EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS.

PubMed

Xiao, Guizhen; Yuan, Fangfang; Geng, Yan; Qiu, Xiaowen; Liu, Zhifeng; Lu, Jiefu; Tang, Liqun; Zhang, Yali; Su, Lei

2015-10-01

Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37°C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography-mass selective detector. Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells. Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.

Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells.

PubMed

Shao, Yuxin; Wolf, Patricia G; Guo, Shuangshuang; Guo, Yuming; Gaskins, H Rex; Zhang, Bingkun

2017-05-01

Zinc plays an important role in maintaining intestinal barrier function as well as modulating cellular signaling recognition and protein kinase activities. The phosphatidylinositol 3-kinase (PI3K) cascade has been demonstrated to affect intercellular integrity and tight junction (TJ) proteins. The current study investigated the hypothesis that zinc regulates intestinal intercellular junction integrity through the PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. A transwell model of Caco-2 cell was incubated with 0, 50 and 100 μM of zinc at various time points. Transepithelial electrical resistance (TEER), paracellular permeability, TJ proteins, cell proliferation, differentiation and cell damage were measured. Compared with controls, 50 and 100 μM of zinc increased cell growth at 6, 12 and 24 h and the expression of proliferating cell nuclear antigen at 24 h. Zinc (100 μM) significantly elevated TEER at 6-24 h and reduced TJ permeability at 24 h, accompanied by the up-regulation of alkaline phosphatase (AP) activity and zonula occludens (ZO)-1 expression. In addition, zinc (100 μM) affected the PI3K/AKT/mTOR pathway by stimulating phosphorylation of AKT and the downstream target mTOR. Inhibition of PI3K signaling by LY294002 counteracted zinc promotion, as shown by a decrease in AP activity, TEER, the abundance of ZO-1 and phosphorylation of AKT and mTOR. Additionally, TJ permeability and the expression of caspase-3 and LC3II (markers of cell damage) were increased by addition of PI3K inhibitor. In conclusion, the activation of PI3K/AKT/mTOR signaling by zinc is involved in improving intestinal barrier function by enhancing cell differentiation and expression of TJ protein ZO-1. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress.

PubMed

Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K; Nagaraja, Archana S; Dorniak, Piotr L; Pallikuth, Sandeep; Waters, Christopher M; Sood, Anil; Rao, RadhaKrishna

2017-02-20

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca 2+ by 1,2-bis-( o -aminophenoxy)ethane- N , N , N ', N '-tetraacetic acid. Knockdown of Ca V 1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N -Acetyl l-cysteine (NAC) and l- N G -Nitroarginine methyl ester (l-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and l-NAME also blocked stress-induced activation of c-Jun N -terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca 2+ , activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: protection by N-acetyl-l-cysteine

PubMed Central

Shukla, Pradeep K.; Gangwar, Ruchika; Manda, Bhargavi; Meena, Avtar S.; Yadav, Nikki; Szabo, Erzsebet; Balogh, Andrea; Lee, Sue Chin; Tigyi, Gabor

2016-01-01

The goals of this study were to evaluate the effects of ionizing radiation on apical junctions in colonic epithelium and mucosal barrier function in mice in vivo. Adult mice were subjected to total body irradiation (4 Gy) with or without N-acetyl-l-cysteine (NAC) feeding for 5 days before irradiation. At 2–24 h postirradiation, the integrity of colonic epithelial tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton was assessed by immunofluorescence microscopy and immunoblot analysis of detergent-insoluble fractions for TJ and AJ proteins. The barrier function was evaluated by measuring vascular-to-luminal flux of fluorescein isothiocyanate (FITC)-inulin in vivo and luminal-to-mucosal flux in vitro. Oxidative stress was evaluated by measuring protein thiol oxidation. Confocal microscopy showed that radiation caused redistribution of occludin, zona occludens-1, claudin-3, E-cadherin, and β-catenin, as well as the actin cytoskeleton as early as 2 h postirradiation, and this effect was sustained for at least 24 h. Feeding NAC before irradiation blocked radiation-induced disruption of TJ, AJ, and the actin cytoskeleton. Radiation increased mucosal permeability to inulin in colon, which was blocked by NAC feeding. The level of reduced-protein thiols in colon was depleted by radiation with a concomitant increase in the level of oxidized-protein thiol. NAC feeding blocked the radiation-induced protein thiol oxidation. These data demonstrate that radiation rapidly disrupts TJ, AJ, and the actin cytoskeleton by an oxidative stress-dependent mechanism that can be prevented by NAC feeding. PMID:26822914

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.

PubMed

Martínez, Cristina; Rodiño-Janeiro, Bruno K; Lobo, Beatriz; Stanifer, Megan L; Klaus, Bernd; Granzow, Martin; González-Castro, Ana M; Salvo-Romero, Eloisa; Alonso-Cotoner, Carmen; Pigrau, Marc; Roeth, Ralph; Rappold, Gudrun; Huber, Wolfgang; González-Silos, Rosa; Lorenzo, Justo; de Torres, Inés; Azpiroz, Fernando; Boulant, Steeve; Vicario, María; Niesler, Beate; Santos, Javier

2017-09-01

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin1

PubMed Central

Litkouhi, Babak; Kwong, Joseph; Lo, Chun-Min; Smedley, James G; McClane, Bruce A; Aponte, Margarita; Gao, Zhijian; Sarno, Jennifer L; Hinners, Jennifer; Welch, William R; Berkowitz, Ross S; Mok, Samuel C; Garner, Elizabeth I O

2007-01-01

Background Claudin-4, a tight junction (TJ) protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), is overexpressed in epithelial ovarian cancer (EOC). Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4-expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. Methods Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular) resistance (Rb) in EOC cells after claudin-4 silencing and after C-CPE treatment. Results Claudin-4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose- and claudin-4-dependent noncytotoxic manner. Conclusions C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies. PMID:17460774

Diadenosine tetraphosphate induces tight junction disassembly thus increasing corneal epithelial permeability

PubMed Central

Loma, P; Guzman-Aranguez, A; Pérez de Lara, M J; Pintor, J

2015-01-01

Background and Purpose Here, we have studied the effects of the dinucleotide P1, P4-Di (adenosine-5′) tetraphosphate (Ap4A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency. Experimental Approach Experiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4A (100 μM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y2 receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens-1 (ZO-1) staining. The hypotensive compound 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5-MCA-NAT, P2Y receptor antagonists and P2Y2 siRNAs. Key Results Two hours after Ap4A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y2 siRNAs. In vivo, topical application of Ap4A disrupted ZO-1 membrane distribution. 5-MCA-NAT levels in the aqueous humour were higher when Ap4A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y2 siRNA. Conclusions and Implications Ap4A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency. PMID:25297531

Filamin A Is a Regulator of Blood-Testis Barrier Assembly during Postnatal Development in the Rat Testis

PubMed Central

Su, Wenhui; Mruk, Dolores D.; Lie, Pearl P. Y.; Lui, Wing-yee

2012-01-01

The blood-testis barrier (BTB) is an important ultrastructure in the testis. A delay in its assembly during postnatal development leads to meiotic arrest. Also, a disruption of the BTB by toxicants in adult rats leads to a failure in spermatogonial differentiation. However, the regulation of BTB assembly remains unknown. Herein, filamin A, an actin filament cross-linker that is known to maintain and regulate cytoskeleton structure and function in other epithelia, was shown to be highly expressed during the assembly of Sertoli cell BTB in vitro and postnatal development of BTB in vivo, perhaps being used to maintain the actin filament network at the BTB. A knockdown of filamin A by RNA interference was found to partially perturb the Sertoli cell tight junction (TJ) permeability barrier both in vitro and in vivo. Interestingly, this down-regulating effect on the TJ barrier function after the knockdown of filamin A was associated with a mis-localization of both TJ and basal ectoplasmic specialization proteins. Filamin A knockdown also induced a disorganization of the actin filament network in Sertoli cells in vitro and in vivo. Collectively, these findings illustrate that filamin A regulates BTB assembly by recruiting these proteins to the microenvironment in the seminiferous epithelium to serve as the building blocks. In short, filamin A participates in BTB assembly by regulating protein recruitment during postnatal development in the rat testis. PMID:22872576

