pools involved in CM assembly and secretion, the number or size of CLDs present in enterocytes, and the enterocyte CLD proteome. Overall, these results support a model where Dgat1 and Dgat2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing TAG for incorporation into distinct subcellular TAG pools in enterocytes. PMID:28249764

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat.

PubMed

Hung, Yu-Han; Carreiro, Alicia L; Buhman, Kimberly K

2017-06-01

Enterocytes, the absorptive cells of the small intestine, mediate efficient absorption of dietary fat (triacylglycerol, TAG). The digestive products of dietary fat are taken up by enterocytes, re-esterified into TAG, and packaged on chylomicrons (CMs) for secretion into blood or temporarily stored within cytoplasmic lipid droplets (CLDs). Altered enterocyte TAG distribution impacts susceptibility to high fat diet associated diseases, but molecular mechanisms directing TAG toward these fates are unclear. Two enzymes, acyl CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2, catalyze the final, committed step of TAG synthesis within enterocytes. Mice with intestine-specific overexpression of Dgat1 (Dgat1 Int ) or Dgat2 (Dgat2 Int ), or lack of Dgat1 (Dgat1 -/- ), were previously found to have altered intestinal TAG secretion and storage. We hypothesized that varying intestinal Dgat1 and Dgat2 levels alters TAG distribution in subcellular pools for CM synthesis as well as the morphology and proteome of CLDs. To test this we used ultrastructural and proteomic methods to investigate intracellular TAG distribution and CLD-associated proteins in enterocytes from Dgat1 Int , Dgat2 Int , and Dgat1 -/- mice 2h after a 200μl oral olive oil gavage. We found that varying levels of intestinal Dgat1 and Dgat2 altered TAG pools involved in CM assembly and secretion, the number or size of CLDs present in enterocytes, and the enterocyte CLD proteome. Overall, these results support a model where Dgat1 and Dgat2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing TAG for incorporation into distinct subcellular TAG pools in enterocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a chicken enterocyte culture to study its functional physiology

USDA-ARS?s Scientific Manuscript database

We developed a method to culture chicken intestinal enterocytes, the cells that absorb and form protective barriers against enteric bacteria, to study their functional physiologies. Using intestinal villi, harvested from day old broiler chicks, the enterocytes were isolated by sequential digestion ...

Which Self-Presentation Style Is More Effective? A Comparison of Instructors' Self-Enhancing and Self-Effacing Styles across the Culture

ERIC Educational Resources Information Center

Kim, Eun Joo; Berger, Charles; Kim, Joohan; Kim, Min-Sun

2014-01-01

Many studies have investigated how people perceive others' self-presentation styles (such as enhancement and effacement) in forming first impressions and how culture influences the process. Most of those studies have, however, investigated self-presentation styles in the context of informal and intimate interpersonal relations. Few studies have…

Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis.

PubMed

Capoulade, Romain; Teoh, Jonathan G; Bartko, Philipp E; Teo, Eliza; Scholtz, Jan-Erik; Tastet, Lionel; Shen, Mylene; Mihos, Christos G; Park, Yong H; Garcia, Julio; Larose, Eric; Isselbacher, Eric M; Sundt, Thoralf M; MacGillivray, Thomas E; Melnitchouk, Serguei; Ghoshhajra, Brian B; Pibarot, Philippe; Hung, Judy

2018-05-01

The aim of this study was to examine the association between abnormal morphology of the proximal aorta and aortic stenosis (AS) progression rate. The main hypothesis was that morphologic changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), result in increased biomechanical stresses and contribute to calcification and progression of AS. Between 2010 and 2012, 426 patients with mild to moderate AS were included in this study. Proximal aortic dimensions were measured at three different levels (i.e., sinus of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending aorta/STJ ratios were used to determine degree of aortic deformity. AS progression rate was assessed by annualized increase in mean gradient (median follow-up time, 3.1 years; interquartile range, 2.6-3.9 years). The degree of aortic flow turbulence was examined in 18 matched patients with and without STJ effacement using cardiac magnetic resonance phase-contrast imaging. Patients' mean age was 71 ± 13 years, and 64% were men. Patients with low ratios had greater AS progression (P < .05). After comprehensive adjustment, sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were independently associated with greater AS progression rate. Compared with patients without STJ effacement, those with effacement of the STJ had higher degrees of aortic flow turbulence (24.4% vs 17.2%, P = .038). Effacement of the STJ is independently associated with greater AS progression, regardless of arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients with abnormal proximal aortic geometry had disturbed aortic flow patterns. These findings suggest an interrelation between proximal aorta morphology and stenosis progression. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease

PubMed Central

George, Britta; Verma, Rakesh; Soofi, Abdulsalam A.; Garg, Puneet; Zhang, Jidong; Park, Tae-Ju; Giardino, Laura; Ryzhova, Larisa; Johnstone, Duncan B.; Wong, Hetty; Nihalani, Deepak; Salant, David J.; Hanks, Steven K.; Curran, Tom; Rastaldi, Maria Pia; Holzman, Lawrence B.

2012-01-01

The morphology of healthy podocyte foot processes is necessary for maintaining the characteristics of the kidney filtration barrier. In most forms of glomerular disease, abnormal filter barrier function results when podocytes undergo foot process spreading and retraction by remodeling their cytoskeletal architecture and intercellular junctions during a process known as effacement. The cell adhesion protein nephrin is necessary for establishing the morphology of the kidney podocyte in development by transducing from the specialized podocyte intercellular junction phosphorylation-mediated signals that regulate cytoskeletal dynamics. The present studies extend our understanding of nephrin function by showing that nephrin activation in cultured podocytes induced actin dynamics necessary for lamellipodial protrusion. This process required a PI3K-, Cas-, and Crk1/2-dependent signaling mechanism distinct from the previously described nephrin-Nck1/2 pathway necessary for assembly and polymerization of actin filaments. Our present findings also support the hypothesis that mechanisms governing lamellipodial protrusion in culture are similar to those used in vivo during foot process effacement in a subset of glomerular diseases. In mice, podocyte-specific deletion of Crk1/2 prevented foot process effacement in one model of podocyte injury and attenuated foot process effacement and associated proteinuria in a delayed fashion in a second model. In humans, focal adhesion kinase and Cas phosphorylation — markers of focal adhesion complex–mediated Crk-dependent signaling — was induced in minimal change disease and membranous nephropathy, but not focal segmental glomerulosclerosis. Together, these observations suggest that activation of a Cas-Crk1/2–dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases. PMID:22251701

Identification of intestinal ion transport defects in microvillus inclusion disease.

PubMed

Kravtsov, Dmitri V; Ahsan, Md Kaimul; Kumari, Vandana; van Ijzendoorn, Sven C D; Reyes-Mugica, Miguel; Kumar, Anoop; Gujral, Tarunmeet; Dudeja, Pradeep K; Ameen, Nadia A

2016-07-01

Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl(-)) and sodium (Na(+)) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na(+)), CFTR (Cl(-)), and SLC26A3 (DRA) (Cl(-)/HCO3 (-)) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl(-) and Na(+) stool loss in MVID diarrhea.

Identification of intestinal ion transport defects in microvillus inclusion disease

PubMed Central

Kravtsov, Dmitri V.; Ahsan, Md Kaimul; Kumari, Vandana; van Ijzendoorn, Sven C. D.; Reyes-Mugica, Miguel; Kumar, Anoop; Gujral, Tarunmeet; Dudeja, Pradeep K.

2016-01-01

Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl−) and sodium (Na+) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na+), CFTR (Cl−), and SLC26A3 (DRA) (Cl−/HCO3−) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl− and Na+ stool loss in MVID diarrhea. PMID:27229121

Regulators of Intestinal Epithelial Migration in Sepsis.

PubMed

Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

2018-02-08

The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof.

PubMed

Lucas, Michael L

2010-04-01

For almost 40 years, one of the principal causes of diarrhoeal disease has been thought to be fluid secretion emanating from the epithelial cells of the small and large intestine. Given the extremely large fluid losses seen in cholera, where secretion can be up to several litres per day, this seems a plausible hypothesis. The enterocyte (epithelial cell) secretion hypothesis rapidly displaced all other alternatives, such as vasodilatation coupled with enhanced paracellular permeability. An essential mechanism underlying enterocyte secretion has always been assumed to be electrogenic chloride secretion, leading to a localized osmotic imbalance at the mucosal surface of the enterocytes that causes fluid entry into the lumen by osmosis. The chloride secretion basis for enterotoxin-deranged secretion is assumed to be measurable by changes in electrical currents and by altered transport of chloride ion. These can be detected after the small intestine is exposed to a heat-stable enterotoxin (STa) produced by Escherichia coli. However, in vivo, when the recovered volume technique is used, STa is found not to be secretory. The heat-stable enterotoxin is therefore a test case toxin, because the complex techniques used to demonstrate enterocyte secretion after STa exposure show apparent secretion, while the simplest technique based on fluid recovery and genuinely measuring the mass transport of fluid does not. This review scrutinizes the nature of the evidence put forward for enterocyte secretion and reaches the conclusion that there is no evidence for it. Debilitating secretion undoubtedly does take place in severe diarrhoeal disease, but secretion from enterocytes is unlikely to be the cause.

Susceptibility of porcine ileal enterocytes to the cytotoxin of Serpulina hyodysenteriae and the resolution of the epithelial lesions: an electron microscopic study.

PubMed

Bland, A P; Frost, A J; Lysons, R J

1995-01-01

The cytotoxin from Serpulina hyodysenteriae was injected into ileal loops of eight germ-free pigs, and the effects on the villi were observed after 1, 3, and 18 hours of exposure. The mature vacuolated villus enterocytes of the proximal part of the absorptive villi were most susceptible to the lethal effects of the cytotoxin and were extensively exfoliated. The enterocytes at the base of the villi, the goblet cells, and the follicle-associated epithelium of the dome villi, particularly the M cells, were less affected. As the enterocytes were shed, the villi progressively shortened and the basement membrane became extensively folded. The absorptive villi were markedly stunted at 3 hours, and flattened globlet cells predominated at the site of restitution of the lesion. The myofibroblasts were also damaged, apparently subsequent to the exfoliation of the enterocytes. There was no further damage at 18 hours. The absorptive villi were stunted and were devoid of the large interstitial spaces of the normal lamina propria; the enterocytes were generally columnar, and at the apex of each villus there was an accumulation of goblet cells. There was a preponderance of M cells at the apices of the dome villi. Restitution of the lesions was not as rapid as observed in in vitro systems. The changes observed indicated that as the proximal enterocytes of the absorptive villi were shed, the loss of hydrostatic forces in the lamina propria allowed the myofibroblasts to collapse the villi by progressively retracting the basement membrane. This reduced the surface area to be covered during restitution. Resolution of the lesions was still incomplete after 18 hours.

Early establishment of epithelial apoptosis in the developing human small intestine.

PubMed

Vachon, P H; Cardin, E; Harnois, C; Reed, J C; Vézina, A

2000-12-01

In the adult small intestine, the dynamic renewal of the epithelium is characterized by a sequence of cell production in the crypts, cell maturation and cell migration to the tip of villi, where apoptosis is undertaken. Little is known about enterocytic apoptosis during development. In man, intestinal architectural features and functions are acquired largely by mid-gestation (18-20 wks); the question whether the establishment of enterocytic apoptotic processes parallels or not the acquisition of other intestinal functional features remains open. In the present study, we approached this question by examining enterocytic apoptosis during development of the human jejunum (9-20 wks gestation), using the ISEL (in situ terminal uridine deoxynucleotidyl nick-end labelling) method. Between 9 and 17 wks, apoptotic enterocytes were not evidenced. However, beginning at the 18 wks stage, ISEL-positive enterocytes were regularly observed at the tip of villi. Since the Bcl-2 family of proteins constitutes a critical checkpoint in apoptosis, acting upstream of the apoptotic machinery, we investigated the expression of six Bcl-2 homologs (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak, Bad) and one non-homologous associated molecule (Bag-1). By immunofluorescence, we found that all homologs analyzed were expressed by enterocytes between 9 and 20 wks. However, Bcl-2 homologs underwent a gradual compartmentalization of epithelial expression along the maturing crypt-villus axis, to establish gradients of expression by 18-20 wks. Western blot analyses indicated that the expression levels of Bcl-2 homologs were modulated during morphogenesis of the crypt-villus axis, in parallel to their gradual compartmentalization of expression. Altogether, these data suggest that regulatory mechanisms of human enterocytic apoptosis become established by mid-gestation (18-20 wks) and coincide with the maturation of the crypt-villus axis of cell proliferation, differentiation and renewal.

Strain-dependent induction of epithelial cell oncosis by Campylobacter jejuni is correlated with invasion ability and is independent of cytolethal distending toxin.

PubMed

Kalischuk, Lisa D; Inglis, G Douglas; Buret, Andre G

2007-09-01

Induction of host cell death is thought to play an important role in bacterial pathogenesis. Campylobacter jejuni is a prevalent cause of bacterial enteritis; however, its effects on enterocytes remain unclear. The present study indicates for the first time that C. jejuni induces oncotic, rather than apoptotic death of T84 enterocytes. C. jejuni-treated enterocytes exhibited extensive cytoplasmic vacuolation, rapid (3-6 h) loss of plasma membrane integrity ('cytotoxicity'), loss of mitochondrial transmembrane potential, and ATP depletion. Enterocytes also exhibited increased oligonucleosomal DNA fragmentation, a feature characteristic of apoptosis. However, consistent with a non-apoptotic process, DNA fragmentation and cytotoxicity were not caspase dependent. During apoptosis, caspases mediate cleavage of poly(ADP-ribose) polymerase; however, cleavage was not observed in C. jejuni-treated monolayers. Cytotoxicity, ATP depletion and DNA fragmentation were not prevented by the deletion of the cytolethal distending toxin (CDT) gene, indicating that C. jejuni causes enterocyte oncosis via a mechanism that is CDT independent. The ability to cause oncosis was significantly decreased in a FlaAFlaB mutant (CDT(+)) that was defective in the ability to adhere and invade enterocytes. Analysis of clinical isolates revealed that oncosis was strain dependent and correlated with increased invasive ability. These observations offer new insights into the pathogenesis of C. jejuni infection.

Constitutive apical membrane recycling in Aplysia enterocytes.

PubMed

Keeton, Robert Aaron; Runge, Steven William; Moran, William Michael

2004-11-01

In Aplysia californica enterocytes, alanine-stimulated Na+ absorption increases both apical membrane exocytosis and fractional capacitance (fCa; a measure of relative apical membrane surface area). These increases are thought to reduce membrane tension during periods of nutrient absorption that cause the enterocytes to swell osmotically. In the absence of alanine, exocytosis and fCa are constant. These findings imply equal rates of constitutive endocytosis and exocytosis and constitutive recycling of the apical plasma membrane. Thus, the purpose of this study was to confirm and determine the relative extent of constitutive apical membrane recycling in Aplysia enterocytes. Biotinylated lectins are commonly used to label plasma membranes and to investigate plasma membrane recycling. Of fourteen biotinylated lectins tested, biotinylated wheat germ agglutinin (bWGA) bound preferentially to the enterocytes apical surface. Therefore, we used bWGA, avidin D (which binds tightly to biotin), and the UV fluorophore 7-amino-4-methylcoumarin-3-acetic acid (AMCA)-conjugated avidin D to assess the extent of constitutive apical membrane recycling. A temperature-dependent (20 vs. 4 degrees C) experimental protocol employed the use of two tissues from each of five snails and resulted in a approximately 60% difference in apical surface fluorescence intensity. Because the extent of membrane recycling is proportional to the difference in surface fluorescence intensity, this difference reveals a relatively high rate of constitutive apical membrane recycling in Aplysia enterocytes.

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine.

PubMed

Muglia, C; Mercer, N; Toscano, M A; Schattner, M; Pozner, R; Cerliani, J P; Gobbi, R Papa; Rabinovich, G A; Docena, G H

2011-05-26

Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1(-/-)) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1(-/-) mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function.

Role of the Enterocyte in Fructose-Induced Hypertriglyceridaemia.

PubMed

Steenson, Simon; Umpleby, A Margot; Lovegrove, Julie A; Jackson, Kim G; Fielding, Barbara A

2017-04-01

Dietary fructose has been linked to an increased post-prandial triglyceride (TG) level; which is an established independent risk factor for cardiovascular disease. Although much research has focused on the effects of fructose consumption on liver-derived very-low density lipoprotein (VLDL); emerging evidence also suggests that fructose may raise post-prandial TG levels by affecting the metabolism of enterocytes of the small intestine. Enterocytes have become well recognised for their ability to transiently store lipids following a meal and to thus control post-prandial TG levels according to the rate of chylomicron (CM) lipoprotein synthesis and secretion. The influence of fructose consumption on several aspects of enterocyte lipid metabolism are discussed; including de novo lipogenesis; apolipoprotein B48 and CM-TG production; based on the findings of animal and human isotopic tracer studies. Methodological issues affecting the interpretation of fructose studies conducted to date are highlighted; including the accurate separation of CM and VLDL. Although the available evidence to date is limited; disruption of enterocyte lipid metabolism may make a meaningful contribution to the hypertriglyceridaemia often associated with fructose consumption.

Role of the Enterocyte in Fructose-Induced Hypertriglyceridaemia

PubMed Central

Steenson, Simon; Umpleby, A. Margot; Lovegrove, Julie A.; Jackson, Kim G.; Fielding, Barbara A.

2017-01-01

Dietary fructose has been linked to an increased post-prandial triglyceride (TG) level; which is an established independent risk factor for cardiovascular disease. Although much research has focused on the effects of fructose consumption on liver-derived very-low density lipoprotein (VLDL); emerging evidence also suggests that fructose may raise post-prandial TG levels by affecting the metabolism of enterocytes of the small intestine. Enterocytes have become well recognised for their ability to transiently store lipids following a meal and to thus control post-prandial TG levels according to the rate of chylomicron (CM) lipoprotein synthesis and secretion. The influence of fructose consumption on several aspects of enterocyte lipid metabolism are discussed; including de novo lipogenesis; apolipoprotein B48 and CM-TG production; based on the findings of animal and human isotopic tracer studies. Methodological issues affecting the interpretation of fructose studies conducted to date are highlighted; including the accurate separation of CM and VLDL. Although the available evidence to date is limited; disruption of enterocyte lipid metabolism may make a meaningful contribution to the hypertriglyceridaemia often associated with fructose consumption. PMID:28368310

Autophagosomes contribute to intracellular lipid distribution in enterocytes

PubMed Central

Khaldoun, Salem Ait; Emond-Boisjoly, Marc-Alexandre; Chateau, Danielle; Carrière, Véronique; Lacasa, Michel; Rousset, Monique; Demignot, Sylvie; Morel, Etienne

2014-01-01

Enterocytes, the intestinal absorptive cells, have to deal with massive alimentary lipids upon food consumption. They orchestrate complex lipid-trafficking events that lead to the secretion of triglyceride-rich lipoproteins and/or the intracellular transient storage of lipids as lipid droplets (LDs). LDs originate from the endoplasmic reticulum (ER) membrane and are mainly composed of a triglyceride (TG) and cholesterol-ester core surrounded by a phospholipid and cholesterol monolayer and specific coat proteins. The pivotal role of LDs in cellular lipid homeostasis is clearly established, but processes regulating LD dynamics in enterocytes are poorly understood. Here we show that delivery of alimentary lipid micelles to polarized human enterocytes induces an immediate autophagic response, accompanied by phosphatidylinositol-3-phosphate appearance at the ER membrane. We observe a specific and rapid capture of newly synthesized LD at the ER membrane by nascent autophagosomal structures. By combining pharmacological and genetic approaches, we demonstrate that autophagy is a key player in TG targeting to lysosomes. Our results highlight the yet-unraveled role of autophagy in the regulation of TG distribution, trafficking, and turnover in human enterocytes. PMID:24173715

Finding Coefficients of the Full Array of Motion-Independent N-Body Potentials of Metric Gravity from Gravity's Exterior and Interior Effacement Algebra

NASA Astrophysics Data System (ADS)

Nordtvedt, Kenneth

2018-01-01

In the author's previous publications, a recursive linear algebraic method was introduced for obtaining (without gravitational radiation) the full potential expansions for the gravitational metric field components and the Lagrangian for a general N-body system. Two apparent properties of gravity— Exterior Effacement and Interior Effacement—were defined and fully enforced to obtain the recursive algebra, especially for the motion-independent potential expansions of the general N-body situation. The linear algebraic equations of this method determine the potential coefficients at any order n of the expansions in terms of the lower-order coefficients. Then, enforcing Exterior and Interior Effacement on a selecedt few potential series of the full motion-independent potential expansions, the complete exterior metric field for a single, spherically-symmetric mass source was obtained, producing the Schwarzschild metric field of general relativity. In this fourth paper of this series, the complete spatial metric's motion-independent potentials for N bodies are obtained using enforcement of Interior Effacement and knowledge of the Schwarzschild potentials. From the full spatial metric, the complete set of temporal metric potentials and Lagrangian potentials in the motion-independent case can then be found by transfer equations among the coefficients κ( n, α) → λ( n, ɛ) → ξ( n, α) with κ( n, α), λ( n, ɛ), ξ( n, α) being the numerical coefficients in the spatial metric, the Lagrangian, and the temporal metric potential expansions, respectively.

Atypical enteropathogenic Escherichia coli as aetiologic agents of sporadic and outbreak-associated diarrhoea in Brazil.

PubMed

Vieira, Melissa A; Dos Santos, Luís F; Dias, Regiane C B; Camargo, Carlos H; Pinheiro, Sandra R S; Gomes, Tânia A T; Hernandes, Rodrigo T

2016-09-01

Enteropathogenic Escherichia coli (EPEC) are important agents of diarrhoea in industrialized as well as developing countries, such as Brazil. The hallmark of EPEC pathogenesis is the establishment of attaching and effacing lesions in enterocytes, in which pedestal-like structures are formed underneath adherent bacteria. EPEC are divided into two subgroups, typical (tEPEC) and atypical (aEPEC), based on the presence of the EPEC adherence factor plasmid in tEPEC and its absence in aEPEC. This study was designed to characterize 82 aEPEC isolates obtained from stool samples of diarrhoeic patients during 2012 and 2013 in Brazil. The majority of the aEPEC were assigned to the phylo-group B1 (48.8 %), and intimin subtypes θ (20.7 %), β1 (9.7 %) and λ (9.7 %) were the most prevalent among the isolates. The nleB and nleE genes were concomitantly detected in 32.9 % of the isolates, demonstrating the occurrence of the pathogenicity island O122 among them. The O157-plasmid genes (ehxA and/or espP) were detected in 7.3 % of the isolates, suggesting that some aEPEC could be derived from Shiga-toxin-producing E. coli that lost the stx genes while trafficking in the host. PFGE of 14 aEPEC of serotypes O2 : H16, O33 : H34, O39 : H9, O108 : H- and ONT : H19 isolated from five distinct outbreaks showed serotype-specific PFGE clusters, indicating a high degree of similarity among the isolates from the same event, thus highlighting these serotypes as potential aetiologic agents of diarrhoeal outbreaks in Brazil.

Shiga toxin-converting phages and the emergence of new pathogenic Escherichia coli: a world in motion

PubMed Central

Tozzoli, Rosangela; Grande, Laura; Michelacci, Valeria; Ranieri, Paola; Maugliani, Antonella; Caprioli, Alfredo; Morabito, Stefano

2014-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) are pathogenic E. coli causing diarrhea, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). STEC are characterized by a constellation of virulence factors additional to Stx and have long been regarded as capable to cause HC and HUS when possessing the ability of inducing the attaching and effacing (A/E) lesion to the enterocyte, although strains isolated from such severe infections sometimes lack this virulence feature. Interestingly, the capability to cause the A/E lesion is shared with another E. coli pathogroup, the Enteropathogenic E. coli (EPEC). In the very recent times, a different type of STEC broke the scene causing a shift in the paradigm for HUS-associated STEC. In 2011, a STEC O104:H4 caused a large outbreak with more than 800 HUS and 50 deaths. Such a strain presented the adhesion determinants of Enteroaggregative E. coli (EAggEC). We investigated the possibility that, besides STEC and EAggEC, other pathogenic E. coli could be susceptible to infection with stx-phages. A panel of stx2-phages obtained from STEC isolated from human disease was used to infect experimentally E. coli strains representing all the known pathogenic types, including both diarrheagenic E. coli (DEC) and extra-intestinal pathogenic E. coli (ExPEC). We observed that all the E. coli pathogroups used in the infection experiments were susceptible to the infection. Our results suggest that the stx2-phages used may not have specificity for E. coli adapted to the intestinal environment, at least in the conditions used. Additionally, we could only observe transient lysogens suggesting that the event of stable stx2-phage acquisition occurs rarely. PMID:24999453

Carbachol-induced MUC17 endocytosis is concomitant with NHE3 internalization and CFTR membrane recruitment in enterocytes.

PubMed

Pelaseyed, Thaher; Gustafsson, Jenny K; Gustafsson, Ida J; Ermund, Anna; Hansson, Gunnar C

2013-08-15

We have reported that transmembrane mucin MUC17 binds PDZ protein PDZK1, which retains MUC17 apically in enterocytes. MUC17 and transmembrane mucins MUC3 and MUC12 are suggested to build the enterocyte apical glycocalyx. Carbachol (CCh) stimulation of the small intestine results in gel-forming mucin secretion from goblet cells, something that requires adjacent enterocytes to secrete chloride and bicarbonate for proper mucin formation. Surface labeling and confocal imaging demonstrated that apically expressed MUC17 in Caco-2 cells and Muc3(17) in murine enterocytes were endocytosed upon stimulation with CCh. Relocation of MUC17 in response to CCh was specific as MUC3 and MUC12 did not relocate following CCh stimulation. MUC17 colocalized with PDZK1 under basal conditions, while MUC17 relocated to the terminal web and into early endosomes after CCh stimulation. CCh stimulation concomitantly internalized the Na(+/)H(+) exchanger 3 (NHE3) and recruited cystic fibrosis transmembrane conductance regulator (CFTR) to the apical membranes, a process that was important for CFTR-mediated bicarbonate secretion necessary for proper gel-forming mucin unfolding. The reason for the specific internalization of MUC17 is not understood, but it could limit the diffusion barrier for ion secretion caused by the apical enterocyte glycocalyx or alternatively act to sample luminal bacteria. Our results reveal well-orchestrated mucus secretion and trafficking of ion channels and the MUC17 mucin.

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine

PubMed Central

Muglia, C; Mercer, N; Toscano, M A; Schattner, M; Pozner, R; Cerliani, J P; Gobbi, R Papa; Rabinovich, G A; Docena, G H

2011-01-01

Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1−/−) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1−/− mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function. PMID:21614093

GLUT2 Accumulation in Enterocyte Apical and Intracellular Membranes

PubMed Central

Ait-Omar, Amal; Monteiro-Sepulveda, Milena; Poitou, Christine; Le Gall, Maude; Cotillard, Aurélie; Gilet, Jules; Garbin, Kevin; Houllier, Anne; Château, Danièle; Lacombe, Amélie; Veyrie, Nicolas; Hugol, Danielle; Tordjman, Joan; Magnan, Christophe; Serradas, Patricia; Clément, Karine; Leturque, Armelle; Brot-Laroche, Edith

2011-01-01

OBJECTIVE In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance. RESEARCH DESIGN AND METHODS Subcellular location of GLUT2 in jejunal enterocytes was analyzed by confocal and electron microscopy imaging and Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral metformin or in high-fat low-carbohydrate diet–fed C57Bl/6 mice. Glucose absorption and secretion were respectively estimated by oral glucose tolerance test and secretion of [U-14C]-3-O-methyl glucose into lumen. RESULTS In human enterocytes, GLUT2 was consistently located in basolateral membranes. Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia. In addition, intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose release into intestinal lumen. CONCLUSIONS In morbidly obese insulin-resistant subjects, GLUT2 was accumulated in apical and/or endosomal membranes of enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes are a sign of intestinal adaptations to human metabolic pathology. PMID:21852673

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-05-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions.

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed Central

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-01-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions. PMID:8734984

Glutamate and CO2 production from glutamine in incubated enterocytes of adult and very old rats.

PubMed

Meynial-Denis, Dominique; Bielicki, Guy; Beaufrère, Anne-Marie; Mignon, Michelle; Mirand, Philippe Patureau; Renou, Jean-Pierre

2013-04-01

Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial cells (~300×10(6) cells) were incubated in oxygenated Krebs-Henseleit buffer for 30 min containing [1-(13)C] glutamine (~17 M) for analysis of glutamine metabolites by (13)C nuclear magnetic resonance ((13)C NMR). An aliquot fraction was incubated in the presence of [U-(14)C] glutamine to measure produced CO2. Glutamine pretreatment increased glutamate production and decreased CO2 production in very old rats. The ratio CO2/glutamate, which was very high in control very old rats, was similar at both ages after glutamine pretreatment, as if enterocytes from very old rats recovered the metabolic abilities of enterocytes from adult rats. Our results suggest that long-term treatment with glutamine started before advanced age (a) prevented the loss of rat body weight without limiting sarcopenia and (b) had a beneficial effect on enterocytes from very old rats probably by favoring the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis, which was not detected in (13)C NMR spectra in our experimental conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Life cycle of Hammondia hammondi (Apicomplexa: Sarcocystidae) in cats

USDA-ARS?s Scientific Manuscript database

Hammondia hammondi and Toxoplasma gondii are feline coccidian that are morphologically, antigenically, and phylogenitically related. Both parasites multiply asexually and sexually in feline intestinal enterocytes but H. hammondi remains confined to enterocytes whereas T. gondii also parasitizes extr...

Dietary Fat Feeding Alters Lipid Peroxidation in Surfactant-like Particles Secreted by Rat Small Intestine.

PubMed

Turan, Aasma; Mahmood, Akhtar; Alpers, David H

2009-04-01

Long-term feeding of fish oil (n-3) and corn oil (n-6) markedly enhances levels of lipid peroxidation within isolated rat enterocytes. The effect is 10-fold greater at the villus tip than in the crypt region, correlating with the distribution of deleterious oxidative systems (glutathione reductase) in the tip and beneficial systems (superoxide dismutase) at the base of the villus. Because of this vertical gradient of peroxidation, the process was thought to play a role in apoptosis of enterocytes at the villus tip. Surfactant-like particles (SLPs) are membranes secreted by the enterocyte and a component of these membranes is directed to the intestinal surface overlying villus tips. One suggested role for SLPs has been to protect the mucosal surface from the harsh luminal conditions that might enhance apoptotic loss of enterocytes. The hypothesis to be tested was whether SLP lipids, like those in enterocytes, were also peroxidized, although they were external to the cellular processes that seem to oxidize enterocyte lipids, or whether SLP were immune to these biological processes. Feeding with groundnut oil (n-9) was compared with fish oil (n-3) and corn oil (predominantly n-6) to determine whether oils with various lipid composition would affect peroxidation in both SLP and enterocytes. After an overnight fast, Wistar rats were fed 2 mL of dietary oil by gavage. Five hours later SLPs and underlying microvillus membranes (MVM) were isolated and analyzed for generation of thiobarbituric acid reactive substances (TBARS) and for hydrolase activities, at baseline and after addition of an Fe +2 /ascorbate system to induce peroxidation. In vitro lipid peroxidation using the Fe 2+ /ascorbate system produced greater peroxidation than in MVM. Intestinal alkaline phosphatase (IAP), sucrase and lactase activities were decreased in SLPs, but were unaltered in MVM except for IAP. The activities of maltase, trehalase, Leucine aminopeptidase and γ-glutamyltranspeptidase, were unaffected both in SLPs and MVM under these conditions. SLPs are more susceptible to oxidative damage than are the underlying MVMs. This may reflect results of a hostile luminal environment. It is not clear whether SLPs are acting as a lipid 'sink' to protect the MVM from greater oxidation, or are providing an initial stimulus for apoptosis of villus tip enterocytes, or both.

Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.

PubMed

McFarlane, Matthew R; Liang, Guosheng; Engelking, Luke J

2014-01-24

Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes.

Insig Proteins Mediate Feedback Inhibition of Cholesterol Synthesis in the Intestine*

PubMed Central

McFarlane, Matthew R.; Liang, Guosheng; Engelking, Luke J.

2014-01-01

Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes. PMID:24337570

Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer's patch M cells.

PubMed

Owen, R L; Bhalla, D K

1983-10-01

M cells in Peyer's patch follicle epithelium endocytose and transport luminal materials to intraepithelial lymphocytes. We examined (1) enzymatic characteristics of the epithelium covering mouse and rat Peyer's patches by using cytochemical techniques, (2) distribution of lectin-binding sites by peroxidase-labeled lectins, and (3) anionic site distribution by using cationized ferritin to develop a profile of M cell surface properties. Alkaline phosphatase activity resulted in deposits of dense reaction product over follicle surfaces but was markedly reduced over M cells, unlike esterase which formed equivalent or greater product over M cells. Concanavalin A, ricinus communis agglutinin, wheat germ agglutinin and peanut agglutinin reacted equally with M cells and with surrounding enterocytes over follicle surfaces. Cationized ferritin distributed in a random fashion along microvillus membranes of both M cells and enterocytes, indicating equivalent anionic site distribution. Staining for alkaline phosphatase activity provides a new approach for distinguishing M cells from enterocytes at the light microscopic level. Identical binding of lectins indicates that M cells and enterocytes share common glycoconjugates even though molecular groupings may differ. Lectin binding and anionic charge similarities of M cells and enterocytes may facilitate antigen sampling by M cells of particles and compounds that adhere to intestinal surfaces in non-Peyer's patch areas.

Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes.

PubMed

Kodama, Nao; Iwao, Takahiro; Kabeya, Tomoki; Horikawa, Takashi; Niwa, Takuro; Kondo, Yuki; Nakamura, Katsunori; Matsunaga, Tamihide

2016-06-01

We previously reported that small-molecule compounds were effective in generating pharmacokinetically functional enterocytes from human induced pluripotent stem (iPS) cells. In this study, to determine whether the compounds promote the differentiation of human iPS cells into enterocytes, we investigated the effects of a combination of mitogen-activated protein kinase kinase (MEK), DNA methyltransferase (DNMT), and transforming growth factor (TGF)-β inhibitors on intestinal differentiation. Human iPS cells cultured on feeder cells were differentiated into endodermal cells by activin A. These endodermal-like cells were then differentiated into intestinal stem cells by fibroblast growth factor 2. Finally, the cells were differentiated into enterocyte cells by epidermal growth factor and small-molecule compounds. After differentiation, mRNA expression levels and drug-metabolizing enzyme activities were measured. The mRNA expression levels of the enterocyte marker sucrase-isomaltase and the major drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 were increased by a combination of MEK, DNMT, and TGF-β inhibitors. The mRNA expression of CYP3A4 was markedly induced by 1α,25-dihydroxyvitamin D3. Metabolic activities of CYP1A1/2, CYP2B6, CYP2C9, CYP2C19, CYP3A4/5, UDP-glucuronosyltransferase, and sulfotransferase were also observed in the differentiated cells. In conclusion, MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Shteinberg, Dan; Karry, Rahel; Lurie, Michael; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2009-05-01

Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. In the present study, we tested whether leptin can protect gut epithelial cells from methotrexate (MTX)-induced intestinal damage. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of leptin for 24 h. Cell proliferation and apoptosis were assessed using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-rats were treated with a single dose of MTX, and MTX-LEP rats were also treated with leptin for 3 d. Intestinal mucosal damage (Park score), mucosal structural changes (bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth), enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. RT-PCR was used to determine the level of bax and bcl-2 mRNA expression. In the vitro experiment, treatment with leptin of Caco-2 cells pre-treated with MTX resulted in a significant stimulation of cell proliferation and inhibition of cell apoptosis in a dose-dependent manner. In the vivo experiment, MTX-LEP rats demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, as well as a greater enterocyte proliferation index compared to MTX-animals. MTX-LEP rats also showed a trend toward an increase in enterocyte apoptosis that was accompanied by an increase in bax mRNA and decrease in bcl-2 mRNA expression. In conclusion, leptin enhances proliferation and decreases apoptosis in Caco-2 cells pretreated with MTX. In a rat model of MTX-induced mucositis, treatment with leptin improves intestinal recovery and enhances enterocyte turnover.

Threonine Affects Intestinal Function, Protein Synthesis and Gene Expression of TOR in Jian Carp (Cyprinus carpio var. Jian)

PubMed Central

Feng, Lin; Peng, Yan; Wu, Pei; Hu, Kai; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Li, Shu-Hong; Zhou, Xiao-Qiu

2013-01-01

This study aimed to investigate the effects of threonine (Thr) on the digestive and absorptive ability, proliferation and differentiation of enterocytes, and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian). First, seven isonitrogenous diets containing graded levels of Thr (7.4–25.2 g/kg diet) were fed to the fishes for 60 days. Second, enterocyte proliferation and differentiation were assayed by culturing enterocytes with graded levels of Thr (0–275 mg/l) in vitro. Finally, enterocytes were cultured with 0 and 205 mg/l Thr to determine protein synthesis. The percent weight gain (PWG), specific growth rate, feed intake, feed efficiency, protein retention value, activities of trypsin, lipase and amylase, weights and protein contents of hepatopancreas and intestine, folds heights, activities of alkaline phosphatase (AKP), γ- glutamyl transpeptidase and Na+/K+-ATPase in all intestinal segments, glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities in hepatopancreas, and 4E-BP2 gene expression in muscle, hepatopancreas and intestinal segments were significantly enhanced by Thr (p<0.05). However, the plasma ammonia concentration and TOR gene expression decreased (p<0.05). In vitro, Thr supplement significantly increased cell numbers, protein content, the activities of GOT, GPT, AKP and Na+/K+-ATPase, and protein synthesis rate of enterocytes, and decreased LDH activity and ammonia content in cell medium (p<0.05). In conclusion, Thr improved growth, digestive and absorptive capacity, enterocyte proliferation and differentiation, and protein synthesis and regulated TOR and 4E-BP2 gene expression in juvenile Jian carp. The dietary Thr requirement of juvenile Jian carp was 16.25 g/kg diet (51.3 g/kg protein) based on quadratic regression analysis of PWG. PMID:23922879

Enterocyte protein tyrosine nitration in response to Eimeria infection in broilers

USDA-ARS?s Scientific Manuscript database

Activation of pathogen-sensing mechanisms in intestinal cells initiate the generation of pathway effectors that perturb normal nutritional enterocyte (ETC) functions. Among the conserved pathway mediator molecules generated are nitric oxide (NO) and superoxide anion (SOA) which are known to interac...

Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine.

PubMed

Gajda, Angela M; Storch, Judith

2015-02-01

Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte. Copyright © 2014 Elsevier Ltd. All rights reserved.

Shiga toxin 1 interaction with enterocytes causes apical protein mistargeting through the depletion of intracellular galectin-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laiko, Marina; Murtazina, Rakhilya; Malyukova, Irina

Shiga toxins (Stx) 1 and 2 are responsible for intestinal and systemic sequelae of infection by enterohemorrhagic Escherichia coli (EHEC). However, the mechanisms through which enterocytes are damaged remain unclear. While secondary damage from ischemia and inflammation are postulated mechanisms for all intestinal effects, little evidence excludes roles for more primary toxin effects on intestinal epithelial cells. We now document direct pathologic effects of Stx on intestinal epithelial cells. We study a well-characterized rabbit model of EHEC infection, intestinal tissue and stool samples from EHEC-infected patients, and T84 intestinal epithelial cells treated with Stx1. Toxin uptake by intestinal epithelial cellsmore » in vitro and in vivo causes galectin-3 depletion from enterocytes by increasing the apical galectin-3 secretion. This Shiga toxin-mediated galectin-3 depletion impairs trafficking of several brush border structural proteins and transporters, including villin, dipeptidyl peptidase IV, and the sodium-proton exchanger 2, a major colonic sodium absorptive protein. The mistargeting of proteins responsible for the absorptive function might be a key event in Stx1-induced diarrhea. These observations provide new evidence that human enterocytes are directly damaged by Stx1. Conceivably, depletion of galectin-3 from enterocytes and subsequent apical protein mistargeting might even provide a means whereby other pathogens might alter intestinal epithelial absorption and produce diarrhea.« less

Ursodeoxycholic and deoxycholic acids: Differential effects on intestinal Ca(2+) uptake, apoptosis and autophagy of rat intestine.

PubMed

Rodríguez, Valeria A; Rivoira, María A; Pérez, Adriana del V; Marchionatti, Ana M; Tolosa de Talamoni, Nori G

2016-02-01

The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca(2+) uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca(2+) uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca(2+) uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca(2+) absorption occur by decreasing the Ca(2+) uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca(2+) uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca(2+) pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes[S

PubMed Central

Engelking, Luke J.; McFarlane, Matthew R.; Li, Christina K.; Liang, Guosheng

2012-01-01

Enterocyte cholesterol homeostasis reflects aggregated rates of sterol synthesis, efflux, and uptake from plasma and gut lumen. Cholesterol synthesis and LDL uptake are coordinately regulated by sterol regulatory element-binding proteins (SREBP), whereas sterol efflux is regulated by liver X receptors (LXR). How these processes are coordinately regulated in enterocytes, the site of cholesterol absorption, is not well understood. Here, we treat mice with ezetimibe to investigate the effect of blocking cholesterol absorption on intestinal SREBPs, LXRs, and their effectors. Ezetimibe increased nuclear SREBP-2 8-fold. HMG-CoA reductase (HMGR) and LDL receptor (LDLR) mRNA levels increased less than 3-fold, whereas their protein levels increased 30- and 10-fold, respectively. Expression of inducible degrader of LDLR (IDOL), an LXR-regulated gene that degrades LDLRs, was reduced 50% by ezetimibe. Coadministration of ezetimibe with the LXR agonist T0901317 abolished the reduction in IDOL and prevented the increase in LDLR protein. Ezetimibe-stimulated LDLR expression was independent of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. To maintain cholesterol homeostasis in the face of ezetimibe, enterocytes boost LDL uptake by increasing LDLR number, and they boost sterol synthesis by increasing HMGR and other cholesterologenic genes. These studies reveal a hitherto undescribed homeostatic network in enterocytes triggered by blockade of cholesterol absorption. PMID:22523394

Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Karry, Rahel; Shamian, Benhoor; Lurie, Michael; Kokhanovsky, Natalie; Ure, Benno M; Coran, Arnold G

2009-01-01

The objective of this study was to evaluate the effects of oral glutamine in preventing intestinal mucosal damage caused by methotrexate (MTX) in rats. Male Sprague-Dawley rats were divided into 3 experimental groups: control rats, rats treated intraperitoneally with MTX (MTX rats) and rats treated with oral glutamine in the drinking water (2%) 72 h following intraperitoneal injection of a single dose of MTX (MTX-glutamine rats). Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 h following MTX injection. RT-PCR was used to determine Bax and Bcl-2 mRNA expression. MTX-glutamine rats demonstrated greater jejunal and ileal mucosal weight and mucosal DNA, greater ileal villus height and crypt depth, and a greater index of proliferation in the jejunum and ileum compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-glutamine rats (vs. MTX) was accompanied by decreased Bax and increased Bcl-2 mRNA expression. Treatment with oral glutamine prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

Epidermal growth factor selectively enhances functional enterocyte adaptation after massive small bowel resection.

PubMed

Dunn, J C; Parungo, C P; Fonkalsrud, E W; McFadden, D W; Ashley, S W

1997-01-01

After massive small bowel resection, the intestine adapts to compensate. In addition to proliferation, enterocytes also undergo selective functional adaptation. In this study we examined the effect of intraperitoneal administration of epidermal growth factor (EGF) on the expression of the brush border dissacharidase sucrase, the sodium glucose cotransporter (SGLT1), and the sodium-potassium ATPase pump (NaK ATPase) by enterocytes in the remnant intestine after massive small bowel resection. Adult Lewis rats underwent either ileal transection or 70% proximal intestinal resection. These animals were subdivided into groups that received either saline or EGF intraperitoneally for 1 week. Ilea from each group were harvested 4 weeks postoperatively. Enterocytes were separated from these segments by calcium chelation. The total protein from the isolated cells was subjected to Western blot analysis. Administration of EGF to animals that underwent transection did not significantly alter the expression of sucrase, SGLT1, or NaK ATPase. After intestinal resection, the expressions of sucrase and SGLT1 were significantly increased. The combination of EGF administration and intestinal resection resulted in a further increase in SGLT1 expression. The intraperitoneal administration of EGF selectively enhanced the expression of SGLT1 by enterocytes after massive small bowel resection. Administration of EGF to sham-operated animals did not have similar effects. These results suggest that EGF augments the adaptive response and may therefore have a therapeutic role in the management of patients with short bowel syndrome.

Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2008-11-01

The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.

Maillard neoglycans as inhibitors for in vitro adhesion of F4+ enterotoxigenic Escherichia coli to piglet intestinal cells.

PubMed

Sarabia-Sainz, Héctor Manuel; Mata Haro, Verónica; Sarabia Sainz, José Andre-I; Vázquez-Moreno, Luz; Montfort, Gabriela Ramos-Clamont

2017-01-01

Adhesion of enterotoxigenic (ETEC) E. coli to host intestinal cells is mediated by lectin-like fimbriae that bind to specific glycan moieties on the surfaces of enterocytes. To prevent in vitro binding of E. coli F4 fimbriae (F4 ETEC + ) to piglet enterocytes, neoglycans were synthesized by the Maillard reaction conjugating lactose (Lac), galacto-oligosaccharides (GOS) or chitin oligosaccharides (Ochit) to porcine serum albumin (PSA). Neoglycans were characterized by SDS-PAGE, intrinsic tryptophan fluorescence and recognition by plant lectins, as well as by F4 ETEC variants. Electrophoretic patterns suggested the binding to PSA of 63, 13 and 2 molecules of Lac, GOS and Ochit, respectively. All neoglycans displayed quenching of tryptophan fluorescence consistent with the degree of glycation estimated by SDS-PAGE. Plant lectins recognized the neoglycans according to their specificity, whereas antigenic variants of F4 ETEC (ab, ac and ad) recognized PSA-Ochit and PSA-Lac with higher affinity than that for GOS. Neoglycans partially hindered the in vitro binding of F4 + ETEC to piglet enterocytes in a dose-dependent manner. The most effective blocking was observed with PSA-Lac that partially inhibited the adhesion of bacteria to enterocytes in a dose dependent manner, as quantified by flow cytometry. Increased production of the cytokines IL-6 and TNF-α was observed in response to F4 + ETEC infection of enterocytes and production was reduced in the presence of PSA-Ochit and PSA-GOS. These results suggest that neoglycans synthesized by the Maillard reaction could be useful in the prophylaxis of diarrhea in piglets.

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

PubMed Central

Drengstig, Tormod; Ruoff, Peter

2014-01-01

The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na+ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na+/K+ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis. PMID:24898586

Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

PubMed

Cruz-Garcia, Lourdes; Schlegel, Amnon

2014-09-01

Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Lerner, Aaron; Sabo, Edmund; Krausz, Michael M; Siplovich, Leonardo; Coran, Arnold G; Mogilner, Jorge; Shiloni, Eitan

2003-07-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal morphology and intestinal absorptive function. The purpose of the present study was to determine the effect of enteral ARG supplementation on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Thirty male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-ARG rats underwent bowel resection and were treated with ARG given in the drinking water (2%). Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-ARG animals had a lower jejunal and ileal mucosal weight, jejunal mucosal DNA and protein, ileal mucosal protein, jejunal villus height, jejunal and ileal crypt depth, and enterocyte proliferation index and a greater enterocyte apoptosis compared to SBS untreated animals. We conclude that in a rat model of SBS enteral L-arginine inhibits structural intestinal adaptation. Possible mechanism for this effect may be decreased cell proliferation and increased cell apoptosis.

Lactoferrin and lactoferrin chimera inhibit damage caused by enteropathogenic Escherichia coli in HEp-2 cells.

PubMed

Flores-Villaseñor, Héctor; Canizalez-Román, Adrian; de la Garza, Mireya; Nazmi, Kamran; Bolscher, Jan G M; Leon-Sicairos, Nidia

2012-09-01

Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea in developing countries. It produces a characteristic intestinal histopathological lesion on enterocytes known as 'attaching and effacing' (A/E), and these two steps are mediated by a type-III secretory system. In the present study, we evaluated the effect on the initial host cell attachment step produced by bovine lactoferrin (bLF) and three synthetic peptides: lactoferricin (LFcin), lactoferrampin (LFampin) and LFchimera. A special focus was given to the hemolytic activity and EPEC-induced actin polymerization in HEp-2 cells, as well as to the espA gene expression, which produces the protein responsible for primary contact with the host cells. Results show that EPEC attachment to HEp-2 cells was significantly suppressed by bLF and LFchimera at 125 and 40 μM, respectively. EPEC-mediated actin polymerization was blocked by bLF and LFchimera at 88 and 99%, respectively. LFchimera inhibited the attachment and A/E lesion caused by EPEC in a dose-dependent manner. In the presence of 125 μM bLF, the expression level of the espA gene was decreased by 50% compared to the untreated control. LFchimera at concentrations of 20 μM and 40 μM diminished the level of espA gene expression 100 and 1000 fold, respectively (P < 0.001). Although bLF, LFchimera, LFcin, and LFampin all significantly blocked the hemolysis produced by EPEC (P < 0.001), the two former compounds produced this effect at lower concentrations. These two compounds, bLF and LFchimera, were able to inhibit the first steps of the mechanism of the damage used by EPEC. This data suggests that LFchimera could provide protection against enteropathogens that share this mechanism. Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.

Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes

USDA-ARS?s Scientific Manuscript database

We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with C...

Responsiveness of intestinal epithelial cell turnover to TGF-alpha after bowel resection in a rat is correlated with EGF receptor expression along the villus-crypt axis.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Shaoul, Ron; Karry, Rahel; Lieber, Michael; Suss-Toby, Edith; Ure, Benno M; Coran, Arnold G

2008-01-01

Recent evidence suggests that transforming growth factor alpha (TGF-alpha) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-alpha on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-alpha rats underwent bowel resection and were treated with TGF-alpha (75 microg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-alpha resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 +/- 0.013 vs 0.010 +/- 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 +/- 8 vs 138 +/- 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-alpha administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 +/- 0.002 vs 0.029 +/- 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 +/- 0.001 vs 0.028 +/- 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-alpha (group C). In a rat model of SBS, TGF-alpha increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-alpha on enterocyte turnover is correlated with EGF receptor expression along the villus-crypt axis.

Acute Effects of Sugars and Artificial Sweeteners on Small Intestinal Sugar Transport: A Study Using CaCo-2 Cells As an In Vitro Model of the Human Enterocyte.

PubMed

O'Brien, Patrick; Corpe, Christopher Peter

2016-01-01

The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function. To study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte. Uptake of 10mM 14C D-Glucose and D-Fructose into confluent CaCo-2/TC7 cells was assessed following 3hr preincubation with sugars and artificial sweeteners in the presence and absence of the sweet taste receptor inhibitor, lactisole. Expression of the intestinal sugar transporters and sweet-taste receptors were also determined by RT-PCR. In response to short term changes in extracellular glucose and glucose/fructose concentrations (2.5mM to 75mM) carrier-mediated sugar uptake mediated by SGLT1 and/or the facilitative hexose transporters (GLUT1,2,3 and 5) was increased. Lactisole and artificial sweeteners had no effect on sugar transport regulated by glucose alone; however, lactisole increased glucose transport in cells exposed to glucose/fructose. RT-PCR revealed Tas1r3 and SGLT3 gene expression in CaCo-2/TC7 cells, but not Tas1r2. In the short term, enterocyte sugar transport activities respond directly to extracellular glucose levels, but not fructose or artificial sweeteners. We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells. However, when glucose/fructose is administered together there is an inhibitory effect on glucose transport possibly mediated by T1R3.

Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Negoro, Ryosuke; Takayama, Kazuo; The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research

Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cellsmore » were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or 1α,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8-fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. - Highlights: • The hiPS-ELCs were matured by Matrigel overlay. • The hiPS-ELCs expressed intestinal nuclear receptors, such as PXR, GR and VDR. • The hiPS-ELC is a useful model for the drug-mediated CYP3A4 induction test.« less

Host Response to Probiotics Determined by Nutritional Status of Rotavirus-infected Neonatal Mice

PubMed Central

Preidis, Geoffrey A.; Saulnier, Delphine M.; Blutt, Sarah E.; Mistretta, Toni-Ann; Riehle, Kevin P.; Major, Angela M.; Venable, Susan F.; Barrish, James P.; Finegold, Milton J.; Petrosino, Joseph F.; Guerrant, Richard L.; Conner, Margaret E.; Versalovic, James

2014-01-01

Objectives Beneficial microbes and probiotics are promising agents for the prevention and treatment of enteric and diarrheal diseases in children; however, little is known about their in vivo mechanisms of action. We used a neonatal mouse model of rotavirus diarrhea to gain insight into how probiotics ameliorate acute gastroenteritis. Methods Rotavirus-infected mice were treated with 1 of 2 strains of human-derived Lactobacillus reuteri. We assessed intestinal microbiome composition with 16S metagenomic sequencing, enterocyte migration and proliferation with 5-bromo-2′-deoxyuridine, and antibody and cytokine concentrations with multiplex analyses of intestinal explant cultures. Results Probiotics reduced diarrhea duration, improved intestinal histopathology, and enhanced intestinal microbiome richness and phylogenetic diversity. The magnitude of reduction of diarrhea by probiotics was strain specific and influenced by nutritional status. L reuteri DSM 17938 reduced diarrhea duration by 0, 1, and 2 days in underweight, normal weight, and overweight pups, respectively. The magnitude of reduction of diarrhea duration correlated with increased enterocyte proliferation and migration. Strain ATCC PTA 6475 reduced diarrhea duration by 1 day in all of the mice without increasing enterocyte proliferation. Both probiotic strains decreased concentrations of proinflammatory cytokines, including macrophage inflammatory protein-1α and interleukin-1β, in all of the animals, and increased rotavirus-specific antibodies in all but the underweight animals. Body weight also influenced the host response to rotavirus, in terms of diarrhea duration, enterocyte turnover, and antibody production. Conclusions These data suggest that probiotic enhancement of enterocyte proliferation, villus repopulation, and virus-specific antibodies may contribute to diarrhea resolution, and that nutritional status influences the host response to both beneficial microbes and pathogens. PMID:22343914

In vitro and in vivo protective effect of arginine against lipopolysaccharide induced inflammatory response in the intestine of juvenile Jian carp (Cyprinus carpio var. Jian).

PubMed

Jiang, Jun; Shi, Dan; Zhou, Xiao-Qiu; Hu, Yi; Feng, Lin; Liu, Yang; Jiang, Wei-Dan; Zhao, Ye

2015-02-01

The present study was designed to assess the possible protective effects of arginine (Arg) against lipopolysaccharide (LPS) induced inflammatory response in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. Firstly, inflammatory response was established by exposing enterocytes to different concentrations of LPS for 24 h. Secondly, the protective effects of Arg against subsequent LPS exposure were studied in enterocytes. Finally, we investigated whether dietary Arg supplementation could attenuate immune challenge induced by LPS in vivo. The result indicated that 10 mg/L LPS could induced inflammatory response in enterocytes. Cells exposed to LPS (10-30 mg/L) alone for 24 h resulted in a significant increase in lactate dehydrogenase release (LDH) (P < 0.05). The cell viability, protein content, alkaline phosphatase activity were decreased by LPS (P < 0.05). Moreover, LPS exposure significantly increased TNF-α, IL-1β, and IL-6 mRNA expression in vitro (P < 0.05). However, pre-treatment with Arg remarkably prevented the increase of TNF-α, IL-1β, and IL-6 by inhibiting the excessive activation of TLR4-Myd88 signaling pathway through down-regulating TLR4, Myd88, NFκB p65, and MAPK p38 mRNA expression (P < 0.05). Interestingly, the experiment in vivo showed that Arg pre-supplementation could attenuate immune challenge induced by LPS via TLR4-Myd88 signaling pathway, and thus protect fish against LPS-induced inflammatory response. In conclusion, all of these results indicated pre-supplementation with Arg decreased LPS induced immune damage and regulated TLR4-Myd88 signaling pathway in juvenile Jian carp in vivo and in enterocytes in vitro. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen

PubMed Central

Pauquai, Thomas; Bouchoux, Julien; Chateau, Danielle; Vidal, Romain; Rousset, Monique; Chambaz, Jean; Demignot, Sylvie

2006-01-01

Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia. PMID:16393142

Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis

PubMed Central

Zhang, Jidong; Verma, Rakesh; Park, Tae-Ju; Wong, Hetty; Curran, Tom; Nihalani, Deepak; Holzman, Lawrence B.

2014-01-01

Activation of the slit diaphragm protein Nephrin induces actin cytoskeletal remodeling resulting in lamellipodia formation in podocytes in vitro in a phosphatidylinositol-3 kinase, focal adhesion kinase, Cas, and Crk1/2-dependent fashion. In mice, podocyte-specific deletion of Crk1/2 prevents or attenuates foot process effacement in two models of podocyte injury. This suggests that cellular mechanisms governing lamellipodial protrusion in vitro are similar to those in vivo during foot process effacement. Since Crk1/2 null mice develop and aged normally, we tested whether the Crk1/2 paralog, CrkL, functionally complements Crk1/2 in a podocyte-specific context. Podocyte-specific CrkL null mice, like podocyte-specific Crk1/2 null mice, developed and aged normally but were protected from protamine sulfate-induced foot process effacement. Simultaneous podocyte-specific deletion of Crk1/2 and CrkL resulted in albuminuria detected by six weeks post-partum and associated with altered podocyte process architecture. Nephrin-induced lamellipodia formation in podocytes in vitro was CrkL-dependent. CrkL formed a heterooligomer with Crk2 and, like Crk2, was recruited to tyrosine phosphorylated Nephrin. Thus, Crk1/2 and CrkL are physically-linked, functionally complement each other during podocyte foot process spreading, and together are required for developing typical foot process architecture. PMID:24499776

Osteopontin Mediates Citrobacter rodentium-Induced Colonic Epithelial Cell Hyperplasia and Attaching-Effacing Lesions

PubMed Central

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G.; Goldberg, Harvey A.; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S.; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M.

2010-01-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN−/− fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN−/− mice, and spleen enlargement by infection was absent in OPN−/− mice. Rectal administration of OPN to OPN−/− mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN−/− mice, compared with wild-type mice, which was accompanied by reduced attaching–effacing lesions, both in infected OPN−/− mice and OPN−/− mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN−/− cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses. PMID:20651246

Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

PubMed

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

2010-09-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat.

PubMed

Koppelmann, Tal; Pollak, Yulia; Mogilner, Jorge; Bejar, Jacob; Coran, Arnold G; Sukhotnik, Igor

2012-04-30

Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes.

PubMed

Paparo, L; Aitoro, R; Nocerino, R; Fierro, C; Bruno, C; Canani, R Berni

2018-01-29

Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

Characterization of the sensor domain of QseE histidine kinase from Escherichia coli.

PubMed

Yeo, Kwon Joo; Park, Jin-Wan; Kim, Eun-Hee; Jeon, Young Ho; Hwang, Kwang Yeon; Cheong, Hae-Kap

2016-10-01

In enterohemorrhagic Escherichia coli (EHEC), the QseEF two-component system causes attaching and effacing (AE) lesion on epithelial cells. QseE histidine kinase senses the host hormone epinephrine, sulfate, and phosphate; it also regulates QseF response regulator, which activates LEE gene that encodes AE lesion. In order to understand the recognition of ligand molecules and signal transfer mechanism in pathogenic bacteria, structural studies of the sensor domain of QseE of Escherichia coli should be conducted. In this study, we describe the overexpression, purification, and structural and biophysical properties of the sensor domain of QseE. The fusion protein had a 6×His tag at its N-terminus; this protein was overexpressed as inclusion bodies in E. coli BL21 (DE3). The protein was denatured in 7M guanidine hydrochloride and refolded by dialysis. The purification of the refolded protein was carried out using Ni-NTA affinity column and size-exclusion chromatography. Thereafter, the characteristics of the refolded protein were determined from NMR, CD, and MALS spectroscopies. In a pH range of 7.4-5.0, the folded protein existed in a monomeric form with a predominantly helical structure. (1)H-(15)N HSQC NMR spectra shows that approximately 93% backbone amide peaks are detected at pH 5.0, suggesting that the number of backbone signals is sufficient for NMR studies. These data might provide an opportunity for structural and functional studies of the sensor domain of QseE. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-Dependent Enterocyte Invasion and Microcolony Formation by Salmonella

PubMed Central

Zhang, Kaiyi; Dupont, Aline; Torow, Natalia; Gohde, Fredrik; Leschner, Sara; Lienenklaus, Stefan; Weiss, Siegfried; Brinkmann, Melanie M.; Kühnel, Mark; Hensel, Michael; Fulde, Marcus; Hornef, Mathias W.

2014-01-01

The coordinated action of a variety of virulence factors allows Salmonella enterica to invade epithelial cells and penetrate the mucosal barrier. The influence of the age-dependent maturation of the mucosal barrier for microbial pathogenesis has not been investigated. Here, we analyzed Salmonella infection of neonate mice after oral administration. In contrast to the situation in adult animals, we observed spontaneous colonization, massive invasion of enteroabsorptive cells, intraepithelial proliferation and the formation of large intraepithelial microcolonies. Mucosal translocation was dependent on enterocyte invasion in neonates in the absence of microfold (M) cells. It further resulted in potent innate immune stimulation in the absence of pronounced neutrophil-dominated pathology. Our results identify factors of age-dependent host susceptibility and provide important insight in the early steps of Salmonella infection in vivo. We also present a new small animal model amenable to genetic manipulation of the host for the analysis of the Salmonella enterocyte interaction in vivo. PMID:25210785

Acute Effects of Sugars and Artificial Sweeteners on Small Intestinal Sugar Transport: A Study Using CaCo-2 Cells As an In Vitro Model of the Human Enterocyte

PubMed Central

2016-01-01

Background The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function. Aims To study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte. Methods Uptake of 10mM 14C D-Glucose and D-Fructose into confluent CaCo-2/TC7 cells was assessed following 3hr preincubation with sugars and artificial sweeteners in the presence and absence of the sweet taste receptor inhibitor, lactisole. Expression of the intestinal sugar transporters and sweet-taste receptors were also determined by RT-PCR. Results In response to short term changes in extracellular glucose and glucose/fructose concentrations (2.5mM to 75mM) carrier-mediated sugar uptake mediated by SGLT1 and/or the facilitative hexose transporters (GLUT1,2,3 and 5) was increased. Lactisole and artificial sweeteners had no effect on sugar transport regulated by glucose alone; however, lactisole increased glucose transport in cells exposed to glucose/fructose. RT-PCR revealed Tas1r3 and SGLT3 gene expression in CaCo-2/TC7 cells, but not Tas1r2. Conclusions In the short term, enterocyte sugar transport activities respond directly to extracellular glucose levels, but not fructose or artificial sweeteners. We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells. However, when glucose/fructose is administered together there is an inhibitory effect on glucose transport possibly mediated by T1R3. PMID:27992462

Effects of water temperature and diets containing palm oil on fatty acid desaturation and oxidation in hepatocytes and intestinal enterocytes of rainbow trout (Oncorhynchus mykiss).

PubMed

Tocher, Douglas R; Fonseca-Madrigal, Jorge; Dick, James R; Ng, Wing-Keong; Bell, J Gordon; Campbell, Patrick J

2004-01-01

Food grade fisheries have reached their sustainable limits while aquaculture production has increased to meet consumer demands. However, for growth in aquaculture to continue and utilise sustainable, feeding ingredients, alternatives to fish oil (FO), the predominant lipid component of fish diets, must be developed. Therefore, there is currently considerable interest in the regulation of fatty acid metabolism in fish in order to determine strategies for the best use of plant oils in diets for commercially important cultured fish species. Plant oils are characteristically rich in C18 polyunsaturated fatty acids (PUFA) but devoid of C20 and C22 highly unsaturated fatty acids (HUFA) found in FO. The fatty acyl desaturase enzyme activities involved in the biosynthesis of HUFA from PUFA are known to be under nutritional regulation and can be increased in fish fed diets rich in plant oils. However, fatty acid desaturase activity is also known to be modulated by water temperature in fish. The present study aimed to investigate the interaction between water temperature and diet in the regulation of fatty acid metabolism in rainbow trout. Trout, acclimatized to 7, 11 or 15 degrees C, were fed for 4 weeks on diets in which the FO was replaced in a graded manner by palm oil. At the end of the trial, fatty acyl desaturation/elongation and beta-oxidation activities were determined in isolated hepatocytes and intestinal enterocytes using [1-14C]18:3n-3 as substrate, and samples of liver were collected for analysis of lipid and fatty acid composition. The most obvious effect of temperature was that fatty acid desaturation/elongation and beta-oxidation were reduced in both hepatocytes and intestinal enterocytes from fish maintained at the highest water temperature (15 degrees C). There were differences between the two tissues with the highest desaturation/elongation and beta-oxidation activities tending to be in fish held at 11 degrees C in the case of hepatocytes, but 7 degrees C in enterocytes. Correlations between fatty acid metabolism and dietary palm oil were most clearly observed in desaturation/elongation activities in both hepatocytes and enterocytes at 11 degrees C. The highest beta-oxidation activities were generally observed in fish fed FO alone in both hepatocytes and enterocytes with palm oil having differential effects in the two cell types.

Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

PubMed Central

Dawson, Paul A.

2011-01-01

Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTα. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions. PMID:21103970

Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

PubMed Central

2012-01-01

Background Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Methods Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. Results MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Conclusions Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat. PMID:22545735

Edwin Lee | NREL

Science.gov Websites

Edwin Lee Photo of Edwin Lee Edwin Lee Researcher III-Mechanical Engineering Edwin.Lee@nrel.gov | 303-275-3110 Edwin Lee joined NREL in 2013 and works in the Commercial Buildings Research Group. He

Development of large intestinal attaching and effacing lesions in pigs in association with the feeding of a particular diet.

PubMed Central

Neef, N A; McOrist, S; Lysons, R J; Bland, A P; Miller, B G

1994-01-01

Hysterotomy-derived piglets were kept in gnotobiotic isolators and artificially colonized at 7 days of age with an adult bovine enteric microflora. At 3 weeks of age, the pigs were transferred to conventional experimental accommodation and weaned, either onto a solid diet that had been associated with field cases of typhlocolitis in pigs or onto a solid control diet. At necropsy at 5 weeks of age, groups of pigs fed the diet associated with field cases of typhlocolitis were found to have developed typhlocolitis. This was absent from the groups fed the control diet. The typhlocolitis was characterized by attaching and effacing lesions typical of those described following experimental inoculation of various species with enteropathogenic Escherichia coli. A nonverocytotoxic, eae probe-positive E. coli serotype O116 was isolated from pigs on the colitis-associated diet but not from any of the pigs on the control diet. Coliform bacteria attached to the colonic lesions reacted with polyclonal antiserum to E. coli O116 in an immunoperoxidase assay of histological sections of affected tissue. No reaction with this antiserum was observed in corresponding tissue sections taken from pigs on the control diet. No colon lesions were observed in germfree pigs fed either of the diets. It is postulated that proliferation and possibly expression of pathogenicity of the attaching and effacing E. coli responsible for the lesions are strongly influenced by diet. Images PMID:7927691

Development of large intestinal attaching and effacing lesions in pigs in association with the feeding of a particular diet.

PubMed

Neef, N A; McOrist, S; Lysons, R J; Bland, A P; Miller, B G

1994-10-01

Hysterotomy-derived piglets were kept in gnotobiotic isolators and artificially colonized at 7 days of age with an adult bovine enteric microflora. At 3 weeks of age, the pigs were transferred to conventional experimental accommodation and weaned, either onto a solid diet that had been associated with field cases of typhlocolitis in pigs or onto a solid control diet. At necropsy at 5 weeks of age, groups of pigs fed the diet associated with field cases of typhlocolitis were found to have developed typhlocolitis. This was absent from the groups fed the control diet. The typhlocolitis was characterized by attaching and effacing lesions typical of those described following experimental inoculation of various species with enteropathogenic Escherichia coli. A nonverocytotoxic, eae probe-positive E. coli serotype O116 was isolated from pigs on the colitis-associated diet but not from any of the pigs on the control diet. Coliform bacteria attached to the colonic lesions reacted with polyclonal antiserum to E. coli O116 in an immunoperoxidase assay of histological sections of affected tissue. No reaction with this antiserum was observed in corresponding tissue sections taken from pigs on the control diet. No colon lesions were observed in germfree pigs fed either of the diets. It is postulated that proliferation and possibly expression of pathogenicity of the attaching and effacing E. coli responsible for the lesions are strongly influenced by diet.

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Effects of fasting and semistarvation on the kinetics of active and passive sugar absorption across the small intestine in vivo.

PubMed Central

Debnam, E S; Levin, R J

1975-01-01

The effects of dietary restriction on the kinetics of absorption in vivo of glucose, galactose and alpha-methyl glucoside were assessed by electrical and chemical methods in the rat jejunum. 2. The 'apparent Km', maximum absorption or Vmax (mu-mole/10 cm. 15 min) and maximum potential difference (p.d.max) were obtained for the jejunal electrogenic active transfer mechanism from the transfer p.d.s and the chemical absorption data corrected for diffusion using various graphical kinetic plots. 3. Fasting for 3 days greatly decreased the 'apparent Kms', obtained from electrical or chemical data, for all the sugars but had no effect on those for L-valine or L-methionine. Semistarvation caused a less pronounced reduction of the 'apparent Kms' for the sugars. The dietary-induced change in 'apparent Km' for glucose was also observed in the fasted hamster. One interpretation of these changes is that the affinity of the carriers for sugars increases during dietary restriction; the greater the level of restriction the greater the increase. 4. Fasting and semistarvation caused large reductions in the Vmax. These reductions were correlated with a reduced enterocyte population estimated by changes in enterocyte column size. 5. The reduction in the Vmax for galactose was mainly accounted for by the decrease in enterocyte population. In the case of glucose, other factors such as reduced enterocyte metabolism or changes in the carriers must be involved to explain the discrepancy between the large decrease in Vmax and the enterocyte column size. 6. Fasting and semi-starvation had complex, differential actions on the p.d.max for glucose, galactose and alpha-methyl glucoside. These changes did not correlate with those observed in the Vmax measured chemically. 7. A standard diet obtained from two commercial sources was found to differ greatly in its effect on the electrogenic transfer system for alpha-methyl glucoside but had no effect on those for galactose and glucose. PMID:1206572

Cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals.

PubMed

Qin, Bolin; Polansky, Marilyn M; Sato, Yuzo; Adeli, Khosrow; Anderson, Richard A

2009-11-01

We have reported previously that a cinnamon extract (CE), high in type A polyphenols, prevents fructose feeding-induced decreases in insulin sensitivity and suggested that improvements of insulin sensitivity by CE were attributable, in part, to enhanced insulin signaling. In this study, we examined the effects of CE on postprandial apolipoprotein (apo) B-48 increase in fructose-fed rats, and the secretion of apoB48 in freshly isolated intestinal enterocytes of fructose-fed hamsters. In an olive oil loading study, a water-soluble CE (Cinnulin PF, 50 mg/kg body weight, orally) decreased serum triglyceride (TG) levels and the over production of total- and TG-rich lipoprotein-apoB48. In ex vivo (35)S labeling study, significant decreases were also observed in apoB48 secretion into the media in enterocytes isolated from fructose-fed hamsters. We also investigated the molecular mechanisms of the effects of CE on the expression of genes of the insulin signaling pathway [insulin receptor (IR), IR substrate (IRS)1, IRS2 and Akt1], and lipoprotein metabolism [microsomal TG transfer protein (MTP), sterol regulatory element-binding protein (SREBP1c) in isolated primary enterocytes of fructose-fed hamsters, using quantitative real-time polymerase chain reaction. The CE reversed the expression of the impaired IR, IRS1, IRS2 and Akt1 mRNA levels and inhibited the overexpression of MTP and SREBP1c mRNA levels of enterocytes. Taken together, our data suggest that the postprandial hypertriglycerides and the overproduction of apoB48 can be acutely inhibited by a CE by a mechanism involving improvements of insulin sensitivity of intestinal enterocytes and regulation of MTP and SREBP1c levels. We present both in vivo and ex vivo evidence that a CE improves the postprandial overproduction of intestinal apoB48-containing lipoproteins by ameliorating intestinal insulin resistance and may be beneficial in the control of lipid metabolism.

Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian).

PubMed

Jiang, Jun; Shi, Dan; Zhou, Xiao-Qiu; Yin, Long; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Tang, Ling; Wu, Pei; Zhao, Ye

2015-11-28

The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

Conserved Genetic Pathways Controlling the Development of the Diffuse Endocrine System in Vertebrates and Drosophila

PubMed Central

Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina

2014-01-01

The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. PMID:20005229

Intestinal surfactant permeation enhancers and their interaction with enterocyte cell membranes in a mucosal explant system.

PubMed

Danielsen, E Michael; Hansen, Gert H

2017-07-03

Intestinal permeation enhancers (PEs) are agents aimed to improve oral delivery of therapeutic drugs with poor bioavailability. The main permeability barrier for oral delivery is the intestinal epithelium, and PEs act to increase the paracellular and/or transcellular passage of drugs. Transcellular passage can be achieved by cell membrane permeabilization and/or by endocytic uptake and subsequent transcytosis. One broad class of PEs is surfactants which act by inserting into the cell membrane, thereby perturbing its integrity, but little is known about how the dynamics of the membrane are affected. In the present work, the interaction of the surfactants lauroyl-L-carnitine, 1-decanoyl-rac-glycerol, and nonaethylene glycol monododecyl ether with the intestinal epithelium was studied in organ cultured pig jejunal mucosal explants. As expected, at 2 mM, these agents rapidly permeabilized the enterocytes for the fluorescent polar tracer lucifer yellow, but surprisingly, they all also blocked both constitutive -and receptor-mediated pathways of endocytosis from the brush border, indicating a complete arrest of apical membrane trafficking. At the ultrastructural level, the PEs caused longitudinal fusion of brush border microvilli. Such a membrane fusogenic activity could also explain the observed formation of vesicle-like structures and large vacuoles along the lateral cell membranes of the enterocytes induced by the PEs. We conclude that the surfactant action of the PEs selected in this study not only permeabilized the enterocytes, but profoundly changed the dynamic properties of their constituent cell membranes.

Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway

PubMed Central

Takashima, Shigeo; Adams, Katrina L.; Ortiz, Paola A.; Ying, Chong T.; Moridzadeh, Rameen; Younossi-Hartenstein, Amelia; Hartenstein, Volker

2013-01-01

In this paper we have investigated the developmental-genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation, and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells. PMID:21382366

The effectiveness of humor in persuasion: the case of business ethics training.

PubMed

Lyttle, J

2001-04-01

In this study, persuasion theory was used to develop the following predictions about use of humor in persuasive messages for business ethics training: (a) cartoon drawings will enhance persuasion by creating liking for the source, (b) ironic wisecracks will enhance persuasion by serving as a distraction from counterarguments, and (c) self-effacing humor will enhance persuasion by improving source credibility. Canadian business students (N = 148) participated in 1 of 4 versions of "The Ethics Challenge," a training exercise used by the Lockheed Martin Corporation. Three versions were modified by adding or removing cartoon drawings (of cartoon characters Dilbert and Dogbert) and humorous responses (Dogbert's wisecracks). Removing the cartoon drawings had little effect on persuasiveness. Removing ironic wisecracks had more effect, and interfering with the self-effacing combination of cartoons and wisecracks had the strongest effect. The results suggest that researchers should ground their predictions in existing theory and that practitioners should differentiate among humor types.

On the linear programming bound for linear Lee codes.

PubMed

Astola, Helena; Tabus, Ioan

2016-01-01

Based on an invariance-type property of the Lee-compositions of a linear Lee code, additional equality constraints can be introduced to the linear programming problem of linear Lee codes. In this paper, we formulate this property in terms of an action of the multiplicative group of the field [Formula: see text] on the set of Lee-compositions. We show some useful properties of certain sums of Lee-numbers, which are the eigenvalues of the Lee association scheme, appearing in the linear programming problem of linear Lee codes. Using the additional equality constraints, we formulate the linear programming problem of linear Lee codes in a very compact form, leading to a fast execution, which allows to efficiently compute the bounds for large parameter values of the linear codes.

United States Forces Korea > Home

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commander; Gen. Leem Ho Young, Combined Forces Command deputy commander; and Gen. Lee Sun-jin, Gen. Lee, Sun Forces Command deputy commander; and Gen. Lee Sun-jin, Gen. Lee, Sun-Jin, Chairman of the Republic of deputy commander; and Gen. Lee Sun-jin, Gen. Lee, Sun-Jin, Chairman of the Republic of Korea Joint Chiefs

Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

PubMed

Huntington, Susie; Thorne, Claire; Newell, Marie-Louise; Anderson, Jane; Taylor, Graham P; Pillay, Deenan; Hill, Teresa; Tookey, Pat A; Sabin, Caroline

2015-04-24

The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4). Women starting ART in 2000-2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4 cell count, drug regimen and hepatitis B virus/hepatitis C virus (HBV/HCV) coinfection. One-quarter (25.7%, 982/3815) of women were pregnant during follow-up, 14.2% (n = 541) when starting ART. The rate of LEE was 14.5/100 person-years in and 6.0/100 person-years outside of pregnancy. The rate of severe LEE was 3.9/100 person-years in and 0.6/100 person-years outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy [LEE: adjusted hazard ratio (aHR) 1.66 (1.31-2.09); severe LEE: aHR 3.57 (2.30-5.54)], including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4 cell count (<250 cells/μl), HBV/HCV coinfection and calendar year. Although few women developed severe LEE, this study provides further evidence that pregnancy is associated with an increased risk of LEE and severe LEE, reinforcing the need for regular monitoring of liver biomarkers during pregnancy.

An alternative explanation for the occurrence of short circuit current increases in the small intestine following challenge by bacterial enterotoxins.

PubMed

Lucas, M L

2013-10-01

Secretory diarrhoeal disease due to enterotoxins is thought to arise from the enhancement to pathologically high rates of normally occurring chloride ion and therefore fluid secretion from enterocytes. In support of this concept, many enterotoxins increase intestinal short-circuit current, regarded now as faithfully reflecting the increased chloride ion secretion. Contradicting this assumption, STa reduces absorption but does not cause secretion in vivo although short-circuit current is increased in vitro. There is therefore a mismatch between an assumed enterocyte mediated secretory event that should but does not cause net fluid secretion and an undoubtedly increased short-circuit current. It is proposed here that short-circuit current increases are not themselves secretory events but result from interrupted fluid absorption. A noteworthy feature of compounds that inhibit the increase in short-circuit current is that the majority are vasoactive, neuroactive or both. In general, vasodilator substances increase current. An alternative hypothesis for the origin of short-circuit current increases is that these result from reflex induction of electrogenic fluid absorption. This reflex enhances a compensatory response that is also present at a cellular level. An intestinal reflex is therefore proposed by which decreases in interstitial and intravascular volume or pressure within the intestine initiate an electrogenic fluid absorption mechanism that compensates for the loss of electrically neutral fluid absorption. This hypothesis would explain the apparently complex pharmacology of short-circuit current increases since many depressor substances have receptors in common with enterocytes and enteric nerves. The proposed alternative view of the origin of short-circuit current increases assumes that these do not represent chloride secretion from the enterocytes. This view may therefore aid the successful development of anti-diarrhoeal drugs to overcome a major cause of infant mortality worldwide, if short-circuit current data are being persistently misinterpreted. The putative but testable link between interstitial volume or pressure and fluid absorption also provides support for the alternative view of secretion; namely, that enhanced capillary and epithelial cell tight junctional permeability together with increased intracapillary pressure may cause secretion and not chloride exit from the enterocytes. Copyright © 2013. Published by Elsevier Ltd.

Membrane Lipid Microenvironment Modulates Thermodynamic Properties of the Na+-K+-ATPase in Branchial and Intestinal Epithelia in Euryhaline Fish In vivo

PubMed Central

Díaz, Mario; Dópido, Rosa; Gómez, Tomás; Rodríguez, Covadonga

2016-01-01

We have analyzed the effects of different native membrane lipid composition on the thermodynamic properties of the Na+-K+-ATPase in different epithelia from the gilthead seabream Sparus aurata. Thermodynamic parameters of activation for the Na+-K+-ATPase, as well as contents of lipid classes and fatty acids from polar lipids were determined for gill epithelia and enterocytes isolated from pyloric caeca, anterior intestine and posterior intestine. Arrhenius analyses of control animals revealed differences in thermal discontinuity values (Td) and activation energies determined at both sides of Td between intestinal and gill epithelia. Eyring plots disclosed important differences in enthalpy of activation (ΔH‡) and entropy of activation (ΔS‡) between enterocytes and branchial cells. Induction of n-3 LCPUFA deficiency dramatically altered membrane lipid composition in enterocytes, being the most dramatic changes the increase in 18:1n-9 (oleic acid) and the reduction of n-3 LCPUFA (mainly DHA, docosahexaenoic acid). Strikingly, branchial cells were much more resistant to diet-induced lipid alterations than enterocytes, indicating the existence of potent lipostatic mechanisms preserving membrane lipid matrix in gill epithelia. Paralleling lipid alterations, values of Ea1, ΔH‡ and ΔS‡ for the Na+-K+-ATPase were all increased, while Td values vanished, in LCPUFA deficient enterocytes. In turn, Differences in thermodynamic parameters were highly correlated with specific changes in fatty acids, but not with individual lipid classes including cholesterol in vivo. Thus, Td was positively related to 18:1n-9 and negatively to DHA. Td, Ea1 and ΔH‡ were exponentially related to DHA/18:1n-9 ratio. The exponential nature of these relationships highlights the strong impact of subtle changes in the contents of oleic acid and DHA in setting the thermodynamic properties of epithelial Na+-K+-ATPase in vivo. The effects are consistent with physical effects on the lipid membrane surrounding the enzyme as well as with direct interactions with the Na+-K+-ATPase. PMID:28018232

Does apical membrane GLUT2 have a role in intestinal glucose uptake?

PubMed

Naftalin, Richard J

2014-01-01

It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations.

Does apical membrane GLUT2 have a role in intestinal glucose uptake?

PubMed Central

Naftalin, Richard J

2014-01-01

It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations. PMID:25671087

Migration of Drosophila intestinal stem cells across organ boundaries

PubMed Central

Takashima, Shigeo; Paul, Manash; Aghajanian, Patrick; Younossi-Hartenstein, Amelia; Hartenstein, Volker

2013-01-01

All components of the Drosophila intestinal tract, including the endodermal midgut and ectodermal hindgut/Malpighian tubules, maintain populations of dividing stem cells. In the midgut and hindgut, these stem cells originate from within larger populations of intestinal progenitors that proliferate during the larval stage and form the adult intestine during metamorphosis. The origin of stem cells found in the excretory Malpighian tubules (‘renal stem cells’) has not been established. In this paper, we investigate the migration patterns of intestinal progenitors that take place during metamorphosis. Our data demonstrate that a subset of adult midgut progenitors (AMPs) move posteriorly to form the adult ureters and, consecutively, the renal stem cells. Inhibiting cell migration by AMP-directed expression of a dominant-negative form of Rac1 protein results in the absence of stem cells in the Malpighian tubules. As the majority of the hindgut progenitor cells migrate posteriorly and differentiate into hindgut enterocytes, a group of the progenitor cells, unexpectedly, invades anteriorly into the midgut territory. Consequently, these progenitor cells differentiate into midgut enterocytes. The midgut determinant GATAe is required for the differentiation of midgut enterocytes derived from hindgut progenitors. Wingless signaling acts to balance the proportion of hindgut progenitors that differentiate as midgut versus hindgut enterocytes. Our findings indicate that a stable boundary between midgut and hindgut/Malpighian tubules is not established during early embryonic development; instead, pluripotent progenitor populations cross in between these organs in both directions, and are able to adopt the fate of the organ in which they come to reside. PMID:23571215

Metabolism of sn-1(3)-Monoacylglycerol and sn-2-Monoacylglycerol in Caecal Enterocytes and Hepatocytes of Brown Trout (Salmo trutta).

PubMed

Li, Keshuai; Olsen, Rolf Erik

2017-01-01

sn-2-Monoacylglycerol (2-MAG) and sn-1(3)-monoacylglycerol [1(3)-MAG] are important but yet little studied intermediates in lipid metabolism. The current study compared the metabolic fate of 2-MAG and 1(3)-MAG in isolated caecal enterocytes and hepatocytes of brown trout (Salmo trutta). 1(3)-Oleoyl [9,10-3H(N)]-glycerol and 2-Oleoyl [9,10-3H(N)]-glycerol were prepared by pancreatic lipase digestion of triolein [9,10-3H(N)]. The 1(3)-MAG and 2-MAG were efficiently absorbed by enterocytes and hepatocytes at similar rates. The 2-MAG was quickly resynthesized into TAG through the monoacylglycerol acyltransferase (EC: 2.3.1.22, MGAT) pathway in both tissues, whereas 1(3)-MAG was processed into TAG and phospholipids at a much slower rate, suggesting 2-MAG was the preferred substrates for MGAT. Further analysis showed that 1(3)-MAG was synthesized into 1,3-DAG, but there were no accumulation of 1,3-DAG in either enterocytes or hepatocytes, which contrasts that of mammalian studies. Some of the 1(3)-MAG may be acylated to 1,2(2,3)-DAG and then utilized for TAG synthesis. Alternatively, 1(3)-MAG can be hydrolyzed to free fatty acid and glycerol, and re-synthesized into TAG through the glycerol-3-phosphate (Gro-3-P) pathway. The overall data suggested that the limiting step of the intracellular 1(3)-MAG metabolism is the conversion of 1(3)-MAG itself.

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

PubMed Central

Liévin-Le Moal, Vanessa

2013-01-01

SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses. PMID:24006470

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine

PubMed Central

Jakab, Robert L.; Collaco, Anne M.

2012-01-01

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO3−-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO3− retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO3− induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization. PMID:22936272

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine.

PubMed

Jakab, Robert L; Collaco, Anne M; Ameen, Nadia A

2012-10-15

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO(3)(-)-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO(3)(-) retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO(3)(-) induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization.

Characterization of the Proteome of Cytoplasmic Lipid Droplets in Mouse Enterocytes after a Dietary Fat Challenge

PubMed Central

D’Aquila, Theresa; Sirohi, Devika; Grabowski, Jeffrey M.; Hedrick, Victoria E.; Paul, Lake N.; Greenberg, Andrew S.; Kuhn, Richard J.; Buhman, Kimberly K.

2015-01-01

Dietary fat absorption by the small intestine is a multistep process that regulates the uptake and delivery of essential nutrients and energy. One step of this process is the temporary storage of dietary fat in cytoplasmic lipid droplets (CLDs). The storage and mobilization of dietary fat is thought to be regulated by proteins that associate with the CLD; however, mechanistic details of this process are currently unknown. In this study we analyzed the proteome of CLDs isolated from enterocytes harvested from the small intestine of mice following a dietary fat challenge. In this analysis we identified 181 proteins associated with the CLD fraction, of which 37 are associated with known lipid related metabolic pathways. We confirmed the localization of several of these proteins on or around the CLD through confocal and electron microscopy, including perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family member 5. The identification of the enterocyte CLD proteome provides new insight into potential regulators of CLD metabolism and the process of dietary fat absorption. PMID:25992653

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health.

PubMed

Zou, Jun; Chassaing, Benoit; Singh, Vishal; Pellizzon, Michael; Ricci, Matthew; Fythe, Michael D; Kumar, Matam Vijay; Gewirtz, Andrew T

2018-01-10

Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function. Copyright © 2017 Elsevier Inc. All rights reserved.

Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

PubMed

Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

2010-05-01

The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. Copyright 2009. Published by Elsevier Inc.

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study

PubMed Central

Bertini, Marina; Sbarbati, Andrea; Valletta, Enrico; Pinelli, Leonardo; Tatò, Luciano

2001-01-01

Background The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. Methods We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. Results All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. Conclusions The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia. PMID:11466133

Inactivation of Lactobacillus rhamnosus GG by fixation modifies its probiotic properties.