P-glycoprotein regulates blood–testis barrier dynamics via its effects on the occludin/zonula occludens 1 (ZO-1) protein complex mediated by focal adhesion kinase (FAK)

PubMed Central

Su, Linlin; Mruk, Dolores D.; Lui, Wing-Yee; Lee, Will M.; Cheng, C. Yan

2011-01-01

The blood–testis barrier (BTB), one of the tightest blood–tissue barriers in the mammalian body, creates an immune-privileged site for postmeiotic spermatid development to avoid the production of antibodies against spermatid-specific antigens, many of which express transiently during spermiogenesis and spermiation. However, the BTB undergoes extensive restructuring at stage VIII of the epithelial cycle to facilitate the transit of preleptotene spermatocytes and to prepare for meiosis. This action thus prompted us to investigate whether this stage can be a physiological window for the delivery of therapeutic and/or contraceptive drugs across the BTB to exert their effects at the immune-privileged site. Herein, we report findings that P-glycoprotein, an ATP-dependent efflux drug transporter and an integrated component of the occludin/zonula occludens 1 (ZO-1) adhesion complex at the BTB, structurally interacted with focal adhesion kinase (FAK), creating the occludin/ZO-1/FAK/P-glycoprotein regulatory complex. Interestingly, a knockdown of P-glycoprotein by RNAi was found to impede Sertoli cell BTB function, making the tight junction (TJ) barrier “leaky.” This effect was mediated by changes in the protein phosphorylation status of occludin via the action of FAK, thereby affecting the endocytic vesicle-mediated protein trafficking events that destabilized the TJ barrier. However, the silencing of P-glycoprotein, although capable of impeding drug transport across the BTB and TJ permeability barrier function, was not able to induce the BTB to be “freely” permeable to adjudin. These findings indicate that P-glycoprotein is involved in BTB restructuring during spermatogenesis but that P-glycoprotein–mediated restructuring does not “open up” the BTB to make it freely permeable to drugs. PMID:22106313

EMP-induced alterations of tight junction protein expression and disruption of the blood-brain barrier.

PubMed

Ding, Gui-Rong; Qiu, Lian-Bo; Wang, Xiao-Wu; Li, Kang-Chu; Zhou, Yong-Chun; Zhou, Yan; Zhang, Jie; Zhou, Jia-Xing; Li, Yu-Rong; Guo, Guo-Zhen

2010-07-15

The blood-brain barrier (BBB) is critical to maintain cerebral homeostasis. In this study, we examined the effects of exposure to electromagnetic pulse (EMP) on the functional integrity of BBB and, on the localization and expression of tight junction (TJ) proteins (occludin and ZO-1) in rats. Animals were sham or whole-body exposed to EMP at 200 kV/m for 400 pulses. The permeability of BBB in rat cerebral cortex was examined by using Evans Blue (EB) and lanthanum nitrate as vascular tracers. The localization and expression of TJ proteins were assessed by western blot and immunofluorescence analysis, respectively. The data indicated that EMP exposure caused: (i) increased permeability of BBB, and (ii) altered localization as well as decreased levels of TJ protein ZO-1. These results suggested that the alteration of ZO-1 may play an important role in the disruption of tight junctions, which may lead to dysfunction of BBB after EMP exposure. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice

PubMed Central

Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua

2012-01-01

AIM: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. METHODS: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. RESULTS: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). CONCLUSION: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway. PMID:22912548

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice.

PubMed

Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua

2012-08-14

To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.

Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and tight junctions with paracellular permselective barrier function.

PubMed

Tsukita, Sachiko; Katsuno, Tatsuya; Yamazaki, Yuji; Umeda, Kazuaki; Tamura, Atsushi; Tsukita, Shoichiro

2009-05-01

Tight junctions (TJs) create the primary permselective barrier to diffusion of solutes and ions through the paracellular pathway. The molecular architecture of TJs has gradually been unraveled in recent years, providing the basis for "barriology" (defined by Shoichiro Tsukita as the science of the barrier in multicellular organisms). Claudins are now considered to be the essential basic components of TJ strands, with which other integral membrane proteins, such as occludin, tricellulin, JAMs, and CAR, are associated. Peripherally associated scaffolding proteins are required for the organization of the integral membrane proteins. Among these, ZO-1, -2, and -3 have attracted a great deal of attention as TJ organizers, since ZO-1 (and in some cases, also ZO-2/3) was reported to be directly associated with claudins, occludin, and JAMs, as well as with AF-6/afadin and alpha-catenin. Here we summarize recent studies on ZO-1/2/3-deficiency in mice and cells, which have provided clear and important information regarding the functions of ZO-1/2/3 in vivo. In addition to the respective suppression of ZO-1/2/3 expression, simultaneous suppression of all three proteins has revealed the essential and nonessential in vivo roles of ZO-1/2 and ZO-3, respectively. ZO-3 shows an epithelial-specific TJ localization in a ZO-1/2-dependent fashion. ZO-1 and ZO-2 play pivotal roles in the final establishment of the belt-like adherens junctions (zonula adherens), followed by the formation of the belt-like TJs (zonula occludens) with paracellular barrier function, thereby providing the general basis for selective paracellular permeability in epithelial and endothelial cells.

A high-grain diet alters the omasal epithelial structure and expression of tight junction proteins in a goat model.

PubMed

Liu, Jun-Hua; Xu, Ting-Ting; Zhu, Wei-Yun; Mao, Sheng-Yong

2014-07-01

The omasal epithelial barrier plays important roles in maintaining nutrient absorption and immune homeostasis in ruminants. However, little information is currently available about the changes in omasal epithelial barrier function at the structural and molecular levels during feeding of a high-grain (HG) diet. Ten male goats were randomly assigned to two groups, fed either a hay diet (0% grain; n = 5) or HG diet (65% grain; n = 5). Changes in omasal epithelial structure and expression of tight junction (TJ) proteins were determined via electron microscopy and Western blot analysis. After 7 weeks on each diet, omasal contents in the HG group showed significantly lower pH (P <0.001) and significantly higher concentrations of free lipopolysaccharides (LPS; P = 0.001) than the hay group. The goats fed a HG diet showed profound alterations in omasal epithelial structure and TJ proteins, corresponding to depression of thickness of total epithelia, stratum granulosum, and the sum of the stratum spinosum and stratum basale, marked epithelial cellular damage, erosion of intercellular junctions and down-regulation in expression of the TJ proteins, claudin-4 and occludin. The study demonstrates that feeding a HG diet is associated with omasal epithelial cellular damage and changes in expression of TJ proteins. These research findings provide an insight into the possible significance of diet on the omasal epithelial barrier in ruminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier.

PubMed

Bowie, Rachel V; Donatello, Simona; Lyes, Clíona; Owens, Mark B; Babina, Irina S; Hudson, Lance; Walsh, Shaun V; O'Donoghue, Diarmuid P; Amu, Sylvie; Barry, Sean P; Fallon, Padraic G; Hopkins, Ann M

2012-04-15

Intestinal epithelial barrier disruption is a feature of inflammatory bowel disease (IBD), but whether barrier disruption precedes or merely accompanies inflammation remains controversial. Tight junction (TJ) adhesion complexes control epithelial barrier integrity. Since some TJ proteins reside in cholesterol-enriched regions of the cell membrane termed lipid rafts, we sought to elucidate the relationship between rafts and intestinal epithelial barrier function. Lipid rafts were isolated from Caco-2 intestinal epithelial cells primed with the proinflammatory cytokine interferon-γ (IFN-γ) or treated with methyl-β-cyclodextrin as a positive control for raft disruption. Rafts were also isolated from the ilea of mice in which colitis had been induced in conjunction with in vivo intestinal permeability measurements, and lastly from intestinal biopsies of ulcerative colitis (UC) patients with predominantly mild or quiescent disease. Raft distribution was analyzed by measuring activity of the raft-associated enzyme alkaline phosphatase and by performing Western blot analysis for flotillin-1. Epithelial barrier integrity was estimated by measuring transepithelial resistance in cytokine-treated cells or in vivo permeability to fluorescent dextran in colitic mice. Raft and nonraft fractions were analyzed by Western blotting for the TJ proteins occludin and zonula occludens-1 (ZO-1). Our results revealed that lipid rafts were disrupted in IFN-γ-treated cells, in the ilea of mice with subclinical colitis, and in UC patients with quiescent inflammation. This was not associated with a clear pattern of occludin or ZO-1 relocalization from raft to nonraft fractions. Significantly, a time-course study in colitic mice revealed that disruption of lipid rafts preceded the onset of increased intestinal permeability. Our data suggest for the first time that lipid raft disruption occurs early in the inflammatory cascade in murine and human colitis and, we speculate, may contribute to subsequent disruption of epithelial barrier function.

Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failure.

PubMed

Shimojima, Naoki; Eckman, Christopher B; McKinney, Michael; Sevlever, Daniel; Yamamoto, Satoshi; Lin, Wenlang; Dickson, Dennis W; Nguyen, Justin H

2008-01-01

Brain edema secondary to increased blood-brain barrier (BBB) permeability is a lethal complication in fulminant hepatic failure (FHF). Intact tight junctions (TJ) between brain capillary endothelial cells are critical for normal BBB function. However, the role of TJ in FHF has not been explored. We hypothesized that alterations in the composition of TJ proteins would result in increased BBB permeability in FHF. In this study, FHF was induced in C57BL/6J mice by using azoxymethane. BBB permeability was assessed with sodium fluorescein. Expression of TJ proteins was determined by Western blot, and their cellular distribution was examined using immunofluorescent microscopy. Comatose FHF mice had significant cerebral sodium fluorescein extravasation compared with control and precoma FHF mice, indicating increased BBB permeability. Western blot analysis showed a significant decrease in zonula occludens (ZO)-2 expression starting in the precoma stage. Immunofluorescent microscopy showed a significantly altered distribution pattern of ZO-2 in isolated microvessels from precoma FHF mice. These changes were more prominent in comatose FHF animals. Significant alterations in ZO-2 expression and distribution in the tight junctions preceded the increased BBB permeability in FHF mice. These results suggest that ZO-2 may play an important role in the pathogenesis of brain edema in FHF.

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

PubMed Central

Dörfel, Max Johannes; Huber, Otmar

2012-01-01

Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics. PMID:22315516

Fibroblast Growth Factor-Peptide Improves Barrier Function and Proliferation in Human Keratinocytes After Radiation

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

Zhang Kunzhong; Tian Yeping; Yin Liangjie

2011-09-01

Purpose: Epidermal keratinocytes, which can be severely damaged after ionizing radiation (IR), are rapid turnover cells that function as a barrier, protecting the host from pathogenic invasion and fluid loss. We tested fibroblast growth factor-peptide (FGF-P), a small peptide derived from the receptor-binding domain of FGF-2, as a potential mitigator of radiation effects via proliferation and the barrier function of keratinocytes. Methods and Materials: Keratinocytes isolated from neonatal foreskin were grown on transwells. After being exposed to 0, 5, or 10 Gy IR, the cells were treated with a vehicle or FGF-P. The permeability of IR cells was assessed bymore » using transepithelial electrical resistance (TEER) and a paracellular tracer flux of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) with Ussing chambers. The cell proliferation was measured with yellow tetrazolium salt (MTT) and tritiated thymidine ([{sup 3}H]-TdR) assays. The phosphorylation of extracellular signal-regulated kinases (ERK) was measured in an enzyme-linked immunosorbent (ELISA)-like assay, and the proteins related to tight junctions (TJ) and adherens junctions (AJ) were examined with Western blotting. We used a mouse model to assess the ability of FGF-P to promote the healing of skin {beta} burns created with a strontium applicator. Results: We found (1) FGF-P reduced the permeability of irradiated keratinocytes, as evidenced by increased TEER and decreased diffusion of FITC-BSA, both associated with the regulation of different proteins and levels of TJ and AJ; and (2) FGF-P enhanced the proliferation of irradiated keratinocytes, as evidenced by increased MTT activity and [{sup 3}H]-TdR incorporation, which was associated with activation of the ERK pathway; and (3) FGF-P promoted the healing of skin {beta} burns. Conclusions: FGF-P enhances the barrier function, including up-regulation of TJ proteins, increases proliferation of human keratinocytes, and accelerates the healing of skin {beta} burns. FGF-P is a promising mitigator that improves the proliferation and barrier function of keratinocytes after IR.« less

Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

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

Li, Zhao; Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu

2012-08-31

Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiacmore » TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.« less

Characterization of tight junction proteins in cultured human urothelial cells.

PubMed

Rickard, Alice; Dorokhov, Nikolay; Ryerse, Jan; Klumpp, David J; McHowat, Jane

2008-01-01

Tight junctions (TJs) are essential for normal function of epithelia, restricting paracellular diffusion and contributing to the maintenance of cell surface polarity. Superficial cells of the urothelium develop TJs, the basis for the paracellular permeability barrier of the bladder against diffusion of urinary solutes. Focusing on the superficial cell layer of stratified cell cultures of an immortalized human ureteral cell line, TEU-2 cells, we have examined the presence of TJ and TJ-associated proteins. TEU-2 cells were treated with calcium chloride and fetal bovine serum culture conditions used to induce stratification that resembles the normal transitional epithelial phenotype. Cultures were examined for TJ and TJ-associated proteins by confocal immunofluorescence microscopy and evaluated for TJ mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). TEU-2 cultures exhibited immunoreactivity at intercellular margins for claudins 1, 4, 5, 7, 14, and 16 whereas claudins 2, 8, and 12 were intracellular. RT-PCR corroborated the presence of these claudins at the mRNA level. The TJ-associated proteins occludin, JAM-1, and zonula occludens (ZO-1, ZO-2, and ZO-3) were localized at cell margins. We have found that numerous TJs and TJ-associated proteins are expressed in stratified TEU-2 cultures. Further, we propose TEU-2s provide a useful ureteral model for future studies on the involvement of TJs proteins in the normal and pathological physiology of the human urinary system.

Tight junctions form a barrier in porcine hair follicles.

PubMed

Mathes, Christiane; Brandner, Johanna M; Laue, Michael; Raesch, Simon S; Hansen, Steffi; Failla, Antonio V; Vidal, Sabine; Moll, Ingrid; Schaefer, Ulrich F; Lehr, Claus-Michael

2016-02-01

Follicular penetration has gained increasing interest regarding (i) safety concerns about (environmentally born) xenobiotics available to the hair follicle (HF), e.g. nanomaterials or allergens which should not enter the skin, and (ii) the possibility for non-invasive follicular drug and antigen delivery. However, not much is known about barriers in the HF which have to be surpassed upon uptake and/or penetration into surrounding tissue. Thus, aim of this work was a detailed investigation of this follicular barrier function, as well as particle uptake into the HF of porcine skin which is often used as a model system for human skin for such purposes. We show that follicular tight junctions (TJs) form a continuous barrier from the infundibulum down to the suprabulbar region, complementary to the stratum corneum in the most exposed upper follicular region, but remaining as the only barrier in the less accessible lower follicular regions. In the bulbar region of the HF no TJ barrier was found, demonstrating the importance of freely supplying this hair-forming part with e.g. nutrients or hormones from the dermal microenvironment. Moreover, the dynamic character of the follicular TJ barrier was shown by modulating its permeability using EDTA. After applying polymeric model-nanoparticles (154 nm) to the skin, transmission electron microscopy revealed that the majority of the particles were localized in the upper part of the HF where the double-barrier is present. Only few penetrated deeper, reaching regions where TJs act as the only barrier, and no particles were observed in the bulbar, barrier-less region. Lastly, the equivalent expression and distribution of TJ proteins in human and porcine HF further supports the suitability of porcine skin as a predictive model to study the follicular penetration and further biological effects of dermally applied nanomaterials in humans. Copyright © 2016 Elsevier GmbH. All rights reserved.