PubMed

Markowicz, C; Kubiak, P; Grajek, W; Schmidt, M T

2016-01-01

Probiotics are microorganisms that have beneficial effects on the host and are safe for oral intake in a suitable dose. However, there are situations in which the administration of living microorganisms poses a risk for immunocompromised host. The objective of this study was to evaluate the influence of several fixation methods on selected biological properties of Lactobacillus rhamnosus GG that are relevant to its probiotic action. Fixation of the bacterial cells with ethanol, 2-propanol, glutaraldehyde, paraformaldehyde, and heat treatment resulted in a significant decrease of alkaline phosphatase, peroxidase, and β-galactosidase activities. Most of the fixation procedures reduced bacterial cell hydrophobicity and increased adhesion capacity. The fixation procedures resulted in a different perception of the bacterial cells by enterocytes, which was shown as changes in gene expression in enterocytes. The results show that some procedures of inactivation allow a fraction of the enzymatic activity to be maintained. The adhesion properties of the bacterial cells were enhanced, but the response of enterocytes to fixed cells was different than to live bacteria. Inactivation allows maintenance and modification of some of the properties of the bacterial cells.

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..., LLC; William States Lee III Combined License Application; Notice of Intent To Conduct a Supplemental... an application for combined licenses (COL) for its William States Lee III Nuclear Station (Lee) site.../new-licensing/col/lee.html . In addition, the Cherokee County Public Library, 300 E. Rutledge Avenue...

The Exploitation of Low-Energy Electrons in Cancer Treatment.

PubMed

Rezaee, Mohammad; Hill, Richard P; Jaffray, David A

2017-08-01

Given the distinct characteristics of low-energy electrons (LEEs), particularly at energies less than 30 eV, they can be applied to a wide range of therapeutic modalities to improve cancer treatment. LEEs have been shown to efficiently produce complex molecular damage resulting in substantial cellular toxicities. Since LEEs are produced in copious amounts from high-energy radiation beam, including photons, protons and ions; the control of LEE distribution can potentially enhance the therapeutic radio of such beams. LEEs can play a substantial role in the synergistic effect between radiation and chemotherapy, particularly halogenated and platinum-based anticancer drugs. Radiosensitizing entities containing atoms of high atomic number such as gold nanoparticles can be a source of LEE production if high-energy radiation interacts with them. This can provide a high local density of LEEs in a cell and produce cellular toxicity. Auger-electron-emitting radionuclides also create a high number of LEEs in each decay, which can induce lethal damage in a cell. Exploitation of LEEs in cancer treatment, however, faces a few challenges, such as dosimetry of LEEs and selective delivery of radiosensitizing and chemotherapeutic molecules close to cellular targets. This review first discusses the rationale for utilizing LEEs in cancer treatment by explaining their mechanism of action, describes theoretical and experimental studies at the molecular and cellular levels, then discusses strategies for achieving modification of the distribution and effectiveness of LEEs in cancerous tissue and their associated clinical benefit.

Fractionated Stereotactic Radiotherapy in the Treatment of Vestibular Schwannoma (Acoustic Neuroma): Predicting the Risk of Hydrocephalus;Vestibular schwannoma; Hydrocephalus; Fractionated; Stereotactic radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, Ceri; Micallef, Caroline; Gonsalves, Adam

2011-07-15

Purpose: To determine the incidence and predictive factors for the development of hydrocephalus in patients with acoustic neuromas (AN) treated with fractionated stereotactic radiotherapy. Patients and Methods: Seventy-two patients with AN were treated with fractionated stereotactic radiotherapy between 1998 and 2007 (45-50 Gy in 25-30 fractions over 5 to 6 weeks). The pretreatment MRI scan was assessed for tumor characteristics and anatomic distortion independently of subsequent outcome and correlated with the risk of hydrocephalus. Results: At a median follow-up of 49 months (range, 1-120 months), 5-year event-free survival was 95%. Eight patients (11%) developed hydrocephalus within 19 months of radiotherapy,more » which was successfully treated. On univariate analysis, pretreatment factors predictive of hydrocephalus were maximum diameter (p = 0.005), proximity to midline (p = 0.009), displacement of the fourth ventricle (p = 0.02), partial effacement of the fourth ventricle (p < 0.001), contact with the medulla (p = 0.005), and more brainstem structures (p = 0.004). On multivariate analysis, after adjusting for fourth ventricular effacement, no other variables remained independently associated with hydrocephalus formation. Conclusions: Fractionated stereotactic radiotherapy results in excellent tumor control of AN, albeit with a risk of developing hydrocephalus. Patients at high risk, identified as those with larger tumors with partial effacement of the fourth ventricle before treatment, should be monitored more closely during follow-up. It would also be preferable to offer treatment to patients with progressive AN while the risk of hydrocephalus is low, before the development of marked distortion of fourth ventricle before tumor diameter significantly exceeds 2 cm.« less

75 FR 30451 - Duke Energy Carolinas, LLC; Duke Energy Carolinas, LLC; William States Lee III Combined License...

Federal Register 2010, 2011, 2012, 2013, 2014

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... Energy Carolinas, LLC; William States Lee III Combined License Application; Notice of Intent To Conduct a... environmental review of the William States Lee III Nuclear Station, Units 1 and 2 combined licenses application...-licensing/col/lee.html '' to `` http://www.nrc.gov/reactors/new-reactors/col/lee.html ''. Dated at Rockville...

76 FR 39869 - Lee 8 Storage Partnership; Notice of Motion for Extension of Rate Case Filing Deadline

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... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR09-5-003] Lee 8 Storage..., Lee 8 Storage Partnership (Lee 8) filed a request for an extension consistent with the Commission's... extend the cycle for such reviews from three to five years.\\1\\ Therefore, Lee 8 requests that the date...

Persistence of the longnose darter (P. nasuta) in Lee Creek, Oklahoma

USGS Publications Warehouse

Gatlin, Michael R.; Long, James M.

2011-01-01

Lee Creek is one of Oklahoma’s six rivers designated as "scenic" by the Oklahoma Legislature. Lee Creek is located on the Oklahoma-Arkansas border in far eastern Oklahoma. The headwaters originate in northwestern Arkansas and flow south towards the Arkansas River. While the majority of the stream is in Arkansas, a portion flows into Oklahoma northwest of Uniontown, AR and continues for 28.2 river-km before crossing back into Arkansas near Van Buren, AR. The hydrology of lower Lee Creek has been altered by Lee Creek Reservoir near Van Buren, AR. It was believed that pre-impounded Lee Creek had the largest existing population of longnose darters (8). However, the most recent fish surveys in Lee Creek were conducted approximately twenty years ago. Robinson (8) surveyed Lee Creek in Arkansas, upstream of the Oklahoma border, and found longnose darters upstream of Natural Dam, AR. Wagner et al. (10) were the last to document longnose darter presence in the Oklahoma segment of Lee Creek. No efforts to collect this species in Oklahoma have occurred since the completion of Lee Creek Reservoir. Our objective was to determine whether the species persist in this segment of its historic range since impoundment.

Heteropsis (Nymphalidae: Satyrinae: Satyrini: Mycalesina): 19 new species from Madagascar and interim revision.

PubMed

Lees, David C

2016-06-03

The genus Heteropsis Westwood, 1850 is monophyletic and contains the most diverse evolutionary radiation of butterflies in the Malagasy Region, with 46 up to now known species (53 accepted taxa) and at least 23 undescribed species in collections to date. Mixed species in historical descriptions and lost types in this genus have hindered taxonomic progress until now. A lectotype female is thus designated for the only surviving syntype that can be found for Mycalesis andravahana Mabille, 1878. Mycalesis difficilis Mabille, 1880 and three names of Oberthür, 1916 lectotypified here, Henotesia undulosa, Henotesia undulosa var. luctuosa and Henotesia andravahana var. macrophthalma, newly become its synonyms. A lectotype is also specified for Gallienia alaokola Oberthür, 1916. These acts now clarify potential confusion among the minimum of five species that these two nominal taxa represent, and thus facilitate description of related species compromised by the original descriptions (for one of which, the name Henotesia andravahana ab. marmorata Aurivillius, 1925 is unavailable). To solidify description of similar species, lectotypes are also designated for the following nominal species of Oberthür, 1916: Culapa comorana, C. pauper, Culapa ("var. ou espèce séparée") pseudonarcissus, C. laeta, C. laetifica, C. anceps, C. undulata, C. turbans, C. curvatula, C. ornata, C. pallida, and of Oberthür, 1923: C. houlbertiana, and also for Mycalesis iboina Ward, 1870, M. strigula Mabille, 1877, M. maeva Mabille, 1878, M. ankoma Mabille, 1878, M. irrorata Mabille, 1880 and M. butleri Mabille, 1880. The following 19 new species are described within Heteropsis from Madagascar, which are organised within species groups that are briefly characterised and discussed: in the Ht. exocellata group, Heteropsis mimetica Lees & Kremen, sp. nov.; in the Ht. antahala group, Heteropsis hazovola Lees & Raharitsimba, sp. nov.; in the Ht. drepana group, Heteropsis harveyi Lees & Kremen, sp. nov.; Heteropsis vanewrighti Lees, sp. nov.; Heteropsis westwoodi Lees, sp. nov., Heteropsis pauliani Lees, sp. nov.; Heteropsis imerina Lees, sp. nov.; in the Ht. subsimilis group, Heteropsis kremenae Lees, sp. nov.; Heteropsis avaratra Lees & Kremen, sp. nov. Heteropsis sogai Lees, sp. nov., and in the Ht. strigula group, Heteropsis tornado Lees, Allaoui & Aduse-Poku, sp. nov., Heteropsis lanyvary Lees, sp. nov.; Heteropsis barbarae Lees & Kremen, sp. nov.; Heteropsis menamenoides Lees, sp. nov.; Heteropsis roussettae Lees & Kremen, sp. nov.; Heteropsis tianae Lees & Kremen, sp. nov.; Heteropsis oberthueri Lees, sp. nov.; Heteropsis borgo Lees, sp. nov. and Heteropsis vertigo Lees & Raharitsimba, sp. nov. Counting the resulting synonymy of Heteropsis difficilis (Mabille, 1880), with Ht. andravahana (Mabille, 1878), this brings the Malagasy Heteropsis fauna to 64 species, about 2/3 of which are here revised.

Power Source

ERIC Educational Resources Information Center

Schooley, Michael L.

2010-01-01

Principals are powerful: They are the primary catalysts for creating a lasting foundation for learning, driving school and student performance, and shaping the long-term impact of school improvement efforts. Yet few principals would characterize themselves as powerful. Rather, they're self-effacing, adaptable, pragmatic, and quick to share credit…

The Taylor saddle effacement: a new technique for correction of saddle nose deformity.

PubMed

Taylor, S Mark; Rigby, Matthew H

2008-02-01

To describe a novel technique, the Taylor saddle effacement (TSE), for correction of saddle nose deformity using autologous grafts from the lower lateral cartilages. A prospective evaluation of six patients, all of whom had the TSE performed. Photographs were taken in combination with completion of a rhinoplasty outcomes questionnaire preoperatively and at 6 months. The questionnaire included a visual analogue scale (VAS) of nasal breathing and a rhinoplasty outcomes evaluation (ROE) of nasal function and esthetics. All six patients had improvement in both their global nasal airflow on the VAS and on their ROE that was statistically significant. The mean preoperative VAS score was 5.8 compared with our postoperative mean of 8.5 of a possible 10. Mean ROE scores improved from 34.7 to 85.5. At 6 months, all patients felt that their nasal appearance had improved. The TSE is a simple and reliable technique for correction of saddle nose deformity. This prospective study has demonstrated improvement in both nasal function and esthetics when it is employed.

Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria

PubMed Central

Deutsch, Konstantin; Bolanos-Palmieri, Patricia; Hanke, Nils; Schroder, Patricia; Staggs, Lynne; Bräsen, Jan H.; Roberts, Ian S.D.; Sheehan, Susan; Savage, Holly; Haller, Hermann

2016-01-01

Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes. PMID:27020856

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76 FR 79228 - Combined Licenses at William States Lee III Nuclear Station Site, Units 1 and 2; Duke Energy...

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2011-12-21

... William States Lee III Nuclear Station Site, Units 1 and 2; Duke Energy Carolinas, LLC AGENCY: Nuclear... Statement for Combined Licenses (COL) for William States Lee III Nuclear Station Units 1 and 2 [Lee Nuclear... draft EIS can be accessed online at the NRC's William States Lee III Nuclear Site Web page at http://www...

Molecular mechanism of G1 arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells.

PubMed

Tao, Yan-Fang; Wang, Na-Na; Xu, Li-Xiao; Li, Zhi-Heng; Li, Xiao-Lu; Xu, Yun-Yun; Fang, Fang; Li, Mei; Qian, Guang-Hui; Li, Yan-Hong; Li, Yi-Ping; Wu, Yi; Ren, Jun-Li; Du, Wei-Wei; Lu, Jun; Feng, Xing; Wang, Jian; He, Wei-Qi; Hu, Shao-Yan; Pan, Jian

2017-01-01

Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16 INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G 1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16 INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G 1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence.

Transport of selenium across the plasma membrane of primary hepatocytes and enterocytes of rainbow trout.

PubMed

Misra, Sougat; Kwong, Raymond W M; Niyogi, Som

2012-05-01

Transport of essential solutes across biological membranes is one of the fundamental characteristics of living cells. Although selenium is an essential micronutrient, little is known about the cellular mechanisms of chemical species-specific selenium transport in fish. We report here the kinetic and pharmacological transport characteristics of selenite and its thiol (glutathione and l-cysteine) derivatives in primary cultures of hepatocytes and isolated enterocytes of rainbow trout. Findings from the current study suggest an apparent low-affinity linear transport system for selenite in both cell types. However, we recorded high-affinity Hill kinetics (K(d)=3.61±0.28 μmol l(-1)) in enterocytes exposed to selenite in the presence of glutathione. The uptake of selenite in the presence of thiols was severalfold higher than uptake of selenite alone (at equimolar concentration) in both hepatocytes and enterocytes. Cellular accumulation of selenium was found to be energy independent. Interestingly, we observed a decrease in selenite transport with increasing pH, whereas selenite uptake increased with increasing pH in the presence glutathione in both cell types. The cellular uptake of selenite demonstrated a pronounced competitive interaction with a structurally similar compound, sulfite. The uptake of selenite as well as its thiol derivatives was found to be sensitive to the anion transport blocker DIDS, irrespective of the cell type. Inorganic mercury (Hg(2+)) elicited an inhibition of selenite transport in both cell types, but augmented the transport of reduced forms of selenite in hepatocytes. Based on the substrate choice and comparable pharmacological properties, we advocate that multiple anion transport systems are probably involved in the cellular transport of selenite in fish.

Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

PubMed

Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

2009-09-01

Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.

Mechanisms of chitosan-coated poly(lactic-co-glycolic acid) nanoparticles for improving oral absorption of 7-ethyl-10-hydroxycamptothecin

NASA Astrophysics Data System (ADS)

Guo, Miao; Rong, Wen-Ting; Hou, Jie; Wang, Dong-Fang; Lu, Yu; Wang, Ying; Yu, Shu-Qin; Xu, Qian

2013-06-01

Chitosan-modified poly(lactic-co-glycolic acid) nanoparticles (CHI/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), named CHI/PLGA/SN-38 NPs, were successfully prepared using an oil-in-water (O/W) solvent evaporation method. The physicochemical properties of the novel NPs were characterized by DLS, Zeta potential, SEM, DSC, XRD, and FTIR. The encapsulation efficiency and drug loading content were 71.83 (±2.77)% and 6.79 (±0.26)%, respectively. In vitro drug release in the simulated gastric juice was lower than that in the intestinal juice. In situ single-pass intestinal perfusion (SPIP) studies indicated a dramatic improvement of drug absorption as a result of the synergistic effect between CHI and PLGA on P-glycoprotein (Pgp) inhibition. CHI/PLGA NPs showed high cellular uptake and low efflux for drugs in Caco-2 cells. The cytotoxicity studies revealed that CHI/PLGA NPs had a transient effect on the membrane integrity, but did not have an influence on cell viability. Based on the in vitro release studies, SPIP, and intracellular drug accumulation and transport investigations, we speculate rationally that CHI/PLGA NPs were mainly internalized in the form of intact NPs, thus escaping the recognition of enterocyte Pgp and avoiding efflux into the apical part of the enterocytes. After partial release of drugs inside the enterocytes, CHI/PLGA interfered with the microenvironment of Pgp and further weakened the Pgp-mediated efflux. Then, the drug-loaded NPs exited via the exocytose effect from the basal part of the enterocytes and entered the blood circulation. These results showed that CHI/PLGA NPs would be smart oral delivery carriers for antineoplastic agents that are also Pgp substrates.

A Comparison of mucosal surface area and villous histology in small intestines of the Brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus).

PubMed

Zhang, Zhi-Qiang; Brun, Antonio; Price, Edwin R; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

2015-01-01

Studies on birds have led to the hypothesis that increased intestinal absorption between enterocytes (paracellular) evolved as a compensation for smaller intestinal size in fliers, which was perhaps selected to minimize the mass of digesta carried. This hypothesis predicts that bats will also exhibit relatively reduced intestinal size and high paracellular absorption, compared with nonflying mammals. Published studies on three bat species indicate relatively high paracellular absorption. One mechanism for increasing paracellular absorption per cm2 small intestine (SI) is increased number of tight junctions (TJs) across which paracellular absorption occurs. To our knowledge, we provide the first comparative analysis of enterocyte size and number in flying and nonflying mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared with Mus musculus using hematoxylin and eosin staining method. Bats had shorter and narrower SIs than mice, and after correction for body size difference by normalizing to mass3/4, the bats had 40% less nominal surface area than the mouse, as predicted. Villous enhancement of surface area was 90% greater in the bat than in the mouse, mainly because of longer villi and a greater density of villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of enterocytes per cm2 of the nominal surface area of the SI. Therefore, an increased density of TJs per cm2 SI may be a mechanistic explanation that helps to understand the high paracellular absorption observed in bats compared to nonflying mammals. © 2014 Wiley Periodicals, Inc.

Two stages of enteropathogenic Escherichia coli intestinal pathogenicity are up and down-regulated by the epithelial cell differentiation.

PubMed

Gabastou, J M; Kernéis, S; Bernet-Camard, M F; Barbat, A; Coconnier, M H; Kaper, J B; Servin, A L

1995-09-01

Pathogens and eucaryotic cells are active partners during the process of pathogenicity. To gain access to enterocytes and to cross the epithelial membrane, many enterovirulent microorganisms interact with the brush border membrane-associated components as receptors. Recent reports provide evidence that intestinal cell differentiation plays a role in microbial pathogenesis. Human enteropathogenic Escherichia coli (EPEC) develop their pathogenicity upon infecting enterocytes. To determine if intestinal epithelial cell differentiation influences EPEC pathogenicity, we examined the infection of human intestinal epithelial cells by JPN 15 (pMAR7) [EAF+ eae+] EPEC strain as a function of the cell differentiation. The human embryonic intestinal INT407 cells, the human colonic T84 cells, the human undifferentiated HT-29 cells (HT-29 Std) and two enterocytic cell lines, HT-29 glc-/+ and Caco-2 cells, were used as cellular models. Cells were infected apically with the EPEC strain and the cell-association and cell-entry were examined by quantitative determination using metabolically radiolabeled bacteria, as well as by light, scanning and transmission electron microscopy. [EAF+ eae+] EPEC bacteria efficiently colonized the cultured human intestinal cells. Diffuse bacterial adhesion occurred to undifferentiated HT-29 Std and INT407 cells, whereas characteristic EPEC cell clusters were observed on fully differentiated enterocytic HT-29 glc-/+ cells and on colonic crypt T84 cells. As shown using the Caco-2 cell line, which spontaneously differentiates in culture, the formation of EPEC clusters increased as a function of the epithelial cell differentiation. In contrast, efficient cell-entry of [EAF+ eae+] EPEC bacteria occurred in recently differentiated Caco-2 cells and decreased when the cells were fully differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional supplementation with transforming growth factor-beta inhibits intestinal adaptation after massive small bowel resection in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Ben Lulu, Shani; Bashenko, Yulia; Shaoul, Ron; Chemodanov, Elena; Coran, Arnold G

2011-02-01

Transforming growth factor beta (TGF-β) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-β2-enriched polymeric diet (Modulen) on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats and Sham-TGF-β rats underwent bowel transection, and were treated with TGF-β from the 4th postoperative day, SBS rats underwent a 75% bowel resection, and SBS-TGF-β rats underwent bowel resection and were treated with TGF-β-enriched diet similar to Group B. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine Bax and Bcl-2 mRNA expression. Treatment of SBS animals with TGF-β2 supplemented diet led to a significant decrease (vs. SBS rats) in bowel weight in ileum (18%, P < 0.05), mucosal DNA content in jejunum (threefold decrease, P < 0.05) and ileum (2.5-fold decrease, P < 0.05), and mucosal protein in jejunum (twofold decrease, P < 0.05) compared to SBS-untreated animals (Group B). Treatment with TGF-β resulted in a mild decrease in enterocyte proliferation in jejunum (25%, P < 0.05) and ileum (18%, P < 0.05). A decreased cell apoptosis in the SBS-TGF-β group was accompanied by a decreased Bax and increased Bcl-2 mRNA expression. In a rat model of SBS, dietary TGF-β inhibits intestinal adaptation. Decreased enterocyte proliferation is responsible for this effect.

Human, rat and chicken small intestinal Na+-Cl−-creatine transporter: functional, molecular characterization and localization

PubMed Central

Peral, M J; García-Delgado, M; Calonge, M L; Durán, J M; De La Horra, M C; Wallimann, T; Speer, O; Ilundáin, A A

2002-01-01

In spite of all the fascinating properties of oral creatine supplementation, the mechanism(s) mediating its intestinal absorption has(have) not been investigated. The purpose of this study was to characterize intestinal creatine transport. [14C]Creatine uptake was measured in chicken enterocytes and rat ileum, and expression of the creatine transporter CRT was examined in human, rat and chicken small intestine by reverse transcription-polymerase chain reaction, Northern blot, in situ hybridization, immunoblotting and immunohistochemistry. Results show that enterocytes accumulate creatine against its concentration gradient. This accumulation was electrogenic, Na+- and Cl−-dependent, with a probable stoichiometry of 2 Na+: 1 Cl−: 1 creatine, and inhibited by ouabain and iodoacetic acid. The kinetic study revealed a Km for creatine of 29 μm. [14C]Creatine uptake was efficiently antagonized by non-labelled creatine, guanidinopropionic acid and cyclocreatine. More distant structural analogues of creatine, such as GABA, choline, glycine, β-alanine, taurine and betaine, had no effect on intestinal creatine uptake, indicating a high substrate specificity of the creatine transporter. Consistent with these functional data, messenger RNA for CRT was detected only in the cells lining the intestinal villus. The sequences of partial clones, and of the full-length cDNA clone, isolated from human and rat small intestine were identical to previously cloned CRT cDNAs. Immunological analysis revealed that CRT protein was mainly associated with the apical membrane of the enterocytes. This study reports for the first time that mammalian and avian enterocytes express CRT along the villus, where it mediates high-affinity, Na+- and Cl−-dependent, apical creatine uptake. PMID:12433955

Flagellar Cap Protein FliD Mediates Adherence of Atypical Enteropathogenic Escherichia coli to Enterocyte Microvilli

PubMed Central

Sampaio, Suely C. F.; Luiz, Wilson B.; Vieira, Mônica A. M.; Ferreira, Rita C. C.; Garcia, Bruna G.; Sinigaglia-Coimbra, Rita; Sampaio, Jorge L. M.; Ferreira, Luís C. S.

2016-01-01

The expression of flagella correlates with different aspects of bacterial pathogenicity, ranging from adherence to host cells to activation of inflammatory responses by the innate immune system. In the present study, we investigated the role of flagella in the adherence of an atypical enteropathogenic Escherichia coli (aEPEC) strain (serotype O51:H40) to human enterocytes. Accordingly, isogenic mutants deficient in flagellin (FliC), the flagellar structural subunit; the flagellar cap protein (FliD); or the MotAB proteins, involved in the control of flagellar motion, were generated and tested for binding to differentiated Caco-2 cells. Binding of the aEPEC strain to enterocytes was significantly impaired in strains with the fliC and fliD genes deleted, both of which could not form flagella on the bacterial surface. A nonmotile but flagellated MotAB mutant also showed impaired adhesion to Caco-2 cells. In accordance with these observations, adhesion of aEPEC strain 1711-4 to Caco-2 cells was drastically reduced after the treatment of Caco-2 cells with purified FliD. In addition, incubation of aEPEC bacteria with specific anti-FliD serum impaired binding to Caco-2 cells. Finally, incubation of Caco-2 cells with purified FliD, followed by immunolabeling, showed that the protein was specifically bound to the microvillus tips of differentiated Caco-2 cells. The aEPEC FliD or anti-FliD serum also reduced the adherence of prototype typical enteropathogenic, enterohemorrhagic, and enterotoxigenic E. coli strains to Caco-2 cells. In conclusion, our findings further strengthened the role of flagella in the adherence of aEPEC to human enterocytes and disclosed the relevant structural and functional involvement of FliD in the adhesion process. PMID:26831466

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation

PubMed Central

Rostami, Kamran; Marsh, Michael N; Johnson, Matt W; Mohaghegh, Hamid; Heal, Calvin; Holmes, Geoffrey; Ensari, Arzu; Aldulaimi, David; Bancel, Brigitte; Bassotti, Gabrio; Bateman, Adrian; Becheanu, Gabriel; Bozzola, Anna; Carroccio, Antonio; Catassi, Carlo; Ciacci, Carolina; Ciobanu, Alexandra; Danciu, Mihai; Derakhshan, Mohammad H; Elli, Luca; Ferrero, Stefano; Fiorentino, Michelangelo; Fiorino, Marilena; Ganji, Azita; Ghaffarzadehgan, Kamran; Going, James J; Ishaq, Sauid; Mandolesi, Alessandra; Mathews, Sherly; Maxim, Roxana; Mulder, Chris J; Neefjes-Borst, Andra; Robert, Marie; Russo, Ilaria; Rostami-Nejad, Mohammad; Sidoni, Angelo; Sotoudeh, Masoud; Villanacci, Vincenzo; Volta, Umberto; Zali, Mohammad R; Srivastava, Amitabh

2017-01-01

Objectives Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive ‘normal’ IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. Design The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. Results The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2–88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. Conclusion Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose–response by IEL to environmental (gluten) antigenic influence. PMID:28893865

Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro.

PubMed

Meir, Michael; Flemming, Sven; Burkard, Natalie; Bergauer, Lisa; Metzger, Marco; Germer, Christoph-Thomas; Schlegel, Nicolas

2015-10-15

Recent data suggest that neurotrophic factors from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). We further investigated the potential role and mechanisms of GDNF in the regulation of intestinal barrier functions. Immunostaining of human gut specimen showed positive GDNF staining in enteric neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial cell lines Caco2 and HT29B6, significant amounts of GDNF were detected, suggesting that enterocytes represent an additional source of GDNF. Application of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant epithelial barrier stabilization in monolayers with immature barrier functions. Wound-healing assays showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had adverse effects on barrier maturation, as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF-induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89. Our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38 MAPK signaling. Copyright © 2015 the American Physiological Society.

What Happens to Educational Administration When Organization Trumps Ethics?

ERIC Educational Resources Information Center

Kumar, Rahul; Mitchell, Coral

2004-01-01

The managerial strategies of governance prevalent in the private sector have become more and more normalized within educational institutions. These strategies, according to Dutch philosopher Zygmund Bauman, are "denial of proximity," "effacement of face," and "reduction to traits." This article describes these managerial tactics within an…

[Epidemic of gastroenteritis in Noumea (New Caledonia) caused by an enterotoxinogenic strain of Escherichia coli (0l26:B16) believed to be enteropathogenic].

PubMed

Germani, Y; Amat, F; Brethes, B; Begaud, E; Plassart, H

1985-01-01

A strain of enteropathogenic Escherichia coli 0126:B16 has been isolated in fifteen children and one adult during a severe outbreak. One infant is dead. The strain produced heat-stable enterotoxin, attach to rabbit enterocytes but did not have colonization factor antigen CFA/I or CFA/II. Its hemagglutination type was the same that the E. coli H10407, CFA/I+. It presented a resistance at eight antibiotics and, with the loss of enterotoxigenicity, there was a loss of resistance at ampicillin and of the capacity to attach to enterocytes.

The interaction of F4 fimbriae with porcine enterocytes as analysed by surface plasmon resonance.

PubMed

Verdonck, Frank; Cox, Eric; Vancaeneghem, Sabine; Goddeeris, Bruno M

2004-07-01

Fimbriae often play a prominent role in anchoring bacterial cells to host tissue and mediate the first step in pathogenesis. As a consequence, there is a continuous development of new strategies to block the binding of fimbriae to their specific receptor on host cells. The present study demonstrates the specific interaction of F4 (K88) fimbriae and porcine enterocytes using a real-time biomolecular interaction analysis system (BIAcore 3000), based on the principles of surface plasmon resonance (SPR). This method offers new opportunities to screen therapeutics for prevention of adhesion and subsequent disease without receptor purification.

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

PubMed Central

Batman, P A; Miller, A R; Forster, S M; Harris, J R; Pinching, A J; Griffin, G E

1989-01-01

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV. Images Fig 1 Fig 2 PMID:2703544

Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes.

PubMed

Vareille, Marjolaine; Rannou, François; Thélier, Natacha; Glasser, Anne-Lise; de Sablet, Thibaut; Martin, Christine; Gobert, Alain P

2008-04-15

Enterohemorrhagic Escherichia coli (EHEC) are the causative agent of hemolytic-uremic syndrome. In the first stage of the infection, EHEC interact with human enterocytes to modulate the innate immune response. Inducible NO synthase (iNOS)-derived NO is a critical mediator of the inflammatory response of the infected intestinal mucosa. We therefore aimed to analyze the role of EHEC on iNOS induction in human epithelial cell lines. In this regard, we show that EHEC down-regulate IFN-gamma-induced iNOS mRNA expression and NO production in Hct-8, Caco-2, and T84 cells. This inhibitory effect occurs through the decrease of STAT-1 activation. In parallel, we demonstrate that EHEC stimulate the rapid inducible expression of the gene hmox-1 that encodes for the enzyme heme oxygenase-1 (HO-1). Knock-down of hmox-1 gene expression by small interfering RNA or the blockade of HO-1 activity by zinc protoporphyrin IX abrogated the EHEC-dependent inhibition of STAT-1 activation and iNOS mRNA expression in activated human enterocytes. These results highlight a new strategy elaborated by EHEC to control the host innate immune response.

Histopathological, immunohistochemical, and ultrastructural evidence of spontaneous Senecavirus A-induced lesions at the choroid plexus of newborn piglets.

PubMed

Oliveira, Thalita E S; Michelazzo, Mariana M Z; Fernandes, Thiago; de Oliveira, Admilton G; Leme, Raquel A; Alfieri, Alice F; Alfieri, Amauri A; Headley, Selwyn A

2017-11-29

Epidemic Transient Neonatal Losses (ETNL) is a disease of piglets caused by Senecavirus A (SVA) in which the method of dissemination and associated lesions are not well-defined. This study investigated the possible SVA-induced lesions by examining spontaneous infections in newborn piglets. Histopathology revealed ballooning degeneration of transitional epithelium, nonsuppurative meningoencephalitis, plexus choroiditis, and atrophic enteritis. RT-PCR identified SVA in all tissues evaluated and sequencing confirmed these results. Positive immunoreactivity to SVA was observed in endothelial and epithelial tissues of all organs evaluated. Semithin analysis revealed vacuolization of apical enterocytes of the small intestine, balloon degeneration and necrosis of endothelial cells of the choroid plexus (CP) and nonsuppurative choroid plexitis. Ultrathin evaluation demonstrated hydropic degeneration of apical enterocytes, degeneration and necrosis of endothelium of CP fenestrated capillaries, degeneration of ependymocytes associated with intralesional viral particles. It is proposed that SVA initially infects apical enterocytes of newborn piglets and probably enters the circulatory system with entry to the brain via the CP, by first producing an initial inflammatory reaction, with subsequent encephalitic dissemination. Consequently, SVA probably uses an enteric-neurological method of dissemination.

Polarizing intestinal epithelial cells electrically through Ror2

PubMed Central

Cao, Lin; McCaig, Colin D.; Scott, Roderick H.; Zhao, Siwei; Milne, Gillian; Clevers, Hans; Zhao, Min; Pu, Jin

2014-01-01

ABSTRACT The apicobasal polarity of enterocytes determines where the brush border membrane (apical membrane) will form, but how this apical membrane faces the lumen is not well understood. The electrical signal across the epithelium could serve as a coordinating cue, orienting and polarizing enterocytes. Here, we show that applying a physiological electric field to intestinal epithelial cells, to mimic the natural electric field created by the transepithelial potential difference, polarized phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodeled the actin cytoskeleton selectively on the cathode side. In addition, an applied electric field also activated ERK1/2 and LKB1 (also known as STK11), key molecules in apical membrane formation. Disruption of the tyrosine protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and LKB1 significantly, and subsequently inhibited apical membrane formation in enterocytes. Our findings indicate that the endogenous electric field created by the transepithelial potential difference might act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2–ERK signaling. PMID:24928904

The effect of amino acids and dipeptides on sodium-ion transport in rat enterocytes.

PubMed

Cheeseman, C I; Devlin, D

1985-02-14

Sodium efflux from isolated intestinal epithelial cells was measured during incubation with several different free amino acids and dipeptides. L-Leucine, which is cotransported with sodium across the brush border membrane, significantly stimulated the total sodium efflux and almost all of this increase involved the ouabain-sensitive flux, i.e., the active component. In contrast, glycyl-L-leucine had little or no effect on active sodium efflux either in the presence or absence of 0.1 mM bestatin, a peptide hydrolase inhibitor. A second dipeptide L-carnosine (beta-alanyl-L-histidine) which is poorly hydrolysed by enterocytes also had no effect upon sodium efflux. However, glycylglycine, which has been shown to be cotransported with sodium, did stimulate the ionic efflux. In addition, measurement of sodium uptake by sheets of small intestine showed that glycyl-L-leucine, carnosine and glycyl-L-proline failed to increase the uptake of the ion, while glycylglycine did significantly stimulate sodium uptake. These data indicate that some dipeptides are not cotransported with sodium, while others are. This suggests that there may well be multiple peptide transporters with very different characteristics in the brush border membrane of enterocytes.

Infrared Spectroscopy as a Tool to Study the Antioxidant Activity of Polyphenolic Compounds in Isolated Rat Enterocytes

PubMed Central

Barraza-Garza, Guillermo; Castillo-Michel, Hiram; de la Rosa, Laura A.; Martinez-Martinez, Alejandro; Pérez-León, Jorge A.; Cotte, Marine; Alvarez-Parrilla, Emilio

2016-01-01

The protective effect of different polyphenols, catechin (Cat), quercetin (Qc) (flavonoids), gallic acid (GA), caffeic acid (CfA), chlorogenic acid (ChA) (phenolic acids), and capsaicin (Cap), against H2O2-induced oxidative stress was evaluated in rat enterocytes using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy and Fourier Transform Infrared Microspectroscopy (FTIRM), and results were compared to standard lipid peroxidation techniques: conjugated dienes (CD) and Thiobarbituric Acid Reactive Substances (TBARS). Analysis of ATR-FTIR and FTIRM spectral data allowed the simultaneous evaluation of the effects of H2O2 and polyphenols on lipid and protein oxidation. All polyphenols showed a protective effect against H2O2-induced oxidative stress in enterocytes, when administered before or after H2O2. Cat and capsaicin showed the highest protective effect, while phenolic acids had weaker effects and Qc presented a mild prooxidative effect (IR spectral profile of biomolecules between control and H2O2-treated cells) according to FTIR analyses. These results demonstrated the viability to use infrared spectroscopy to evaluate the oxidant and antioxidant effect of molecules in cell systems assays. PMID:27213031

Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

PubMed

Chegeni, Mohammad; Amiri, Mahdi; Nichols, Buford L; Naim, Hassan Y; Hamaker, Bruce R

2018-02-20

Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have higher affinity to lipid rafts, which are associated with enhanced targeting to the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing action was enhanced in the maltose-treated cells. Thus, starch digestion products at the luminal surface of small intestinal enterocytes are sensed and accelerate the intracellular processing of SI to enhance starch digestion capacity in the intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker, B. R. Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Shamian, Benhoor; Coran, Arnold G

2008-12-01

Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells. Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant. The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa. Treatment with TGF-alpha prevents mucosal injury, enhances ERK-induced enterocyte proliferation, and improves intestinal recovery following MTX-induced intestinal mucositis in rats. These findings correlated with the observation that TGF-alpha also caused a significant stimulation of cell proliferation in a Caco-2 cell culture model treated with MTX. These observations may have significant implications for the treatment of patients on chemotherapy who develop severe mucositis.

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

PubMed

Cho, Young-Eun; Yu, Li-Rong; Abdelmegeed, Mohamed A; Yoo, Seong-Ho; Song, Byoung-Joon

2018-07-01

Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins, in promoting binge alcohol-induced gut leakiness and endotoxemia, contributing to inflammatory liver disease. Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury. Our results demonstrated for the first time the critical roles of apoptosis of enterocytes and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins in promoting this gut leakiness and endotoxemia. These results provide insight into the molecular mechanisms of alcohol-induced inflammatory liver disease. Published by Elsevier B.V.

Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Female Goats

PubMed Central

Nagamine, Itsuki; Sunagawa, Katsunori; Kishi, Tetsuya

2012-01-01

Okinawan Awamori is produced by fermenting steamed indica rice with black mold, yeast, and water. Awamori-pressed lees is a by-product of the Awamori production process. Tofu lees is a by-product of the Tofu production process. This research consisted of two experiments conducted to elucidate whether or not dried Awamori-pressed lees and Tofu lees can be used as a mixed feed ingredient for raising female goats. In experiment 1, digestion trials were conducted to ascertain the nutritive values of dried Awamori-pressed lees and dried Tofu lees for goats. The digestible crude protein (DCP) and total digestible nutrients (TDN) contents of dried Awamori-pressed lees and Tofu lees were 22.5%, 22.5% (DCP), and 87.2%, 94.4% (TDN) respectively. In experiment 2, 18 female goats (Japanese Saanen×Nubian, three months old, body weight 15.4±0.53 kg) were divided into three groups of six animals (control feed group (CFG), Awamori-pressed lees mixed feed group (AMFG), Tofu lees mixed feed group (TMFG)). The CFG control used feed containing 20% soybean meal as the main protein source, while the AMFG and TMFG treatments used feed mixed with 20% dried Awamori-pressed lees or dried Tofu lees. The groups were fed mixed feed (volume to provide 100 g/d increase in body weight) twice a day (10:00, 16:00). The klein grass hay and water was given ad libitum. The hay intake was measured at 08:00 and 16:00. Body weight and size measurements were taken once a month. At the end of the experiment, a blood sample was drawn from the jugular vein of each animal. The DCP and TDN intakes in AMFG and TMFG showed no significant difference to the CFG. Cumulative measurements of growth in body weight, withers height, chest depth, chest girth, and hip width over the 10 mo period in the AMFG and TMFG were similar to the CFG. By contrast, cumulative growth in body length and hip height in the AMFG and TMFG tended to be larger than the CFG. Cumulative growth in chest width in the AMFG was significantly larger (p<0.05) than the CFG. Blood parameter values were similar to those in normal goats reported by other scientists. The coats of the AMFG and TMFG animals looked shinier than the animals in the CFG. The results demonstrate that dried Awamori-pressed lees and Tofu lees can be used as a feed ingredient for the raising female goats. PMID:25049535

The Peter Effect in Early Experimental Education Research.

ERIC Educational Resources Information Center

Little, Joseph

2003-01-01

Traces the ways in which educational researchers referred to Ronald A. Fisher's analysis of variance (ANOVA) between 1932 and 1944 in the "Journal of Experimental Education" (JXE). Shows how the changes in citational practices served to separate the ANOVA from its affiliation with Fisher, essentially effacing the memory of its human…

Tracing Boundaries, Effacing Boundaries: Information Literacy as an Academic Discipline

ERIC Educational Resources Information Center

Veach, Grace

2012-01-01

Both librarianship and composition have been shaken by recent developments in higher education. In libraries ebooks and online databases threaten the traditional "library as warehouse model," while in composition, studies like The Citation Project show that students are not learning how to incorporate sources into their own writing…

Some Unsettling Thoughts about Settling in with Pot.

ERIC Educational Resources Information Center

Hawley, Richard A.

1978-01-01

Popular culture now considers marijuana harmless, but research shows it has definite physiological and neurological effects, effacing memory and attention and producing cell damage and learning deficits. Young people turn to pot to escape the emotional pressures of adolescence. Parents and schools can help adolescents by setting firm prohibitions.…

Understanding the host-adapted state of Citrobacter rodentium by transcriptomic analysis

USDA-ARS?s Scientific Manuscript database

Citrobacter rodentium (Cr) is a mouse pathogen that mimics many aspects of enteropathogenic Escherichia coli infections including producing attaching and effacing (A/E) lesions. Host-adapted (HA) Cr cells that are shed at the peak of infection have been reported to be hyperinfective. The exact mecha...

Regulation of Biofilm Formation in Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

Escherichia coli O157:H7 encodes a variety of genetic factors for adherence to epithelial cells and to abiotic surfaces. While adherence to epithelial cells culminates in the formation of characteristic attaching and effacing (A/E) lesions, adherence to abiotic surfaces represents a prelude to the f...

76 FR 30947 - Stephen Lee Seldon: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

...] Stephen Lee Seldon: Debarment Order AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY... Act (the FD&C Act) permanently debarring Stephen Lee Seldon, M.D. from providing services in any... authority delegated to the Director (Staff Manual Guide 1410.35), finds that Stephen Lee Seldon has been...

F-35A Training Basing Environmental Impact Statement. Volume 2. Appendix D - Comment Response Document. Book 1

DTIC Science & Technology

2012-06-01

Brening Sharon Peoria AZ 10560 Breniser Suzanne Phoenix AZ 4567 Brennan Barbara Sun City West AZ 6556 Brennan Leo Litchfield Park AZ 11324 Bresler...Goodyear AZ 9865 Comer Karen Litchfield Park AZ 10019 Commandeur Leo Anthem AZ 7363 Compton Charles Avondale AZ 7787 Compton Esther Litchfield Park AZ...Goodyear AZ 8503 Lee Jeffrey Glendale AZ 4248 Lee Joel Peoria AZ 9649 Lee John Sun City AZ 10037 Lee Lawrence Phoenix AZ 6557 Lee Leo Lakeside

Lee Jay Fingersh | NREL

Science.gov Websites

Lee.Fingersh@nrel.gov | 303-384-6929 Lee Jay joined NREL in 1993. For seven years, he was the test engineer on the Unsteady Aerodynamics Experiment turbine, which culminated in the NASA Ames wind tunnel test. Lee has worked on the design and controls for the variable-speed test bed and administered many

Spike Lee and Commentaries on His Work. Occasional Papers Series 2, No. 1.

ERIC Educational Resources Information Center

Hudson, Herman C., Ed.

This monograph presents a critical essay and a comprehensive 454-item bibliography on the contemporary African-American filmmaker, Spike Lee. The essay, entitled "African-American Folklore and Cultural History in the Films of Spike Lee" (Gloria J. Gibson-Hudson), analyzes Lee's filmmaking approach from a cultural and historical…

Generalization of Friedberg-Lee symmetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Chaoshang; Li Tianjun; George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, Texas 77843

2008-07-01

We study the possible origin of Friedberg-Lee symmetry. First, we propose the generalized Friedberg-Lee symmetry in the potential by including the scalar fields in the field transformations, which can be broken down to the Friedberg-Lee symmetry spontaneously. We show that the generalized Friedberg-Lee symmetry allows a typical form of Yukawa couplings, and the realistic neutrino masses and mixings can be generated via the seesaw mechanism. If the right-handed neutrinos transform nontrivially under the generalized Friedberg-Lee symmetry, we can have the testable TeV scale seesaw mechanism. Second, we present two models with the SO(3)xU(1) global flavor symmetry in the lepton sector.more » After the flavor symmetry breaking, we can obtain the charged lepton masses, and explain the neutrino masses and mixings via the seesaw mechanism. Interestingly, the complete neutrino mass matrices are similar to those of the above models with generalized Friedberg-Lee symmetry. So the Friedberg-Lee symmetry is the residual symmetry in the neutrino mass matrix after the SO(3)xU(1) flavor symmetry breaking.« less

Characterization of Phenolic Compounds in Wine Lees

PubMed Central

Zhijing, Ye; Shavandi, Amin; Harrison, Roland; Bekhit, Alaa El-Din A.