Hybrid Tunnel Junction-Graphene Transparent Conductive Electrodes for Nitride Lateral Light Emitting Diodes.

PubMed

Wang, Liancheng; Cheng, Yan; Liu, Zhiqiang; Yi, Xiaoyan; Zhu, Hongwei; Wang, Guohong

2016-01-20

Graphene transparent conductive electrode (TCE) applications in nitride light emitting diodes (LEDs) are still limited by the large contact resistance and interface barrier between graphene and p-GaN. We propose a hybrid tunnel junction (TJ)-graphene TCE approach for nitride lateral LEDs theoretically and experimentally. Through simulation using commercial advanced physical models of semiconductor devices (APSYS), we found that low tunnel resistance can be achieved in the n(+)-GaN/u-InGaN/p(+)-GaN TJ, which has a lower tunneling barrier and an enhanced electric field due to the polarization effect. Graphene TCEs and hybrid graphene-TJ TCEs are then modeled. The designed hybrid TJ-graphene TCEs show sufficient current diffusion length (Ls), low introduced series resistance, and high transmittance. The assembled TJ LED with the triple-layer graphene (TLG) TCEs show comparable optoelectrical performance (3.99 V@20 mA, LOP = 10.8 mW) with the reference LED with ITO TCEs (3.36 V@20 mA, LOP = 12.6 mW). The experimental results further prove that the TJ-graphene structure can be successfully incorporated as TCEs for lateral nitride LEDs.

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

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

Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2)more » after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP2A/MMP-2 induced PCB153-induced dysfunction of occludin. • Disrupted lipid rafts modulated PCB153-induced increase of permeability. • Lipid rafts act as a signaling platform for PCB153-induced dysfunction of occludin.« less

Regulation of blood-testis barrier dynamics by desmosome, gap junction, hemidesmosome and polarity proteins

PubMed Central

Wong, Elissa WP; Lie, Pearl PY; Li, Michelle WM; Mruk, Dolores D; Yan, Helen HN; Mok, Ka-Wai; Mannu, Jayakanthan; Mathur, Premendu P; Lui, Wing-yee; Lee, Will M; Bonanomi, Michele; Silvestrini, Bruno

2011-01-01

The blood-testis barrier (BTB) is a unique ultrastructure in the mammalian testis. Unlike other blood-tissue barriers, such as the blood-brain barrier and the blood-ocular (or blood-retina) barrier which formed by tight junctions (TJ) between endothelial cells of the microvessels, the BTB is constituted by coexisting TJ, basal ectoplasmic specialization (basal ES), desmosomes and gap junctions between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. The BTB also divides the seminiferous epithelium into the apical (or adluminal) and basal compartments so that meiosis I and II and post-meiotic germ cell development can all take place in a specialized microenvironment in the apical compartment behind the BTB. While the unusual anatomical features of the BTB have been known for decades, the physiological function of the coexisting junctions, in particular the desmosome and gap junction, that constitute the BTB was unknown until recently. Based on recently published findings, we critically evaluate the role of the desmosome and gap junction that serve as a signaling platform to coordinate the “opening” and “closing” of the TJ-permeability barrier conferred by TJ and basal ES during the seminiferous epithelial cycle of spermatogenesis. This is made possible by polarity proteins working in concert with nonreceptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and c-Src, at the site to regulate endosome-mediated protein trafficking events (e.g., endocytosis, transcytosis, recycling or protein degradation). These events not only serve to destabilize the existing “old” BTB above preleptotene spermatocytes in transit in “clones” at the BTB, but also contribute to the assembly of “new” BTB below the transiting spermatocytes. Furthermore, hemidesmosomes at the Sertoli cell-basement membrane interface also contribute to the BTB restructuring events at stage VIII of the epithelial cycle. Additionally, the findings that a gap junction at the BTB provides a possible route for the passage of toxicants [e.g., bisphenol A (BPA)] and potential male contraceptives (e.g., adjudin) across the BTB also illustrate that these coexisting junctions, while helpful to maintain the immunological barrier integrity during the transit of spermatocytes, can be the “gateway” to making the BTB so vulnerable to toxicants and/or chemicals, causing male reproductive dysfunction. PMID:22319658

Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

PubMed

Robinson, J M; Henderson, W A

2018-01-12

We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function

PubMed Central

Muenyi, Clarisse S.; Carrion, Sandra Leon; Jones, Lynn A.; Kennedy, Lawrence H.; Slominski, Andrzej T.

2014-01-01

Background: Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis. Objective: We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB. Methods: Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 μg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day (E) 15, E16, E17, and postnatal day (PND) 1. Results: A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification, and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, with increased dye leakage at the terminal claudin-1–staining TJs of the stratum granulosum. Because the animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group. Conclusions: These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial TJ integrity, and atopic disease. Citation: Muenyi CS, Leon Carrion S, Jones LA, Kennedy LH, Slominski AT, Sutter CH, Sutter TR. 2014. Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin on epidermal permeability barrier development and function. Environ Health Perspect 122:1052–1058; http://dx.doi.org/10.1289/ehp.1308045 PMID:24904982

Bifidobacterium animalis ssp. lactis CNCM-I2494 Restores Gut Barrier Permeability in Chronically Low-Grade Inflamed Mice.

PubMed

Martín, Rebeca; Laval, Laure; Chain, Florian; Miquel, Sylvie; Natividad, Jane; Cherbuy, Claire; Sokol, Harry; Verdu, Elena F; van Hylckama Vlieg, Johan; Bermudez-Humaran, Luis G; Smokvina, Tamara; Langella, Philippe

2016-01-01

Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4(+) lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4(+) Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability.

Visceral adipose tissue and leptin increase colonic epithelial tight junction permeability via a RhoA-ROCK-dependent pathway.

PubMed

Le Dréan, Gwenola; Haure-Mirande, Vianney; Ferrier, Laurent; Bonnet, Christian; Hulin, Philippe; de Coppet, Pierre; Segain, Jean-Pierre

2014-03-01

Proinflammatory cytokines produced by immune cells play a central role in the increased intestinal epithelial permeability during inflammation. Expansion of visceral adipose tissue (VAT) is currently considered a consequence of intestinal inflammation. Whether VAT per se plays a role in early modifications of intestinal barrier remains unknown. The aim of this study was to demonstrate the direct role of adipocytes in regulating paracellular permeability of colonic epithelial cells (CECs). We show in adult rats born with intrauterine growth retardation, a model of VAT hypertrophy, and in rats with VAT graft on the colon, that colonic permeability was increased without any inflammation. This effect was associated with altered expression of tight junction (TJ) proteins occludin and ZO-1. In coculture experiments, adipocytes decreased transepithelial resistance (TER) of Caco-2 CECs and induced a disorganization of ZO-1 on TJs. Intraperitoneal administration of leptin to lean rats increased colonic epithelial permeability and altered ZO-1 expression and organization. Treatment of HT29-19A CECs with leptin, but not adiponectin, dose-dependently decreased TER and altered TJ and F-actin cytoskeleton organization through a RhoA-ROCK-dependent pathway. Our data show that adipocytes and leptin directly alter TJ function in CECs and suggest that VAT could impair colonic epithelial barrier.

Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

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

Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.

2010-07-02

The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors ormore » siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.« less

Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

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

Imamura, Masafumi; Department of Pathology, Sapporo Medical University School of Medicine, S1. W17. Sapporo 060-8556; Kojima, Takashi

2007-05-15

In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions inmore » fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi.« less

Could tight junctions regulate the barrier function of the aged skin?

PubMed

Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš

2016-03-01

The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

“You Shall Not Pass”—tight junctions of the blood brain barrier

PubMed Central

Bauer, Hans-Christian; Krizbai, István A.; Bauer, Hannelore; Traweger, Andreas

2014-01-01

The structure and function of the barrier layers restricting the free diffusion of substances between the central nervous system (brain and spinal cord) and the systemic circulation is of great medical interest as various pathological conditions often lead to their impairment. Excessive leakage of blood-borne molecules into the parenchyma and the concomitant fluctuations in the microenvironment following a transient breakdown of the blood-brain barrier (BBB) during ischemic/hypoxic conditions or because of an autoimmune disease are detrimental to the physiological functioning of nervous tissue. On the other hand, the treatment of neurological disorders is often hampered as only minimal amounts of therapeutic agents are able to penetrate a fully functional BBB or blood cerebrospinal fluid barrier. An in-depth understanding of the molecular machinery governing the establishment and maintenance of these barriers is necessary to develop rational strategies allowing a controlled delivery of appropriate drugs to the CNS. At the basis of such tissue barriers are intimate cell-cell contacts (zonulae occludentes, tight junctions) which are present in all polarized epithelia and endothelia. By creating a paracellular diffusion constraint TJs enable the vectorial transport across cell monolayers. More recent findings indicate that functional barriers are already established during development, protecting the fetal brain. As an understanding of the biogenesis of TJs might reveal the underlying mechanisms of barrier formation during ontogenic development numerous in vitro systems have been developed to study the assembly and disassembly of TJs. In addition, monitoring the stage-specific expression of TJ-associated proteins during development has brought much insight into the “developmental tightening” of tissue barriers. Over the last two decades a detailed molecular map of transmembrane and cytoplasmic TJ-proteins has been identified. These proteins not only form a cell-cell adhesion structure, but integrate various signaling pathways, thereby directly or indirectly impacting upon processes such as cell-cell adhesion, cytoskeletal rearrangement, and transcriptional control. This review will provide a brief overview on the establishment of the BBB during embryonic development in mammals and a detailed description of the ultrastructure, biogenesis, and molecular composition of epithelial and endothelial TJs will be given. PMID:25520612

Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis.

PubMed

Pradhan-Sundd, Tirthadipa; Zhou, Lili; Vats, Ravi; Jiang, An; Molina, Laura; Singh, Sucha; Poddar, Minakshi; Russell, Jacquelyn; Stolz, Donna B; Oertel, Michael; Apte, Udayan; Watkins, Simon; Ranganathan, Sarangarajan; Nejak-Bowen, Kari N; Sundd, Prithu; Monga, Satdarshan Pal

2018-06-01

β-Catenin, the downstream effector of the Wnt signaling, plays important roles in hepatic development, regeneration, and tumorigenesis. However, its role at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly due to spontaneous compensation by γ-catenin. We simultaneously ablated β- and γ-catenin expression in mouse liver by interbreeding β-catenin-γ-catenin double-floxed mice and Alb-Cre transgenic mice. Double knockout mice show failure to thrive, impaired hepatocyte differentiation, cholemia, ductular reaction, progressive cholestasis, inflammation, fibrosis, and tumorigenesis, which was associated with deregulation of tight junctions (TJ) and bile acid transporters, leading to early morbidity and mortality, a phenotype reminiscent of progressive familial intrahepatic cholestasis (PFIC). To address the mechanism, we specifically and temporally eliminated both catenins from hepatocytes using adeno-associated virus 8 carrying Cre-recombinase under the thyroid-binding globulin promoter (AAV8-TBG-Cre). This led to a time-dependent breach of the blood-biliary barrier associated with sequential disruption of AJ and TJ verified by ultrastructural imaging and intravital microscopy, which revealed unique paracellular leaks around individual hepatocytes, allowing mixing of blood and bile and leakage of blood from one sinusoid to another. Molecular analysis identified sequential losses of E-cadherin, occludin, claudin-3, and claudin-5 due to enhanced proteasomal degradation, and of claudin-2, a β-catenin transcriptional target, which was also validated in vitro. We report partially redundant function of catenins at AJ in regulating TJ and contributing to the blood-biliary barrier. Furthermore, concomitant hepatic loss of β- and γ-catenin disrupts structural and functional integrity of AJ and TJ via transcriptional and posttranslational mechanisms. Mice with dual catenin loss develop progressive intrahepatic cholestasis, providing a unique model to study diseases such as PFIC. (Hepatology 2018;67:2320-2337). © 2017 by the American Association for the Study of Liver Diseases.

Mammalian target of rapamycin complex (mTOR) pathway modulates blood-testis barrier (BTB) function through F-actin organization and gap junction

PubMed Central

Li, Nan; Cheng, C. Yan

2016-01-01

mTOR (mammalian target of rapamycin) is one of the most important signaling molecules in mammalian cells which regulates an array of cellular events, ranging from cell metabolism to cell proliferation. Based on the association of mTOR with the core component proteins, such as Raptor or Rictor, mTOR can become the mTORC1 (mammalian target of rapamycin complex 1) or mTORC2, respectively. Studies have shown that during the epithelial cycle of spermatogenesis, mTORC1 promotes remodeling and restructuring of the blood-testis barrier (BTB) in vitro and in vivo, making the Sertoli cell tight junction (TJ)-permeability barrier “leaky”; whereas mTORC2 promotes BTB integrity, making the Sertoli cell TJ-barrier “tighter”. These contrasting effects, coupled with the spatiotemporal expression of the core signaling proteins at the BTB that confer the respective functions of mTORC1 vs. mTORC2 thus provide a unique mechanism to modulate BTB dynamics, allowing or disallowing the transport of biomolecules and also preleptotene spermatocytes across the immunological barrier. More importantly, studies have shown that these changes to BTB dynamics conferred by mTORC1 and mTORC2 are mediated by changes in the organization of the actin microfilament networks at the BTB, and involve gap junction (GJ) intercellular communication. Since GJ has recently been shown to be crucial to reboot spermatogenesis and meiosis following toxicant-induced aspermatogenesis, these findings thus provide new insightful information regarding the integration of mTOR and GJ to regulate spermatogenesis. PMID:26957088

Modeling Tight Junction Dynamics and Oscillations

PubMed Central

Kassab, Fuad; Marques, Ricardo Paulino; Lacaz-Vieira, Francisco

2002-01-01

Tight junction (TJ) permeability responds to changes of extracellular Ca2+ concentration. This can be gauged through changes of the transepithelial electrical conductance (G) determined in the absence of apical Na+. The early events of TJ dynamics were evaluated by the fast Ca2+ switch assay (FCSA) (Lacaz-Vieira, 2000), which consists of opening the TJs by removing basal calcium (Ca2+ bl) and closing by returning Ca2+ bl to normal values. Oscillations of TJ permeability were observed when Ca2+ bl is removed in the presence of apical calcium (Ca2+ ap) and were interpreted as resulting from oscillations of a feedback control loop which involves: (a) a sensor (the Ca2+ binding sites of zonula adhaerens), (b) a control unit (the cell signaling machinery), and (c) an effector (the TJs). A mathematical model to explain the dynamical behavior of the TJs and oscillations was developed. The extracellular route (ER), which comprises the paracellular space in series with the submucosal interstitial fluid, was modeled as a continuous aqueous medium having the TJ as a controlled barrier located at its apical end. The ER was approximated as a linear array of cells. The most apical cell is separated from the apical solution by the TJ and this cell bears the Ca2+ binding sites of zonula adhaerens that control the TJs. According to the model, the control unit receives information from the Ca2+ binding sites and delivers a signal that regulates the TJ barrier. Ca2+ moves along the ER according to one-dimensional diffusion following Fick's second law. Across the TJ, Ca2+ diffusion follows Fick's first law. Our first approach was to simulate the experimental results in a semiquantitative way. The model tested against experiment results performed in the frog urinary bladder adequately predicts the responses obtained in different experimental conditions, such as: (a) TJ opening and closing in a FCSA, (b) opening by the presence of apical Ca2+ and attainment of a new steady-state, (c) the escape phase which follows the halt of TJ opening induced by apical Ca2+, (d) the oscillations of TJ permeability, and (e) the effect of Ca2+ ap concentration on the frequency of oscillations. PMID:12149284

Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers.