2018-01-01

The effect of vinification techniques on phenolic compounds and antioxidant activity of wine lees are poorly understood. The present study investigated the antioxidant activity of white and red wine lees generated at early fermentation and during aging. In this study, the total phenol content (TPC), total tannin content (TTC), mean degree of polymerization (mDP), and antioxidant activities of five white and eight red wine lees samples from different vinification backgrounds were determined. The results showed that vinification techniques had a significant (p < 0.05) impact on total phenol and tannin content of the samples. White wine lees had high mDP content compared with red ones. Catechin (50–62%) and epicatechin contents were the predominant terminal units of polymeric proanthocyanidin extracted from examined samples. Epigallocatechin was the predominant extension unit of white wine lees, whereas epicatechin was the predominant compound in red wine marc. The ORAC (oxygen radical absorbance capacity) assay was strongly correlated with the DPPH (α,α-diphenyl-β-picrylhydrazyl) assay, and the results showed the strong antioxidant activities associated with red wine lees (PN > 35 mg Trolox/g FDM) (PN: Pinot noir lees; FDM: Freeze-dried Material). This study indicates that tannin is one of the major phenolic compounds available in wine lees that can be useful in human and animal health applications. PMID:29587406

Characterization of Phenolic Compounds in Wine Lees.

PubMed

Zhijing, Ye; Shavandi, Amin; Harrison, Roland; Bekhit, Alaa El-Din A

2018-03-25

The effect of vinification techniques on phenolic compounds and antioxidant activity of wine lees are poorly understood. The present study investigated the antioxidant activity of white and red wine lees generated at early fermentation and during aging. In this study, the total phenol content (TPC), total tannin content (TTC), mean degree of polymerization (mDP), and antioxidant activities of five white and eight red wine lees samples from different vinification backgrounds were determined. The results showed that vinification techniques had a significant ( p < 0.05) impact on total phenol and tannin content of the samples. White wine lees had high mDP content compared with red ones. Catechin (50-62%) and epicatechin contents were the predominant terminal units of polymeric proanthocyanidin extracted from examined samples. Epigallocatechin was the predominant extension unit of white wine lees, whereas epicatechin was the predominant compound in red wine marc. The ORAC (oxygen radical absorbance capacity) assay was strongly correlated with the DPPH (α, α-diphenyl-β-picrylhydrazyl) assay, and the results showed the strong antioxidant activities associated with red wine lees (PN > 35 mg Trolox/g FDM) (PN: Pinot noir lees; FDM: Freeze-dried Material). This study indicates that tannin is one of the major phenolic compounds available in wine lees that can be useful in human and animal health applications.

Interactions between yeast lees and wine polyphenols during simulation of wine aging. II. Analysis of desorbed polyphenol compounds from yeast lees.

PubMed

Mazauric, Jean-Paul; Salmon, Jean-Michel

2006-05-31

In the first part of this work, the analysis of the polyphenolic compounds remaining in the wine after different contact times with yeast lees during simulation of red wine aging was undertaken. To achieve a more precise view of the wine polyphenols adsorbed on lees during red wine aging and to establish a clear balance between adsorbed and remnant polyphenol compounds, the specific analysis of the chemical composition of the adsorbed polyphenolic compounds (condensed tannins and anthocyanins) after their partial desorbtion from yeast lees by denaturation treatments was realized in the second part of the study. The total recovery of polyphenol compounds from yeast lees was not complete, since a rather important part of the initial wine colored polyphenols, especially those with a dominant blue color component, remained strongly adsorbed on yeast lees, as monitored by color tristimulus and reflectance spectra measurements. All anthocyanins were recovered at a rather high percentage (about 62%), and it was demonstrated that they were not adsorbed in relation with their sole polarity. Very few monomeric phenolic compounds were extracted from yeast lees. With the use of drastic denaturing treatments, the total recovery of condensed tannins reached 83%. Such tannins extracted from yeast lees exhibited very high polymeric size and a rather high percentage of galloylated residues by comparison with initial wine tannins, indicating that nonpolar tannins were preferentially desorbed from yeast lees by the extraction treatments.

Accuracy of advanced cancer patients' life expectancy estimates: The role of race and source of life expectancy information.

PubMed

Trevino, Kelly M; Zhang, Baohui; Shen, Megan J; Prigerson, Holly G

2016-06-15

The objective of this study was to examine the source of advanced cancer patients' information about their prognosis and determine whether this source of information could explain racial disparities in the accuracy of patients' life expectancy estimates (LEEs). Coping With Cancer was a prospective, longitudinal, multisite study of terminally ill cancer patients followed until death. In structured interviews, patients reported their LEEs and the sources of these estimates (ie, medical providers, personal beliefs, religious beliefs, and other). The accuracy of LEEs was calculated through a comparison of patients' self-reported LEEs with their actual survival. The sample for this analysis included 229 patients: 31 black patients and 198 white patients. Only 39.30% of the patients estimated their life expectancy within 12 months of their actual survival. Black patients were more likely to have an inaccurate LEE than white patients. A minority of the sample (18.3%) reported that a medical provider was the source of their LEEs; none of the black patients (0%) based their LEEs on a medical provider. Black race remained a significant predictor of an inaccurate LEE, even after the analysis had been controlled for sociodemographic characteristics and the source of LEEs. The majority of advanced cancer patients have an inaccurate understanding of their life expectancy. Black patients with advanced cancer are more likely to have an inaccurate LEE than white patients. Medical providers are not the source of information for LEEs for most advanced cancer patients and especially for black patients. The source of LEEs does not explain racial differences in LEE accuracy. Additional research into the mechanisms underlying racial differences in prognostic understanding is needed. Cancer 2016;122:1905-12. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

78 FR 77508 - Duke Energy Carolinas, LLC; William States Lee III Nuclear Station, Units 1 and 2; Combined...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

..., LLC; William States Lee III Nuclear Station, Units 1 and 2; Combined Licenses Application Review... Environmental Impact Statement [EIS] for Combined Licenses (COLs) for William States Lee III Nuclear Station... be accessed online at the NRC's William States Lee III Nuclear Station--specific Web page at: www.nrc...

Reduction of proteinuria through podocyte alkalinization.

PubMed

Altintas, Mehmet M; Moriwaki, Kumiko; Wei, Changli; Möller, Clemens C; Flesche, Jan; Li, Jing; Yaddanapudi, Suma; Faridi, Mohd Hafeez; Gödel, Markus; Huber, Tobias B; Preston, Richard A; Jiang, Jean X; Kerjaschki, Dontscho; Sever, Sanja; Reiser, Jochen

2014-06-20

Podocytes are highly differentiated cells and critical elements for the filtration barrier of the kidney. Loss of their foot process (FP) architecture (FP effacement) results in urinary protein loss. Here we show a novel role for the neutral amino acid glutamine in structural and functional regulation of the kidney filtration barrier. Metabolic flux analysis of cultured podocytes using genetic, toxic, and immunologic injury models identified increased glutamine utilization pathways. We show that glutamine uptake is increased in diseased podocytes to couple nutrient support to increased demand during the disease state of FP effacement. This feature can be utilized to transport increased amounts of glutamine into damaged podocytes. The availability of glutamine determines the regulation of podocyte intracellular pH (pHi). Podocyte alkalinization reduces cytosolic cathepsin L protease activity and protects the podocyte cytoskeleton. Podocyte glutamine supplementation reduces proteinuria in LPS-treated mice, whereas acidification increases glomerular injury. In summary, our data provide a metabolic opportunity to combat urinary protein loss through modulation of podocyte amino acid utilization and pHi. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria.

PubMed

Korstanje, Ron; Deutsch, Konstantin; Bolanos-Palmieri, Patricia; Hanke, Nils; Schroder, Patricia; Staggs, Lynne; Bräsen, Jan H; Roberts, Ian S D; Sheehan, Susan; Savage, Holly; Haller, Hermann; Schiffer, Mario

2016-11-01

Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes. Copyright © 2016 by the American Society of Nephrology.

Skull fracture with effacement of the superior sagittal sinus following drone impact: a case report.

PubMed

Chung, Lawrance K; Cheung, Yuri; Lagman, Carlito; Au Yong, Nicholas; McBride, Duncan Q; Yang, Isaac

2017-09-01

The popularity of unmanned aerial vehicles, or drones, raises safety concerns as they become increasingly common for commercial, personal, and recreational use. Collisions between drones and people may result in serious injuries. A 13-year-old male presented with a comminuted depressed skull fracture causing effacement of the superior sagittal sinus secondary to a racing drone impact. The patient experienced a brief loss of consciousness and reported lower extremity numbness and weakness after the accident. Imaging studies revealed bone fragments crossing the superior sagittal sinus with a short, focal segment of blood flow interruption. Neurosurgical intervention was deferred given the patient's improving neurological deficits, and the patient was treated conservatively. He was discharged home in stable condition. Drones may represent a hazard when operated inappropriately due to their capacity to fly at high speeds and altitudes. Impacts from drones can carry enough force to cause skull fractures and significant head injuries. The rising popularity of drones likely translates to an increased incidence of drone-related injuries. Thus, clinicians should be aware of this growing trend.

77 FR 14032 - John H. Chafee Coastal Barrier Resources System; Lee County, FL, and Newport County, RI...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

..., FXHC11240900000T5, 123] John H. Chafee Coastal Barrier Resources System; Lee County, FL, and Newport County, RI... Lee County, Florida. The second map, dated September 30, 2009, is for four CBRS units located in... by Lee County, and 1 restaurant. The Service's assessment of 2011 aerial imagery estimates that the...

77 FR 34285 - Safety Zone; 2012 Ironman U.S. Championship Swim, Hudson River, Fort Lee, NJ

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

...-AA00 Safety Zone; 2012 Ironman U.S. Championship Swim, Hudson River, Fort Lee, NJ AGENCY: Coast Guard... safety zone on the navigable waters of the Hudson River in the vicinity of Englewood Cliffs and Fort Lee... the Hudson River in the vicinity of Englewood Cliffs and Fort Lee, New Jersey. This swim event poses...

77 FR 46613 - Safety Zone; 2012 Ironman US Championship Swim, Hudson River, Fort Lee, NJ

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... 1625-AA00 Safety Zone; 2012 Ironman US Championship Swim, Hudson River, Fort Lee, NJ AGENCY: Coast... navigable waters of the Hudson River in the vicinity of Englewood Cliffs and Fort Lee, NJ for the 2012... Championship Swim, Hudson River, Fort Lee, NJ in the Federal Register (77 FR 34285). We received no comments on...

40 CFR Appendix A to Part 97 - Final Section 126 Rule: EGU Allocations, 2004-2007

Code of Federal Regulations, 2011 CFR

2011-07-01

... NC L V SUTTON 2713 3 717 NC L V SUTTON 2713 CT2B 2 NC LEE 2709 1 129 NC LEE 2709 2 142 NC LEE 2709 3 414 NC LEE 2709 CT4 1 NC LINCOLN 7277 1 33 NC LINCOLN 7277 10 31 NC LINCOLN 7277 11 33 NC LINCOLN 7277...

Experimental Determination of Dynamical Lee-Yang Zeros

NASA Astrophysics Data System (ADS)

Brandner, Kay; Maisi, Ville F.; Pekola, Jukka P.; Garrahan, Juan P.; Flindt, Christian

2017-05-01

Statistical physics provides the concepts and methods to explain the phase behavior of interacting many-body systems. Investigations of Lee-Yang zeros—complex singularities of the free energy in systems of finite size—have led to a unified understanding of equilibrium phase transitions. The ideas of Lee and Yang, however, are not restricted to equilibrium phenomena. Recently, Lee-Yang zeros have been used to characterize nonequilibrium processes such as dynamical phase transitions in quantum systems after a quench or dynamic order-disorder transitions in glasses. Here, we experimentally realize a scheme for determining Lee-Yang zeros in such nonequilibrium settings. We extract the dynamical Lee-Yang zeros of a stochastic process involving Andreev tunneling between a normal-state island and two superconducting leads from measurements of the dynamical activity along a trajectory. From the short-time behavior of the Lee-Yang zeros, we predict the large-deviation statistics of the activity which is typically difficult to measure. Our method paves the way for further experiments on the statistical mechanics of many-body systems out of equilibrium.

Microscopic anatomy of the digestive system in normal and regenerating specimens of the brittlestar Amphipholis kochii.

PubMed

Frolova, Lidia T; Dolmatov, Igor Yu

2010-06-01

The morphology and regeneration of the digestive system of the ophiuroid Amphipholis kochii were investigated. The epithelia of the esophagus and stomach of A. kochii were composed of typical enterocytes and mucous cells. The digestive epithelium of the stomach contained two types of granular secretory cells. After autotomy of the disk, the animals retained the esophagus and a small part of the stomach. The dedifferentiation of enterocytes and mucous cells began on the first day after autotomy. On day 3 the cells formed an anlage of stomach around the mouth opening. Later, the stomach anlage grew as a result of cell proliferation. The opening on the aboral side of the body was closed by day 7. By this time differentiating cells were already observed in the stomach lining. The stomach mesothelium was formed by peritoneocytes and myoepithelial cells, which migrated from other coelomic epithelia of the body. Our study showed that the formation of the digestive system in A. kochii during regeneration depended on cells from the esophagus and the stomach remnant. Both enterocytes and mucous cells were able to dedifferentiate, migrate, and proliferate to give rise to the luminal epithelium. The basic mechanism of stomach formation was epithelial morphogenesis.

Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

PubMed Central

Halbleib, Jennifer M.; Sääf, Annika M.

2007-01-01

Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes. PMID:17699590

A role for antimicrobial peptides in intestinal microsporidiosis

PubMed Central

Leitch, Gordon J.; Ceballos, Carolina

2009-01-01

SUMMARY Clinical isolates from three microsporidia species, Encephalitozoon intestinalis and Encephalitozoon hellem, and the insect parasite Anncaliia (Brachiola, Nosema) algerae, were used in spore germination and enterocyte-like (C2Bbe1) cell infection assays to determine the effect of a panel of antimicrobial peptides. Spores were incubated with lactoferrin (Lf), lysozyme (Lz), and human beta defensin 2 (HBD2), human alpha defensin 5 (HD5), and human alpha defensin 1 (HNP1), alone and in combination with Lz, prior to germination. Of the Encephalitozoon species only E. hellem spore germination was inhibited by HNP1, while A. algerae spore germination was inhibited by Lf, HBD2, HD5 and HNP1, although HBD2 and HD5 inhibition required the presence of Lz. The effects of HBD2 and HD5 on microsporidia enterocyte infection paralleled their effects on spore germination. Lysozyme alone only inhibited infection with A. algerae, while Lf inhibited infection by E. intestinalis and A. algerae. HNP1 significantly reduced enterocyte infection by all three parasite species and a combination of Lf, Lz and HNP1 caused a further reduced infection with A. algerae. These data suggest that intestinal antimicrobial peptides contribute to the defense of the intestine against infection by luminal microsporidia spores and may partially determine which parasite species infects the intestine. PMID:19079820

Enterocyte-afferent nerve interactions in dietary fat sensing.

PubMed

Mansouri, A; Langhans, W

2014-09-01

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. © 2014 John Wiley & Sons Ltd.

77 FR 69598 - Procurement List Proposed Addition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... Support, Directorate of Public Works, Fort Lee, Virginia. NPA: Skookum Educational Programs, Bremerton, WA Contracting Activity: Mission and Installation Contracting Command-- Fort Lee, Fort Lee, VA Barry S. Lineback...

Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Male Goats

PubMed Central

Nagamine, Itsuki; Sunagawa, Katsunori; Kina, Takashi

2013-01-01

Awamori is produced by fermenting steamed indica rice. Awamori-pressed lees is a by-product of the Awamori production process. Tofu lees is a by-product of the Tofu production process. Research was conducted to test if dried Awamori-pressed lees and Tofu lees can be used as a mixed feed ingredient for raising male goats. Eighteen male kids were divided into three groups of six animals (control feed group (CFG), Awamori-pressed lees mixed feed group (AMFG), Tofu lees mixed feed group (TMFG)). The CFG used feed containing 20% soybean meal as the main protein source, while the AMFG and TMFG used feed mixed with 20% dried Awamori-pressed lees or dried Tofu lees. The groups were fed mixed feed (volume to provide 100 g/d increase in body weight) and alfalfa hay cubes (2.0 kg/d) twice a day (10:00, 16:00). Klein grass hay and water was given ad libitum. Hay intake was measured at 10:00 and 16:00. Body weight and size measurements were taken once a month. At the end of the experiment, a blood sample was drawn from the jugular vein of each animal and the carcass characteristics, the physical and chemical characteristics of loin were analyzed. DCP and TDN intakes in AMFG and TMFG showed no significant difference to the CFG. Cumulative measurements of growth in body weight and size over the 10 mo period in the AMFG and TMFG were similar to the CFG. Blood parameter values were similar to those in normal goats. Dressing carcass weight and percentages, and total weight of meat in the AMFG were similar to that in the CFG, but smaller in the TMFG. The compressed meat juice ratio was higher in both the TMFG and AMFG than the CFG. While the fat in corn, Awamori-pressed lees, and Tofu lees contains more than 50% linoleic acid, the loin fat in both the AMFG and TMFG was very low in linoleic acid due to the increase in the content of oleic acid, stearic acid, and palmitic acid. This indicates that feeding on AMF and TMF does not inhibit hydrogenation by ruminal microorganisms. As in the CFG, the total essential and non-essential amino acids in the loin of the AMFG and TMFG were well balanced. Compared to the CFG, the AMFG and TMFG were high in taurine and carnosine. The results indicate dried Awamori-pressed lees and Tofu lees can be used as a feed ingredient for raising male goats. PMID:25049908

The Role of Wnt/β-Catenin Signaling in Enterocyte Turnover during Methotrexate-Induced Intestinal Mucositis in a Rat

PubMed Central

Sukhotnik, Igor; Geyer, Tatiana; Pollak, Yulia; Mogilner, Jorge G.; Coran, Arnold G.; Berkowitz, Drora

2014-01-01

Background/Aims Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX)-induced intestinal damage in a rat model. Methods Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. Results In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. Conclusions Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat. PMID:25375224

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

PubMed

Rostami, Kamran; Marsh, Michael N; Johnson, Matt W; Mohaghegh, Hamid; Heal, Calvin; Holmes, Geoffrey; Ensari, Arzu; Aldulaimi, David; Bancel, Brigitte; Bassotti, Gabrio; Bateman, Adrian; Becheanu, Gabriel; Bozzola, Anna; Carroccio, Antonio; Catassi, Carlo; Ciacci, Carolina; Ciobanu, Alexandra; Danciu, Mihai; Derakhshan, Mohammad H; Elli, Luca; Ferrero, Stefano; Fiorentino, Michelangelo; Fiorino, Marilena; Ganji, Azita; Ghaffarzadehgan, Kamran; Going, James J; Ishaq, Sauid; Mandolesi, Alessandra; Mathews, Sherly; Maxim, Roxana; Mulder, Chris J; Neefjes-Borst, Andra; Robert, Marie; Russo, Ilaria; Rostami-Nejad, Mohammad; Sidoni, Angelo; Sotoudeh, Masoud; Villanacci, Vincenzo; Volta, Umberto; Zali, Mohammad R; Srivastava, Amitabh

2017-12-01

Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

76 FR 38178 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

..., New York, New York 10045-0001: 1. Thomas H. Lee (Alternative) Fund VI, L.P., Thomas H. Lee (Alternative) Parallel Fund VI, L.P., Thomas H. Lee (Alternative) Parallel (DT) Fund VI, L.P., THL FBC Equity Investors, L.P., THL Advisors (Alternative) VI, L.P., Thomas H. Lee (Alternative) VI, Ltd., THL Managers VI...

Cicadas (Hemiptera: Cicadidae) from Camiguin of Mindanao Province and Dinagat Island in the Philippines, with a new genus and three new species.

PubMed

Lee, Young June; Marshall, David C; Mohagan, Alma; Hill, Kathy B R

2016-03-30

This paper provides the first faunal checklist for the family Cicadidae (Hemiptera) from Camiguin of Mindanao Province and Dinagat Island in the Philippines, comprising ten species belonging to nine genera. Cryptotympana shillana Lee & Mohagan sp. nov., Orientopsaltria inermis (Stål, 1870), Purana crassinotata Lee, 2015, and Huechys parvula Haupt, 1924 are recorded for the first time from Camiguin. Platypleura dinagatensis Lee sp. nov., Chremistica kyoungheeae Lee, 2010, Dundubia vaginata (Fabricius, 1787), Oncotympana pallidiventris Stål, 1870, and Philipsalta nigrina Lee, Marshall & Hill sp. nov. are newly recorded from Dinagat Island. A new genus Philipsalta Lee, Marshall & Hill gen. nov. is erected. Huechysini Distant, 1905 syn. nov. is synonymized with Cicadettini Buckton, 1889. Information on geographic distributions of the Camiguin and Dinagat species is also provided.

Interactions between yeast lees and wine polyphenols during simulation of wine aging: I. Analysis of remnant polyphenolic compounds in the resulting wines.

PubMed

Mazauric, Jean-Paul; Salmon, Jean-Michel

2005-07-13

Wine aging on yeast lees is a traditional enological practice used during the manufacture of wines. This technique has increased in popularity in recent years for the aging of red wines. Although wine polyphenols interact with yeast lees to a limited extent, such interactions have a large effect on the reactivity toward oxygen of wine polyphenolic compounds and yeast lees. Various domains of the yeast cell wall are protected by wine polyphenols from the action of extracellular hydrolytic enzymatic activities. Polysaccharides released during autolysis are thought to exert a significant effect on the sensory qualities of wine. We studied the chemical composition of polyphenolic compounds remaining in solution or adsorbed on yeast lees after various contact times during the simulation of wine aging. The analysis of the remnant polyphenols in the wine indicated that wine polyphenols adsorption on yeast lees follows biphasic kinetics. An initial and rapid fixation is followed by a slow, constant, and saturating fixation that reaches its maximum after about 1 week. Only very few monomeric phenolic compounds remained adsorbed on yeast lees, and no preferential adsorption of low or high polymeric size tannins occurred. The remnant condensed tannins in the wine contained fewer epigallocatechin units than the initial tannins, indicating that polar condensed tannins were preferentially adsorbed on yeast lees. Conversely, the efficiency of anthocyanin adsorption on yeast lees was unrelated to its polarity.

Preemptive Approach to Improving Survival in Epithelial Ovarian Cancer

DTIC Science & Technology

2012-06-01

Metab 2008;93:3471–7. 692[87] Cho JH, Lee JG, Yang YI, Kim JH, Ahn JH, Baek NI, Lee KT, Choi JH. Eupatilin, a die- 693tary flavonoid , induces G2/M cell...Metab 2008;93:3471–7. 692[87] Cho JH, Lee JG, Yang YI, Kim JH, Ahn JH, Baek NI, Lee KT, Choi JH. Eupatilin, a die- 693tary flavonoid , induces G2/M

Privacy Preservation in Context-Aware Systems

DTIC Science & Technology

2011-01-01

Policies and the Semantic Web The Semantic Web refers to both a vision and a set of technologies. The vision was first articulated by Tim Berners - Lee ... Berners - lee 2005) is a distributed framework for describing and reasoning over policies in the Semantic Web. It supports N3 rules ( Berners - Lee ...Connolly 2008), ( Berners - Lee et al. 2005) for representing intercon- nections between policies and resources and uses the CWM forward-chaining reasoning

An Ontological Approach to Developing Information Operations Applications for Use on the Semantic Web

DTIC Science & Technology

2008-09-01

IWPC 21 Berners - Lee , Tim . (1999). Weaving the Web. New York: HarperCollins Publishers, Inc. 22... Berners - Lee , Tim . (1999). Weaving the Web. New York: HarperCollins Publishers, Inc. Berners - Lee , T., Hendler, J., & Lassila, O. (2001). The Semantic...environment where software agents roaming from page to page can readily carry out sophisticated tasks for users. T. Berners - Lee , J. Hendler, and O

Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.

PubMed

De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G

2015-03-01

Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes. © 2015 John Wiley & Sons Ltd.

Amino acid sequence and the cellular location of the Na(+)-dependent D-glucose symporters (SGLT1) in the ovine enterocyte and the parotid acinar cell.

PubMed Central

Tarpey, P S; Wood, I S; Shirazi-Beechey, S P; Beechey, R B

1995-01-01

The Na(+)-dependent D-glucose symporter has been shown to be located on the basolateral domain of the plasma membrane of ovine parotid acinar cells. This is in contrast to the apical location of this transporter in the ovine enterocyte. The amino acid sequences of these two proteins have been determined. They are identical. The results indicated that the signals responsible for the differential targeting of these two proteins to the apical and the basal domains of the plasma membrane are not contained within the primary amino acid sequence. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7492327

LEE VINING INTAKE LOOKING SOUTH. (MOTTLED SKY FROM CONDENSED MOISTURE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LEE VINING INTAKE LOOKING SOUTH. (MOTTLED SKY FROM CONDENSED MOISTURE ON NEGATIVE AFFECTING EVEN PROCESSING OF SKY, SAVED FOR DOCUMENTARY PURPOSES) - Los Angeles Aqueduct, Lee Vining Intake Structure, Los Angeles, Los Angeles County, CA

29. SECOND FLOOR EAST SIDE APARTMENT EAST BEDROOM INTERIOR. ALUMINUMFRAME ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. SECOND FLOOR EAST SIDE APARTMENT EAST BEDROOM INTERIOR. ALUMINUM-FRAME SLIDING-GLASS WINDOWS ARE REPLACEMENTS. VIEW TO NORTHEAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

33 CFR 110.155 - Port of New York.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 915 yards from the Fort Lee flagpole) on a line ranging approximately 100°22′ from the Fort Lee... said line ranging between the Fort Lee flagpole and the square chimney on the Medical Center Building...

33 CFR 110.155 - Port of New York.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 915 yards from the Fort Lee flagpole) on a line ranging approximately 100°22′ from the Fort Lee... said line ranging between the Fort Lee flagpole and the square chimney on the Medical Center Building...

78 FR 58342 - Proposed Fee Schedule for Commercial Filming and Still Photography Permits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... ; put ``Commercial Filming Fee Schedule'' in the subject line. Mail: Lee Dickinson, Special Park Uses... FURTHER INFORMATION CONTACT: Lee Dickinson, National Park Service at 202-513-7092 or by email at lee...

NATIONAL SECURITY: Relief, Rebukes Follow Agreement on Lee.

PubMed

Lawler, A

2000-09-15

What began as an explosive case of alleged nuclear espionage is expected to end quietly soon when physicist Wen Ho Lee walks free from an Albuquerque, New Mexico, courtroom after 9 months in jail. The ignominious collapse of the government's case and Lee's release have embarrassed federal prosecutors. However, the news was a relief to Asian-American researchers and others who say Lee's status as a suspect had heightened racial tensions at the national labs.

40 CFR 81.301 - Alabama.

Code of Federal Regulations, 2010 CFR

2010-07-01

... County Lawrence County Lee County Limestone County Lowndes County Macon County Madison County Marengo... Lauderdale County Lawrence County Lee County Limestone County Lowndes County Macon County Madison County... Lamar County Lauderdale County Lawrence County Lee County Limestone County Lowndes County Macon County...

40 CFR 81.301 - Alabama.

Code of Federal Regulations, 2011 CFR

2011-07-01

... County Lawrence County Lee County Limestone County Lowndes County Macon County Madison County Marengo... County Houston County Jackson County Lamar County Lauderdale County Lawrence County Lee County Limestone... County Houston County Jackson County Lamar County Lauderdale County Lawrence County Lee County Limestone...

Curli Temper Adherence of Escherichia coli O157:H7 to Squamous Epithelial Cells from the Bovine Recto-Anal Junction in a Strain-Dependent Manner

PubMed Central

Carter, Michelle Q.; Sharma, Vijay K.; Stasko, Judith A.; Giron, Jorge A.

2016-01-01

ABSTRACT Our recent studies have shown that intimin and the locus of enterocyte effacement-encoded proteins do not play a role in Escherichia coli O157:H7 (O157) adherence to the bovine recto-anal junction squamous epithelial (RSE) cells. To define factors that play a contributory role, we investigated the role of curli, fimbrial adhesins commonly implicated in adherence to various fomites and plant and human epithelial cells, in O157 adherence to RSE cells. Specifically, we examined (i) wild-type strains of O157; (ii) curli variants of O157 strains; (iii) isogenic curli deletion mutants of O157; and (iv) adherence inhibition of O157 using anti-curlin sera. Results of these experiments conducted under stringent conditions suggest that curli do not solely contribute to O157 adherence to RSE cells and in fact demonstrate a modulating effect on O157 adherence to RSE cells in contrast to HEp-2 cells (human epidermoid carcinoma of the larynx cells with HeLa contamination). The absence of curli and presence of blocking anti-curli antibodies enhanced O157-RSE cell interactions among some strains, thus alluding to a spatial, tempering effect of curli on O157 adherence to RSE cells when present. At the same time, the presence or absence of curli did not alter RSE cell adherence patterns of another O157 strain. These observations are at variance with the reported role of curli in O157 adherence to human cell lines such as HEp-2 and need to be factored in when developing anti-adherence modalities for preharvest control of O157 in cattle. IMPORTANCE This study demonstrated that O157 strains interact with epithelial cells in a host-specific manner. The fimbriae/adhesins that are significant for adherence to human cell lines may not have a role or may have a modulating role in O157 adherence to bovine cells. Targeting such adhesins may not prevent O157 attachment to bovine cells but instead may result in improved adherence. Hence, conducting host-specific evaluations is critical when selecting targets for O157 control strategies. PMID:27742683

Subinertial Slope-Trapped Waves in the Northeastern Gulf of Mexico

DTIC Science & Technology

2009-06-01

describe low-frequency varia- bility in the GOM and its interaction with the topo- graphy. Oey and Lee (2002) describe modeled deep eddy kinetic...deep energy can penetrate onto the upper part of the slope in this region; Oey and Lee (2002) state that their model cannot adequately resolve...slope topography in the NE GOM is described by Cames et al. (2008), Hamilton and Lee (2005), and Wang et al. (2003). Hamilton and Lee (2005) found

22. FIRST FLOOR APARTMENT SOUTH BEDROOM INTERIOR SHOWING PAIRED 6LIGHT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. FIRST FLOOR APARTMENT SOUTH BEDROOM INTERIOR SHOWING PAIRED 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAMED WINDOWS. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

PubMed Central

Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

2007-01-01

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

PubMed Central

2010-01-01

Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients. PMID:21040540

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei[S

PubMed Central

Esteves, Adriana; Knoll-Gellida, Anja; Canclini, Lucia; Silvarrey, Maria Cecilia; André, Michèle; Babin, Patrick J.

2016-01-01

Intracellular lipid binding proteins, including fatty acid binding proteins (FABPs) 1 and 2, are highly expressed in tissues involved in the active lipid metabolism. A zebrafish model was used to demonstrate differential expression levels of fabp1b.1, fabp1b.2, and fabp2 transcripts in liver, anterior intestine, and brain. Transcription levels of fabp1b.1 and fabp2 in the anterior intestine were upregulated after feeding and modulated according to diet formulation. Immunofluorescence and electron microscopy immunodetection with gold particles localized these FABPs in the microvilli, cytosol, and nuclei of most enterocytes in the anterior intestinal mucosa. Nuclear localization was mostly in the interchromatin space outside the condensed chromatin clusters. Native PAGE binding assay of BODIPY-FL-labeled FAs demonstrated binding of BODIPY-FLC12 but not BODIPY-FLC5 to recombinant Fabp1b.1 and Fabp2. The binding of BODIPY-FLC12 to Fabp1b.1 was fully displaced by oleic acid. In vivo experiments demonstrated, for the first time, that intestinal absorption of dietary BODIPY-FLC12 was followed by colocalization of the labeled FA with Fabp1b and Fabp2 in the nuclei. These data suggest that dietary FAs complexed with FABPs are able to reach the enterocyte nucleus with the potential to modulate nuclear activity. PMID:26658423

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei.

PubMed

Esteves, Adriana; Knoll-Gellida, Anja; Canclini, Lucia; Silvarrey, Maria Cecilia; André, Michèle; Babin, Patrick J

2016-02-01

Intracellular lipid binding proteins, including fatty acid binding proteins (FABPs) 1 and 2, are highly expressed in tissues involved in the active lipid metabolism. A zebrafish model was used to demonstrate differential expression levels of fabp1b.1, fabp1b.2, and fabp2 transcripts in liver, anterior intestine, and brain. Transcription levels of fabp1b.1 and fabp2 in the anterior intestine were upregulated after feeding and modulated according to diet formulation. Immunofluorescence and electron microscopy immunodetection with gold particles localized these FABPs in the microvilli, cytosol, and nuclei of most enterocytes in the anterior intestinal mucosa. Nuclear localization was mostly in the interchromatin space outside the condensed chromatin clusters. Native PAGE binding assay of BODIPY-FL-labeled FAs demonstrated binding of BODIPY-FLC(12) but not BODIPY-FLC(5) to recombinant Fabp1b.1 and Fabp2. The binding of BODIPY-FLC(12) to Fabp1b.1 was fully displaced by oleic acid. In vivo experiments demonstrated, for the first time, that intestinal absorption of dietary BODIPY-FLC(12) was followed by colocalization of the labeled FA with Fabp1b and Fabp2 in the nuclei. These data suggest that dietary FAs complexed with FABPs are able to reach the enterocyte nucleus with the potential to modulate nuclear activity. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

[Space-time organization of systems of membrane hydrolysis and transport in rat small intestine].

PubMed

Loginov, G I

1977-05-01

Glucose transport by the concentration gradient with the incubation for 90 min in 0.2% glucose and soluble starch solutions was studied in Wistar rats in 5 segments of the small intestine by the "sac turned inside out" method. Serous fluid was completely replaced by a new portion of Ringer's solution every 15 or 30 min. Substrate load synchronized the enterocyte population and stabilized the transport systems. The changes of glucose absorption during the period of about an hour proved to differ in the 5 segments against the background of continuous and interrupted substrate load. These differences were due to the properties of the transported systems autocontrol and the reactivity level of the given enterocyte population. Areas with different reactivity were found to alternate along the intestine. Between the 8th and 16th hour (rats were sacrificed every 2 hours) starch glucose transport fell sharply in the proximal, and, to a lesser extent, in the middle segments. On the contrary, absorption between the 8th and the 12th hour was considerably intensified in the distal segments. The changes of the strach glucose transport during the period of about an hour along the intestine differed. The data obtained are discussed with consideration to the possible role of the undulating processes in the individual enterocyte population and in the small intestine as an integral system.

Potential of lees from wine, beer and cider manufacturing as a source of economic nutrients: An overview.

PubMed

Pérez-Bibbins, B; Torrado-Agrasar, A; Salgado, J M; Oliveira, R Pinheiro de Souza; Domínguez, J M

2015-06-01

Lees are the wastes generated during the fermentation and aging processes of different industrial activities concerning alcoholic drinks such as wine, cider and beer. They must be conveniently treated to avoid uncontrolled dumping which causes environmental problems due to their high content of phenols, pesticides, heavy metals, and considerable concentrations of nitrogen, phosphate and potassium as well as high organic content. The companies involved must seek alternative environmental and economic physicochemical and biological treatments for their revalorization consisting in the recovery or transformation of the components of the lees into high value-added compounds. After describing the composition of lees and market of wine, beer and cider industries in Spain, this work aims to review the recent applications of wine, beer and cider lees reported in literature, with special attention to the use of lees as an endless sustainable source of nutrients and the production of yeast extract by autolysis or cell disruption. Lees and/or yeast extract can be used as nutritional supplements with potential exploitation in the biotechnological industry for the production of natural compounds such as xylitol, organic acids, and biosurfactants, among others. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitation and structural determination of glucosylceramides contained in sake lees.

PubMed

Takahashi, Koshiro; Izumi, Kazuki; Nakahata, Eriko; Hirata, Miyo; Sawada, Kazutaka; Tsuge, Keisuke; Nagao, Koji; Kitagaki, Hiroshi

2014-01-01

Sake lees are solid parts filtered from the mash of sake, the traditional rice wine of Japan, which is brewed with Aspergillus oryzae and Saccharomyces cerevisiae. The moisture-holding activity of sake lees has long been recognized in Japan. However, the constituent responsible for this activity has not been elucidated. In this study, we first determined the structure of the glucosylceramides contained in sake lees. The glucosylceramides contained in sake lees were N-2'-hydroxyoctadecanoyl-l-O-β-D-glucopyranosyl-9-methyl-4,8-sphingadienine (d19:2/C18:0h), N-2'-hydroxyoctadecanoyl-l-O-β-D-glucopyranosyl-4,8-sphingadienine (d18:2/C18:0h), N-2'-hydroxyicosanoyl-l-O-β-D-glucopyranosyl-4,8-sphingadienine (d18:2/C20:0h) and N-2'-hydroxyicosanoyl-l-O-β-D-glucopyranosyl-4,8-sphingadienine (d18:2/C22:0h), which corresponded to those of A. oryzae and rice. The glucosylceramide produced by A. oryzae constituted the most abundant species (43% of the total glucosylceramide) in the sake lees. These results will be of value in the utilization of sake lees for cosmetics and functional foods.

15. FIRST FLOOR APARTMENT LIVING ROOM INTERIOR. OPEN DOORWAY AT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. FIRST FLOOR APARTMENT LIVING ROOM INTERIOR. OPEN DOORWAY AT PHOTO CENTER OPENS TO KITCHEN. OPEN DOORWAY AT PHOTO LEFT OPENS TO BATHROOM. VIEW TO NORTHWEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

40 CFR 81.310 - Florida.

Code of Federal Regulations, 2011 CFR

2011-07-01

... County Indian River County Jackson County Jefferson County Lafayette County Lake County Lee County Leon... County Lee County Leon County Levy County Liberty County Madison County Manatee County Marion County... Indian River County Jackson County Jefferson County Lafayette County Lake County Lee County Leon County...

77 FR 39244 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... South LaSalle Street, Chicago, Illinois 60690-1414: 1. Sidney J. Lee, as an individual, and together with Medora Lee, both of Chicago, Illinois, and Serena Lee, Greenwich, Connecticut; as a group acting...

75 FR 11225 - Environmental Impact Statement; Lee and Collier Counties, Florida

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

... DEPARTMENT OF TRANSPORTATION Federal Highway Administration Environmental Impact Statement; Lee and Collier Counties, Florida AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of...) for the proposed County Road 951 highway project in Lee and Collier Counties, Florida. This is formal...

40 CFR 81.310 - Florida.

Code of Federal Regulations, 2010 CFR

2010-07-01

... County Indian River County Jackson County Jefferson County Lafayette County Lake County Lee County Leon... Lafayette County Lake County Lee County Leon County Levy County Liberty County Madison County Manatee County... Indian River County Jackson County Jefferson County Lafayette County Lake County Lee County Leon County...

Template-free modeling by LEE and LEER in CASP11.

PubMed

Joung, InSuk; Lee, Sun Young; Cheng, Qianyi; Kim, Jong Yun; Joo, Keehyoung; Lee, Sung Jong; Lee, Jooyoung

2016-09-01

For the template-free modeling of human targets of CASP11, we utilized two of our modeling protocols, LEE and LEER. The LEE protocol took CASP11-released server models as the input and used some of them as templates for 3D (three-dimensional) modeling. The template selection procedure was based on the clustering of the server models aided by a community detection method of a server-model network. Restraining energy terms generated from the selected templates together with physical and statistical energy terms were used to build 3D models. Side-chains of the 3D models were rebuilt using target-specific consensus side-chain library along with the SCWRL4 rotamer library, which completed the LEE protocol. The first success factor of the LEE protocol was due to efficient server model screening. The average backbone accuracy of selected server models was similar to that of top 30% server models. The second factor was that a proper energy function along with our optimization method guided us, so that we successfully generated better quality models than the input template models. In 10 out of 24 cases, better backbone structures than the best of input template structures were generated. LEE models were further refined by performing restrained molecular dynamics simulations to generate LEER models. CASP11 results indicate that LEE models were better than the average template models in terms of both backbone structures and side-chain orientations. LEER models were of improved physical realism and stereo-chemistry compared to LEE models, and they were comparable to LEE models in the backbone accuracy. Proteins 2016; 84(Suppl 1):118-130. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

24. SECOND FLOOR EAST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. SECOND FLOOR EAST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING DOORWAY INTO KITCHEN AT PHOTO CENTER LEFT AND OPEN DOORWAY INTO BATHROOM AT PHOTO RIGHT. VIEW TO SOUTHWEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

32. SECOND FLOOR WEST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. SECOND FLOOR WEST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING DOORWAY INTO KITCHEN AT PHOTO CENTER RIGHT, AND OPEN DOORWAY IN BATHROOM AT PHOTO LEFT. VIEW TO SOUTHWEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

5. EXTERIOR OF TRIPLEX COTTAGE ROOF SHOWING MANVILLE COMPOSITION SHINGLES, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. EXTERIOR OF TRIPLEX COTTAGE ROOF SHOWING MANVILLE COMPOSITION SHINGLES, POURED CONCRETE CHIMNEYS, AND TRANSLUCENT PLASTIC COVERING OVER WALKWAY AT REAR OF HOUSE (PHOTO LEFT). VIEW TO NORTHWEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

40 CFR 81.318 - Kentucky.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Lee County X Leslie County X Letcher County X Lewis County X Lincoln County X Livingston County X... Lawrence County X Lee County X Leslie County X Letcher County X Lewis County X Lincoln County X Livingston... County Unclassifiable/Attainment Lawrence County Unclassifiable/Attainment Lee County Unclassifiable...

76 FR 68107 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-03

... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Lee County, Alabama... Areas of Saugahatchee Creek. Lee County. Approximately 1.9 miles +537 upstream of the confluence with..., Saugahatchee Creek. Unincorporated Areas of Lee County. Approximately 640 feet +693 upstream of Gatewood Drive...

40 CFR 81.318 - Kentucky.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Lee County X Leslie County X Letcher County X Lewis County X Lincoln County X Livingston County X... Lawrence County X Lee County X Leslie County X Letcher County X Lewis County X Lincoln County X Livingston... County Unclassifiable/Attainment Lawrence County Unclassifiable/Attainment Lee County Unclassifiable...

37. SECOND FLOOR WEST SIDE APARTMENT EAST BEDROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. SECOND FLOOR WEST SIDE APARTMENT EAST BEDROOM INTERIOR SHOWING PAIRED 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS ON NORTH WALL. VIEW TO NORTHEAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes.

PubMed

D'Aquila, Theresa; Hung, Yu-Han; Carreiro, Alicia; Buhman, Kimberly K

2016-08-01

Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles that function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of CLDs within this process. Copyright © 2016 Elsevier B.V. All rights reserved.

Nursing Care Hour Standards Study. Part 1. Section A. Patient Classification System Model Development

DTIC Science & Technology

1981-09-01

Change = 2311 (257) Teaching - Diabetic = 2313 (258) Labor Room Examination and Preparation, Routine = 2434 (259) Fetal Heart Tones, Manual = 2412 (260... Fetal Heart Tones, Doppler = 2413 (261) Dilatation and Effecement Assessment = 2403 (262) Dilatation and Effacement Assessment, Assisting Physician...Ultrasonic Transducer/Tocotransducer = 2435 (270) Monitoring Fetal Heart Tones, Ultrasonic Transducer = 2436 (271) Monitoring Fetal Heart Tones, Ultrasonic

A Time of Quiet Activism: Research, Practice, and Policy in American Women's Higher Education, 1945-1965

ERIC Educational Resources Information Center

Eisenmann, Linda

2005-01-01

This article reflects on three narratives that affected American women's participation in higher education during the first twenty years after World War II. In hindsight, the educators of the 1950s and early 1960s may seem gratuitously meek and self-effacing. In comparison to later efforts, their activism can appear unnecessarily limited and too…

Tentative identification of polar and mid-polar compounds in extracts from wine lees by liquid chromatography-tandem mass spectrometry in high-resolution mode.