PubMed

DiGuilio, K M; Valenzano, M C; Rybakovsky, E; Mullin, J M

2018-01-05

Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of "chemical hypoxia" to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals. Transepithelial electrical resistance and transepithelial diffusion of 14 C-D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports. Western immunoblot analyses of integral tight junctional proteins (occludin and claudins) are used as further indicators of barrier function change. Cobalt, an inhibitor of the prolyl hydroxylase enzymes governing HIF-1α breakdown in the cell, induces transepithelial leakiness in CaCo-2 BBe cell layers in a time and concentration-dependent manner. This increased leakiness is accompanied by significant changes in certain specific integral tight junctional (TJ) proteins such as a decreased level of occludin and increased level of claudin-5. Similar results regarding barrier function compromise also occur with other chemical inhibitors of HIF-1α breakdown, namely ciclopiroxolamine (CPX) and dimethyloxalylglycine (DMOG). The increased leak is manifested by both decreased transepithelial electrical resistance (R t ) and increased paracellular diffusion of D-mannitol (J m ). The induced transepithelial leak shows significant size selectivity, consistent with induced effects on TJ permeability. Less-differentiated cell layers were significantly more affected than well-differentiated cell layers regarding induced transepithelial leak. A genetically modified CaCo-2 variant with reduced levels of HIF-1β, showed reduced transepithelial leak in response to cobalt exposure, further indicating that elevation of HIF-1α levels induced by agents of "chemical hypoxia" is responsible for the compromised barrier function of the CaCo-2 BBe cell layers. Exposure to inducers of chemical hypoxia elevated HIF-1α levels and increased transepithelial leak. The degree of epithelial differentiation has significant effects on this action, possibly explaining the varying effects of HIF-1 modulation in epithelial and endothelial barrier function in different physiological and pathophysiological conditions.

Phosphorylation of the Tight Junction Protein Occludin Regulates Epithelial Monolayer Proliferation and Maturation

NASA Astrophysics Data System (ADS)

Bolinger, Mark Thomas

Barriers against the external environment are crucial for sustaining life in multicellular organisms, and form following convergent growth and development of cell-cell junctions. At least four types of epithelial cell-cell junctions exist, the most apical of which is known as the tight junction (TJ). A specific transmembrane protein known as occludin is highly phosphorylated on its C-terminal coiled-coil, and certain sites have been found to regulate specific aspects of TJ function, including the response to certain cytokines. Previously, our lab discovered a novel phosphosite at serine 471 that is located at a contact site with an important central organizer of the TJ, zonula occludens-1. Phosphoinhibitory, serine to alanine (S471A) occludin point mutant MDCK cell lines demonstrate that S471A monolayers are poorly organized compared to WT occludin (WT Occ) or phosphomimetic, serine to aspartic acid (S471D) lines. Additionally, S471A monolayers are composed of fewer, larger cells than controls, and exhibit proliferative arrest almost immediately following confluency, in contrast to control lines, which go through at least one additional round of proliferation. This phenotype can be recapitulated with a cell cycle inhibitor, demonstrating that confluent proliferation or cell packing is necessary for barrier maturation. G-protein coupled receptor kinase (GRK) was confirmed to be an S471 kinase by inhibitor experiments from a bioinformatically compiled candidate kinase list, and GRK inhibitors were able to recapitulate the phenotype of S471A lines. Finally, S471A expression perturbed purified coiled-coil stability as determined by NMR. Modeling of inter-coil interactions identified several possible hydrogen bonds that differ between the phosphorylated and non-phosphorylated forms. Expression of S471N (asparagine) transgenic occludin in vitro demonstrated highly organized border organization despite the lack of a negative charge at the S471 position. This result suggests that the border organization of p-S471 is not due to the negative charge at S471, and may be the result of differential intra-coil hydrogen bonding. In conclusion, cell packing is necessary for barrier maturation, and is regulated by the novel phosphosite, occludin S471. S471 is an important contributor to confluent proliferation, monolayer maturation, and barrier resistance, and plays a role in the barrier regulatory function of occludin.

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

NASA Astrophysics Data System (ADS)

Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

2016-07-01

Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury.

PubMed

Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei

2013-01-01

Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells.

PubMed

Appelt-Menzel, Antje; Cubukova, Alevtina; Günther, Katharina; Edenhofer, Frank; Piontek, Jörg; Krause, Gerd; Stüber, Tanja; Walles, Heike; Neuhaus, Winfried; Metzger, Marco

2017-04-11

In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm 2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Fermented Herbal Formulas KIOM-MA128 Ameliorate IL-6-Induced Intestinal Barrier Dysfunction in Colon Cancer Cell Line

PubMed Central

Park, Kwang Il; Kim, Dong Gun; Lee, Bo Hyoung

2016-01-01

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD increases the risk of colorectal cancer (CRC), depending on the extent and duration of intestinal inflammation. Increased IL-6 expression has been reported in IBD patients, which may be associated with intestinal barrier function through discontinuous tight junction (TJ). KIOM-MA is a specific agent for allergic diseases and cancer, and it is composed of several plants; these herbs have been used in traditional oriental medicine. We fermented KIOM-MA, the product of KIOM-MA128, using probiotics to improve the therapeutic efficacy via the absorption and bioavailability of the active ingredients. In this study, we demonstrated that KIOM-MA/MA128 exhibited anticolitis effects via the modulation of TJ protein. Interleukin-6 resulted in a dose-dependent decrease in the TER and an increase in the FITC-dextran permeability; however, pretreatment with 400 µg/ml KIOM-MA/MA128 resulted in a significant increase in the TER and a decrease in the FITC-dextran permeability via IL-6 induction. Furthermore, protein and mRNA TJ levels remained stable after pretreatment with 400 µg/ml KIOM-MA/MA128. Moreover, KIOM-MA/MA128 suppressed the expression of PLCγ1 and PKC. Taken together, these findings suggest novel information and clue of the anticolitis effects of KIOM-MA128 via regulation of tight junction. PMID:27980357

Fermented Herbal Formulas KIOM-MA128 Ameliorate IL-6-Induced Intestinal Barrier Dysfunction in Colon Cancer Cell Line.

PubMed

Park, Kwang Il; Kim, Dong Gun; Lee, Bo Hyoung; Ma, Jin Yeul

2016-01-01

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD increases the risk of colorectal cancer (CRC), depending on the extent and duration of intestinal inflammation. Increased IL-6 expression has been reported in IBD patients, which may be associated with intestinal barrier function through discontinuous tight junction (TJ). KIOM-MA is a specific agent for allergic diseases and cancer, and it is composed of several plants; these herbs have been used in traditional oriental medicine. We fermented KIOM-MA, the product of KIOM-MA128, using probiotics to improve the therapeutic efficacy via the absorption and bioavailability of the active ingredients. In this study, we demonstrated that KIOM-MA/MA128 exhibited anticolitis effects via the modulation of TJ protein. Interleukin-6 resulted in a dose-dependent decrease in the TER and an increase in the FITC-dextran permeability; however, pretreatment with 400  µ g/ml KIOM-MA/MA128 resulted in a significant increase in the TER and a decrease in the FITC-dextran permeability via IL-6 induction. Furthermore, protein and mRNA TJ levels remained stable after pretreatment with 400  µ g/ml KIOM-MA/MA128. Moreover, KIOM-MA/MA128 suppressed the expression of PLC γ 1 and PKC. Taken together, these findings suggest novel information and clue of the anticolitis effects of KIOM-MA128 via regulation of tight junction.