PubMed

Delgado de la Torre, M P; Priego-Capote, F; Luque de Castro, M D

2015-06-01

Sustainable agriculture has a pending goal in the revalorization of agrofood residues. Wine lees are an abundant residue in the oenological industry. This residue, so far, has been used to obtain tartaric acid or pigments but not for being qualitatively characterized as a source of polar and mid-polar compounds such as flavonoids, phenols and essential amino acids. Lees extracts from 11 Spanish wineries have been analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in high resolution mode. The high-resolution power of LC-MS/MS has led to the tentative identification of the most representative compounds present in wine lees, comprising primary amino acids, anthocyans, flavanols, flavonols, flavones and non-flavonoid phenolic compounds, among others. Attending to the profile and content of polar and mid-polar compounds in wine lees, this study underlines the potential of wine lees as an exploitable source to isolate interesting compounds. Copyright © 2015 John Wiley & Sons, Ltd.

Euterpe edulis Extract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats.

PubMed

Freitas, Rodrigo Barros; Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Mendonça, Bianca Gazolla; Santos, Eliziária Cardoso; Ribeiro, Andréia Queiroz; Lima, Luciana Moreira; Fietto, Luciano Gomes; Peluzio, Maria do Carmo Gouveia; Leite, João Paulo Viana

2016-01-01

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals' diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.

Euterpe edulis Extract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats

PubMed Central

Freitas, Rodrigo Barros; Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Mendonça, Bianca Gazolla; Santos, Eliziária Cardoso; Ribeiro, Andréia Queiroz; Lima, Luciana Moreira; Fietto, Luciano Gomes; Peluzio, Maria do Carmo Gouveia

2016-01-01

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals' diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins. PMID:27418954

Adsorption Characteristics of Pb(2+) onto Wine Lees-Derived Biochar.

PubMed

Zhu, Qihong; Wu, Jun; Wang, Lilin; Yang, Gang; Zhang, Xiaohong

2016-08-01

Biochar has great advantages in soil amendment and polluted soil remediation. Herein, the pore and adsorption properties of wine lees-derived biochar were explored. Specifically, the adsorption isotherm and kinetics of Pb(2+) onto wine lees-derived biochar were examined. Experimental results revealed that wine lees-derived biochar featured large specific surface area and total pore volume, and high contents of -COOH and -OH on its surface. Adsorption of Pb(2+) onto wine lees-derived biochar proceeded via a multilayer adsorption mechanism, as described by the Freundlich adsorption model. Adsorption kinetics followed the Lagergren pseudo-second-order kinetics model; adsorption equilibrium was achieved within 30-60 min. Furthermore, the effect of solution pH on the adsorption of Pb(2+) was investigated. Within the studied pH range of 3-6, the adsorption capacity increased with increasing pH. Under established optimized conditions, wine lees-derived biochar achieved a Pb(2+) adsorption capacity of 79.12 mg/g.

Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.

PubMed

Mack, D R; Michail, S; Wei, S; McDougall, L; Hollingsworth, M A

1999-04-01

Probiotic agents, live microorganisms with beneficial effects for the host, may offer an alternative to conventional antimicrobials in the treatment and prevention of enteric infections. The probiotic agents Lactobacillus plantarum 299v and Lactobacillus rhamnosus GG quantitatively inhibited the adherence of an attaching and effacing pathogenic Escherichia coli to HT-29 intestinal epithelial cells but did not inhibit adherence to nonintestinal HEp-2 cells. HT-29 cells were grown under conditions that induced high levels of either MUC2 or MUC3 mRNA, but HEp-2 cells expressed only minimal levels of MUC2 and no MUC3 mRNA. Media enriched for MUC2 and MUC3 mucin were added exogenously to binding assays and were shown to be capable of inhibiting enteropathogen adherence to HEp-2 cells. Incubation of L. plantarum 299v with HT-29 cells increased MUC2 and MUC3 mRNA expression levels. From these in vitro studies, we propose the hypothesis that the ability of probiotic agents to inhibit adherence of attaching and effacing organisms to intestinal epithelial cells is mediated through their ability to increase expression of MUC2 and MUC3 intestinal mucins.

40 CFR 81.325 - Mississippi.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Lee County X Leflore County X Lincoln County X Lowndes County X Madison County X Marion County X... Lee County X Leflore County X Lincoln County X Lowndes County X Madison County X Marion County X... County Kemper County Lafayette County Lamar County Lauderdale County Lawrence County Leake County Lee...

76 FR 4725 - Apria Healthcare Customer Service Department; Fourteen Locations in Missouri Cameron, Cape...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

..., Fenton, Joplin, Lee's Summit, Pleasant Valley, Poplar Bluff, Rolla, Springfield, St. Joseph, St. Peters... in Missouri: Cameron, Cape Girardeau, Columbia, Farmington, Fenton, Joplin, Lee's Summit, Pleasant..., Farmington, Fenton, Joplin, Lee's Summit, Pleasant Valley, Poplar Bluff, Rolla, Springfield, St. Joseph, St...

75 FR 30021 - South Carolina Electric and Gas Company; Saluda Hydroelectric Project; Notice of Teleconference...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... telephone. The FERC contact for the Saluda Hydroelectric Project is Lee Emery. Please call Lee Emery at (202) 502-8379 by 4 p.m. EST, June 11, 2010, or by e-mail at lee[email protected] , to receive specific...

76 FR 34123 - Culturally Significant Objects Imported for Exhibition Determinations: “Lee Ufan: Marking Infinity”

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... DEPARTMENT OF STATE [Public Notice 7501] Culturally Significant Objects Imported for Exhibition Determinations: ``Lee Ufan: Marking Infinity'' SUMMARY: Notice is hereby given of the following determinations... the exhibition ``Lee Ufan: Marking Infinity,'' imported from abroad for temporary exhibition within...

47 CFR 90.614 - Segments of the 806-824/851-869 MHz band for non-border areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., Henry, Houston, Jackson, Jefferson, Lamar, Lauderdale, Lawrence, Lee, Limestone, Lowndes, Macon, Madison..., Jasper, Jeff Davis, Jefferson, Jenkins, Johnson, Jones, Lamar, Lanier, Laurens, Lee, Liberty, Lincoln..., Lawrence, Leake, Lee, Lincoln, Lowndes, Madison, Marion, Monroe, Montgomery, Neshoba, Newton, Noxubee...

47 CFR 90.614 - Segments of the 806-824/851-869 MHz band for non-border areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., Henry, Houston, Jackson, Jefferson, Lamar, Lauderdale, Lawrence, Lee, Limestone, Lowndes, Macon, Madison..., Jasper, Jeff Davis, Jefferson, Jenkins, Johnson, Jones, Lamar, Lanier, Laurens, Lee, Liberty, Lincoln..., Lawrence, Leake, Lee, Lincoln, Lowndes, Madison, Marion, Monroe, Montgomery, Neshoba, Newton, Noxubee...

40 CFR 81.325 - Mississippi.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Lee County X Leflore County X Lincoln County X Lowndes County X Madison County X Marion County X... Lee County X Leflore County X Lincoln County X Lowndes County X Madison County X Marion County X... County Kemper County Lafayette County Lamar County Lauderdale County Lawrence County Leake County Lee...

LEE VINING INTAKE LOOKING NORTH. DIVERTED WATER FOR CITY OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LEE VINING INTAKE LOOKING NORTH. DIVERTED WATER FOR CITY OF LOS ANGELES USED TO GO OUT VIA COVERED CONDUIT TO RIGHT OF PICTURE SPACE. SCORCHED SAGE IN FOREGROUND FROM RECENT FOREST FIRE - Los Angeles Aqueduct, Lee Vining Intake Structure, Los Angeles, Los Angeles County, CA

16. FIRST FLOOR APARTMENT KITCHEN INTERIOR SHOWING OPEN DOORWAY TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. FIRST FLOOR APARTMENT KITCHEN INTERIOR SHOWING OPEN DOORWAY TO LIVING ROOM AND PAIRED 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS OVER SINK. VIEW TO EAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Retrospective: Ivy Lee and the German Dye Trust.

ERIC Educational Resources Information Center

Hainsworth, Brad E.

1987-01-01

Examines the relationship between public relations trailblazer Ivy Lee and the German Dye Trust, which became an agent for the policies of Adolf Hitler. Discusses how Lee's efforts to use this relationship to persuade his contacts to influence the Nazi leadership failed because of his formal connection with this group. (JD)

12. INTERIOR OF COVERED WALKWAY BEHIND SECOND FLOOR APARTMENTS FROM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. INTERIOR OF COVERED WALKWAY BEHIND SECOND FLOOR APARTMENTS FROM OPPOSITE VIEW OF CA-XXX-11. DOOR AT PHOTO LEFT OPENS INTO THE KITCHEN OF THE WEST SIDE SECOND FLOOR APARTMENT. VIEW TO EAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

34. SECOND FLOOR WEST SIDE APARTMENT KITCHEN INTERIOR. DOORWAY AT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

34. SECOND FLOOR WEST SIDE APARTMENT KITCHEN INTERIOR. DOORWAY AT PHOTO LEFT LEADS TO PANTRY. GROUP OF THREE 6-LIGHT WOOD-FRAME CASEMENT WINDOWS OPEN TO WALKWAY AT REAR OF BUILDING. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

36. SECOND FLOOR WEST SIDE APARTMENT EAST BEDROOM INTERIOR. OPEN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. SECOND FLOOR WEST SIDE APARTMENT EAST BEDROOM INTERIOR. OPEN DOORWAY AT PHOTO LEFT CENTER LEADS TO CLOSET, AND OPEN DOORWAY AT PHOTO RIGHT CENTER LEADS TO LIVING ROOM. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

49 CFR Appendix F to Subchapter B... - Commercial Zones

Code of Federal Regulations, 2011 CFR

2011-10-01

....J.; the area within the borough limits of Alpine, Tenafly, Englewood Cliffs, Leonia, Fort Lee... along U.S. Highway 40 to its junction with the Lee's Summit, Mo., corporate limits. Thence along the eastern Lee's Summit corporate limits to the Jackson-Cass County line, thence west along Jackson-Cass...

40 CFR 81.311 - Georgia.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Lamar County X Lanier County X Laurens County X Lee County X Liberty County X Lincoln County X Long... Lamar County X Lanier County X Laurens County X Lee County X Liberty County X Lincoln County X Long... County Jenkins County Johnson County Jones County Lamar County Lanier County Laurens County Lee County...

40 CFR 81.314 - Illinois.

Code of Federal Regulations, 2010 CFR

2010-07-01

... County X Woodford County X Lee County X AQCR 66: Champaign County X Clark County X Coles County X... Washington County X AQCR 71: Bureau County: Shelby Twp X All other Bureau twps X La Salle County X Lee County.../Attainment La Salle County Unclassifiable/Attainment Lawrence County Unclassifiable/Attainment Lee County...

75 FR 10460 - Yakutat Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... at the Kwaan Conference Room, 712 Ocean Cape Drive, Yakutat, Alaska. Send written comments to Lee A... [email protected] . FOR FURTHER INFORMATION CONTACT: Lee A. Benson, District Ranger and Designated Federal... opportunity to address the Council at those sessions. Dated: February 19, 2010. Lee A. Benson, District Ranger...

75 FR 26255 - Change in Bank Control Notices; Acquisition of Shares of Bank or Bank Holding Companies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... Street, San Francisco, California 94105-1579: 1. Thomas H. Lee Equity Fund VI, L.P.; Thomas H. Lee Parallel Fund VI, L.P.; Thomas H. Lee Parallel (DT) Fund VI, L.P.; and THL Sterling Equity Investors, L.P...

40 CFR 81.341 - South Carolina.

Code of Federal Regulations, 2011 CFR

2011-07-01

... County X Laurens County X Lee County X Lexington County X McCormick County X Marion County X Marlboro... X Jasper County X Kershaw County X Lancaster County X Laurens County X Lee County X Lexington County... County Kershaw County Lancaster County Laurens County Lee County Lexington County Marion County Marlboro...

40 CFR 81.341 - South Carolina.

Code of Federal Regulations, 2010 CFR

2010-07-01

... County X Laurens County X Lee County X Lexington County X McCormick County X Marion County X Marlboro... X Jasper County X Kershaw County X Lancaster County X Laurens County X Lee County X Lexington County... County Kershaw County Lancaster County Laurens County Lee County Lexington County Marion County Marlboro...

40 CFR 81.311 - Georgia.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Lamar County X Lanier County X Laurens County X Lee County X Liberty County X Lincoln County X Long... Lamar County X Lanier County X Laurens County X Lee County X Liberty County X Lincoln County X Long... County Jenkins County Johnson County Jones County Lamar County Lanier County Laurens County Lee County...

76 FR 12691 - Yakutat Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Lee A. Benson, c/o Forest Service, USDA, P.O. Box 327, Yakutat, AK 99689, electronically to labenson... INFORMATION CONTACT: Lee A. Benson, District Ranger and Designated Federal Official, Yakutat Ranger District... written statements with the Committee staff before or after the meeting. Dated: February 25, 2011. Lee A...

40 CFR 81.316 - Iowa.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Remainder of Lee County X Cedar Rapids—a portion of Linn County contained entirely within T 82 N., R 7 W... County Johnson County Jones County Keokuk County Kossuth County Lee County Linn County Louisa County... County Johnson County Jones County Keokuk County Kossuth County Lee County Linn County Louisa County...

78 FR 73886 - Schweitzer-Mauduit International, Inc., Paper Machine #21, Ancram, New York; Schweitzer-Mauduit...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

...., Columbia Mill, Lee, Massachusetts; Amended Certification Regarding Eligibility To Apply for Worker... revealed that workers of Schweitzer-Mauduit International, Inc., Columbia Mill, Lee, Massachusetts are... working at Schweitzer-Mauduit International, Inc., Columbia Mill, Lee, Massachusetts (TA-W-82,718A). The...

40 CFR 81.316 - Iowa.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Remainder of Lee County X Cedar Rapids—a portion of Linn County contained entirely within T 82 N., R 7 W... County Johnson County Jones County Keokuk County Kossuth County Lee County Linn County Louisa County... County Johnson County Jones County Keokuk County Kossuth County Lee County Linn County Louisa County...

40 CFR 81.314 - Illinois.

Code of Federal Regulations, 2011 CFR

2011-07-01

... County X Woodford County X Lee County X AQCR 66: Champaign County X Clark County X Coles County X... Washington County X AQCR 71: Bureau County: Shelby Twp X All other Bureau twps X La Salle County X Lee County.../Attainment La Salle County Unclassifiable/Attainment Lawrence County Unclassifiable/Attainment Lee County...

23. SECOND FLOOR EAST SIDE APARTMENT LIVING ROOM INTERIOR. PAIRED ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. SECOND FLOOR EAST SIDE APARTMENT LIVING ROOM INTERIOR. PAIRED 4-LIGHT OVER 1-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS FLANK ENTRY DOOR. DOORWAY AT PHOTO RIGHT OPENS TO KITCHEN. VIEW TO SOUTHEAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

38. SECOND FLOOR WEST SIDE APARTMENT WEST BEDROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

38. SECOND FLOOR WEST SIDE APARTMENT WEST BEDROOM INTERIOR SHOWING PAIRED 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS ON WEST WALL AND OPEN DOORWAY TO LIVING ROOM. VIEW TO WEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

33. SECOND FLOOR WEST SIDE APARTMENT KITCHEN INTERIOR. 6LIGHT PANEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. SECOND FLOOR WEST SIDE APARTMENT KITCHEN INTERIOR. 6-LIGHT PANEL DOOR AND 6-LIGHT CASEMENT WINDOW AT PHOTO CENTER AND PHOTO RIGHT RESPECTIVELY OPEN TO EXTERIOR STAIRWAY LANDING. VIEW TO WEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Constraints on the Lee-Wick Higgs sector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carone, Christopher D.; Primulando, Reinard

2009-09-01

Lee-Wick partners to the standard model Higgs doublet may appear at a mass scale that is significantly lower than that of the remaining Lee-Wick partner states. The relevant effective theory is a two-Higgs doublet model in which one doublet has wrong-sign kinetic and mass terms. We determine bounds on this effective theory, including those from neutral B-meson mixing, b{yields}X{sub s}{gamma}, and Z{yields}bb. The results differ from those of conventional two-Higgs doublet models and lead to meaningful constraints on the Lee-Wick Higgs sector.

Eddies and Filaments of the Western Adriatic Current near Cape Gargano: Analysis and Prediction

DTIC Science & Technology

2008-10-21

circulation in the lee of the cape. By 4 Sep. (Fig. 7b), the winds have relaxed, and the meanders are larger in amplitude. The anti-cyclone in the lee of...branch, which forms an anti- cyclonic ‘ lee ’ eddy near the cape, and an eastward branch, which forms a matching cyclonic eddy further downstream. In some...separation of the resulting combined flow and its subsequent point of impingement on the coast vary from frame to frame. The lee eddy resembles one described

'Items for criticism (not in sequence)': Joseph DeLee, Pare Lorentz and The Fight for Life (1940).

PubMed

Gainty, Caitjan

2017-09-01

In the late 1920s, the American obstetrician Joseph DeLee brought the motion-picture camera into the birth room. Following that era's trend of adapting industrial efficiency practices for medical environments, DeLee's films give spectacular and unexpected expression to the engineering concept of 'streamlining'. Accomplishing what more tangible obstetric streamlining practices had failed to, DeLee's cameras, and his post-production manipulation, shifted birth from messy and dangerous to rationalized, efficient, death-defying. This was film as an active and effective medical tool. Years later, the documentarian Pare Lorentz produced and wrote his own birth film, The Fight for Life (1940). The documentary subject of the film was DeLee himself, and the film was set in his hospitals, on the same maternity 'sets' that had once showcased film's remarkable streamlining capacity to give and keep life. Yet relatively little of DeLee was retained in the film's content, resulting in a showdown that, by way of contrast, further articulated DeLee's understanding of film's medical powers and, in so doing, hinted at a more dynamic moment in the history of medicine while speaking also to the process by which that understanding ceased to be historically legible.

Oxygen Consumption by Postfermentation Wine Yeast Lees: Factors Affecting Its Rate and Extent under Oenological Conditions

PubMed Central

Müller, Jonas; Schmidt, Dominik

2016-01-01

Summary Postfermentation wine yeast lees show antioxidant properties based on their ability to consume dissolved oxygen. The oxygen consumption capacity of suspended yeast lees obtained after fermentations with six commercial active dry yeast strains was investigated in model, white and red wines using fluorescence-based oxygen sensors operating in a nondestructive way. In model solution, the oxygen consumption rate of yeast lees was shown to depend on their amount, yeast strain, sulfur dioxide and temperature. It is slightly lower in red than in white wines. It is strongly decreased by current levels of free sulfur dioxide, thus excluding the complementary use of both as antioxidants in wine. However, in 25 randomly sampled white wines produced under commercial conditions, the rate and extent of oxygen consumption during the first six months of postfermentation had no significant correlation with any of these interacting factors, making it difficult to predict the actual antioxidant effect of yeast lees. In these wines, yeast lees consumed 0 to 47% of the dissolved oxygen. Although total oxygen consumption capacity of yeast lees is not a limiting factor under commercial winemaking conditions, their oxygen consumption proceeds at a limited rate that reduces but cannot totally prevent concomitant chemical oxidation of the wine. PMID:28115896

Oxygen Consumption by Postfermentation Wine Yeast Lees: Factors Affecting Its Rate and Extent under Oenological Conditions.

PubMed

Schneider, Volker; Müller, Jonas; Schmidt, Dominik

2016-12-01

Postfermentation wine yeast lees show antioxidant properties based on their ability to consume dissolved oxygen. The oxygen consumption capacity of suspended yeast lees obtained after fermentations with six commercial active dry yeast strains was investigated in model, white and red wines using fluorescence-based oxygen sensors operating in a nondestructive way. In model solution, the oxygen consumption rate of yeast lees was shown to depend on their amount, yeast strain, sulfur dioxide and temperature. It is slightly lower in red than in white wines. It is strongly decreased by current levels of free sulfur dioxide, thus excluding the complementary use of both as antioxidants in wine. However, in 25 randomly sampled white wines produced under commercial conditions, the rate and extent of oxygen consumption during the first six months of postfermentation had no significant correlation with any of these interacting factors, making it difficult to predict the actual antioxidant effect of yeast lees. In these wines, yeast lees consumed 0 to 47% of the dissolved oxygen. Although total oxygen consumption capacity of yeast lees is not a limiting factor under commercial winemaking conditions, their oxygen consumption proceeds at a limited rate that reduces but cannot totally prevent concomitant chemical oxidation of the wine.

Duodenal bicarbonate secretion and mucosal protection. Neurohumoral influence and transport mechanisms.

PubMed

Säfsten, B

1993-01-01

Duodenal mucosal bicarbonate secretion (DMBS) plays an important role in the defence against acid discharged from the stomach. The secretion by duodenum immediately distal to the Brunner's glands area and devoid of pancreatic and biliary secretions, was investigated in vivo in anaesthetized Sprague-Dawley rats and in vitro in mucosae isolated from the American bullfrog. Transport mechanisms were studied in isolated rat duodenal enterocytes and identified by use of digitized microfluorometry and the fluoroprobe BCECF. Cyclic AMP production in enterocytes of villus vs. crypt origin was measured with radioimmunoassay. The benzodiazepines diazepam and Ro 15-1788 stimulated DMBS in the rat when administered intravenously or intracerebroventricularly; however, their stimulatory effect was abolished by bilateral proximal vagotomy, and they had no effect on the secretion by isolated bullfrog mucosa. It is concluded that these benzodiazepines stimulate secretion by acting upon the central nervous system and that their effects are vagally mediated. Dopamine, the catechol-O-methyl-transferase-inhibitor nitecapone, and the dopamine D1 agonist SKF-38393 all stimulated DMBS. The peripherally acting antagonist domperidone while having no influence on basal DMBS did prevent the influences of SKF-38393 and nitecapone. The alpha 1-antagonist prazosin had no such effects and the combined results suggest that DMBS is stimulated via peripheral dopamine D1 receptors. Intravenous, but not central nervous, administration of the muscarinic M1 receptor antagonists pirenzepine and telenzepine effectively stimulated DMBS; however their effectiveness was dependent on intact vagal nerves. Phentolamine, an unselective alpha-adrenergic antagonist, prevented the stimulation by pirenzepine and telenzepine and stimulation by carbachol was abolished by hexamethonium. It is concluded that peripheral nicotinergic and muscarinergic M1 receptors mediate stimulation of DMBS, in part by acting upon peripheral sympathetic ganglia. Whereas dopamine and SKF-38393 caused a time-dependent increase in the accumulation of cyclic AMP in duodenal enterocytes of crypt and villous origin, the D2 agonist quinpirole had an inhibitive influence. Crypt and villus cells differed in their respective time-courses in response to vasoactive intestinal polypeptide. Finally, Cl-/HCO3- exchange, Na+/H+ exchange and NaHCO3 cotransport were identified as membrane acid/base transport mechanisms in isolated duodenal enterocytes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Rino; Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp; Murota, Kaeko

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation ofmore » peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.« less

[Birth and succession of a current of learning in Korean medicine: the supporting yang current of learning].

PubMed

Oh, Chaekun

2014-04-01

In this study, I aim to reveal how Lee Gyoojoons medicine has given birth to a current of learning, the supporting yang current of learning, and describe its historical significance. Before anything, I'd like to throw the question of whether if there were any currents within the traditional Korean medicine. There are no records of medical currents being widely discussed until now in medical history of Korea; however, the current of Lee Jema's sasang medicine is the most noticeable one. Among the contemporaries of Lee Jema, during the late Chosun, there was also another famed medical practitioner called Lee Gyoojoon. Lee Gyoojoon mainly practiced his medicine within Pohang, Gyeongsangbuk-do area, his apprentices have formed a group and have succeeded his medical practice. Based on the analyses of Lee Gyoojoon's apprentices and the Somun Oriental Medical Society, which is known as a successor group to Lee Gyoojoon's medicine today, they are fully satisfying the five requirements to establish a medical current: first, they held Lee Gyoojoon as the first and foremost, representative practitioner of their current; second, they advocate the supporting yang theory suggested by Lee Gyoojoon, which is originated from his theory of Mind; third, books such as the Major Essentials of Huangdi's Internal Classic Plain Questions, and the Double Grinded Medical Mirror, were being used as the main textbooks to educate their students or to practice medicine. Fourth, Lee Gyoojoon's medical ideas were being transcended quite clearly within his group of apprentices, including Seo Byungoh, Lee Wonse, and the Somun Oriental Medical Society. Fifth, Lee Gyoojoon's apprentices were first produced through the Sukgok School, however, nowadays they are being produced through medical groups formed by Lee Wonse, the Somun Oriental Medical Society, regarding the propagation of medical theories, compilation of textbooks, publication of academic journals, etc. Then, what do the existence of the supporting yang current have their significances in history? First of all, Heo Joon, the great medical practitioner in 16th century Chosun, have revealed through his book the Treasured Mirror of Eastern Medicine (TMEM), that the essence of Eastern medicine differentiated from South and North medicine of China is being transcended in Korean medicine. However, we have not got a clear conclusion on what his views of the essence of Eastern medicine is. The TMEM is the legacy of Neo-confucianism, dominant in the Chosun at the time, and is considered the reference which covers from Taoism to Korean Medicine, that is practical as well as systematical in categorizing illnesses, their respective prescriptions, and herbs. Maybe, it seems that such characteristics of the TMEM naturally led the medical practitioners and Confucian scholars, Lee Jema and Lee Gyoojoon to adopt its principles, and furthermore, possibly contributed in materializing the tradition of Eastern Medicine. Secondly, both currents appeared in the late period of Chosun dynasty. Then, weren't there any preceding medical currents before them? The bureaucratic and centralized government of the Chosun dynasty demanded and supplied talents through a nationwide examination system. However, since the late-16th century, a few family from the Chungin class have come to dominate the important medical positions as inheritance doctors , bringing about the expansion of the private medical sector, as well as growth in the number of medical practitioners. This naturally brought about fierce competition among the practitioners, and it is probable that the competition sparked the need for standardized groups and societies that follow a single medical doctrine or theory, to differentiate from the others. Probably, the birth of current of learning, which succeeded to Lee Jema and Lee Gyoojoon's medical theory, exists as an extension of this social background. The major changes in systems to build a new Chosun in 1894 brought about the abolitions of old and antique institutions. Inheritance doctors naturally collapsed, and every medical practitioners had to compete in an open market. However, Lee Jema and Lee Gyoojoon, as a medical practitioner and Confucian scholar, weren't from medical families; instead, they have successfully established and led their medical groups. The Sasang medicine current, which first began in the Hamhung area, had creative medical theories and excellent practices, naturally led the discourses traditional medicine in the center areas of the Korean peninsula. In contrast, the supporting yang current, more popular in the Youngnam area at one time, struggled to keep their current during the period of Korean War, National Industrialization and Modernization. And it was only Lee Wonse's personal dedication to the current that made it survive through the times. It was not until the late 1990s, when the apprentices have gathered Lee Gyoojoon's accomplishments, that formed the Somun Oriental Medical Society as well as the supporting yang current. In summary, the birth and the succession of the supporting yang current clearly depicts how the various traditional medical groups and societies on the periphery have survived and transcended through difficult times. And at the same time, they can provide chance to ruminate the historical flow of traditional medicine in Korea.

Polyphenols from Wine Lees as a Novel Functional Bioactive Compound in the Protection Against Oxidative Stress and Hyperlipidaemia

PubMed Central

Landeka, Irena; Jurčević; Dora, Mirna; Guberović, Iva; Petras, Marija; Rimac, Suzana; Brnčić

2017-01-01

Summary The study examines the potential of wine industry by-product, the lees, as a rich mixture of natural polyphenols, and its physiological potential to reduce postprandial metabolic and oxidative stress caused by a cholesterol-rich diet in in vivo model. Chemical analysis of wine lees showed that their total solid content was 94.2%. Wine lees contained total phenols, total nonflavonoids and total flavonoids expressed in mg of gallic acid equivalents per 100 g of dry mass: 2316.6±37.9, 1332.5±51.1 and 984.1±28.2, respectively. The content of total anthocyanins expressed in mg of cyanidin-3-glucoside equivalents per 100 g of dry mass was 383.1±21.6. Antioxidant capacity of wine lees determined by the DPPH and FRAP methods and expressed in mM of Trolox equivalents per 100 g was 259.8±1.8 and 45.7±1.05, respectively. The experiment lasted 60 days using C57BL/6 mice divided in four groups: group 1 was fed normal diet and used as control, group 2 was fed normal diet with added wine lees, group 3 was fed high-cholesterol diet (HCD), i.e. normal diet with the addition of sunflower oil, and group 4 was fed HCD with wine lees. HCD increased serum total cholesterol (TC) by 2.3-fold, triacylglycerol (TAG) by 1.5-fold, low-density lipoprotein (LDL) by 3.5-fold and liver malondialdehyde (MDA) by 50%, and reduced liver superoxide dismutase (SOD) by 50%, catalase (CAT) by 30% and glutathione (GSH) by 17.5% compared to control. Conversely, treatment with HCD and wine lees reduced TC and LDL up to 1.4 times more than with HCD only, with depletion of lipid peroxidation (MDA) and restoration of SOD and CAT activities in liver, approximating values of the control. HDL levels were unaffected in any group. Serum transaminase activity showed no hepatotoxic properties in the treatment with lees alone. In the proposed model, wine lees as a rich polyphenol source could be a basis for functional food products without alcohol. PMID:28559739

2. OVERVIEW OF TRIPLEX COTTAGE IN POOLE POWERHOUSE SETTING. TRIPLEX ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. OVERVIEW OF TRIPLEX COTTAGE IN POOLE POWERHOUSE SETTING. TRIPLEX COTTAGE IS VISIBLE AT PHOTO CENTER LEFT. POOLE POWERHOUSE IS ADJACENT TRIPLEX COTTAGE AT PHOTO CENTER RIGHT. SWITCHRACKS ARE VISIBLE ADJACENT TO POWERHOUSE BUILDING. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Southern Clerics and the Passing of Lee: Mythic Rhetoric and the Construction of a Sacred Symbol.

ERIC Educational Resources Information Center

Fulmer, Hal W.

1990-01-01

Examines the symbolic content of eulogies delivered by Southern clergymen following the 1870 death of Confederate General Robert E. Lee. Explores the clergy's discussions of Lee's immortality and the redemptive power of audience unity which were foundations for later mythic discourse on the general's life. (SG)

75 FR 74711 - Duke Energy Lee II, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-01

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER11-2069-000] Duke Energy Lee II, LLC; Supplemental Notice That Initial Market- Based Rate Filing Includes Request for Blanket... proceeding, of Duke Energy Lee II, LLC's application for market-based rate authority, with an accompanying...

40 CFR 81.334 - North Carolina.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Lee County X Lenoir County X Lincoln County X McDowell County X Macon County X Madison County X Martin... Lee County X Lenoir County X Lincoln County X McDowell County X Macon County X Madison County X Martin... Hertford County Hoke County Hyde County Iredell County Jackson County Johnston County Jones County Lee...

75 FR 29657 - Establishment of Class E Airspace; Marianna, AR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

...) at Marianna/Lee County Airport--Steve Edwards Field, Marianna, AR. The FAA is taking this action to... controlled airspace at Marianna/Lee County Airport--Steve Edwards Field (75 FR 12161) Docket No. FAA-2009... from 700 feet above the surface to accommodate SIAPs at Marianna/Lee County Airport-- Steve Edwards...

77 FR 3324 - Release of Airport Property: Page Field, Fort Myers, FL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... subject airport and the Federal Aviation Administration. The release of property will allow the Lee County.... The property is located in the southwest corner of airport property, north of South Road, in Lee... released of its federal obligations to sell the property at Fair Market Value to Lee County for municipal...

40 CFR 81.334 - North Carolina.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Lee County X Lenoir County X Lincoln County X McDowell County X Macon County X Madison County X Martin... Lee County X Lenoir County X Lincoln County X McDowell County X Macon County X Madison County X Martin... Hertford County Hoke County Hyde County Iredell County Jackson County Johnston County Jones County Lee...

76 FR 59168 - Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

..., Sara Lee Corporation, Including On-Site Leased Workers From EDS, Hewitt Packard, Sapphire Technology..., IL; TA-W-71,499A, Sara Lee Corporation, Master Data, Cash Applications, Deductions, Collections, Call... Group, TraSys, VIP Staffing, and Workforce Temps, Earth City, MO; TA-W-71,499B, Sara Lee Corporation...

30. SECOND FLOOR EAST SIDE APARTMENT WEST BEDROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

30. SECOND FLOOR EAST SIDE APARTMENT WEST BEDROOM INTERIOR SHOWING PAIRED 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS THROUGH NORTH WALL. ORIGINAL LOUVERED DOORS FRAME CLOSET AT PHOTO LEFT. VIEW TO NORTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

9. EXTERIOR OF ENCLOSED PORTION OF SECOND FLOOR WEST SIDE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. EXTERIOR OF ENCLOSED PORTION OF SECOND FLOOR WEST SIDE APARTMENT ENTRYWAY SHOWING STAIR LANDING AND OPEN FRONT DOOR FLANKED BY PAIRED 4-LIGHT OVER 4-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS. VIEW TO NORTHEAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

20. FIRST FLOOR APARTMENT NORTH BEDROOM INTERIOR LOOKING THROUGH DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. FIRST FLOOR APARTMENT NORTH BEDROOM INTERIOR LOOKING THROUGH DOOR FROM LIVING ROOM. GROUP OF THREE 6-LIGHT OVER 6-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS AT PHOTO CENTER THROUGH NORTH (FRONT) WALL OF HOUSE. VIEW TO EAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Mixing, ergodicity and slow relaxation phenomena

NASA Astrophysics Data System (ADS)

Costa, I. V. L.; Vainstein, M. H.; Lapas, L. C.; Batista, A. A.; Oliveira, F. A.

2006-11-01

Investigations on diffusion in systems with memory [I.V.L. Costa, R. Morgado, M.V.B.T. Lima, F.A. Oliveira, Europhys. Lett. 63 (2003) 173] have established a hierarchical connection between mixing, ergodicity, and the fluctuation-dissipation theorem (FDT). This hierarchy means that ergodicity is a necessary condition for the validity of the FDT, and mixing is a necessary condition for ergodicity. In this work, we compare those results with recent investigations using the Lee recurrence relations method [M.H. Lee, Phys. Rev. B 26 (1982) 2547; M.H. Lee, Phys. Rev. Lett. 87 (2001) 250601; M.H. Lee, J. Phys. A: Math. Gen. 39 (2006) 4651]. Lee shows that ergodicity is violated in the dynamics of the electron gas [M.H. Lee, J. Phys. A: Math. Gen. 39 (2006) 4651]. This reinforces both works and implies that the results of [I.V.L. Costa, R. Morgado, M.V.B.T. Lima, F.A. Oliveira, Europhys. Lett. 63 (2003) 173] are more general than the framework in which they were obtained. Some applications to slow relaxation phenomena are discussed.

C. elegans as a Model for EPEC Infection

DTIC Science & Technology

2005-11-30

Salmonella enterica, an invasive diarrheal pathogen, Yersinia pestis, the agent causing bubonic plague, and Chlamydia pneumoniae, which has been implicated...2003 - 8/31/2005 2 Background Our laboratory investigates the molecular pathogenesis of enteropathogenic E. coli (EPEC), a leading cause of...organism of a group of pathogenic bacteria that cause attaching and effacing (AE) intestinal lesions (Levine et al., 1978; Nataro and Kaper, 1998). AE

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Lerner, Aaron; Coran, Arnold G; Lurie, Michael; Miselevich, Iness; Shiloni, Eitan

2005-06-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia in rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Krausz, Michael M; Lurie, Michael; Hirsh, Mark; Coran, Arnold G; Shiloni, Eitan

2004-12-01

The objective of this study was to evaluate the effects of lipopolysaccharide (LPS) endotoxemia and enteral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis in rat. Male Sprague-Dawley rats, weighing 250-280 g, were divided into three experimental groups: control rats, LPS rats treated with lipopolysaccharide given ip at a dose of 10 mg/kg every 24 h (two injections), and LPS-ARG rats treated with enteral arginine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined on day 3 following the first LPS injection. LPS rats demonstrated a significant decrease in bowel weight in duodenum, mucosal weight in duodenum, jejunum, and ileum, mucosal DNA and protein in jejunum and ileum, and villus height in jejunum and ileum compared to control animals. LPS rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in jejunum and ileum compared to control rats. LPS-ARG animals demonstrated greater duodenal bowel weight, duodenal and ileal mucosal weight, ileal mucosal DNA and protein, ileal villus height, and jejunal and ileal cell proliferation index compared to LPS animals. LPS endotoxemia impairs the integrity of the gastrointestinal mucosa in rat. Decreased cell proliferation and increased apoptosis may be considered the main mechanisms responsible for the decreased cell mass. Enteral arginine administration decreases the mucosal injury caused by lipopolysaccharide.

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat.

PubMed

Sukhotnik, Igor; Helou, Habib; Mogilner, Jorge; Lurie, Michael; Bernsteyn, Aleksander; Coran, Arnold G; Shiloni, Eitan

2005-03-01

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia-reperfusion (IR) in the rat. Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.

Hydroxypropyl-sulfobutyl-β-cyclodextrin improves the oral bioavailability of edaravone by modulating drug efflux pump of enterocytes.

PubMed

Rong, Wen-Ting; Lu, Ya-Peng; Tao, Qing; Guo, Miao; Lu, Yu; Ren, Yong; Yu, Shu-Qin

2014-02-01

The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-βCD) on the bioavailability and intestinal absorption of edaravone, and identify its mechanism of action. We devised HP-SBE-βCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and edaravone as a model drug, and prepared edaravone/HP-SBE-βCD inclusion complex. HP-SBE-βCD improved the water solubility and enhanced the bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass intestinal perfusion showed that HP-SBE-βCD had an effect of improving the permeability and inhibiting the efflux of edaravone. Furthermore, the effects of HP-SBE-βCD on Pgp were achieved through interfering with the lipid raft and depleting the cholesterol of enterocytes membrane. From the results, we presented the novel mechanisms. First, edaravone/HP-SBE-βCD had a lower release from the inclusion compound to protect edaravone from the low pH of the stomach. Then, HP-SBE-βCD modulated the membrane microenvironment of intestinal absorption epithelial cells. At last, the result was that HP-SBE-βCD enhanced the absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-βCD improves the bioavailability of drug not only because of its enhancing water solubility of the drug, but also because it modulates the Pgp-mediated efflux from enterocytes. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs.

PubMed

Odes, H S; Muallem, R; Reimer, R; Ioffe, S; Beil, W; Schwenk, M; Sewing, K F

1995-03-01

The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- output from the isolated, perfused (24 mM NaHCO3 + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E2 (PGE2). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO3- secretion (3.5 +/- 0.2 mumol/cm/10 min) was reduced dose dependently by somatostatin-14 (10(-11) mol/kg, 10(-9) mol/kg, and 10(-7) mol/kg). Carbachol, VIP, and PGE2 (all 10(-8) mol/kg) increased basal duodenal HCO3- secretion two- to threefold. Somatostatin-14 (10(-7) mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE2. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4 +/- 1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10(-6) mol/liter) or carbachol (10(-3) mol/liter). VIP (10(-8) mol/liter) and PGE2 (10(-7) mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10(-6) mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.

Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease.

PubMed

Das, Prasenjit; Gahlot, Gaurav P S; Mehta, Ritu; Makharia, Archita; Verma, Anil K; Sreenivas, Vishnubhatla; Panda, Subrat K; Ahuja, Vineet; Gupta, Siddhartha Datta; Makharia, Govind K

2016-11-01

Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy. We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Mogilner, Jorge; Shamir, Raanan; Shehadeh, Naim; Bejar, Jacob; Hirsh, Mark; Coran, Arnold G

2005-03-01

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Broad MICA/B expression in the small bowel mucosa: a link between cellular stress and celiac disease.

PubMed

Allegretti, Yessica L; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W; Chirdo, Fernando G

2013-01-01

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B(+) T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B(+) B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.

Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

PubMed Central

Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.

2013-01-01

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role. PMID:24058482

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

PubMed

Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

2013-01-01

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

Evidence for a Cystic Fibrosis Enteropathy

PubMed Central

Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

2015-01-01

Background Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. Methods Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. Results Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. Conclusion This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance. PMID:26484665

Tests of conformal field theory at the Yang-Lee singularity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wydro, Tomasz; McCabe, John F.

2009-12-14

This paper studies the Yang-Lee edge singularity of 2-dimensional (2D) Ising model based on a quantum spin chain and transfer matrix measurements on the cylinder. Based on finite-size scaling, the low-lying excitation spectrum is found at the Yang-Lee edge singularity. Based on transfer matrix techniques, the single structure constant is evaluated at the Yang-Lee edge singularity. The results of both types of measurements are found to be fully consistent with the predictions for the (A{sub 4}, A{sub 1}) minimal conformal field theory, which was previously identified with this critical point.

Marion McGregor Lee Loy

ERIC Educational Resources Information Center

Rossi, Joe

2007-01-01

This article presents an interview with Marion Frances Kaleleonalani McGregor Lee Loy who served as a teacher in the Hawai'i Department of Education from 1935 to 1974. Marion McGregor Lee Loy was born in 1911 in Honolulu. She attended Central Grammar and Lincoln Grammar schools before entering Kamehameha School for Girls in the ninth grade. Lee…

Working Connections: Suzan Lee--UBS Securities LLC, New York

ERIC Educational Resources Information Center

Library Journal, 2004

2004-01-01

This article is about Suzan Lee of UBS Securities LLC in New York, a person who is dedicated to connecting aspiring professionals to opportunities in the world of special libraries. In 1999, Lee realized that most library students had only one resource for internships--their library schools--and that these offerings focused largely on public and…

50 CFR 226.218 - Critical habitat for the U.S. DPS of smalltooth sawfish (Pristis pectinata).

Code of Federal Regulations, 2010 CFR

2010-10-01

... portions of Charlotte, Lee, Collier, Monroe, and Miami-Dade Counties. (1) Charlotte Harbor Estuary Unit. The Charlotte Harbor Estuary Unit is located within Charlotte and Lee Counties. The unit includes... Preserve, which is bounded on the south by the Lee/Collier County line. Inland waters are bounded by SR-867...

50 CFR 226.218 - Critical habitat for the U.S. DPS of smalltooth sawfish (Pristis pectinata).

Code of Federal Regulations, 2011 CFR

2011-10-01

... portions of Charlotte, Lee, Collier, Monroe, and Miami-Dade Counties. (1) Charlotte Harbor Estuary Unit. The Charlotte Harbor Estuary Unit is located within Charlotte and Lee Counties. The unit includes... Preserve, which is bounded on the south by the Lee/Collier County line. Inland waters are bounded by SR-867...

"Identity in Flux": Exploring the Work of Nikki S. Lee

ERIC Educational Resources Information Center

Allison, Amanda

2009-01-01

Identity is a vital topic for discussion, exploration, and discovery in the art classroom. The artwork of Nikki S. Lee provides an opportunity for students to begin reformulating their notions about selfhood. The work of Nikki S. Lee is significant because it blends documentary, fashion, and staged and unstaged photography to allow viewers to…

75 FR 27576 - J.N. “Ding” Darling National Wildlife Refuge, Lee County, FL

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R4-R-2010-N052; 40136-1265-0000-S3] J.N. ``Ding'' Darling National Wildlife Refuge, Lee County, FL AGENCY: Fish and Wildlife Service, Interior... variety of species in a highly developed landscape. The city of Sanibel, Lee County, Sanibel-Captiva...

Strategies for Science Student Achievement & Productive School Management

ERIC Educational Resources Information Center

Johnson, William L.