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis.

PubMed

Pfeiffer, Friederike; Schäfer, Julia; Lyck, Ruth; Makrides, Victoria; Brunner, Sarah; Schaeren-Wiemers, Nicole; Deutsch, Urban; Engelhardt, Britta

2011-11-01

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed.

Single-joint outcome measures: preliminary validation of patient-reported outcomes and physical examination.

PubMed

Heald, Alison E; Fudman, Edward J; Anklesaria, Pervin; Mease, Philip J

2010-05-01

To assess the validity, responsiveness, and reliability of single-joint outcome measures for determining target joint (TJ) response in patients with inflammatory arthritis. Patient-reported outcomes (PRO), consisting of responses to single questions about TJ global status on a 100-mm visual analog scale (VAS; TJ global score), function on a 100-mm VAS (TJ function score), and pain on a 5-point Likert scale (TJ pain score) were piloted in 66 inflammatory arthritis subjects in a phase 1/2 clinical study of an intraarticular gene transfer agent and compared to physical examination measures (TJ swelling, TJ tenderness) and validated function questionnaires (Disabilities of the Arm, Shoulder and Hand scale, Rheumatoid Arthritis Outcome Score, and the Health Assessment Questionnaire). Construct validity was assessed by evaluating the correlation between the single-joint outcome measures and validated function questionnaires using Spearman's rank correlation. Responsiveness or sensitivity to change was assessed through calculating effect size and standardized response means (SRM). Reliability of physical examination measures was assessed by determining interobserver agreement. The single-joint PRO were highly correlated with each other and correlated well with validated functional measures. The TJ global score exhibited modest effect size and modest SRM that correlated well with the patient's assessment of response on a 100-mm VAS. Physical examination measures exhibited high interrater reliability, but correlated less well with validated functional measures and the patient's assessment of response. Single-joint PRO, particularly the TJ global score, are simple to administer and demonstrate construct validity and responsiveness in patients with inflammatory arthritis. (ClinicalTrials.gov identifier NCT00126724).

Protective effects of Lactobacillus plantarum against epithelial barrier dysfunction of human colon cell line NCM460

PubMed Central

Liu, Zhi-Hua; Shen, Tong-Yi; Zhang, Peng; Ma, Yan-Lei; Moyer, Mary Pat; Qin, Huan-Long

2010-01-01

AIM: To investigate the effects of Lactobacillus plantarum (L. plantarum) in the intestinal permeability and expression of tight junction (TJ) using the normal human colon cell line NCM460. METHODS: Paracellular permeability of NCM460 monolayers was determined by transepithelial electrical resistance and dextran permeability. Expression of TJ proteins in NCM460 cell monolayers was detected by Western blotting and quantitative real-time polymerase chain reaction. RESULTS: L. plantarum played an important role in increasing transepithelial electrical resistance and decreasing the permeability to macromolecules of NCM460 monolayers against the disruption caused by enteropathogenic Escherichia coli (E. coli) or enteroinvasive E. coli. L. plantarum also prevented the decrease in the expression of TJ proteins and F-actin in NCM460 cells. CONCLUSION: L. plantarum can protect against dysfunction of NCM460 intestinal epithelial barrier caused by enteropathogenic E. coli or enteroinvasive E. coli, and thus can be a potential candidate of therapeutic agents for the treatment of intestinal diseases. PMID:21128328

Claudins in teleost fishes

PubMed Central

Kolosov, Dennis; Bui, Phuong; Chasiotis, Helen; Kelly, Scott P

2013-01-01

Teleost fishes are a large and diverse animal group that represent close to 50% of all described vertebrate species. This review consolidates what is known about the claudin (Cldn) family of tight junction (TJ) proteins in teleosts. Cldns are transmembrane proteins of the vertebrate epithelial/endothelial TJ complex that largely determine TJ permeability. Cldns achieve this by expressing barrier or pore forming properties and by exhibiting distinct tissue distribution patterns. So far, ~63 genes encoding for Cldn TJ proteins have been reported in 16 teleost species. Collectively, cldns (or Cldns) are found in a broad array of teleost fish tissues, but select genes exhibit restricted expression patterns. Evidence to date strongly supports the view that Cldns play a vital role in the embryonic development of teleost fishes and in the physiology of tissues and organ systems studied thus far. PMID:24665402

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

PubMed Central

Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

2016-01-01

Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction. PMID:27436542

Cross-over endocytosis of claudins is mediated by interactions via their extracellular loops.

PubMed

Gehne, Nora; Lamik, Agathe; Lehmann, Martin; Haseloff, Reiner F; Andjelkovic, Anuska V; Blasig, Ingolf E

2017-01-01

Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, the mechanisms allowing TJ remodeling while maintaining barrier integrity are largely unknown. Cldns and occludin are heterophilically and homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed the presence of Cldns in these vesicles and revealed a distinct separation of Cldns derived from opposing cells within cross-over endocytosed vesicles. Colocalization of cross-over endocytosed Cldn with the autophagosome markers as well as inhibition of autophagosome biogenesis verified involvement of the autophagosomal pathway. Accordingly, cross-over endocytosed Cldns underwent lysosomal degradation as indicated by lysosome markers. Cross-over endocytosis of Cldn5 depended on clathrin and caveolin pathways but not on dynamin. Cross-over endocytosis also depended on Cldn-Cldn-interactions. Amino acid substitutions in the second extracellular loop of Cldn5 (F147A, Q156E) caused impaired cis- and trans-interaction, as well as diminished cross-over endocytosis. Moreover, F147A exhibited an increased mobility in the membrane, while Q156E was not as mobile but enhanced the paracellular permeability. In conclusion, the endocytosis of TJ proteins depends on their ability to interact strongly with each other in cis and trans, and the mobility of Cldns in the membrane is not necessarily an indicator of barrier permeability. TJ-remodeling via cross-over endocytosis represents a general mechanism for the degradation of transmembrane proteins in cell-cell contacts and directly links junctional membrane turnover to autophagy.

Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam

PubMed Central

Panchal, Trupti; Chen, Xi; Poon, James; Kouptsova, Jane

2017-01-01

Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2–3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N) pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors. PMID:28542174

Cardiotonic steroid ouabain stimulates expression of blood-testis barrier proteins claudin-1 and -11 and formation of tight junctions in Sertoli cells.

PubMed

Dietze, Raimund; Shihan, Mazen; Stammler, Angelika; Konrad, Lutz; Scheiner-Bobis, Georgios

2015-04-15

The interaction of ouabain with the sodium pump induces signalling cascades resembling those triggered by hormone/receptor interactions. In the rat Sertoli cell line 93RS2, ouabain at low concentrations stimulates the c-Src/c-Raf/Erk1/2 signalling cascade via its interaction with the α4 isoform of the sodium pump expressed in these cells, leading to the activation of the transcription factor CREB. As a result of this signalling sequence, ouabain stimulates expression of claudin-1 and claudin-11, which are also controlled by a CRE promoter. Both of these proteins are known to be essential constituents of tight junctions (TJ) between Sertoli cells, and as a result of the ouabain-induced signalling TJ formation between neighbouring Sertoli cells is significantly enhanced by the steroid. Thus, ouabain-treated cell monolayers display higher transepithelial resistance and reduced free diffusion of FITC-coupled dextran in tracer diffusion assays. Taking into consideration that the formation of TJ is indispensable for the maintenance of the blood-testis barrier (BTB) and therefore for male fertility, the actions of ouabain described here and the fact that this and other related cardiotonic steroids (CTS) are produced endogenously suggest a direct influence of ouabain/sodium pump interactions on the maintenance of the BTB and thereby an effect on male fertility. Since claudin-1 and claudin-11 are also present in other blood-tissue barriers, one can speculate that ouabain and perhaps other CTS influence the dynamics of these barriers as well. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.