2010-01-01

There is an increasing literature pertaining to student achievement and school productivity. This session will present school and classroom strategies used in high school science classes at Robert E. Lee High School (5A) in Tyler, Texas. This year, 84% of the students at Lee passed the science TAKS test. Lee is also ranked in the top 1500 high…

The Ubiquitous Laplacian Assumption: Reply to Lee and Wagenmakers (2005)

ERIC Educational Resources Information Center

Trafimow, David

2005-01-01

In their comment on D. Trafimow, M. D. Lee and E. Wagenmakers argued that the requisite probabilities to use in Bayes's theorem can always be found. In the present reply, the author asserts that M. D. Lee and E. Wagenmakers use a problematic assumption and that finding the requisite probabilities is not straightforward. After describing the…

31. SECOND FLOOR WEST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

31. SECOND FLOOR WEST SIDE APARTMENT LIVING ROOM INTERIOR SHOWING PAIRED 4-LIGHT OVER 4-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS FLANKING ENTRY DOOR WITH UNUSUAL 8-LIGHT WINDOW. OPEN DOORWAY TO PHOTO LEFT LEADS TO KITCHEN. VIEW TO WEST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

One-loop renormalization of Lee-Wick gauge theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grinstein, Benjamin; O'Connell, Donal

2008-11-15

We examine the renormalization of Lee-Wick gauge theory to one-loop order. We show that only knowledge of the wave function renormalization is necessary to determine the running couplings, anomalous dimensions, and vector boson masses. In particular, the logarithmic running of the Lee-Wick vector boson mass is exactly related to the running of the coupling. In the case of an asymptotically free theory, the vector boson mass runs to infinity in the ultraviolet. Thus, the UV fixed point of the pure gauge theory is an ordinary quantum field theory. We find that the coupling runs more quickly in Lee-Wick gauge theorymore » than in ordinary gauge theory, so the Lee-Wick standard model does not naturally unify at any scale. Finally, we present results on the beta function of more general theories containing dimension six operators which differ from previous results in the literature.« less

25. SECOND FLOOR EAST SIDE APARTMENT KITCHEN INTERIOR SHOWING GROUP ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. SECOND FLOOR EAST SIDE APARTMENT KITCHEN INTERIOR SHOWING GROUP OF THREE 6-LIGHT WOOD-FRAME CASEMENT WINDOWS OVER THE SINK, AND OPEN DOORWAY TO TOP OF EXTERIOR STAIR LANDING AND WALKWAY AT REAR OF HOUSE. WALKWAY IS VISIBLE THROUGH KITCHEN WINDOWS. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

The Earl Lee Street Art Campaign

ERIC Educational Resources Information Center

Bubba

2013-01-01

This article describes a catchy phrase with more to its meaning than first view. A slogan "All the girls love Earl Lee," appears in street art around the world. Earl Lee is a lovable, handsome man who owns the fictitious Earl Lube industries. Originally intended to bring a smile to people's faces at a time when there wasn't much to smile…

77 FR 46105 - Endangered and Threatened Wildlife and Plants; Receipt of Application for Incidental Take Permit...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

...; Availability of Proposed Low- Effect Habitat Conservation Plan and Associated Documents; Lee County, FL AGENCY... about 75 acres of Florida scrub-jay habitat in Lee County, Florida, for the construction of a 215-acre... Lee County, Florida. The Service listed the scrub-jay as threatened on June 3, 1987 (52 FR 20715). The...

[Lee Jungsook, a Korean independence activist and a nurse during the Japanese colonial period].

PubMed

Kim, Sook Young

2015-04-01

This article examines the life of Lee Jungsook, a Korean nurse, as a independence activist during the Japanese colonial period. Lee Jungsook(1896-1950) was born in Bukchung in Hamnam province. She studied at Chungshin girl's high school and worked at Severance hospital. The characteristics and culture of her educational background and work place were very important factors which influenced greatly the life of Lee Jungsook. She learned independent spirit and nationalism from Chungshin girls' high school and worked as nurse at the Severance hospital which were full of intense aspiration for Korea's independence. Many of doctors, professors and medical students were participated in the 3.1 Independence Movement. Lee Jungsook was a founding member of Hyulsungdan who tried to help the independence activists in prison and their families and worked as a main member of Korean Women's Association for Korean Independece and Kyungsung branch of the Korean Red Cross. She was sent to jail by the Japanese government for her independence activism. After being released after serving two years confinement, she worked for the Union for Women's Liberation as a founding member. Lee Joungsook was a great independence activist who had a nursing care spirit as a nurse.

Lee-Yang zero analysis for the study of QCD phase structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ejiri, Shinji

2006-03-01

We comment on the Lee-Yang zero analysis for the study of the phase structure of QCD at high temperature and baryon number density by Monte-Carlo simulations. We find that the sign problem for nonzero density QCD induces a serious problem in the finite volume scaling analysis of the Lee-Yang zeros for the investigation of the order of the phase transition. If the sign problem occurs at large volume, the Lee-Yang zeros will always approach the real axis of the complex parameter plane in the thermodynamic limit. This implies that a scaling behavior which would suggest a crossover transition will notmore » be obtained. To clarify this problem, we discuss the Lee-Yang zero analysis for SU(3) pure gauge theory as a simple example without the sign problem, and then consider the case of nonzero density QCD. It is suggested that the distribution of the Lee-Yang zeros in the complex parameter space obtained by each simulation could be more important information for the investigation of the critical endpoint in the (T,{mu}{sub q}) plane than the finite volume scaling behavior.« less

Promoting Transformational Leadership Through Air Force Culture

DTIC Science & Technology

2013-03-01

this, leaders tailor their behavior toward their fellow Airmen’s need for motivation, achievement, and sense of belonging, recognition, self - esteem ...first, service before self and excellence in all we do – while pursuing adaptive and innovative solutions for our nation’s security. —Air Force...extraverted leaders one would expect. In fact, Collins found most of the leaders to be, “ self -effacing, quiet, reserved, even shy – these are a

Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance

PubMed Central

Tian, Xuefei; Kim, Jin Ju; Monkley, Susan M.; Gotoh, Nanami; Nandez, Ramiro; Soda, Keita; Inoue, Kazunori; Balkin, Daniel M.; Hassan, Hossam; Son, Sung Hyun; Lee, Yashang; Moeckel, Gilbert; Calderwood, David A.; Holzman, Lawrence B.; Critchley, David R.; Zent, Roy; Reiser, Jochen; Ishibe, Shuta

2014-01-01

Podocytes are specialized actin-rich epithelial cells that line the kidney glomerular filtration barrier. The interface between the podocyte and the glomerular basement membrane requires integrins, and defects in either α3 or β1 integrin, or the α3β1 ligand laminin result in nephrotic syndrome in murine models. The large cytoskeletal protein talin1 is not only pivotal for integrin activation, but also directly links integrins to the actin cytoskeleton. Here, we found that mice lacking talin1 specifically in podocytes display severe proteinuria, foot process effacement, and kidney failure. Loss of talin1 in podocytes caused only a modest reduction in β1 integrin activation, podocyte cell adhesion, and cell spreading; however, the actin cytoskeleton of podocytes was profoundly altered by the loss of talin1. Evaluation of murine models of glomerular injury and patients with nephrotic syndrome revealed that calpain-induced talin1 cleavage in podocytes might promote pathogenesis of nephrotic syndrome. Furthermore, pharmacologic inhibition of calpain activity following glomerular injury substantially reduced talin1 cleavage, albuminuria, and foot process effacement. Collectively, these findings indicate that podocyte talin1 is critical for maintaining the integrity of the glomerular filtration barrier and provide insight into the pathogenesis of nephrotic syndrome. PMID:24531545

On the foundations of general relativistic celestial mechanics

NASA Astrophysics Data System (ADS)

Battista, Emmanuele; Esposito, Giampiero; Dell'Agnello, Simone

2017-09-01

Towards the end of nineteenth century, Celestial Mechanics provided the most powerful tools to test Newtonian gravity in the solar system and also led to the discovery of chaos in modern science. Nowadays, in light of general relativity, Celestial Mechanics leads to a new perspective on the motion of satellites and planets. The reader is here introduced to the modern formulation of the problem of motion, following what the leaders in the field have been teaching since the nineties, in particular, the use of a global chart for the overall dynamics of N bodies and N local charts describing the internal dynamics of each body. The next logical step studies in detail how to split the N-body problem into two sub-problems concerning the internal and external dynamics, how to achieve the effacement properties that would allow a decoupling of the two sub-problems, how to define external-potential-effacing coordinates and how to generalize the Newtonian multipole and tidal moments. The review paper ends with an assessment of the nonlocal equations of motion obtained within such a framework, a description of the modifications induced by general relativity on the theoretical analysis of the Newtonian three-body problem, and a mention of the potentialities of the analysis of solar-system metric data carried out with the Planetary Ephemeris Program.

Dosage-dependent role of Rac1 in podocyte injury.

PubMed

Wan, Xiaoyang; Lee, Mi-Sun; Zhou, Weibin

2016-04-15

Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin , suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy. Copyright © 2016 the American Physiological Society.

FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.

PubMed

Yasuda-Yamahara, M; Rogg, M; Frimmel, J; Trachte, P; Helmstaedter, M; Schroder, P; Schiffer, M; Schell, C; Huber, T B

2018-01-11

Simplification and retraction of podocyte protrusions, generally termed as foot process effacement, is a uniform pathological pattern observed in the majority of glomerular disease, including focal segmental glomerulosclerosis. However, it is still incompletely understood how the interaction of cortical actin structures, actomyosin contractility and focal adhesions, is being orchestrated to control foot process morphology in health and disease. By uncovering the functional role of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now evidence, how cell-extracellular matrix (ECM) interactions modulate membrane tension and actomyosin contractility. A genetic modeling approach was applied by deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified human podocytes. Loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization associated with plasma membrane blebbing and a remodeling of focal adhesions. We further show that FERMT2 knockout podocytes have high levels of RhoA activation and concomitantly increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype. Thus, our findings establish a direct link between cell-matrix adhesions, cortical actin structures and plasma membrane tension allowing to better explain cell morphological changes in foot process effacement. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.

PubMed

Dunér, Fredrik; Lindström, Karin; Hultenby, Kjell; Hulkko, Jenny; Patrakka, Jaakko; Tryggvason, Karl; Haraldsson, Börje; Wernerson, Annika; Pettersson, Erna

2010-01-01

It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas α-actinin was unchanged. Copyright © 2010 S. Karger AG, Basel.

Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog.

PubMed

Aquino, S M; Hamor, R E; Valli, V E; Kitchell, B E; Tunev, S S; Bailey, K L; Ehrhart, E J

2000-09-01

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.

Advocacy -- Professional School Counselors Closing the Achievement Gap Through Empowerment: A Response to Hipolito-Delgado and Lee

ERIC Educational Resources Information Center

Mitcham-Smith, Michelle

2007-01-01

The author comments on several aspects of an article by Hipolito-Delgado and Lee entitled "Empowerment Theory for the Professional School Counselor: A Manifesto for What Really Matters" (Professional School Counseling, v10 n4 p327-332 Apr 2007; see EJ767346). Hipolito-Delgado and Lee's article highlights a critical need for a comprehensive,…

76 FR 23642 - The “100,000 Strong” Initiative Federal Advisory Committee: Notice of the Inaugural Meeting of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... wishing to attend should contact Lee Anne Shaffer of the Department of State's Bureau of East Asian and... are welcome to do so by e-mail to Lee Anne Shaffer at [email protected] . A member of the public... participate by teleconferencing can contact Lee Anne Shaffer at 202-647-7059 to receive the conference call-in...

14. FIRST FLOOR APARTMENT LIVING ROOM INTERIOR. FRONT ENTRY DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. FIRST FLOOR APARTMENT LIVING ROOM INTERIOR. FRONT ENTRY DOOR IS AT PHOTO CENTER FLANKED BY A PAIRED 4-LIGHT OVER 4-LIGHT DOUBLE-HUNG, WOOD-FRAME WINDOWS. OPEN DOORWAY TO PHOTO RIGHT OPENS TO NORTH BEDROOM. DOORWAY TO PHOTO LEFT OPENS TO KITCHEN. VIEW TO NORTHEAST. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

Radiation bounce from the Lee-Wick construction?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karouby, Johanna; Brandenberger, Robert

2010-09-15

It was recently realized that matter modeled by the scalar field sector of the Lee-Wick standard model yields, in the context of a homogeneous and isotropic cosmological background, a bouncing cosmology. However, bouncing cosmologies induced by pressureless matter are in general unstable to the addition of relativistic matter (i.e. radiation). Here we study the possibility of obtaining a bouncing cosmology if we add not only radiation, but also its Lee-Wick partner, to the matter sector. We find that, in general, no bounce occurs. The only way to obtain a bounce is to choose initial conditions with very special phases ofmore » the radiation field and its Lee-Wick partner.« less

Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle.

PubMed

Lyons, John D; Klingensmith, Nathan J; Otani, Shunsuke; Mittal, Rohit; Liang, Zhe; Ford, Mandy L; Coopersmith, Craig M

2017-12-01

Cell production and death are tightly regulated in the rapidly renewing gut epithelium, with proliferation confined to crypts and apoptosis occurring in villi and crypts. This study sought to determine how stress alters these compartmentalized processes. Wild-type mice made septic via cecal ligation and puncture had decreased crypt proliferation and increased crypt and villus apoptosis. Fabpi -TAg mice expressing large T-antigen solely in villi had ectopic enterocyte proliferation with increased villus apoptosis in unmanipulated animals. Septic fabpi -TAg mice had an unexpected increase in villus proliferation compared with unmanipulated littermates, whereas crypt proliferation was decreased. Cell cycle regulators cyclin D1 and cyclin D2 were decreased in jejunal tissue in septic transgenic mice. In contrast, villus and crypt apoptosis were increased in septic fabpi -TAg mice. To examine the relationship between apoptosis and proliferation in a compartment-specific manner, fabpi -TAg mice were crossed with fabpl -Bcl-2 mice, resulting in expression of both genes in the villus but Bcl-2 alone in the crypt. Septic bi-transgenic animals had decreased crypt apoptosis but had a paradoxical increase in villus apoptosis compared with septic fabpi -TAg mice, associated with decreased proliferation in both compartments. Thus, sepsis unmasks compartment-specific proliferative and apoptotic regulation that is not present under homeostatic conditions.-Lyons, J. D., Klingensmith, N. J., Otani, S., Mittal, R., Liang, Z., Ford, M. L., Coopersmith, C. M. Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle. © FASEB.

Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.

PubMed

Phesse, T J; Myant, K B; Cole, A M; Ridgway, R A; Pearson, H; Muncan, V; van den Brink, G R; Vousden, K H; Sears, R; Vassilev, L T; Clarke, A R; Sansom, O J

2014-06-01

Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p53. Mechanistically, this was linked to an upregulation of the E3 Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient intestinal enterocytes. Further, low level overexpression of c-Myc, which does not impact on basal levels of apoptosis, elicited sustained apoptosis in response to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat following DNA damage. We also identify the importance of MYC during DNA damage-induced apoptosis in several other tissues, including the thymus and spleen, using systemic deletion of c-Myc throughout the adult mouse. Together, we have elucidated for the first time in vivo an essential role for endogenous c-Myc in signalling DNA damage-induced apoptosis through the control of the p53 tumour suppressor protein.

New insights into the molecular mechanism of intestinal fatty acid absorption

PubMed Central

Wang, Tony Y.; Liu, Min; Portincasa, Piero; Wang, David Q.-H.

2013-01-01

Background Dietary fat is the most important energy source of all the nutrients. Fatty acids, stored as triacylglycerols in the body, are an important reservoir of stored energy and derive primarily from animal fats and vegetable oils. Design Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, i.e., fatty acid transporters on the apical membrane of enterocytes. Results These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical-chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. Conclusions A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. PMID:24102389

Myosin 5b loss of function leads to defects in polarized signaling: implication for microvillus inclusion disease pathogenesis and treatment

PubMed Central

Kravtsov, Dmitri; Mashukova, Anastasia; Forteza, Radia; Rodriguez, Maria M.; Ameen, Nadia A.

2014-01-01

Microvillus inclusion disease (MVID) is an autosomal recessive condition resulting in intractable secretory diarrhea in newborns due to loss-of-function mutations in myosin Vb (Myo5b). Previous work suggested that the apical recycling endosomal (ARE) compartment is the primary location for phosphoinositide-dependent protein kinase 1 (PDK1) signaling. Because the ARE is disrupted in MVID, we tested the hypothesis that polarized signaling is affected by Myo5b dysfunction. Subcellular distribution of PDK1 was analyzed in human enterocytes from MVID/control patients by immunocytochemistry. Using Myo5b knockdown (kd) in Caco-2BBe cells, we studied phosphorylated kinases downstream of PDK1, electrophysiological parameters, and net water flux. PDK1 was aberrantly localized in human MVID enterocytes and Myo5b-deficient Caco-2BBe cells. Two PDK1 target kinases were differentially affected: phosphorylated atypical protein kinase C (aPKC) increased fivefold and phosohoprotein kinase B slightly decreased compared with control. PDK1 redistributed to a soluble (cytosolic) fraction and copurified with basolateral endosomes in Myo5b kd. Myo5b kd cells showed a decrease in net water absorption that could be reverted with PDK1 inhibitors. We conclude that, in addition to altered apical expression of ion transporters, depolarization of PDK1 in MVID enterocytes may lead to aberrant activation of downstream kinases such as aPKC. The findings in this work suggest that PDK1-dependent signaling may provide a therapeutic target for treating MVID. PMID:25258405

Human fetal enterocytes in vitro: modulation of the phenotype by extracellular matrix.

PubMed Central

Sanderson, I R; Ezzell, R M; Kedinger, M; Erlanger, M; Xu, Z X; Pringault, E; Leon-Robine, S; Louvard, D; Walker, W A

1996-01-01

The differentiation of small intestinal epithelial cells may require stimulation by microenvironmental factors in vivo. In this study, the effects of mesenchymal and luminal elements in nonmalignant epithelia] cells isolated from the human fetus were studied in vitro. Enterocytes from the human fetus were cultured and microenvironmental factors were added in stages, each stage more closely approximating the microenvironment in vivo. Four stages were examined: epithelial cells derived on plastic from intestinal culture and grown as a cell clone, the same cells grown on connective tissue support, primary epithelial explants grown on fibroblasts with a laminin base, and primary epithelial explants grown on fibroblasts and laminin with n-butyrate added to the incubation medium. The epithelial cell clone dedifferentiated when grown on plastic; however, the cells expressed cytokeratins and villin as evidence of their epithelial cell origin. Human connective tissue matrix from Engelbreth-Holm-Swarm sarcoma cells (Matrigel) modulated their phenotype: alkaline phosphatase activity increased, microvilli developed on their apical surface, and the profile of insulin-like growth factor binding proteins resembled that secreted by differentiated enterocytes. Epithelial cells taken directly from the human fetus as primary cultures and grown as explants on fibroblasts and laminin expressed greater specific enzyme activities in brush border membrane fractions than the cell clone. These activities were enhanced by the luminal molecule sodium butyrate. Thus the sequential addition of connective tissue and luminal molecules to nonmalignant epithelia] cells in vitro induces a spectrum of changes in the epithelial cell phenotype toward full differentiation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8755542

Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model.

PubMed

Sukhotnik, Igor; Bitterman, Sivan; Shahar, Yoav Ben; Pollak, Yulia; Bitterman, Nir; Halabi, Salim; Coran, Arnold G; Bitterman, Arie

2017-02-01

Background  Chelerythrine (CHE) is a benzophenanthridine alkaloid that is a potent, selective, and cell-permeable protein kinase C inhibitor. The purpose of the present study was to examine the effect of CHE on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. Methods  Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-CHE rats underwent laparotomy and were treated with intraperitoneal CHE; (3) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes followed by 48 hours of reperfusion, and (4) IR-CHE rats underwent IR and were treated with intraperitoneal CHE immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real Western blot and immunohistochemistry. Results  Treatment with CHE resulted in a significant decrease in Park injury score in jejunum (threefold decrease) and ileum (twofold decrease), and parallel increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in ileum compared with IR animals. IR-CHE rats also experienced a significantly lower apoptotic index in jejunum and ileum, which was accompanied by a lower Bax/Bcl2 ratio compared with IR animals. Conclusions  Treatment with CHE inhibits programmed cell death and prevents intestinal mucosal damage following intestinal IR in a rat. Georg Thieme Verlag KG Stuttgart · New York.

N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

PubMed

Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao

2016-02-01

Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve intestinal health and treat gastrointestinal diseases. However, the underlying mechanisms are not fully understood. According to previous reports, NAC was thought to exert its effect through glutathione synthesis. This study tested the hypothesis that NAC enhances enterocyte growth and protein synthesis independently of cellular glutathione synthesis. Intestinal porcine epithelial cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0 or 100 μM NAC. To determine a possible role for GSH (the reduced form of glutathione) in mediating the effect of NAC on cell growth and protein synthesis, additional experiments were conducted using culture medium containing 100 μM GSH, 100 μM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10 μM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 μM). NAC increased cell proliferation, GSH concentration, and protein synthesis, while inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or diethylmaleate reduced cell proliferation and GSH concentration without affecting protein synthesis, while promoting protein degradation. At the signaling level, NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in IPEC-1 cells. Collectively, these results indicate that NAC upregulates expression of mTOR signaling proteins to stimulate protein synthesis in enterocytes independently of GSH generation. Our findings provide a hitherto unrecognized biochemical mechanism for beneficial effects of NAC in intestinal cells.

Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA.

PubMed

Alizadeh, Elahe; Orlando, Thomas M; Sanche, Léon

2015-04-01

Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

Low energy electrons and swift ion track structure in PADC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fromm, Michel; Quinto, Michele A.; Weck, Philippe F.

The current work aims at providing an accurate description of the ion track-structure in poly-allyl dyglycol carbonate (PADC) by using an up-to-date Monte-Carlo code-called TILDA-V (a French acronym for Transport d’Ions Lourds Dans l’Aqua & Vivo). In this simulation the ion track-structure in PADC is mainly described in terms of ejected electrons with a particular attention done to the Low Energy Electrons (LEEs). After a brief reminder of the most important channels through which LEEs are prone to break a chemical bond, we will report on the simulated energetic distributions of LEEs along an ion track in PADC for particularmore » incident energies located on both sides of the Bragg-peak position. Lastly, based on the rare data dealing with LEEs interaction with polymers or organic molecules, we will emphasise the role played by the LEEs in the formation of a latent track in PADC, and more particularly the one played by the sub-ionization electrons.« less

Priority and synonymy of some North American cicada genera (Hemiptera: Cicadidae: Cicadinae: Cryptotympanini).

PubMed

Sanborn, Allen F; Heath, Maxine S

2017-03-15

The status of several North American cicada genera is reconsidered based on the recent erection of new genera and historical evidence. Megatibicen Sanborn & Heath, 2016 is shown to have priority over Megatibicen Lee, 2016 (which was changed by the author to Gigatibicen Lee, 2016 prior to formal publication). Ameritibicen Lee, 2016 is shown to be a junior synonym of Megatibicen Sanborn & Heath, 2016 and both Ameritibicen n. syn. and and Gigatibicen Lee, 2016 n. syn. are synonymized here to Megatibicen Sanborn & Heath. The species placed in Gigatibicen are returned to Megatibicen to become Megatibicen auletes (Germar, 1834) n. comb., Megatibicen resh (Haldeman, 1852) n. comb., and Megatibicen resonans (Walker, 1850) n. comb. while the species placed in Ameritibicen remain in Megatibicen due to the junior synonym status of Ameritibicen. The monospecific Paratibicen Lee, 2016 n. syn. is shown to be a junior synonym of Neotibicen Hill & Marshall, 2015 and its species is reassigned to Neotibicen to become Neotibicen similaris (Smith & Grossbeck, 1907) n. comb.

Low energy electrons and swift ion track structure in PADC

DOE PAGES

Fromm, Michel; Quinto, Michele A.; Weck, Philippe F.; ...

2015-05-27

The current work aims at providing an accurate description of the ion track-structure in poly-allyl dyglycol carbonate (PADC) by using an up-to-date Monte-Carlo code-called TILDA-V (a French acronym for Transport d’Ions Lourds Dans l’Aqua & Vivo). In this simulation the ion track-structure in PADC is mainly described in terms of ejected electrons with a particular attention done to the Low Energy Electrons (LEEs). After a brief reminder of the most important channels through which LEEs are prone to break a chemical bond, we will report on the simulated energetic distributions of LEEs along an ion track in PADC for particularmore » incident energies located on both sides of the Bragg-peak position. Lastly, based on the rare data dealing with LEEs interaction with polymers or organic molecules, we will emphasise the role played by the LEEs in the formation of a latent track in PADC, and more particularly the one played by the sub-ionization electrons.« less

STS-64 Official Crew Portrait

NASA Technical Reports Server (NTRS)

1994-01-01

The crewmen assigned to the STS-64 mission include: Astronaut Richard N. Richards (center front), mission commander; L. Blaine Hammond Jr., (front left) pilot and Susan J. Helms (front right) mission specialist. On the back row, from left to right are: Mark C. Lee, Jerry M. Linenger and Carl J. Meade, all mission specialists. All but Lee and Meade are wearing launch and entry suits. Lee and Meade are wearing extravehicular activity units (EMU).

General Robert E. Lee (1807-70) and Philanthropist George Peabody (1795-1869) at White Sulphur Springs, West Virginia, July 23-Aug. 30, 1869.

ERIC Educational Resources Information Center

Parker, Franklin; Parker, Betty J.

This paper discusses the chance meeting at White Sulphur Springs (West Virginia) of two important public figures, Robert E. Lee and George Peabody, whose rare encounter marked a symbolic turn from Civil War bitterness toward reconciliation and the lifting power of education. The paper presents an overview of Lee's life and professional and…

Financing College Facilities: Factors Limit Connie Lee's Ability to Help More Schools. Report to the Ranking Minority Member, Committee on Economic and Educational Opportunities, House of Representatives.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Health, Education, and Human Services Div.

A study was done of how the College Construction Loan Insurance Association (Connie Lee) carried out its mission, particularly in its service to the 102 Historically Black Colleges and Universities (HBCU). The study interviewed officials at Connie Lee, HBCUs and other schools, the Department of Education, and representatives of the bond insurance…

The Effect of Water Management and Land Use Practices on the Restoration of Lee Vining and Rush Creeks

Treesearch

Peter Vorster; G. Mathias Kondolf

1989-01-01

This paper describes water management and land use practices in the Rush and Lee Vining Creek watersheds and evaluates the effect they have had on the stream environment. The management practices will continue to have effects on the flow regime and consequently habitat conditions on lower Lee Vining and Rush Creeks. The implications of existing and potential management...

Comparison of Model-Simulated and Observed Currents in the Central Adriatic During DART

DTIC Science & Technology

2009-01-01

r, , -nnc1 T,, IJJ .... b. ,_ . . ., and modeling programs [ Lee et al...observations [ Lee et al., 2005; Kuzmic et al., 2006; Martin (MAG), and the South Adnatic Gyre (SAG) [Artegiam et { 2QQ6. l chavanne et at...is very small and the model mean current field suggests a shadow zone on the lee current side of Vis Island (Figure 9), whereas the observed mean

Special Issue on Global Health Disparities Focus on Cancer.

PubMed

Lee, Haeok

2016-01-01

Haeok Lee, PhD, RN, FAAN who is a Korean-American nurse scientist, received her doctor al degree from the Nursing Physiology Department, College of Nursing, University of California, San Francisco (UCSF), in 1993, and her post doctor al training from College of Medicine, UCSF. Dr. Lee worked at Case Western Reserve University and University of Colorado Health Sciences Center. She has worked at the UMass Boston since 2008. Dr. Lee has established a long-term commitment to minority health, especially Asian American Pacific Islanders, as a community leader, community health educator, and community researcher, and all these services have become a foundation for her community-based participatory research. Dr. Lee's research addresses current health problems framed in the context of social, political, and economic settings, and her studies have improved racial and ethnic data and developed national health policies to address health disparities in hepatitis B virus (HBV) infections and liver cancer among minorities. Dr. Lee's research, which is noteworthy for its theoretical base, is clearly filling the gap. Especially, Dr. Lee's research is beginning to have a favorable impact on national and international health policies and continuing education programs directed toward the global elimination of cervical and liver cancer-related health disparities in underserved and understudied populations.

Benchmarking quantum mechanical calculations with experimental NMR chemical shifts of 2-HADNT

NASA Astrophysics Data System (ADS)

Liu, Yuemin; Junk, Thomas; Liu, Yucheng; Tzeng, Nianfeng; Perkins, Richard

2015-04-01

In this study, both GIAO-DFT and GIAO-MP2 calculations of nuclear magnetic resonance (NMR) spectra were benchmarked with experimental chemical shifts. The experimental chemical shifts were determined experimentally for carbon-13 (C-13) of seven carbon atoms for the TNT degradation product 2-hydroxylamino-4,6-dinitrotoluene (2-HADNT). Quantum mechanics GIAO calculations were implemented using Becke-3-Lee-Yang-Parr (B3LYP) and other six hybrid DFT methods (Becke-1-Lee-Yang-Parr (B1LYP), Becke-half-and-half-Lee-Yang-Parr (BH and HLYP), Cohen-Handy-3-Lee-Yang-Parr (O3LYP), Coulomb-attenuating-B3LYP (CAM-B3LYP), modified-Perdew-Wang-91-Lee-Yang-Parr (mPW1LYP), and Xu-3-Lee-Yang-Parr (X3LYP)) which use the same correlation functional LYP. Calculation results showed that the GIAO-MP2 method gives the most accurate chemical shift values, and O3LYP method provides the best prediction of chemical shifts among the B3LYP and other five DFT methods. Three types of atomic partial charges, Mulliken (MK), electrostatic potential (ESP), and natural bond orbital (NBO), were also calculated using MP2/aug-cc-pVDZ method. A reasonable correlation was discovered between NBO partial charges and experimental chemical shifts of carbon-13 (C-13).

IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats.

PubMed

Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong

2015-07-08

Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the development of liver cirrhosis, and endotoxemia will develop subsequently. Correspondingly, increased endotoxin in portal system worsens tight junction dysfunction via decreasing intestinal occludin and claudin-1 expressions and increasing enterocytic apoptosis. Endotoxemia and intestinal barrier dysfunction form a vicious circle. External administration of IGF-1 breaks this vicious circle. Improvement of tight junctions might be one possible mechanism of the restoration of intestinal barrier function mediated by IGF-1.

Deep Learning for Discovery of Atmospheric Mountain Waves in MODIS and GPS Data

NASA Astrophysics Data System (ADS)

Pankratius, V.; Li, J. D.; Rude, C. M.; Gowanlock, M.; Herring, T.

2017-12-01

Airflow over mountains can produce gravity waves, called lee waves, which can generate atmospheric turbulence. Since this turbulence poses dangers to aviation, it is critical to identify such regions reliably in an automated fashion. This work leverages two sources of data to go beyond an ad-hoc human visual approach for such identification: MODIS imagery containing cloud patterns formed by lee waves, and patterns in GPS signals resulting from the transmission through atmospheric turbulence due to lee waves. We demonstrate a novel machine learning approach that fuses these two data types to detect atmospheric turbulence associated with lee waves. A convolutional neural network is trained on MODIS tile images to automatically classify the lee wave cloud patterns with 96% correct classifications on a validation set of 20,000 MODIS 64x64 tiles over a test region in the Sierra Nevada Mountains. Signals from GPS stations of the Plate Boundary Observatory are used for feature extraction related to lee waves, in order to improve the confidence of a detection in the MODIS imagery at a given position. To our knowledge, this is the first technique to combine these images and time series data types to improve the spatial and temporal resolutions for large-scale measurements of lee wave formations. First results of this work show great potential for improving weather condition monitoring, hazard and cloud pattern detection, as well as GPS navigation uncertainties. We acknowledge support from NASA AISTNNX15AG84G (PI Pankratius), NASA NNX14AQ03G (PI Herring), and NSF ACI1442997 (PI Pankratius).

A Research Program in Computer Technology. 1985 Annual Technical Report

DTIC Science & Technology

1986-12-01

The essence of the problem is that the modes of communication normally used between people are considerably richer than those ,-tR W V~ 34 between...Hansford Victoria Svoboda David Hollenberg Janna Tuckett Shih-Lien Lu Jasmin Witthoft Lee Richardson Craig Rogers Barden Smith Vance Tyree 10.1 PROBLEM...Jeff Deifik Lee Magnone Victoria Svoboda Joel Goldberg Janna Tuckett Wes Hansford Jasmin Witthoft Lee Richardson Craig Rogers Barden Smith Vance

Combining Offline and Online Computation for Solving Partially Observable Markov Decision Process

DTIC Science & Technology

2015-03-06

David Hsu and Wee Sun Lee, Monte Carlo Bayesian Reinforcement Learning, International Conference on Machine Learning (ICML), 2012. • Haoyu Bai, David...and Automation (ICRA), 2015. • Zhan Wei Lim, David Hsu, and Wee Sun Lee, Adaptive Informative Path Planning in Metric Spaces. Submitted to Int. J... Automation (ICRA), 2015. 2. Bai, H., Hsu, D., Kochenderfer, M. J., and Lee, W. S., Unmanned aircraft collision avoidance using continuous state POMDPs

NCCU/BBRI-Duke/Urology Partnership in Prostate Cancer Research

DTIC Science & Technology

2008-06-01

Somnath Muhopadhyay, Ph.D.; Joellen Schildkraut, Ph.D.; David Tulis , Ph.D.; Leon Sun, Ph.D.; Lee Jones, Ph.D.; Phillip 5e. TASK NUMBER Febbo, Ph.D...Community-Based Intervention Investigators: Dave Tulis Ph.D., NCCU/BBRI Collaborators: Catherine Hoyo, PhD; Lee Jones, PhD; Stephen Freeland...addition, Dr. David Tulis (NCCU PI) who was working on the exercise project with Dr. Lee Jones (Duke PI), has recently accepted a position at East Carolina

Process gg{yields}h{sub 0}{yields}{gamma}{gamma} in the Lee-Wick standard model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, F.; Underwood, T. E. J.; Zwicky, R.

2008-01-01

The process gg{yields}h{sub 0}{yields}{gamma}{gamma} is studied in the Lee-Wick extension of the standard model (LWSM) proposed by Grinstein, O'Connell, and Wise. In this model, negative norm partners for each SM field are introduced with the aim to cancel quadratic divergences in the Higgs mass. All sectors of the model relevant to gg{yields}h{sub 0}{yields}{gamma}{gamma} are diagonalized and results are commented on from the perspective of both the Lee-Wick and higher-derivative formalisms. Deviations from the SM rate for gg{yields}h{sub 0} are found to be of the order of 15%-5% for Lee-Wick masses in the range 500-1000 GeV. Effects on the rate formore » h{sub 0}{yields}{gamma}{gamma} are smaller, of the order of 5%-1% for Lee-Wick masses in the same range. These comparatively small changes may well provide a means of distinguishing the LWSM from other models such as universal extra dimensions where same-spin partners to standard model fields also appear. Corrections to determinations of Cabibbo-Kobayashi-Maskawa (CKM) elements |V{sub t(b,s,d)}| are also considered and are shown to be positive, allowing the possibility of measuring a CKM element larger than unity, a characteristic signature of the ghostlike nature of the Lee-Wick fields.« less

Simulation for light extraction efficiency of OLEDs with spheroidal microlenses in hexagonal array

NASA Astrophysics Data System (ADS)

Bae, Hyungchul; Kim, Jun Soo; Hong, Chinsoo

2018-05-01

A theoretical model based on ray optics is used to simulate the optical performance of organic light-emitting diodes (OLEDs) with spheroidal microlens arrays (MLAs) in a hexagonal array configuration using the Monte Carlo method. In simulations, ray tracing was performed until 20 reflections occurred from the metal cathode, with 10 consecutive reflections permitted in a single lens pattern. The parameters describing the shape and array of the lens pattern of a MLA are its radius, height, contact angle, and fill factor (FF). Many previous results on how these parameters affect light extraction efficiency (LEE) are inconsistent. In this paper, these contradictory results are discussed and explained by introducing a new parameter. To examine light extraction from an OLED through a MLA, the LEE enhancement is studied considering the effect of absorption by indium tin oxide during multiple reflections from the metal cathode. The device size where LEE enhancement is unchanged with changing lens pattern was identified for a fixed FF; under this condition, the optimal LEE enhancement, 84%, can be obtained using an OLED with a close-packed spheroidal MLA. An ideal maximum LEE enhancement of 120% was achieved with a device with an infinite-sized MLA. The angular intensity distribution of light emitted through a MLA is considered in addition to LEE enhancement for an optimized MLA.

Around Marshall

NASA Image and Video Library

1990-01-17

Marshall's sixth Center Director Thomas J. Lee (1989-1994) touring the Payload Operations Control Center (POCC). The Hubble Space Telescope (HST) saw its launch into orbit under the leadership of Dr. Lee's administration.

Effect of constitutive inactivation of the myostatin gene on the gain in muscle strength during postnatal growth in two murine models.

PubMed

Stantzou, Amalia; Ueberschlag-Pitiot, Vanessa; Thomasson, Remi; Furling, Denis; Bonnieu, Anne; Amthor, Helge; Ferry, Arnaud

2017-02-01

The effect of constitutive inactivation of the gene encoding myostatin on the gain in muscle performance during postnatal growth has not been well characterized. We analyzed 2 murine myostatin knockout (KO) models, (i) the Lee model (KO Lee ) and (ii) the Grobet model (KO Grobet ), and measured the contraction of tibialis anterior muscle in situ. Absolute maximal isometric force was increased in 6-month-old KO Lee and KO Grobet mice, as compared to wild-type mice. Similarly, absolute maximal power was increased in 6-month-old KO Lee mice. In contrast, specific maximal force (relative maximal force per unit of muscle mass was decreased in all 6-month-old male and female KO mice, except in 6-month-old female KO Grobet mice, whereas specific maximal power was reduced only in male KO Lee mice. Genetic inactivation of myostatin increases maximal force and power, but in return it reduces muscle quality, particularly in male mice. Muscle Nerve 55: 254-261, 2017. © 2016 Wiley Periodicals, Inc.

Natural language processing and visualization in the molecular imaging domain.

PubMed

Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

2007-06-01

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

Two-photon Lee-Goldburg nuclear magnetic resonance: Simultaneous homonuclear decoupling and signal acquisition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michal, Carl A.; Hastings, Simon P.; Lee, Lik Hang

2008-02-07

We present NMR signals from a strongly coupled homonuclear spin system, {sup 1}H nuclei in adamantane, acquired with simultaneous two-photon excitation under conditions of the Lee-Goldburg experiment. Small coils, having inside diameters of 0.36 mm, are used to achieve two-photon nutation frequencies of {approx}20 kHz. The very large rf field strengths required give rise to large Bloch-Siegert shifts that cannot be neglected. These experiments are found to be extremely sensitive to inhomogeneity of the applied rf field, and due to the Bloch-Siegert shift, exhibit a large asymmetry in response between the upper and lower Lee-Goldburg offsets. Two-photon excitation has themore » potential to enhance both the sensitivity and performance of homonuclear dipolar decoupling, but is made challenging by the high rf power required and the difficulties introduced by the inhomogeneous Bloch-Siegert shift. We briefly discuss a variation of the frequency-switched Lee-Goldburg technique, called four-quadrant Lee-Goldburg (4QLG) that produces net precession in the x-y plane, with a reduced chemical shift scaling factor of 1/3.« less

Large enhancement of light extraction efficiency in AlGaN-based nanorod ultraviolet light-emitting diode structures.

PubMed

Ryu, Han-Youl

2014-02-04

Light extraction efficiency (LEE) of AlGaN-based nanorod deep ultraviolet (UV) light-emitting diodes (LEDs) is numerically investigated using three-dimensional finite-difference time-domain simulations. LEE of deep UV LEDs is limited by strong light absorption in the p-GaN contact layer and total internal reflection. The nanorod structure is found to be quite effective in increasing LEE of deep UV LEDs especially for the transverse magnetic (TM) mode. In the nanorod LED, strong dependence of LEE on structural parameters such as the diameter of a nanorod and the p-GaN thickness is observed, which can be attributed to the formation of resonant modes inside the nanorod structure. Simulation results show that, when the structural parameters of the nanorod LED are optimized, LEE can be higher than 50% and 60% for the transverse electric (TE) and TM modes, respectively. The nanorod structure is expected to be a good candidate for the application to future high-efficiency deep UV LEDs. PACS: 41.20.Jb; 42.72.Bj; 85.60.Jb.

Large enhancement of light extraction efficiency in AlGaN-based nanorod ultraviolet light-emitting diode structures

PubMed Central

2014-01-01

Light extraction efficiency (LEE) of AlGaN-based nanorod deep ultraviolet (UV) light-emitting diodes (LEDs) is numerically investigated using three-dimensional finite-difference time-domain simulations. LEE of deep UV LEDs is limited by strong light absorption in the p-GaN contact layer and total internal reflection. The nanorod structure is found to be quite effective in increasing LEE of deep UV LEDs especially for the transverse magnetic (TM) mode. In the nanorod LED, strong dependence of LEE on structural parameters such as the diameter of a nanorod and the p-GaN thickness is observed, which can be attributed to the formation of resonant modes inside the nanorod structure. Simulation results show that, when the structural parameters of the nanorod LED are optimized, LEE can be higher than 50% and 60% for the transverse electric (TE) and TM modes, respectively. The nanorod structure is expected to be a good candidate for the application to future high-efficiency deep UV LEDs. PACS 41.20.Jb; 42.72.Bj; 85.60.Jb PMID:24495598

Looking for Asian butch-dykes: exploring filmic representations of East Asian butch-dykes in Donna Lee's Enter the Mullet.

PubMed

Lin, Hui-Ling

2009-01-01

Asian butch-dykes have been overlooked in analyses of Chinese cinema, studies that often concentrate on "feminized" transgender roles. This article examines cinematic representations of Asian butch-dykes through film analysis of Enter the Mullet (2004), a five-minute short, and in-depth interviews with the filmmaker, Donna Lee, a Chinese-Canadian in Vancouver. Lee's film is inspired by Enter the Dragon (1973), starring Bruce Lee, the most recognized icon of Asian masculinity. Combining with the mullet hairstyle, which is often associated with White working-class, the filmmaker introduces viewers to the hybrid masculinity of Asian butch-dykes. The article argues that Asian female masculinity can be a strategic means of destabilizing the hegemony of White-male-middle-class masculinity.

Signaling from the Podocyte Intercellular Junction to the Actin Cytoskeleton

PubMed Central

George, Britta; Holzman, Lawrence B.

2012-01-01

Observations of hereditary glomerular disease support the contention that podocyte intercellular junction proteins are essential for junction formation and maintenance. Genetic deletion of most of these podocyte intercellular junction proteins results in foot process effacement and proteinuria. This review focuses on the current understanding of molecular mechanisms by which podocyte intercellular junction proteins such as the Nephrin-Neph1-Podocin receptor complex coordinate cytoskeletal dynamics and thus intercellular junction formation, maintenance and injury-dependent remodeling. PMID:22958485

Cerebellar syndrome with hydrocephalus due to Mycoplasma pneumoniae infection.

PubMed Central

Coleman, R. J.; Brown, J. S.; Butler, P.; Swash, M.

1990-01-01

A 27 year old woman developed a cerebellar syndrome with serological evidence of recent Mycoplasma pneumoniae infection. The cranial computed tomographic scan showed effacement of the fourth ventricle, enhancement of the basal meninges and hydrocephalus affecting the lateral and third ventricles. Clinical and radiological recovery occurred over 5 weeks. We propose that this was a manifestation of immune-mediated encephalomyelitis induced by the infection rather than direct invasion of the central nervous system. Images Figure 1 PMID:2217014

Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

PubMed Central

Blattner, Simone M.; Hodgin, Jeffrey B.; Nishio, Masashi; Wylie, Stephanie; Saha, Jharna; Soofi, Abdul; Vining, Courtenay; Randolph, Ann; Herbach, Nadja; Wanke, Ruediger; Atkins, Kevin B.; Kang, Hee Gyung; Henger, Anna; Brakebusch, Cord; Holzman, Lawrence B.; Kretzler, Matthias

2013-01-01

Podocytes are highly specialized epithelial cells with complex actin cytoskeletal architecture crucial for maintenance of the glomerular filtration barrier. The mammalian Rho GTPases Rac1 and Cdc42 are molecular switches that control many cellular processes, but are best known for their roles in the regulation of actin cytoskeleton dynamics. Here we employed podocyte-specific Cre-lox technology and found that mice with deletion of Rac1 display normal podocyte morphology without glomerular dysfunction well into adulthood. Using the protamine sulfate model of acute podocyte injury, podocyte-specific deletion of Rac1 prevented foot process effacement. In a long-term model of chronic hypertensive glomerular damage, however, loss of Rac1 led to an exacerbation of albuminuria and glomerulosclerosis. In contrast, mice with podocyte-specific deletion of Cdc42 had severe proteinuria, podocyte foot process effacement, and glomerulosclerosis beginning as early as 10 days of age. In addition, slit diaphragm proteins nephrin and podocin were redistributed and cofilin was de-phosphorylated. Cdc42 is necessary for the maintenance of podocyte structure and function, but Rac1 is entirely dispensable in physiologic steady state. However, Rac1 has either beneficial or deleterious effects depending on the context of podocyte impairment. Thus, our study highlights the divergent roles of Rac1 and Cdc42 function in podocyte maintenance and injury. PMID:23677246

Significant improvement in Fabry disease podocytopathy after 3 years of treatment with agalsidase beta.

PubMed

Ito, Shuichi; Ogura, Masao; Kamei, Koichi; Matsuoka, Kentaro; Warnock, David G

2016-08-01

Fabry disease is an X-linked lysosomal disorder caused by decreased activity of α-galactosidase A (GLA). Consequent accumulation of globotriaosylceramide (GL-3) in lysosomes results in damage to a variety of organs, including the kidneys. Enzyme replacement therapy (ERT) is an effective treatment, but whether it should be started before organ damage is evident is a matter of debate. A 10-year-old boy who complained of severe sole pain for 3 years had been misdiagnosed with juvenile idiopathic arthritis. Further investigations revealed decreased GLA activity and a M1T mutation in the GLA gene causing protein truncation, suggestive of Fabry disease. Despite normal renal function and urinalysis, renal biopsy showed abnormal structure, with marked accumulation of GL-3 in podocytes, partial effacement of foot processes and irregularly reduced expression of nephrin in the slit diaphragm. After 1 year of ERT with 1 mg/kg agalsidase beta once every 2 weeks, his pain had resolved with ERT combined with carbamazepine and pregabalin. After 3 years of the ERT, repeat biopsy showed little renal GL-3 deposition, resolution of foot process effacement, and a dramatic improvement in nephrin expression. There may be a window of opportunity in which pain and renal injury can be addressed in the early stages of Fabry disease. Early initiation of ERT should therefore be considered for children with Fabry disease.

Solid intraocular xanthogranuloma in three Miniature Schnauzer dogs.

PubMed

Zarfoss, Mitzi K; Dubielzig, Richard R

2007-01-01

Macrophages that contain abundant intracytoplasmic lipid are called 'foam cells'. In four canine globes submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), foam cells formed a solid intraocular mass. The purpose of this study was to describe the histopathologic findings in these cases. The electronic COPLOW database (1993-2006) was searched for the diagnosis of 'foam cell tumor'. Clinical history, gross pathology and histopathology (5-micron sections, hematoxylin and eosin and Alcian blue periodic acid Schiff) were reviewed in all cases. Cases were included if the globe was grossly filled by a solid mass and if all intraocular structures were effaced by lipid-laden foam cell macrophages admixed with birefringent, Alcian blue-positive crystals oriented in stellate patterns. All three patients (four globes) satisfying the selection criteria were Miniature Schnauzers. In all cases the clinical history included diabetes mellitus, hyperlipidemia and chronic bilateral uveitis that was interpreted to be lens-induced. All globes were enucleated because of glaucoma. The term solid intraocular xanthogranuloma was used to describe these cases because the intraocular contents were effaced by a solid mass of foam cells and birefringent crystals. The cases in this report suggest that diabetic Miniature Schnauzers with hyperlipidemia are at risk for lipid and macrophage-rich uveitis, which may in some cases form a solid inflammatory intraocular mass, precipitate glaucoma, and lead to enucleation.

Environmental cues and symbiont microbe-associated molecular patterns function in concert to drive the daily remodelling of the crypt-cell brush border of the Euprymna scolopes light organ

PubMed Central

Heath-Heckman, Elizabeth A.C.; Foster, Jamie; Apicella, Michael A.; Goldman, William E.; McFall-Ngai, Margaret

2016-01-01

Summary Recent research has shown that the microbiota affects the biology of associated host epithelial tissues, including their circadian rhythms, although few data are available on how such influences shape the microarchitecture of the brush border. The squid-vibrio system exhibits two modifications of the brush border that supports the symbionts: effacement and repolarization. Together these occur on a daily rhythm in adult animals, at the dawn expulsion of symbionts into the environment, and symbiont colonization of the juvenile host induces an increase in microvillar density. Here we sought to define how these processes are related and the roles of both symbiont colonization and environmental cues. Ultrastructural analyses showed that the juvenile-organ brush borders also efface concomitantly with daily dawn-cued expulsion of symbionts. Manipulation of the environmental light cue and juvenile symbiotic state demonstrated that this behaviour requires the light cue, but not colonization. In contrast, symbionts were required for the observed increase in microvillar density that accompanies post dawn brush-border repolarization; this increase was induced solely by host exposure to phosphorylated lipid A of symbiont cells. These data demonstrate that a partnering of environmental and symbiont cues shapes the brush border and that microbe-associated molecular patterns play a role in the regulation of brush-border microarchitecture. PMID:27062511

Intestinal immune cells in Strongyloides stercoralis infection.

PubMed Central

Trajman, A; MacDonald, T T; Elia, C C

1997-01-01

BACKGROUND: Strongyloides stercoralis can cause a wide spectrum of disease in man, ranging from a chronic asymptomatic infection to a hyperinfective, often fatal syndrome. In rodents, spontaneous expulsion of Strongyloides spp occurs after experimental infection. Mast cells, goblet cells, and eosinophils have been identified as possible effectors of this expulsion. AIMS: To investigate intestinal histopathology and mucosal immunity in immunocompetent patients with chronic S stercoralis infection. METHODS: Jejunal biopsies were performed in 19 immunocompetent patients with a positive stool examination for S stercoralis and few or no symptoms, and in seven healthy controls. Specimens were processed for histopathological analysis and stained by the immunoperoxidase technique, using the following monoclonal antibodies: CD2, CD3, CD4, CD8, anti-T cell receptor (TcR) gamma/delta, RFD1 and RFD7 (two different macrophage markers), Ki67+ (proliferating) cells, antihuman leucocyte antigen (HLA)-DR, and anticollagen IV. In addition, CD25+ cells, mast cells, IgE expressing cells, calprotectin containing cells, and neutrophil elastase positive cells were stained by the alkaline phosphatase method. RESULTS: Jejunal morphology and the numbers of different T cell subsets, mast cells, IgE expressing cells, eosinophils, and goblet cells were unaffected by S stercoralis infection. Conversely, the numbers of mature macrophages and dividing enterocytes in the crypts were reduced significantly. Crypt enterocytes did not express HLA-DR in both groups. The expression of HLA-DR by villus enterocytes was also comparable in patients and controls. There were no activated (CD25+) cells in the mucosa of either patients or controls. CONCLUSIONS: Compared with seven healthy uninfected volunteers, a group of 19 Brazilians with clinically mild strongyloides infection showed no abnormality of mucosal structure and no increase in non-specific inflammatory cells. Likewise, there was no increase in mucosal T cells or macrophages. Images PMID:9516879

New insights into the molecular mechanism of intestinal fatty acid absorption.

PubMed

Wang, Tony Y; Liu, Min; Portincasa, Piero; Wang, David Q-H

2013-11-01

Dietary fat is one of the most important energy sources of all the nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in the body, are an important reservoir of stored energy and derived primarily from animal fats and vegetable oils. Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, that is, fatty acid transporters on the apical membrane of enterocytes. These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Chad M.; Wolf, Jeffrey C.; Elbekai, Reem H.

2015-08-01

Lifetime exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal damage and an increase in duodenal tumors in B6C3F1 mice. To assess whether these tumors could be the result of a direct mutagenic or genotoxic mode of action, we conducted a GLP-compliant 7-day drinking water study to assess crypt health along the entire length of the duodenum. Mice were exposed to water (vehicle control), 1.4, 21, or 180 ppm Cr(VI) via drinking water for 7 consecutive days. Crypt enterocytes in Swiss roll sections were scored as normal, mitotic, apoptotic, karyorrhectic, or as having micronuclei. Amore » single oral gavage of 50 mg/kg cyclophosphamide served as a positive control for micronucleus induction. Exposure to 21 and 180 ppm Cr(VI) significantly increased the number of crypt enterocytes. Micronuclei and γ-H2AX immunostaining were not elevated in the crypts of Cr(VI)-treated mice. In contrast, treatment with cyclophosphamide significantly increased numbers of crypt micronuclei and qualitatively increased γ-H2AX immunostaining. Synchrotron-based X-ray fluorescence (XRF) microscopy revealed the presence of strong Cr fluorescence in duodenal villi, but negligible Cr fluorescence in the crypt compartment. Together, these data indicate that Cr(VI) does not adversely effect the crypt compartment where intestinal stem cells reside, and provide additional evidence that the mode of action for Cr(VI)-induced intestinal cancer in B6C3F1 mice involves chronic villous wounding resulting in compensatory crypt enterocyte hyperplasia.« less

Hepatic Adaptation Compensates Inactivation of Intestinal Arginine Biosynthesis in Suckling Mice

PubMed Central

Marion, Vincent; Sankaranarayanan, Selvakumari; de Theije, Chiel; van Dijk, Paul; Hakvoort, Theo B. M.; Lamers, Wouter H.; Köhler, Eleonore S.

2013-01-01

Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass) gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass fl and Villin-Cre mice. Unexpectedly, Ass fl/fl /VilCre tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice). Relative to control mice, citrulline production in the splanchnic region of Ass fl/fl /VilCre tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass fl/fl /VilCre tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2) and transport (Slc25a13, Slc25a15, and Slc3a2), whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver. PMID:23785515

Temporal changes of ethoxyresorufin-o-deethylase (EROD) activities and lysosome accumulation in intestine of fish on chronic exposure to dietary benzo[a]pyrene: linking erod induction to cytological effects.

PubMed

Yuen, Bonny B H; Au, Doris W T

2006-10-01

Temporal changes of intestinal and hepatic ethoxyresorufin-O-deethylase (EROD) activities and quantitative changes of secondary and tertiary (e.g., 2 degrees/3 degrees) lysosomes in enterocytes were compared for the juvenile grouper (Epinephelus coioides) on chronic exposure to foodborne benzo[a]pyrene (BaP) at two environmentally realistic levels (0.25 and 12.5 microg/g fish/d) over a four-week exposure and four-week depuration period. Intestinal EROD induction was rapid (within 3 d) and sustained in the BaP-exposed fish, while a fast recovery (within one week) was observed on withdrawal of BaP intake. A dose-response relationship was demonstrated between intestinal EROD activities and the levels of foodborne BaP. Conversely, hepatic EROD induction was weak and subsided rapidly in the exposed fish, signifying that hepatic EROD activity is not a good indicator of oral intake of BaP. Significant increase of 2 degrees/3 degrees lysosomes, as measured by Vv(lysosome, mucosa), was detected in young enterocytes of fish in the high-dosing group (12.5 microg/g fish/d) at exposure day 3 and persisted until recovery week 2. Importantly, intestinal EROD activity was significantly correlated to 2 degrees/3 degrees lysosome accumulation in enterocytes (r = 0.571, p < 0.001). These results further corroborate our earlier findings that induction of EROD activities in fish do not merely indicate exposure to BaP but also are correlated to harmful biological effects. We recommend the use of these two biochemical and cytological changes in intestines as specific biomarkers to indicate current and recent exposure of fish to BaP via oral intake.

Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat.

PubMed

Ben Shahar, Yoav; Sukhotnik, Igor; Bitterman, Nir; Pollak, Yulia; Bejar, Jacob; Chepurov, Dmitriy; Coran, Arnold; Bitterman, Arie

2016-02-01

N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats underwent laparotomy, (2) sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes, followed by 48 hours of reperfusion, and (4) IR-NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal-Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant. Treatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR-NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals. Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat. Georg Thieme Verlag KG Stuttgart · New York.

PDGF-α stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Pollak, Yulia; Blumenfeld, Shiri; Bejar, Jacob; Coran, Arnold G

2012-06-01

Numerous cytokines have been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal interaction. Growing evidence suggests that platelet-derived growth factor (PDGF) signaling is an important mediator of these interactions. The purpose of this study was to evaluate the effect of PDGF-α on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats underwent bowel transection, Sham-PDGF-α rats underwent bowel transection and were treated with PDGF-α, SBS rats underwent a 75% bowel resection, and SBS-PDGF-α rats underwent bowel resection and were treated with PDGF-α. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at euthanasia. Illumina's Digital Gene Expression analysis was used to determine PDGF-related gene expression profiling. PDGF-α and PDGF-α receptor (PDGFR-α) expression was determined by real-time PCR. Western blotting was used to determine p-ERK, Akt1/2/3, bax, and bcl-2 protein levels. SBS rats demonstrated a significant increase in PDGF-α and PDGFR-α expression in jejunum and ileum compared with sham animals. SBS-PDGF-α rats demonstrated a significant increase in bowel and mucosal weight, villus height, and crypt depth in jejunum and ileum compared with SBS animals. PDGF-α receptor expression in crypts increased in SBS rats (vs. sham) and was accompanied by an increased cell proliferation following PDGF-α administration. A significant decrease in cell apoptosis in this group was correlated with lower bax protein levels. In conclusion, in a rat model of SBS, PDGF-α stimulates enterocyte turnover, which is correlated with upregulated PDGF-α receptor expression in the remaining small intestine.

Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy.

PubMed

Vesterbacka, Jan; Nowak, Piotr; Barqasho, Babilonia; Abdurahman, Samir; Nyström, Jessica; Nilsson, Staffan; Funaoka, Hiroyuki; Kanda, Tatsuo; Andersson, Lars-Magnus; Gisslèn, Magnus; Sönnerborg, Anders

2013-01-01

We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72). The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = -0.47 µg/ml; p = 0.015). Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. ClinicalTrials.gov NCT01445223.

[Effect of enteral supplement of arginine on intestinal adaptation and its mechanism in experimental rats with short bowel syndrome].

PubMed

Jiang, Xiao-hua; Li, Ning; Zhu, Wei-ming; Li, Jie-shou

2009-09-01

To evaluate the effect of enteral supplement of arginine on intestinal adaptation in rats with short bowel syndrome (SBS) and to study its mechanism. SD rats were randomly assigned to three groups: sham rats (Con), SBS rats (SB) and SBS rats supplemented with enteral arginine (SB-Arg). All the animals received isonitrogenic and isocaloric enteral nutrition, except that SB-Arg rats received enteral nutrition supplemented with arginine (300 mg kg(-1) d(-1)). Fat absorbability, plasma free fatty acids, parameters of intestinal adaptation, enterocytes proliferation and apoptosis were determined. After massive small bowel resection, rats had significant bowel adaptation. Compared with SB rats, SB-Arg rats demonstrated a significant increase in fat absorbability [(84.9+/-3.2)% vs [(81.3+/-3.9)%], plasma level of free fatty acids [(650.0+/-86.5) vs (289.5+/-76.9) mg/L], ileal mucosal weight [(18.0+/-3.5) vs (13.5+/-3.0) mg cm(-1) 100 g(-1)], ileal DNA content [(29.6+/-3.3) vs (26.0+/-2.6) microg cm(-1) 100 g(-1)], jejunal mucosal protein content [(65.5+/-7.3) vs (59.8+/-6.2) microg cm(-1) 100 g(-1)], ileal mucosal protein content[(39.2+/-2.3) vs(35.4+/-2.3) microg cm(-1) 100 g(-1)], jejunal mucosal proliferation index [31+/-4 vs 22+/-3] and ileal mucosal proliferation index [32+/-2 vs 25+/-3] (all P<0.05). Moreover, jejunal and ileal villus length, crypt depth and mucosal thickness in SBS-Arg rats were higher than those in SB rats (P<0.05). In rat SBS model, enteral supplement of arginine appears to stimulate intestinal structural and functional adaptation. The mechanism may be that arginine can stimulate enterocyte proliferation and inhibit enterocyte apoptosis.

Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

PubMed

Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

2008-07-15

Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

Southeast Asia’s Relations with Taiwan, 2000-2016: An Assessment of Vietnam and Singapore

DTIC Science & Technology

2017-09-01

were considered good during Taiwan president Lee Teng-hui’s terms (1988–2000) with robust economic ties and de facto diplomatic relations. Studies of...the post -Lee period have described a state of deteriorated relations between Taiwan and Southeast Asian countries when Chen Shui-bian succeeded Lee...Taiwan set up its de facto embassy in Ho Chi Minh City in 1992, and Vietnam set up its own representative office in Taipei in 1993. Vietnam continued to

Purinergic Receptors in Quiescence and Localization of Leukemic Stem Cells

DTIC Science & Technology

2012-05-01

mediating HSPC mobilization. Reportable Outcomes Cho JS, Shen H, Hui Y, Cheng T, Lee SB, Lee BC. 2011. Ewing’s Sarcoma Gene EWS regulates...Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an...PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER Byeong-Chel Lee, Ph.D. 5e. TASK NUMBER E-Mail: leeb4@upmc.edu 5f. WORK UNIT

Proceedings of the Annual U.S. Army Operations Research Symposium (13th) , AORS XIII, Held at Fort Lee, Virginia on 29 October - 1 November 1974, Co- Hosted by Army Logistics Center, Fort Lee, Virginia and Army Quartermaster Center and Fort Lee, Virginia. Volume 2

DTIC Science & Technology

1974-11-01

Directorate, Rock Island, Illinois. 538 TITLE: Significant Difference Technique AUTHOR: Mr. Robert P. Lewis, Jr. US Army Logistics Management Center...was first used in a Decision Risk Analysis in August, 1971, at the Army Logistics Management Center, by John Cocker- ham and Harold Stafford. There is

Generic Friedberg-Lee symmetry of Dirac neutrinos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo Shu; Xing Zhizhong; Li Xin

2008-12-01

We write out the generic Dirac neutrino mass operator which possesses the Friedberg-Lee symmetry and find that its corresponding neutrino mass matrix is asymmetric. Following a simple way to break the Friedberg-Lee symmetry, we calculate the neutrino mass eigenvalues and show that the resultant neutrino mixing pattern is nearly tri-bimaximal. Imposing the Hermitian condition on the neutrino mass matrix, we also show that the simplified ansatz is consistent with current experimental data and favors the normal neutrino mass hierarchy.

VITAL: Vanguard Investigations of Therapeutic Approaches to Lung Cancer

DTIC Science & Technology

2011-07-01

68. PMCID: PMC2893045. Sato M, Vaughan MB, Girard L, Peyton M, Lee W, Shames DS, Ramirez RD, Sunaga N, Gazdar AF, Shay JW, Minna JD. Multiple...Proceedings of AACR 46: 2005. Abstract #3896. Sato M, Lee W, Girard L, Ramirez RD, Shames DS, Gazdar AF, Shay JW, Minna J D. Oncogenic manipulation...absence of viral oncoproteins. Cancer Res 64: 9027–9034. Sato M, Vaughan MB, Girard L, Peyton M, Lee W, Shames DS et al. (2006). Multiple oncogenic

Impact of Backbone Rigidity on the Photomechanical Response of Glassy, Azobenzene-Functionalized Polyimides (Postprint)

DTIC Science & Technology

2014-01-13

Y .; Choi, H . H .; Hwang , H . K.; Kim, Y .; Lee , S .; Jang, S . H .; Kakimoto, M.; Takezoe, H . Jpn. J. Appl. Phys., Part 1: Regul. Pap. Short Notes Rev... H .; Vaia, R. A.; Tan, L. S .; White, T. J. Angew. Chem., Int. Ed. 2012, 51 (17), 4117−4121. (6) Wang, D. H .; Lee , K. M.; Yu, Z. N .; Koerner, H .; Vaia...J. Macromol. Chem. Phys. 2013, 214 (11), 1189−1194. (8) Wang, D. H .; Lee , K. M.;

7 CFR 1007.51 - Class I differential, adjustments to Class I prices, and Class I price.

Code of Federal Regulations, 2010 CFR

2010-01-01

....40 AL JEFFERSON 01073 0.30 AL LAMAR 01075 0.20 AL LAUDERDALE 01077 0.30 AL LAWRENCE 01079 0.30 AL LEE... JEFFERSON 05069 0.00 AR JOHNSON 05071 0.10 AR LAFAYETTE 05073 0.10 AR LAWRENCE 05075 0.10 AR LEE 05077 0.10... LEE 13177 0.85 GA LIBERTY 13179 1.15 GA LINCOLN 13181 0.70 GA LONG 13183 1.15 GA LOWNDES 13185 1.15 GA...

7 CFR 1005.51 - Class I differential, adjustments to Class I prices, and Class I price.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 0.40 KY LAUREL 21125 0.50 KY LEE 21129 0.40 KY LESLIE 21131 0.50 KY LETCHER 21133 0.50 KY LINCOLN... 37101 0.20 NC JONES 37103 0.40 NC LEE 37105 0.30 NC LENOIR 37107 0.40 NC LINCOLN 37109 0.30 NC MC DOWELL... SC LAURENS 45059 0.50 SC LEE 45061 0.70 SC LEXINGTON 45063 0.70 SC MC CORMICK 45065 0.50 SC MARION...

7 CFR 1005.51 - Class I differential, adjustments to Class I prices, and Class I price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 0.40 KY LAUREL 21125 0.50 KY LEE 21129 0.40 KY LESLIE 21131 0.50 KY LETCHER 21133 0.50 KY LINCOLN... 37101 0.20 NC JONES 37103 0.40 NC LEE 37105 0.30 NC LENOIR 37107 0.40 NC LINCOLN 37109 0.30 NC MC DOWELL... SC LAURENS 45059 0.50 SC LEE 45061 0.70 SC LEXINGTON 45063 0.70 SC MC CORMICK 45065 0.50 SC MARION...

7 CFR 1007.51 - Class I differential, adjustments to Class I prices, and Class I price.

Code of Federal Regulations, 2011 CFR

2011-01-01

....40 AL JEFFERSON 01073 0.30 AL LAMAR 01075 0.20 AL LAUDERDALE 01077 0.30 AL LAWRENCE 01079 0.30 AL LEE... JEFFERSON 05069 0.00 AR JOHNSON 05071 0.10 AR LAFAYETTE 05073 0.10 AR LAWRENCE 05075 0.10 AR LEE 05077 0.10... LEE 13177 0.85 GA LIBERTY 13179 1.15 GA LINCOLN 13181 0.70 GA LONG 13183 1.15 GA LOWNDES 13185 1.15 GA...

West Adriatic Coastal Water Excursions into the East Adriatic

DTIC Science & Technology

2009-01-15

anticyclonic eddies in the Gulf of Manfredonia which can form in the lee of the WAC flow around Cape Gargano (Burrage et al., 2009-this issue), although the...caused it to remain trapped in the lee of Cape Gargano. In the presence of stepwise bathymetry only (SW2 runs, Fig. 16), the initial flow was generally...L., Wang, J.D., Lee , T.N., 1996. The fate of river discharge on the continental shelf: 1. Modeling the river plume and the inner shelf coastal

North Adriatic Tides: Observations, Variational Data Assimilation Modeling, and Linear Tide Dynamics

DTIC Science & Technology

2009-12-01

of the North Adriatic ( Lee et al., 2005). In addition to the ADCP measurements of currents through- out the water column, bottom pressure (by ADCP or...of the year with low levels of stratification (Figure 2, Jeffries and Lee , 2007). Actual generation of internal tides in the North Adriatic would...Thompson, K.R., Teague, W. J., Jacobs, G.A., Suk, M.-S., Chang, K.-I., Lee , J.-C. and Choi, B.H. (2004): Data assimilation modeling of the barotropic

INL@Work Hope Lee microbiologist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hope

2010-01-01

INL environmental microbiologist Hope Lee is working to develop and apply tools that clean contaminants out of ground water. You can learn more about INL's environmental projects at http://www.facebook.com/idahonationallaboratory.

INL@Work Hope Lee microbiologist

ScienceCinema

Lee, Hope

2018-02-07

INL environmental microbiologist Hope Lee is working to develop and apply tools that clean contaminants out of ground water. You can learn more about INL's environmental projects at http://www.facebook.com/idahonationallaboratory.

7 CFR 301.81-3 - Quarantined areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... entire county. Lee County. The entire county. Lenoir County. The entire county. Lincoln County. That... County. The entire county. Lee County. The entire county. Leon County. The entire county. Liberty County...

78 FR 4406 - Notice of Commission Staff Attendance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-22

... Carolina Electric & Gas Company For more information, contact Michael Lee, Office of Energy Market Regulation, Federal Energy Regulatory Commission at (202) 502-8658 or Michael.Lee@ferc.gov . Dated: January...

7 CFR 301.81-3 - Quarantined areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... entire county. Lee County. The entire county. Lenoir County. The entire county. Lincoln County. That... County. The entire county. Lee County. The entire county. Leon County. The entire county. Liberty County...

Phenomenology of the N = 3 Lee-Wick Standard Model

NASA Astrophysics Data System (ADS)

TerBeek, Russell Henry

With the discovery of the Higgs Boson in 2012, particle physics has decidedly moved beyond the Standard Model into a new epoch. Though the Standard Model particle content is now completely accounted for, there remain many theoretical issues about the structure of the theory in need of resolution. Among these is the hierarchy problem: since the renormalized Higgs mass receives quadratic corrections from a higher cutoff scale, what keeps the Higgs boson light? Many possible solutions to this problem have been advanced, such as supersymmetry, Randall-Sundrum models, or sub-millimeter corrections to gravity. One such solution has been advanced by the Lee-Wick Standard Model. In this theory, higher-derivative operators are added to the Lagrangian for each Standard Model field, which result in propagators that possess two physical poles and fall off more rapidly in the ultraviolet regime. It can be shown by an auxiliary field transformation that the higher-derivative theory is identical to positing a second, manifestly renormalizable theory in which new fields with opposite-sign kinetic and mass terms are found. These so-called Lee-Wick fields have opposite-sign propagators, and famously cancel off the quadratic divergences that plague the renormalized Higgs mass. The states in the Hilbert space corresponding to Lee-Wick particles have negative norm, and implications for causality and unitarity are examined. This dissertation explores a variant of the theory called the N = 3 Lee-Wick Standard Model. The Lagrangian of this theory features a yet-higher derivative operator, which produces a propagator with three physical poles and possesses even better high-energy behavior than the minimal Lee-Wick theory. An analogous auxiliary field transformation takes this higher-derivative theory into a renormalizable theory with states of alternating positive, negative, and positive norm. The phenomenology of this theory is examined in detail, with particular emphasis on the collider signatures of Lee-Wick particles, electroweak precision constraints on the masses that the new particles can take on, and scenarios in early-universe cosmology in which Lee-Wick particles can play a significant role.

78 FR 36183 - Notice of Commission Staff Attendance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... Electric & Gas Company For More Information Contact: Michael Lee, Office of Energy Market Regulation, Federal Energy Regulatory Commission at (202) 502-8658 or Michael.Lee@ferc.gov . Dated: June 11, 2013...

Rotavirus infection

PubMed Central

Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.

2017-01-01

Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972

Barley β-Glucans-Containing Food Enhances Probiotic Performances of Beneficial Bacteria

PubMed Central

Arena, Mattia P.; Caggianiello, Graziano; Fiocco, Daniela; Russo, Pasquale; Torelli, Michele; Spano, Giuseppe; Capozzi, Vittorio

2014-01-01

Currently, the majority of prebiotics in the market are derived from non-digestible oligosaccharides. Very few studies have focused on non-digestible long chain complex polysaccharides in relation to their potential as novel prebiotics. Cereals β-glucans have been investigated for immune-modulating properties and beneficial effects on obesity, cardiovascular diseases, diabetes, and cholesterol levels. Moreover, β-glucans have been reported to be highly fermentable by the intestinal microbiota in the caecum and colon, and can enhance both growth rate and lactic acid production of microbes isolated from the human intestine. In this work, we report the effects of food matrices containing barley β-glucans on growth and probiotic features of four Lactobacillus strains. Such matrices were able to improve the growth rate of the tested bacteria both in unstressed conditions and, importantly, after exposure to in vitro simulation of the digestive tract. Moreover, the effect of β-glucans-containing food on bacterial adhesion to enterocyte-like cells was analyzed and a positive influence on probiotic-enterocyte interaction was observed. PMID:24562330

62. Detail of bellmouth looking southeast. Photo by Robin Lee ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

62. Detail of bellmouth looking southeast. Photo by Robin Lee Tedder, Puget Power, 1989. - Puget Sound Power & Light Company, White River Hydroelectric Project, 600 North River Avenue, Dieringer, Pierce County, WA

Cancer Data and Statistics Tools

MedlinePlus

... Joseph Jacqueline W. Miller Mona Saraiya Judith Lee Smith Sherri L. Stewart Mary C. White Debra Younginer ... MD, MPH Simple Singh, MD, MPH Judith Lee Smith, PhD Sherri L. Stewart, PhD Eric Tai, MD, ...

77 FR 55454 - Plumas County Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... Supervisors Office, 159 Lawrence Street, Quincy, CA 95971. Please call ahead to Lee Anne Schramel Taylor at...: Lee Anne Schramel Taylor, RAC Coordinator, Plumas National Forest, (530) 283-7850, TTY 711, eataylor...

Comparison of a new digital KM screen test with conventional Hess and Lees screen tests in the mapping of ocular deviations.

PubMed

Thorisdottir, Rannveig Linda; Sundgren, Johanna; Sheikh, Rafi; Blohmé, Jonas; Hammar, Björn; Kjellström, Sten; Malmsjö, Malin

2018-05-28

To evaluate the digital KM screen computerized ocular motility test and to compare it with conventional nondigital techniques using the Hess and Lees screens. Patients with known ocular deviations and a visual acuity of at least 20/100 underwent testing using the digital KM screen and the Hess and Lees screen tests. The examination duration, the subjectively perceived difficulty, and the patient's method of choice were compared for the three tests. The accuracy of test results was compared using Bland-Altman plots between testing methods. A total of 19 patients were included. Examination with the digital KM screen test was less time-consuming than tests with the Hess and Lees screens (P < 0.001 and P = 0.003, resp., compared with the digital KM screen). Patients found the test with the digital KM screen easier to perform than the Lees screen test (P = 0.009) but of similar difficulty to the Hess screen test (P = 0.203). The majority of the patients (83%) preferred the digital KM screen test to both of the other screen methods (P = 0.008). Bland-Altman plots showed that the results obtained with all three tests were similar. The digital KM screen is accurate and time saving and provides similar results to Lees and Hess screen testing. It also has the advantage of a digital data analysis and registration. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

The comparison of DNA damage induced by micro DBD plasma and low energy electron for curing human diseases

NASA Astrophysics Data System (ADS)

Park, Yeunsoo

2015-09-01

It is well known that low energy electrons (LEE, especially below 10 eV) can generate DNA damage via indirect action named dissociative electron attachment (DEA). We can now explain some parts of the exact mechanism on DNA damage by LEE collision with direct ionization effect when cancer patients get the radiotherapy. It is kind of remarkable information in the field of radiation therapy. However, it is practically very difficult to directly apply this finding to human disease cure due to difficulty of LEE therapy actualization and request of further clinical studies. Recently, there is a novel challenge in plasma application, that is, how we can apply plasma technology to diagnosis and treatment of many serious diseases like cancer. Cold atmospheric pressure plasma (CAPP) is a very good source to apply to plasma medicine and bio-applications because of low temperature, low cost, and easy handling. Some scientists have already reported good results related to clinical plasma application. The purposes of this study are to further find out exact mechanisms of DNA damage by LEE at the molecular level, to verify new DNA damage like structural alteration on DNA subunits and to compare DNA damage by LEE and plasma source. We will keep expanding our study to DNA damage by plasma source to develop plasma-based new medical and biological applications. We will show some recent results, DNA damage by LEE and non-thermal plasma.

Temporal characteristics of coherent flow structures generated over alluvial sand dunes, Mississippi River, revealed by acoustic doppler current profiling and multibeam echo sounding

USGS Publications Warehouse

Czuba, John A.; Oberg, Kevin A.; Best, Jim L.; Parsons, Daniel R.; Simmons, S. M.; Johnson, K.K.; Malzone, C.

2009-01-01

This paper investigates the flow in the lee of a large sand dune located at the confluence of the Mississippi and Missouri Rivers, USA. Stationary profiles collected from an anchored boat using an acoustic Doppler current profiler (ADCP) were georeferenced with data from a real-time kinematic differential global positioning system. A multibeam echo sounder was used to map the bathymetry of the confluence and provided a morphological context for the ADCP measurements. The flow in the lee of a low-angle dune shows good correspondence with current conceptual models of flow over dunes. As expected, quadrant 2 events (upwellings of low-momentum fluid) are associated with high backscatter intensity. Turbulent events generated in the lower lee of a dune near the bed are associated with periods of vortex shedding and wake flapping. Remnant coherent structures that advect over the lower lee of the dune in the upper portion of the water column, have mostly dissipated and contribute little to turbulence intensities. The turbulent events that occupy most of the water column in the upper lee of the dune are associated with periods of wake flapping.

ARC-2008-ACD08-0260-022

NASA Image and Video Library

2008-11-04

K-10 (red) plaentary rover at Marscape (Ames Mars Yard): with prototype flight control team remotely operating K-10 'Red' from Ames Future Flight Centeral (FFC) Simulator, L-R; Pascal Lee, Melissa Rice, David Lees, Trey Smith

Yuan T. Lee and Molecular Beam Studies

Science.gov Websites

&D Nuggets Database dropdown arrow Search Tag Cloud Browse Reports Database Help Finding Aids : The Influence of Yuan T. Lee, Journal of Chemical Physics, Volume 125, Issue 13, pp. 132302-132302-19

Genetics Home Reference: multiple familial trichoepithelioma

MedlinePlus

... 13. Citation on PubMed Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. ... Fernandez-Figueras, Maria Tereza]. Citation on PubMed Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of ...

Genetics Home Reference: Brooke-Spiegler syndrome

MedlinePlus

... article on PubMed Central Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. ... 124(5):919-20. Citation on PubMed Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of ...

36 CFR 1253.6 - Records Centers.

Code of Federal Regulations, 2011 CFR

2011-07-01

...., Chicago, IL 60629-5898. The telephone number is 773-948-9000. (h) NARA—Central Plains Region (Lee's Summit, MO) is located at 200 Space Center Drive, Lee's Summit, MO 64064-1182. The telephone number is 816...

76 FR 5209 - Notice of Availability of the Environmental Assessment for New Low Security Beds

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... inmates. The alternatives considered for this proposed action include: Lee Adjustment Center, Beattyville...: County of Lee Public Library, 123 Center Street, Beattyville, KY. Groesbeck Public Library (Maffet...

IN VITRO RAT HEPATIC AND ENTEROCYTE METABOLISM OF THE ORGANOPHOSPHATE PESTICIDES CHLORPYRIFOS AND DIAZINON. (R828608)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A taxonomic review of Korean Liogluta Thomson (Coleoptera, Staphylinidae, Aleocharinae) with descriptions of three new species.

PubMed

Lee, Seung-Gyu; Ahn, Kee-Jeong

2016-11-15

A taxonomic review of the Liogluta Thomson in Korea is presented. The genus is represented in Korea by eight species including three new species, L. changwhani Lee & Ahn, sp. nov., L. jinilli Lee & Ahn, sp. nov. and L. rufescens Lee & Ahn, sp. nov. Two species [L. distans (Sharp) and L. ursi (Sawada)] are new to the Korean peninsula and L. pyonganica is recorded for the first time in South Korea. A key, descriptions, habitus photographs and illustrations of the diagnostic characters are provided.

Robust Lee local statistic filter for removal of mixed multiplicative and impulse noise

NASA Astrophysics Data System (ADS)

Ponomarenko, Nikolay N.; Lukin, Vladimir V.; Egiazarian, Karen O.; Astola, Jaakko T.

2004-05-01

A robust version of Lee local statistic filter able to effectively suppress the mixed multiplicative and impulse noise in images is proposed. The performance of the proposed modification is studied for a set of test images, several values of multiplicative noise variance, Gaussian and Rayleigh probability density functions of speckle, and different characteris-tics of impulse noise. The advantages of the designed filter in comparison to the conventional Lee local statistic filter and some other filters able to cope with mixed multiplicative+impulse noise are demonstrated.

Causality as an emergent macroscopic phenomenon: The Lee-Wick O(N) model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grinstein, Benjamin; O'Connell, Donal; Wise, Mark B.

2009-05-15

In quantum mechanics the deterministic property of classical physics is an emergent phenomenon appropriate only on macroscopic scales. Lee and Wick introduced Lorentz invariant quantum theories where causality is an emergent phenomenon appropriate for macroscopic time scales. In this paper we analyze a Lee-Wick version of the O(N) model. We argue that in the large-N limit this theory has a unitary and Lorentz invariant S matrix and is therefore free of paradoxes in scattering experiments. We discuss some of its acausal properties.

Achieving DoD’s Net Centric Vision of Information Sharing While Overcoming Cultural Biases to Control Information

DTIC Science & Technology

2008-05-09

using better technology as a means might be an effective strategy to achieve desired effects and to reduce risk. Tim Berners - Lee , founder of the World...of information disclosure persecution. Tim Berners - Lee advises, “human communication scales up only if we can be tolerant of the differences while we...the government to define intended use Figure 1: Slide by Tim Berners - Lee at http://www.w3.org/2000/Talks/1206-xml2k- tbl.27 The Author added the

Loss of cellular transformation efficiency induced by DNA irradiation with low-energy (10 eV) electrons.

PubMed

Kouass Sahbani, Saloua; Sanche, Leon; Cloutier, Pierre; Bass, Andrew D; Hunting, Darel J

2014-11-20

Low energy electrons (LEEs) of energies less than 20 eV are generated in large quantities by ionizing radiation in biological matter. While LEEs are known to induce single (SSBs) and double strand breaks (DSBs) in DNA, their ability to inactivate cells by inducing nonreparable lethal damage has not yet been demonstrated. Here we observe the effect of LEEs on the functionality of DNA, by measuring the efficiency of transforming Escherichia coli with a [pGEM-3Zf (-)] plasmid irradiated with 10 eV electrons. Highly ordered DNA films were prepared on pyrolitic graphite by molecular self-assembly using 1,3-diaminopropane ions (Dap(2+)). The uniformity of these films permits the inactivation of approximately 50% of the plasmids compared to <10% using previous methods, which is sufficient for the subsequent determination of their functionality. Upon LEE irradiation, the fraction of functional plasmids decreased exponentially with increasing electron fluence, while LEE-induced isolated base damage, frank DSB, and non DSB-cluster damage increased linearly with fluence. While DSBs can be toxic, their levels were too low to explain the loss of plasmid functionality observed upon LEE irradiation. Similarly, non-DSB cluster damage, revealed by transforming cluster damage into DSBs by digestion with repair enzymes, also occurred relatively infrequently. The exact nature of the lethal damage remains unknown, but it is probably a form of compact cluster damage in which the lesions are too close to be revealed by purified repair enzymes. In addition, this damage is either not repaired or is misrepaired by E. coli, since it results in plasmid inactivation, when they contain an average of three lesions. Comparison with previous results from a similar experiment performed with γ-irradiated plasmids indicates that the type of clustered DNA lesions, created directly on cellular DNA by LEEs, may be more difficult to repair than those produced by other species from radiolysis.

[The medical theory of Lee Je-ma and its character].

PubMed

Lee, Kyung-Lock

2005-12-01

Lee Je-ma 1837-1900) was a prominent scholar as well as an Korean physician. classified every people into four distinctive types: greater yang [tai yang] person, lesser yin [shao yin] person, greater yin [tai yin] person, lesser yin [shao yin] person. This theory would dictate proper treatment for each type in accordance with individual differences of physical and temperament features. Using these four types he created The Medical Science of Four Types. This article is intended to look into the connection between Lee Je-Ma's 'The Medical Science of Four Types' and 'The Modern' with organizing his ideas about the human body and the human being. Through The Modern, the theory of human being underwent a complete change. Human being in The Premodern, which was determined by sex, age and social status has been changed to the individual human being, which is featured by equality. Lee Je-Ma's medical theory of The Medical Science of Four Types would be analyzed as follow. His concept of human body is oriented toward observable objectivity. But on the other hand, it still remains transcendent status of medical science, which is subordinated by philosophy. According to Lee Je-Ma's theory of human being, human is an equal individual in a modern way of thinking, not as a part of hierarchical group. But on the other hand, it still remains incomplete from getting rid of morality aspect that includes virtue and vice in the concept of human body. The common factors in Lee Je-Ma's ideas about the human body and the human being is 'Dualism of mind and body that means all kinds of status and results depends on each individual. As is stated above, Lee Je-Ma's medical theory has many aspects of The Modern and it proves that Korean traditional medicine could be modernized by itself.

1. Historic American Buildings Survey Photocopy of old view, date ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey Photocopy of old view, date unknown From collection of Anna B. Scherer, Lees Summit, Mo. NORTH FACADE - Longview Farm, Hog & Sale Barn, Longview Road, Lees Summit, Jackson County, MO

27 CFR 9.195 - Alta Mesa.

Code of Federal Regulations, 2010 CFR

2010-04-01

... northeast 2.6 miles on Dillard Road to its intersection with Lee Shorthorn Road, T7N, R7E (Sloughhouse Quadrangle); then (6) Proceed southeast 0.9 mile on Lee Shorthorn Road to its intersection with Tavernor Road...

27 CFR 9.195 - Alta Mesa.

Code of Federal Regulations, 2011 CFR

2011-04-01

... northeast 2.6 miles on Dillard Road to its intersection with Lee Shorthorn Road, T7N, R7E (Sloughhouse Quadrangle); then (6) Proceed southeast 0.9 mile on Lee Shorthorn Road to its intersection with Tavernor Road...

27 CFR 9.201 - Sloughhouse.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Tavernor Road to its intersection with Lee Shorthorn Road, T7N, R7E (Sloughhouse Quadrangle); then (7) Proceed northwest 0.9 mile on Lee Shorthorn Road to its intersection with Dillard Road, T7N, R7E...

76 FR 31006 - Requested Administrative Waiver of the Coastwise Trade Laws

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... for the vessel OLIVIA LEE. SUMMARY: As authorized by 46 U.S.C. 12121, the Secretary of Transportation... applicant the intended service of the vessel OLIVIA LEE is: Intended Commercial Use of Vessel: ``Occasional...

27 CFR 9.201 - Sloughhouse.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Tavernor Road to its intersection with Lee Shorthorn Road, T7N, R7E (Sloughhouse Quadrangle); then (7) Proceed northwest 0.9 mile on Lee Shorthorn Road to its intersection with Dillard Road, T7N, R7E...

Observational changes to the natural flow regime in Lee Creek in relation to altered precipitation patterns and its implication for fishes

USGS Publications Warehouse

Gatlin, Michael R.; Long, James M.; Turton, Donald J.

2015-01-01

The natural flow regime is important for structuring streams and their resident ichthyofauna and alterations to this regime can have cascading consequences. We sought to determine if changes in hydrology could be attributed to changes in precipitation in a minimally altered watershed (Lee Creek). The stream flow regime was analyzed using Indicators of Hydrologic Alteration (IHA) software, and data from a nearby climate station were used to summarize concurrent precipitation patterns. We discovered that Lee Creek hydrology had become flashier (i.e., increased frequency of extreme events of shorter duration) since 1992 coincident with changes in precipitation patterns. Specifically, our results show fewer but more intense rain events within the Lee Creek watershed. Our research provides evidence that climate-induced changes to the natural flow regime are currently underway and additional research on its effects on the fish community is warranted.

No Lee-Wick fields out of gravity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodigast, Andreas; Schuster, Theodor

2009-06-15

We investigate the gravitational one-loop divergences of the standard model in large extra dimensions, with gravitons propagating in the (4+{delta})-dimensional bulk and gauge fields as well as scalar and fermionic multiplets confined to a three-brane. To determine the divergences we establish a cutoff regularization which allows us to extract gauge-invariant counterterms. In contrast to the claim of a recent paper [F. Wu and M. Zhong, Phys. Rev. D 78, 085010 (2008).], we show that the fermionic and scalar higher derivative counterterms do not coincide with the higher derivative terms in the Lee-Wick standard model. We argue that even if themore » exact Lee-Wick higher derivative terms were found, as in the case of the pure gauge sector, this would not allow to conclude the existence of the massive ghost fields corresponding to these higher derivative terms in the Lee-Wick standard model.« less

ECOSTRESS and LEE - SpaceX CRS-15 Mission

NASA Image and Video Library

2018-06-02

The ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station (ECOSTRESS), pictured at the bottom, and the Latching End Effector (LEE), pictured at the top, are integrated into the unpressurized SpaceX Dragon truck June 2, 2018, at the SpaceX facility on Cape Canaveral Air Force Station in Florida. The payloads will be carried to the International Space Station on SpaceX's 15th Commercial Resupply Services mission. ECOSTRESS will measure the temperature of plants and use that information to better understand how much water plants need and how they respond to stress. The Canadian Space Agency is supplying LEE for the Canadarm2 as a spare to replace a failed unit removed by astronauts during a spacewalk in 2017. Each end of the Canadarm2 robotic arm has an identical LEE, which acts like a "hand" to grapple payloads and visiting cargo spaceships.

Translation, Cross Cultural Adaptation and Validation of the Lee Chronic Graft-versus-Host Disease (GVHD) Symptom Scale in a Brazilian Population

PubMed Central

de Souza, Clarissa Vasconcellos; Vigorito, Afonso Celso; Miranda, Eliana C M; Garcia, Celso; Colturato, Vergílio Antonio Rensi; Mauad, Marcos Augusto; Moreira, Maria Cláudia Rodrigues; da Silva Bouzas, Luis Fernando; Lermontov, Simone; Hamerschlak, Nelson; Rodrigues, Morgani; de Almeida Barros, Jose Carlos; Chiattone, Ricardo; Lee, Stephanie J; Flowers, Mary ED

2017-01-01

The Lee chronic graft-versus-disease (cGVHD) Symptom Scale is a patient-reported instrument developed and validated in English to measure symptoms and functional impact of cGVHD. This tool has not been validated in a Latin America population. The Brazil-Seattle Chronic GVHD Consortium conducted a multicenter study at five Brazilian institutions to validate the Lee cGVHD Symptom Scale in adults with chronic GVHD. Study objectives included the translation and validation of the instrument in Brazilian Portuguese and evaluation of the correlation with other quality of life (QoL) tools (i.e., Medical Outcomes Study Short Form 36 [SF-36] and the Functional Assessment of Chronic Illness Therapy with Bone Marrow Transplant subscale [FACT-BMT]). Translation and validation were according to the American Association of Orthopedic Surgeons Outcome Committee guideline. Spearman’s correlation coefficient was used to measure construct validity. Reliability was assessed using Cronbach’s alpha and intraclass correlation coefficients. Between April 2011 and August 2012, 47 patients with cGVHD by the 2005 NIH criteria were enrolled in this study. Cohort median age was 48 (23–69) years and 29 (62%) were male. Lee cGVHD Symptom Scale reliability was adequate (Cronbach’s alpha 0.62–0.83). The correlations between similar domains of the Lee cGVHD Symptom Scale, SF-36 and FACT-BMT were moderate to high. The Brazilian Portuguese version of the Lee cGVHD Symptom Scale is valid and reliable and can be used in clinical trials of cGVHD in Brazil. PMID:27058616

The pro-life argument from substantial identity and the pro-choice argument from asymmetric value: a reply to Patrick Lee.

PubMed

Reiman, Jeffrey

2007-07-01

Lee claims that foetuses and adult humans are phases of the same identical substance, and thus have the same moral status because: first, foetuses and adults are the same physical organism, and second, the development from foetus to adult is quantitative and thus not a change of substance. Versus the first argument, I contend that the fact that foetuses and adults are the same physical organism implies only that they are the same thing but not the same substance, much as living adults and their corpses are the same thing (same body) but not the same substance. Against Lee's second argument, I contend that Lee confuses the nature of a process with the nature of its result. A process of quantitative change can produce a change in substance. Lee also fails to show that foetuses are rational and thus have all the essential properties of adults, as required for them to be the same substance. Against the pro-choice argument from asymmetric value (that only the fact that a human has become conscious of its life and begun to count on its continuing can explain human life's asymmetric moral value, i.e. that it is vastly worse to kill a human than not to produce one), Lee claims that foetus's lives are asymmetrically valuable to them before consciousness. This leads to counterintuitive outcomes, and it confuses the goodness of life (a symmetric value that cannot account for why it is worse to kill a human than not produce one) with asymmetric value.

Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

USDA-ARS?s Scientific Manuscript database

UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in 3 equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats, n=8/age using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin...

Contribution of mucosal maltase-glucoamylase activities to mouse small intestinal starch alpha-glucogenesis

USDA-ARS?s Scientific Manuscript database

Digestion of starch requires activities provided by 6 interactive small intestinal enzymes. Two of these are luminal endo-glucosidases named alpha-amylases. Four are exo-glucosidases bound to the luminal surface of enterocytes. These mucosal activities were identified as 4 different maltases. Two ma...

Tsung-Dao Lee, Weak Interactions, and Nonconservation of Parity

Science.gov Websites

his Ph.D. from the University of Chicago in 1950. After working as a research associate at the University of Chicago and the University of California, Berkeley, Lee joined the Institute for Advanced Study

NASA Aquarius Detects Possible Effects of Tropical Storm Lee in Gulf

NASA Image and Video Library

2011-12-07

Tropical Storm Lee made landfall over New Orleans on Sept. 2-3, 2011, with predicted rainfall of 15 to 20 inches 38 to 51 centimeters over southern Louisiana. These charts are from NASA Aquarius spacecraft.

Sandstone units of the Lee Formation and related strata in eastern Kentucky

USGS Publications Warehouse

Rice, Charles L.

1984-01-01

Most of the Cumberland Plateau region of southeastern Kentucky is underlain by thick sequences of quartzose sandstone which are assigned for the most part to the Lee Formation. Much new information has been gathered about the Lee and related strata as a result of the cooperative mapping program of the U. S. Geological Survey and the Kentucky Geological Survey between 1960 and 1978. This report summarizes the age, lithology, distribution, sedimentary structures, and stratigraphic relations of the sandstone units of the Lee within and between each of three major outcrop belts in Kentucky: Cumberland Mountain, Pine Mountain, and the Pottsville Escarpment area. The Lee Formation generally has been regarded as Early Pennsylvanian in age and separated from Mississippian strata in Kentucky by an unconformity. However, lithostratigraphic units included in the formation as presently defined are broadly time-transgressive and range in age from Late Mississippian in parts of the Cumberland Mountain outcrop belt to Middle Pennsylvanian in the Pottsville Escarpment area. Members of the Lee intertongue with and grade into the underlying Pennington Formation and overlying Breathitt Formation. Sandstone and conglomeratic sandstone members of the Lee of Mississippian age found only in parts of the Cumberland overthrust sheet are closely associated with marine rocks; Pennsylvanian members are mostly associated with continental coal-bearing strata. Sandstone members of the Lee are mostly quartz rich and range from more than 90 percent to more than 99 percent quartz. They are relatively coarse grained, commonly pebbly, and in places conglomeratic. The units are southwest-trending linear or broadly lobate bodies. The Lee Formation is as much as 1,500 ft thick in the type area in Cumberland Mountain where it has been divided into eight members. The Pinnacle Overlook, Chadwell, White Rocks Sandstone, Middlesboro, Bee Rock Sandstone, and Naese Sandstone Members are mostly quartzose sandstone and conglomerate. The Dark Ridge and Hensley Members are mostly shale, siltstone, thin-bedded silty sandstone, and coal. The lower three of these members, the Pinnacle Overlook, Chadwell, and White Rocks Sandstone, are assigned to the Upper Mississippian Series because they intertongue with marine reddish or greenish shale and siltstone of the Pennington Formation or equivalent strata that contain a Late Mississippian fauna. The overlying quartzose sandstone members of the Lee commonly have coalified plant remains and impressions of plants and are Early to Middle Pennsylvanian in age; they are generally associated with terrestrial shale and siltstone containing coal beds and pinch out eastward into subgraywacke, siltstone, and shale. Although marine members commonly are bimodal, resultant transport directions for both marine and terrestrial members are southwesterly as determined by crossbedding. Thickness variations of the Middlesboro Member in the Cumberland overthrust sheet suggest that it represents tills of at least three major southwesterly trending paleovalleys. Thickness variations of the Bee Rock Sandstone Member east of Rocky Face fault and the combined Bee Rock and Naese Sandstone Members west of Rocky Face fault suggest that these members represent tills of at least two major southwesterly trending paleovalleys. East of Rocky Face fault, the Bee Rock is generally the uppermost member of the Lee; west of the fault, the overlying Naese is at the top. The Naese may range in age from Early to Middle Pennsylvanian and is partly or wholly equivalent to the Rockcastle Sandstone member of the Lee Formation in the area of the Pottsville Escarpment. The Mississippian-Pennsylvanian systemic boundary in the area of the Cumberland overthrust sheet in most places has been placed at an unconformity at the base of the Middlesboro Member; locally it is projected at the base of shales of the underlying Dark Ridge Member or equivalent strata in the Penningto

ARC-2008-ACD08-0260-024

NASA Image and Video Library

2008-11-04

K-10 (red) plaentary rover at Marscape (Ames Mars Yard): with prototype flight control team remotely operating K-10 'Red' from Ames Future Flight Centeral (FFC) Simulator, L-R; Kip Hodges, Mark Helper, Marwan Hussein, Pascal Lee, Melissa Rice, Trey Smith, David Lees

9. Photocopy of painting (Painted by the architect, Mr. Lee ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Photocopy of painting (Painted by the architect, Mr. Lee and presented to the Rev. J.J. Roberts, Rector, 1853-1866) April 1960 EXTERIOR, GENERAL VIEW - Church of the Holy Cross, State Route 261, Stateburg, Sumter County, SC

AUTHOR MARGOT LEE SHETTERLY SPEAKS AT MSFC WOMEN'S HISTORY MONTH

NASA Image and Video Library

2017-03-07

DIANE CAIN, STANDING NEAR CENTER, OF NASA MARSHALL SPACE FLIGHT CENTER'S OFFICE OF HUMAN CAPITAL, SPEAKS TO AN AUDIENCE GATHERED FOR AN AGENCY-WIDE LIVESTREAM PRESENTATION BY AUTHOR MARGOT LEE SHETTERLY FROM NASA'S LANGLEY RESEARCH CENTER ON MARCH 7

50 CFR 226.217 - Critical habitat for the Gulf of Maine Distinct Population Segment of Atlantic Salmon (Salmo salar).

Code of Federal Regulations, 2010 CFR

2010-10-01

..., Herseytown Plt, Kingman Twp, Lee, Lincoln, Mattawamkeag, Mount Chase, Patten, Prentiss Twp T7 R3 NBPP..., Hudson, Indian Island, Kenduskeag, Lagrange, Lakeville, Lee, Levant, Lincoln, Lowell, Mattamiscontis Twp...

50 CFR 226.217 - Critical habitat for the Gulf of Maine Distinct Population Segment of Atlantic Salmon (Salmo salar).

Code of Federal Regulations, 2011 CFR

2011-10-01

..., Herseytown Plt, Kingman Twp, Lee, Lincoln, Mattawamkeag, Mount Chase, Patten, Prentiss Twp T7 R3 NBPP..., Hudson, Indian Island, Kenduskeag, Lagrange, Lakeville, Lee, Levant, Lincoln, Lowell, Mattamiscontis Twp...

Comment on "Combination of cupric ion with hydroxylamine and hydrogen peroxide for the control of bacterial biofilms on RO membranes by Hye-Jin Lee, Hyung-Eun Kim, Changha Lee [Water Research 110, 2017, 83-90]".

PubMed

Chen, Long; Peng, Ying; Tang, Min; Wu, Feng

2017-07-01

The methodology employed by Lee et al. to terminate their bactericidal assays was found to be flawed via our demonstrations. Briefly, EDTA or sulfite combining with cupric ion did not fully terminate, and instead even boosted the P. aeruginosa death. We therefore suggested them to seek for other means of reaction termination, such as the combination of buffering agent PBS and Cu(II)-complexing agent EDTA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of metal stress on the thermal infrared emission of soybeans: A greenhouse experiment - Possible utility in remote sensing

NASA Technical Reports Server (NTRS)

Suresh, R.; Schwaller, M. R.; Foy, C. D.; Weidner, J. R.; Schnetzler, C. S.

1989-01-01

Manganese-sensitive forest and manganese-tolerant lee soybean cultivars were subjected to differential manganese stress in loring soil in a greenhouse experiment. Leaf temperature measurements were made using thermistors for forest and lee. Manganese-stressed plants had higher leaf temperatures than control plants in both forest and lee. Results of this experiment have potential applications in metal stress detection using remote sensing thermal infrared data over large areas of vegetation. This technique can be useful in reconnaissance mineral exploration in densely-vegetated regions where conventional ground-based methods are of little help.

Characterization of Bulk GaN Crystals Grown From Solution at Near Atmospheric Pressure

DTIC Science & Technology

2010-01-01

pressureN.Y. Garces a,n, B.N. Feigelson a, J.A. Freitas Jra, Jihyun Kimb, R.L. Myers-Ward a, E.R. Glaser a a Naval Research Laboratory, Codes 6877, 6882...Lee, I.J. Song, Appl. Phys. Lett. 79 (2001) 2570. [13] J.A. Freitas Jr., W.J. Moore, B.V. Shanabrook, G.C.B. Braga, S.K. Lee, S.S. Park , J.Y. Han...Morkoc, S.S. Park , K.Y. Lee, Appl. Phys. Lett. 78 (2001) 3041. [17] J.A. Freitas Jr., G.C.B. Braga, W.J. Moore, J.G. Tischler, J.C. Culbertson, M

Perron-Frobenius theorem on the superfluid transition of an ultracold Fermi gas

NASA Astrophysics Data System (ADS)

Sakumichi, Naoyuki; Kawakami, Norio; Ueda, Masahito

2014-05-01

The Perron-Frobenius theorem is applied to identify the superfluid transition of the BCS-BEC crossover based on a cluster expansion method of Lee and Yang. Here, the cluster expansion is a systematic expansion of the equation of state (EOS) in terms of the fugacity z = exp (βμ) as βpλ3 = 2 z +b2z2 +b3z3 + ⋯ , with inverse temperature β =(kB T) - 1 , chemical potential μ, pressure p, and thermal de Broglie length λ =(2 πℏβ / m) 1 / 2 . According to the method of Lee and Yang, EOS is expressed by the Lee-Yang graphs. A singularity of an infinite series of ladder-type Lee-Yang graphs is analyzed. We point out that the singularity is governed by the Perron-Frobenius eigenvalue of a certain primitive matrix which is defined in terms of the two-body cluster functions and the Fermi distribution functions. As a consequence, it is found that there exists a unique fugacity at the phase transition point, which implies that there is no fragmentation of Bose-Einstein condensates of dimers and Cooper pairs at the ladder-approximation level of Lee-Yang graphs. An application to a BEC of strongly bounded dimers is also made.

Forecasting selected specific age mortality rate of Malaysia by using Lee-Carter model

NASA Astrophysics Data System (ADS)

Shukri Kamaruddin, Halim; Ismail, Noriszura

2018-03-01

Observing mortality pattern and trend is an important subject for any country to maintain a good social-economy in the next projection years. The declining in mortality trend gives a good impression of what a government has done towards macro citizen in one nation. Selecting a particular mortality model can be a tricky based on the approached method adapting. Lee-Carter model is adapted because of its simplicity and reliability of the outcome results with approach of regression. Implementation of Lee-Carter in finding a fitted model and hence its projection has been used worldwide in most of mortality research in developed countries. This paper studies the mortality pattern of Malaysia in the past by using original model of Lee-Carter (1992) and hence its cross-sectional observation for a single age. The data is indexed by age of death and year of death from 1984 to 2012, in which are supplied by Department of Statistics Malaysia. The results are modelled by using RStudio and the keen analysis will focus on the trend and projection of mortality rate and age specific mortality rate in the future. This paper can be extended to different variants extensions of Lee-Carter or any stochastic mortality tool by using Malaysia mortality experience as a centre of the main issue.

Effects of current crowding on light extraction efficiency of conventional GaN-based light-emitting diodes.

PubMed

Cao, Bin; Li, Shuiming; Hu, Run; Zhou, Shengjun; Sun, Yi; Gan, Zhiying; Liu, Sheng

2013-10-21

Current crowding effects (CCEs) on light extraction efficiency (LEE) of conventional GaN-based light-emitting diodes (LEDs) are analyzed through Monte Carlo ray-tracing simulation. The non-uniform radiative power distribution of the active layer of the Monte Carlo model is obtained based on the current spreading theory and rate equation. The simulation results illustrate that CCE around n-pad (n-CCE) has little effect on LEE, while CCE around p-pad (p-CCE) results in a notable LEE droop due to the significant absorption of photons emitted under p-pad. LEE droop is alleviated by a SiO₂ current blocking layer (CBL) and reflective p-pad. Compared to the conventional LEDs without CBL, the simulated LEE of LEDs with CBL at 20 A/cm² and 70 A/cm² is enhanced by 7.7% and 19.0%, respectively. It is further enhanced by 7.6% and 11.4% after employing a reflective p-pad due to decreased absorption. These enhancements are in accordance with the experimental results. Output power of LEDs with CBL is enhanced by 8.7% and 18.2% at 20 A/cm² and 70 A/cm², respectively. And the reflective p-pad results in a further enhancement of 8.9% and 12.7%.

Light extraction efficiency analysis of GaN-based light-emitting diodes with nanopatterned sapphire substrates.

PubMed

Pan, Jui-Wen; Tsai, Pei-Jung; Chang, Kao-Der; Chang, Yung-Yuan

2013-03-01

In this paper, we propose a method to analyze the light extraction efficiency (LEE) enhancement of a nanopatterned sapphire substrates (NPSS) light-emitting diode (LED) by comparing wave optics software with ray optics software. Finite-difference time-domain (FDTD) simulations represent the wave optics software and Light Tools (LTs) simulations represent the ray optics software. First, we find the trends of and an optimal solution for the LEE enhancement when the 2D-FDTD simulations are used to save on simulation time and computational memory. The rigorous coupled-wave analysis method is utilized to explain the trend we get from the 2D-FDTD algorithm. The optimal solution is then applied in 3D-FDTD and LTs simulations. The results are similar and the difference in LEE enhancement between the two simulations does not exceed 8.5% in the small LED chip area. More than 10(4) times computational memory is saved during the LTs simulation in comparison to the 3D-FDTD simulation. Moreover, LEE enhancement from the side of the LED can be obtained in the LTs simulation. An actual-size NPSS LED is simulated using the LTs. The results show a more than 307% improvement in the total LEE enhancement of the NPSS LED with the optimal solution compared to the conventional LED.

Preliminary results of Malaysian nuclear agency plasma focus (MNA-PF) as a slow focus mode device for argon and deuterium filling gas in correlation with Lee model code

NASA Astrophysics Data System (ADS)

Zin, M. F. M.; Baijan, A. H.; Damideh, V.; Hashim, S. A.; Sabri, R. M.

2017-03-01

In this work, preliminary results of MNA-PF device as a Slow Focus Mode device are presented. Four different kinds of Rogowski Coils which have been designed and constructed for dI/dt signals measurements show that response frequency of Rogowski Coil can affect signal time resolution and delay which can change the discharge circuit inductance. Experimental results for 10 to 20 mbar Deuterium and 0.5 mbar to 6 mbar Argon which are captured by 630 MHz Rogowski coil in correlation with Lee Model Code are presented. Proper current fitting using Lee Model Code shows that the speed factor for MNA-PF device working with 13 mbar Deuterium is 30 kA/cm.torr1/2 at 14 kV which indicates that the device is operating at slow focus mode. Model parameters fm and fmr predicted by Lee Model Code during current fitting for 13 mbar Deuterium at 14kV were 0.025 and 0.31 respectively. Microspec-4 Neutron Detector was used to obtain the dose rate which was found to be maximum at 4.78 uSv/hr and also the maximum neutron yield calculated from Lee Model Code is 7.5E+03 neutron per shot.

Glycogen Synthase Kinase 3β Dictates Podocyte Motility and Focal Adhesion Turnover by Modulating Paxillin Activity

PubMed Central

Xu, Weiwei; Ge, Yan; Liu, Zhihong; Gong, Rujun

2015-01-01

Aberrant focal adhesion turnover is centrally involved in podocyte actin cytoskeleton disorganization and foot process effacement. The structural and dynamic integrity of focal adhesions is orchestrated by multiple cell signaling molecules, including glycogen synthase kinase 3β (GSK3β), a multitasking kinase lately identified as a mediator of kidney injury. However, the role of GSK3β in podocytopathy remains obscure. In doxorubicin (Adriamycin)-injured podocytes, lithium, a GSK3β inhibitor and neuroprotective mood stabilizer, obliterated the accelerated focal adhesion turnover, rectified podocyte hypermotility, and restored actin cytoskeleton integrity. Mechanistically, lithium counteracted the doxorubicin-elicited GSK3β overactivity and the hyperphosphorylation and overactivation of paxillin, a focal adhesion–associated adaptor protein. Moreover, forced expression of a dominant negative kinase dead mutant of GSK3β highly mimicked, whereas ectopic expression of a constitutively active GSK3β mutant abolished, the effect of lithium in doxorubicin-injured podocytes, suggesting that the effect of lithium is mediated, at least in part, through inhibition of GSK3β. Furthermore, paxillin interacted with GSK3β and served as its substrate. In mice with doxorubicin nephropathy, a single low dose of lithium ameliorated proteinuria and glomerulosclerosis. Consistently, lithium therapy abrogated GSK3β overactivity, blunted paxillin hyperphosphorylation, and reinstated actin cytoskeleton integrity in glomeruli associated with an early attenuation of podocyte foot process effacement. Thus, GSK3β-modulated focal adhesion dynamics might serve as a novel therapeutic target for podocytopathy. PMID:25239564

A four-culture study of self-enhancement and adjustment using the social relations model: do alternative conceptualizations and indices make a difference?

PubMed

Church, A Timothy; Katigbak, Marcia S; Mazuera Arias, Rina; Rincon, Brigida Carolina; Vargas-Flores, José de Jesús; Ibáñez-Reyes, Joselina; Wang, Lei; Alvarez, Juan M; Wang, Congcong; Ortiz, Fernando A

2014-06-01

In the self-enhancement literature, 2 major controversies remain--whether self-enhancement is a cultural universal and whether it is healthy or maladaptive. Use of the social relations model (SRM; Kenny, 1994) might facilitate resolution of these controversies. We applied the SRM with a round-robin design in both friend and family contexts in 4 diverse cultures: the United States (n = 399), Mexico (n = 413), Venezuela (n = 290), and China (n = 222). Results obtained with social comparison, self-insight, and SRM conceptualizations and indices of self-enhancement were compared for both agentic traits (i.e., egoistic bias) and communal traits (i.e., moralistic bias). Conclusions regarding cultural differences in the prevalence of self-enhancement vs. self-effacement tendencies, and the relationship between self-enhancement and adjustment, varied depending on the index of self-enhancement used. For example, consistent with cultural psychology perspectives, Chinese showed a greater tendency to self-efface than self-enhance using social comparison and self-insight indices, particularly on communal traits in the friend context. However, no cultural differences were observed when perceiver and target effects were controlled using the SRM indices. In all cultures, self-enhancement indices were moderately consistent across friend and family contexts, suggesting traitlike tendencies. To a similar extent in all 4 cultures, self-enhancement tendencies, as measured by the SRM indices, were moderately related to self-rated adjustment, but unrelated, or less so, to observer-rated adjustment.

33. VIEW OF TIOGA ROAD DESCENDING LEE VINING CANYON. SAME ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. VIEW OF TIOGA ROAD DESCENDING LEE VINING CANYON. SAME VIEW AS CA-149-3. LOOKING ESE. GIS: N-37 56 58.2 / W-119 13 28.1 - Tioga Road, Between Crane Flat & Tioga Pass, Yosemite Village, Mariposa County, CA

4. VISTA POINT AND INTERPRETIVE PLAQUE AT LEE VINING CANYON. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VISTA POINT AND INTERPRETIVE PLAQUE AT LEE VINING CANYON. NOTE ROAD CUT ON CANYON WALL. LOOKING NNE. GIS: N-37 56 30.3 / 119 13 44.8 - Tioga Road, Between Crane Flat & Tioga Pass, Yosemite Village, Mariposa County, CA

8. Historic American Buildings Survey Photocopy of an old view, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Historic American Buildings Survey Photocopy of an old view, ca. 1920 From collection of Anna B. Scherer, Lees Summit, Mo. SOUTHEAST AND NORTHEAST FACADES WITH GARAGE/POWERHOUSE PRIOR TO GREENHOUSE MANGER'S HOUSE - Longview Farm, Greenhouses, Lees Summit, Jackson County, MO

Computation and Theory in Large-Scale Optimization

DTIC Science & Technology

1993-01-13

Sang Jin Lee. Research Assistant. - Laura Morley, Research Assistant. - Yonca A. Ozge , Research Assistant. - Stephen M. Robinson. Professor. - Hichem...other participants. M.N. Azadez. S.J. Lee. Y.A. Ozge . and H. Sellami are continuing students in the doctoral program (in Industrial Engineering except

A Comparison Between Internal Waves Observed in the Southern Ocean and Lee Wave Generation Theory

NASA Astrophysics Data System (ADS)

Nikurashin, M.; Benthuysen, J.; Naveira Garabato, A.; Polzin, K. L.

2016-02-01

Direct observations in the Southern Ocean report enhanced internal wave activity and turbulence in a few kilometers above rough bottom topography. The enhancement is co-located with the deep-reaching fronts of the Antarctic Circumpolar Current, suggesting that the internal waves and turbulence are sustained by near-bottom flows interacting with rough topography. Recent numerical simulations confirm that oceanic flows impinging on rough small-scale topography are very effective generators of internal gravity waves and predict vigorous wave radiation, breaking, and turbulence within a kilometer above bottom. However, a linear lee wave generation theory applied to the observed bottom topography and mean flow characteristics has been shown to overestimate the observed rates of the turbulent energy dissipation. In this study, we compare the linear lee wave theory with the internal wave kinetic energy estimated from finestructure data collected as part of the Diapycnal and Isopycnal Mixing Experiment in the Southern Ocean (DIMES). We show that the observed internal wave kinetic energy levels are generally in agreement with the theory. Consistent with the lee wave theory, the observed internal wave kinetic energy scales quadratically with the mean flow speed, stratification, and topographic roughness. The correlation coefficient between the observed internal wave kinetic energy and mean flow and topography parameters reaches 0.6-0.8 for the 100-800 m vertical wavelengths, consistent with the dominant lee wave wavelengths, and drops to 0.2-0.5 for wavelengths outside this range. A better agreement between the lee wave theory and the observed internal wave kinetic energy than the observed turbulent energy dissipation suggests remote breaking of internal waves.

Vertical structure and microphysical characteristics of precipitation on the high terrain and lee side of the Olympic Mountains

NASA Astrophysics Data System (ADS)

Zagrodnik, J. P.; McMurdie, L. A.; Houze, R.

2017-12-01

As mid-latitude cyclones pass over coastal mountain ranges, the processes producing their clouds and precipitation are modified when they encounter complex terrain, leading to a maximum in precipitation fallout on the windward slopes and a minimum on the lee side. The precipitation that does reach the high terrain and lee side of a mountain range can be theoretically determined by a complex interaction between the dynamics of air lifting over the terrain, the thermodynamics of moist air, and the microphysical time required to grow particles large enough to fall out. To date, there have been few observational studies that have focused on the nonlinear microphysical processes contributing to the variability of precipitation that is received on the lee side slopes of a mountain range such as the Olympic Mountains. The 2015-16 Olympic Mountains Experiment (OLYMPEX) collected unprecedented observations on the high terrain and lee side of the Olympic Mountains including frequent soundings on Vancouver Island, dual-polarization Doppler radar, multi-frequency airborne radar, and ground-based particle size and crystal habit observations at the higher elevation Hurricane Ridge site. We utilize these observations to examine the evolution of the vertical structure and microphysical precipitation characteristics over the high terrain and leeside within the context of large-scale dynamic and thermodynamic conditions that evolve during the passage of cold season mid-latitude cyclones. The primary goal is to determine the degree to which the observed variability in lee side precipitation amount and microphysical properties are controlled by variations in temperature, flow speed and direction, shear, and stability associated with characteristic synoptic storm sectors and frontal passages.

Ghost busting: PT-symmetric interpretation of the Lee model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Carl M.; Brandt, Sebastian F.; Chen, J.-H.

2005-01-15

The Lee model was introduced in the 1950s as an elementary quantum field theory in which mass, wave function, and charge renormalization could be carried out exactly. In early studies of this model it was found that there is a critical value of g{sup 2}, the square of the renormalized coupling constant, above which g{sub 0}{sup 2}, the square of the unrenormalized coupling constant, is negative. Thus, for g{sup 2} larger than this critical value, the Hamiltonian of the Lee model becomes non-Hermitian. It was also discovered that in this non-Hermitian regime a new state appears whose norm is negative.more » This state is called a ghost state. It has always been assumed that in this ghost regime the Lee model is an unacceptable quantum theory because unitarity appears to be violated. However, in this regime while the Hamiltonian is not Hermitian, it does possess PT symmetry. It has recently been discovered that a non-Hermitian Hamiltonian having PT symmetry may define a quantum theory that is unitary. The proof of unitarity requires the construction of a new time-independent operator called C. In terms of C one can define a new inner product with respect to which the norms of the states in the Hilbert space are positive. Furthermore, it has been shown that time evolution in such a theory is unitary. In this paper the C operator for the Lee model in the ghost regime is constructed in the V/N{theta} sector. It is then shown that the ghost state has a positive norm and that the Lee model is an acceptable unitary quantum field theory for all values of g{sup 2}.« less

Analysis and functional annotation of expressed sequence tags from in vitro cell lines of elasmobranchs: spiny dogfish shark (Squalus acanthias) and little skate (Leucoraja erinacea)

PubMed Central

Parton, Angela; Bayne, Christopher J.; Barnes, David W.

2010-01-01

Elasmobranchs are the most commonly used experimental models among the jawed, cartilaginous fish (Chondrichthyes). Previously we developed cell lines from embryos of two elasmobranchs, Squalus acanthias the spiny dogfish shark (SAE line), and Leucoraja erinacea the little skate (LEE-1 line). From these lines cDNA libraries were derived and expressed sequence tags (ESTs) generated. From the SAE cell line 4303 unique transcripts were identified, with 1848 of these representing unknown sequences (showing no BLASTX identification). From the LEE-1 cell line, 3660 unique transcripts were identified, and unknown, unique sequences totaled 1333. Gene Ontology (GO) annotation showed that GO assignments for the two cell lines were in general similar. These results suggest that the procedures used to derive the cell lines led to isolation of cell types of the same general embryonic origin from both species. The LEE-1 transcripts included GO categories “envelope” and “oxidoreductase activity” but the SAE transcripts did not. GO analysis of SAE transcripts identified the category “anatomical structure formation” that was not present in LEE-1 cells. Increased organelle compartments may exist within LEE-1 cells compared to SAE cells, and the higher oxidoreductase activity in LEE-1 cells may indicate a role for these cells in responses associated with innate immunity or in steroidogenesis. These EST libraries from elasmobranch cell lines provide information for assembly of genomic sequences and are useful in revealing gene diversity, new genes and molecular markers, as well as in providing means for elucidation of full-length cDNAs and probes for gene array analyses. This is the first study of this type with members of the Chondrichthyes. PMID:20471924

Analysis and functional annotation of expressed sequence tags from in vitro cell lines of elasmobranchs: Spiny dogfish shark (Squalus acanthias) and little skate (Leucoraja erinacea).

PubMed

Parton, Angela; Bayne, Christopher J; Barnes, David W

2010-09-01

Elasmobranchs are the most commonly used experimental models among the jawed, cartilaginous fish (Chondrichthyes). Previously we developed cell lines from embryos of two elasmobranchs, Squalus acanthias the spiny dogfish shark (SAE line), and Leucoraja erinacea the little skate (LEE-1 line). From these lines cDNA libraries were derived and expressed sequence tags (ESTs) generated. From the SAE cell line 4303 unique transcripts were identified, with 1848 of these representing unknown sequences (showing no BLASTX identification). From the LEE-1 cell line, 3660 unique transcripts were identified, and unknown, unique sequences totaled 1333. Gene Ontology (GO) annotation showed that GO assignments for the two cell lines were in general similar. These results suggest that the procedures used to derive the cell lines led to isolation of cell types of the same general embryonic origin from both species. The LEE-1 transcripts included GO categories "envelope" and "oxidoreductase activity" but the SAE transcripts did not. GO analysis of SAE transcripts identified the category "anatomical structure formation" that was not present in LEE-1 cells. Increased organelle compartments may exist within LEE-1 cells compared to SAE cells, and the higher oxidoreductase activity in LEE-1 cells may indicate a role for these cells in responses associated with innate immunity or in steroidogenesis. These EST libraries from elasmobranch cell lines provide information for assembly of genomic sequences and are useful in revealing gene diversity, new genes and molecular markers, as well as in providing means for elucidation of full-length cDNAs and probes for gene array analyses. This is the first study of this type with members of the Chondrichthyes. Copyright 2010 Elsevier Inc. All rights reserved.

Different sucrose-isomaltase response of Caco-2 cells to glucose and maltose suggests dietary maltose sensing

USDA-ARS?s Scientific Manuscript database

Using the small intestine enterocyte Caco-2 cell model, sucrase-isomaltase (SI, the mucosal alpha-glucosidase complex) expression and modification were examined relative to exposure to different mono- and disaccharide glycemic carbohydrates. Caco-2/TC7 cells were grown on porous supports to post-con...

Enterocyte loss of polarity and gut wound healing rely upon the F-actin-severing function of villin

USDA-ARS?s Scientific Manuscript database

Efficient wound healing is required to maintain the integrity of the intestinal epithelial barrier because of its constant exposure to a large variety of environmental stresses. This process implies a partial cell depolarization and the acquisition of a motile phenotype that involves rearrangements ...

Caecal absorption of vitexin-2-O-xyloside and its aglycone apigenin, in the rat

USDA-ARS?s Scientific Manuscript database

The in vivo bioavailability of the flavone-C-glycosides has been little studied compared to their O-glycoside analogues, which are both more common in nature and considered more easily hydrolyzed than C-glycosides, by enterocytes and gut microbiota. In this study, we used vitexin-2-O-xyloside (VOX),...

Mucosal maltase-glucoamylase plays a crucial role in starch digestion and prandial glucose homeostasis of mice

USDA-ARS?s Scientific Manuscript database

Starch is the major source of food glucose, and its digestion requires small intestinal alpha-glucosidic activities provided by the 2 soluble amylases and 4 enzymes bound to the mucosal surface of enterocytes. Two of these mucosal activities are associated with sucrase-isomaltase complex, while anot...

Effects of lactoferrin on the production of interferon-λ by the human intestinal epithelial cell line HT-29.

PubMed

Shin, Kouichirou; Oda, Hirotsugu; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2017-02-01

We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-λ (IFN-λ), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial cell line HT-29. HT-29 cell cultures were treated with LF for 1 h, and the cultures were stimulated with polyinosinic-polycytidylic acid (poly I:C). LF increased the concentration of IFN-λ in the culture supernatant after stimulation in a dose-dependent manner. A similar increase in the concentration of IFN-λ was observed in the supernatant of cells washed between treatment with LF and stimulation with poly I:C. At 6 and 24 h after stimulation with poly I:C (early and late phases, respectively) treated cultures contained significantly higher concentrations of IFN-λ1 in the culture supernatant, and significantly higher IFN-λ1 and IFN-λ2 mRNA levels, than controls. These results suggest that LF activates the innate cellular immunity of the enterocytes to double-stranded RNA and increases the production of IFN-λ.

Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

PubMed

Houtz, Philip; Bonfini, Alessandro; Liu, Xi; Revah, Jonathan; Guillou, Aurélien; Poidevin, Mickael; Hens, Korneel; Huang, Hsin-Yi; Deplancke, Bart; Tsai, Yu-Chen; Buchon, Nicolas

2017-11-01

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.

A single-chain fragment variable recombinant antibody against F5 fimbria of enterotoxigenic Escherichia coli inhibits agglutination of horse red blood cells induced by F5 protein.

PubMed

Bhaskaran, S; Jay, C M; Berghman, L R; Wagner, G G; Waghela, S D

2005-08-01

Bovine colibacillosis caused by enterotoxigenic Escherichia coli (ETEC) is a worldwide problem. Adhesion of ETEC to intestinal cell receptors mediated by the surface protein F5 fimbriae is the initial step in the establishment of colibacillosis. Prevention of ETEC F5(+) adhesion to enterocytes protects newborn calves against collibacillosis. On the enterocytes, the F5 fimbriae bind to a ganglioside that is also found on horse red blood cells. Thus, the presence of F5 fimbriae induces haemagglutination, which is useful as an indicator in a functional assay system. In this study, recombinant anti-F5 scFv antibody fragment produced in E. coli HB2151 reacted with F5 fimbriae in ELISA and Western immunoblot, and prevented haemagglutination induced by the binding of the F5 fimbriae to its natural host receptors on horse red blood cells. Given the ease with which recombinant antibodies can be mass-produced, the presently described scFv may hold promise as a prophylactic agent for colibacillosis.

Kefiran antagonizes cytopathic effects of Bacillus cereus extracellular factors.

PubMed

Medrano, Micaela; Pérez, Pablo Fernando; Abraham, Analía Graciela

2008-02-29

Kefiran, the polysaccharide produced by microorganisms present in kefir grains, is a water-soluble branched glucogalactan containing equal amounts of D-glucose and D-galactose. In this study, the effect of kefiran on the biological activity of Bacillus cereus strain B10502 extracellular factors was assessed by using cultured human enterocytes (Caco-2 cells) and human erythrocytes. In the presence of kefiran concentrations ranging from 300 to 1000 mg/L, the ability of B. cereus B10502 spent culture supernatants to detach and damage cultured human enterocytes was significantly abrogated. In addition, mitochondrial dehydrogenase activity was higher when kefiran was present during the cell toxicity assays. Protection was also demonstrated in hemolysis and apoptosis/necrosis assays. Scanning electron microscopy showed the protective effect of kefiran against structural cell damages produced by factors synthesized by B. cereus strain B10502. Protective effect of kefiran depended on strain of B. cereus. Our findings demonstrate the ability of kefiran to antagonize key events of B. cereus B10502 virulence. This property, although strain-specific, gives new perspectives for the role of bacterial exopolysaccharides in functional foods.

Effect of Lactobacillus plantarum Tennozu-SU2 on Salmonella Typhimurium Infection in Human Enterocyte-Like HT-29-Luc Cells and BALB/c Mice.

PubMed

Hirano, Shino; Yokota, Yasushi; Eda, Mika; Kuda, Takashi; Shikano, Ayane; Takahashi, Hajime; Kimura, Bon

2017-03-01

The probiotic properties and inhibitory effect on Salmonella Typhimurium adhesion on human enterocyte-like HT-29-Luc cells of three Lactobacillus plantarum strains isolated from fermented fish, beach sand and a coastal plant were determined. Compared with the type strain L. plantarum NBRC 15891 T , which was isolated from pickled cabbage, L. plantarum Tennozu-SU2 isolated from the acorn of a coastal tree showed high autoaggregation in de Man, Rogosa and Sharpe (MRS) broth and an antagonistic effect against S. Typhimurium in brain heart infusion (BHI) broth. Furthermore, heat-killed L. plantarum Tennozu-SU2 cells inhibited S. Typhimurium adhesion on HT-29-Luc cells. Both live and heat-killed L. plantarum Tennozu-SU2 cells showed an inhibitory effect on gut colonisation in BALB/c mice, as assessed by viable Salmonella count in faecal samples and by invasion into liver and spleen tissues. The properties shown in this study suggest that L. plantarum Tennozu-SU2 is useful as a starter and probiotic bacteria in functional food material.

Short bowel syndrome in infants: the critical role of luminal nutrients in a management program.

PubMed

Roy, Claude C; Groleau, Véronique; Bouthillier, Lise; Pineault, Marjolain; Thibault, Maxime; Marchand, Valérie

2014-07-01

Short bowel syndrome develops when the remnant mass of functioning enterocytes following massive resections cannot support growth or maintain fluid-electrolyte balance and requires parenteral nutrition. Resection itself stimulates the intestine's inherent ability to adapt morphologically and functionally. The capacity to change is very much related to the high turnover rate of enterocytes and is mediated by several signals; these signals are mediated in large part by enteral nutrition. Early initiation of enteral feeding, close clinical monitoring, and ongoing assessment of intestinal adaptation are key to the prevention of irreversible intestinal failure. The length of the functional small bowel remnant is the most important variable affecting outcome. The major objective of intestinal rehabilitation programs is to achieve early oral nutritional autonomy while maintaining normal growth and nutrition status and minimizing total parenteral nutrition related comorbidities such as chronic progressive liver disease. Remarkable progress has been made in terms of survivability and quality of life, especially in the context of coordinated multidisciplinary programs, but much work remains to be done.

Impairment of Swimming Motility by Antidiarrheic Lactobacillus acidophilus Strain LB Retards Internalization of Salmonella enterica Serovar Typhimurium within Human Enterocyte-Like Cells▿

PubMed Central

Liévin-Le Moal, Vanessa; Amsellem, Raymonde; Servin, Alain L.

2011-01-01

We report that both culture and the cell-free culture supernatant (CFCS) of Lactobacillus acidophilus strain LB (Lactéol Boucard) have the ability (i) to delay the appearance of Salmonella enterica serovar Typhimurium strain SL1344-induced mobilization of F-actin and, subsequently, (ii) to retard cell entry by S. Typhimurium SL1344. Time-lapse imaging and Western immunoblotting showed that S. Typhimurium SL1344 swimming motility, as represented by cell tracks of various types, was rapidly but temporarily blocked without affecting the expression of FliC flagellar propeller protein. We show that the product(s) secreted by L. acidophilus LB that supports the inhibitory activity is heat stable and of low molecular weight. The product(s) caused rapid depolarization of the S. Typhimurium SL1344 cytoplasmic membrane without affecting bacterial viability. We identified inhibition of swimming motility as a newly discovered mechanism by which the secreted product(s) of L. acidophilus strain LB retards the internalization of the diarrhea-associated pathogen S. enterica serovar Typhimurium within cultured human enterocyte-like cells. PMID:21825295

Mechanisms of digestion and absorption of dietary vitamin A.

PubMed

Harrison, Earl H

2005-01-01

Mechanisms involved in the digestion and absorption of dietary vitamin A require the participation of several proteins. Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase, and intestinal brush border enzyme, phospholipase B. Unesterified retinol taken up by the enterocyte is complexed with cellular retinol-binding protein type 2 and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). The retinyl esters are then incorporated into chylomicrons, intestinal lipoproteins containing other dietary lipids, such as triglycerides, phospholipids, and free and esterified cholesterol, and apolipoprotein B. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph. Although under normal dietary conditions much of the dietary vitamin A is absorbed via the chylomicron/lymphatic route, it is also clear that under some circumstances there is substantial absorption of unesterified retinol via the portal route. Evidence supports the idea that the cellular uptake and efflux of unesterified retinol by enterocytes is mediated by lipid transporters, but the exact number, identity, and role of these proteins is not known and is an active area of research.

Phosphate-dependent glutaminase in enterocyte mitochondria and its regulation by ammonium and other ions.

PubMed

Masola, B; Zvinavashe, E

2003-06-01

The effects of ammonium and other ions on phosphate dependent glutaminase (PDG) activity in intact rat enterocyte mitochondria were investigated. Sulphate and bicarbonate activated the enzyme in absence and presence of added phosphate. In presence of 10 mM phosphate, ammonium at concentrations <1 mM inhibited the enzyme. This inhibition was reversed by increased concentration of phosphate or sulphate. The inhibition of PDG by ammonium in presence of 10 mM phosphate was biphasic with respect to glutamine concentration, its effect being through a lowering of V(max) at glutamine concentration of

Optimization Evaluation: Lee Chemical Superfund Site, City Of Liberty, Clay County, Missouri

EPA Pesticide Factsheets

The Lee Chemical Superfund Site (site) is located along Missouri Highway 210 in Liberty, Missouri, approximately 15 miles east of Kansas City, Missouri. Currently, the site is a vacant lot of approximately2.5 acres in a flat alluvial plain.