PubMed

Willis, Colin L; Meske, Diana S; Davis, Thomas P

2010-11-01

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

PubMed

Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

2017-07-01

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability

PubMed Central

Khan, Niamat; Lenz, Christof; Binder, Lutz; Pantakani, Dasaradha Venkata Krishna; Asif, Abdul R.

2016-01-01

Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether MPA induces epigenetic changes which lead to GI complications, especially diarrhea. Methods: We employed a Chromatin Immunoprecipitation-O-Proteomics (ChIP-O-Proteomics) approach to identify proteins associated with active (H3K4me3) as well as repressive (H3K27me3) chromatin histone modifications in MPA-treated cells, and further characterized the role of midkine, a H3K4me3-associated protein, in the context of epithelial monolayer permeability. Results: We identified a total of 333 and 306 proteins associated with active and repressive histone modification marks, respectively. Among them, 241 proteins were common both in active and repressive chromatin, 92 proteins were associated exclusively with the active histone modification mark, while 65 proteins remained specific to repressive chromatin. Our results show that 45 proteins which bind to the active and seven proteins which bind to the repressive chromatin region exhibited significantly altered abundance in MPA-treated cells as compared to DMSO control cells. A number of novel proteins whose function is not known in bowel barrier regulation were among the identified proteins, including midkine. Our functional integrity assays on the Caco-2 cell monolayer showed that the inhibition of midkine expression prior to MPA treatment could completely block the MPA-mediated increase in barrier permeability. Conclusions: The ChIP-O-Proteomics approach delivered a number of novel proteins with potential implications in MPA toxicity. Consequently, it can be proposed that midkine inhibition could be a potent therapeutic approach to prevent the MPA-mediated increase in TJ permeability and leak flux diarrhea in organ transplant patients. PMID:27104530

Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.

PubMed

Yang, Yang; Qiu, Yuan; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Zhang, Chaojun; Yang, Hanwenbo; Teitelbaum, Daniel H; Sun, Li-Hua; Yang, Hua

2014-01-01

Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.

The EhCPADH112 Complex of Entamoeba histolytica Interacts with Tight Junction Proteins Occludin and Claudin-1 to Produce Epithelial Damage

PubMed Central

Betanzos, Abigail; Javier-Reyna, Rosario; García-Rivera, Guillermina; Bañuelos, Cecilia; González-Mariscal, Lorenza; Schnoor, Michael; Orozco, Esther

2013-01-01

Entamoeba histolytica, the protozoan responsible for human amoebiasis, causes between 30,000 and 100,000 deaths per year worldwide. Amoebiasis is characterized by intestinal epithelial damage provoking severe diarrhea. However, the molecular mechanisms by which this protozoan causes epithelial damage are poorly understood. Here, we studied the initial molecular interactions between the E. histolytica EhCPADH112 virulence complex and epithelial MDCK and Caco-2 cells. By confocal microscopy, we discovered that after contact with trophozoites or trophozoite extracts (TE), EhCPADH112 and proteins forming this complex (EhCP112 and EhADH112) co-localize with occludin and claudin-1 at tight junctions (TJ). Immunoprecipitation assays revealed interaction between EhCPADH112 and occludin, claudin-1, ZO-1 and ZO-2. Overlay assays confirmed an interaction of EhCP112 and EhADH112 with occludin and claudin-1, whereas only EhADH112 interacted also with ZO-2. We observed degradation of all mentioned TJ proteins after incubation with TE. Importantly, inhibiting proteolytic activity or blocking the complex with a specific antibody not only prevented TJ protein degradation but also epithelial barrier disruption. Furthermore, we discovered that TE treatment induces autophagy and apoptosis in MDCK cells that could contribute to the observed barrier disruption. Our results suggest a model in which epithelial damage caused by E. histolytica is initiated by the interaction of EhCP112 and EhADH112 with TJ proteins followed by their degradation. Disruption of TJs then induces increased paracellular permeability, thus facilitating the entry of more proteases and other parasite molecules leading eventually to tissue destruction. PMID:23762290

Site-specific distribution of claudin-based paracellular channels with roles in biological fluid flow and metabolism.

PubMed

Tanaka, Hiroo; Tamura, Atsushi; Suzuki, Koya; Tsukita, Sachiko

2017-10-01

The claudins are a family of membrane proteins with at least 27 members in humans and mice. The extracellular regions of claudin proteins play essential roles in cell-cell adhesion and the paracellular barrier functions of tight junctions (TJs) in epithelial cell sheets. Furthermore, the extracellular regions of some claudins function as paracellular channels in the paracellular barrier that allow the selective passage of water, ions, and/or small organic solutes across the TJ in the extracellular space. Structural analyses have revealed a common framework of transmembrane, cytoplasmic, and extracellular regions among the claudin-based paracellular barriers and paracellular channels; however, differences in the claudins' extracellular regions, such as their charges and conformations, determine their properties. Among the biological systems that involve fluid flow and metabolism, it is noted that hepatic bile flow, renal Na + reabsorption, and intestinal nutrient absorption are dynamically regulated via site-specific distributions of paracellular channel-forming claudins in tissue. Here, we focus on how site-specific distributions of claudin-2- and claudin-15-based paracellular channels drive their organ-specific functions in the liver, kidney, and intestine. © 2017 New York Academy of Sciences.

Claudin-4 Deficiency Results in Urothelial Hyperplasia and Lethal Hydronephrosis

PubMed Central

Fujita, Harumi; Hamazaki, Yoko; Noda, Yumi; Oshima, Masanobu; Minato, Nagahiro

2012-01-01

Claudin (Cld)-4 is one of the dominant Clds expressed in the kidney and urinary tract, including selective segments of renal nephrons and the entire urothelium from the pelvis to the bladder. We generated Cldn4 −/− mice and found that these mice had increased mortality due to hydronephrosis of relatively late onset. While the renal nephrons of Cldn4 −/− mice showed a concomitant diminution of Cld8 expression at tight junction (TJ), accumulation of Cld3 at TJ was markedly enhanced in compensation and the overall TJ structure was unaffected. Nonetheless, Cldn4 −/− mice showed slightly yet significantly increased fractional excretion of Ca2+ and Cl−, suggesting a role of Cld4 in the specific reabsorption of these ions via a paracellular route. Although the urine volume tended to be increased concordantly, Cldn4 −/− mice were capable of concentrating urine normally on dehydration, with no evidence of diabetes insipidus. In the urothelium, the formation of TJs and uroplaques as well as the gross barrier function were also unaffected. However, intravenous pyelography analysis indicated retarded urine flow prior to hydronephrosis. Histological examination revealed diffuse hyperplasia and a thickening of pelvic and ureteral urothelial layers with markedly increased BrdU uptake in vivo. These results suggest that progressive hydronephrosis in Cldn4 −/− mice arises from urinary tract obstruction due to urothelial hyperplasia, and that Cld4 plays an important role in maintaining the homeostatic integrity of normal urothelium. PMID:23284964

Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction degradation.

PubMed

Choi, Kang-Ho; Kim, Hyung-Seok; Park, Man-Seok; Lee, Eun-Bin; Lee, Jung-Kil; Kim, Joon-Tae; Kim, Ja-Hae; Lee, Min-Cheol; Lee, Hong-Joon; Cho, Ki-Hyun

2016-10-18

Cerebral edema from the disruption of the blood-brain barrier (BBB) after cerebral ischemia is a major cause of morbidity and mortality as well as a common event in patients with stroke. Caveolins (Cavs) are thought to regulate BBB functions. Here, we report for the first time that Cav-1 overexpression (OE) decreased brain edema from BBB disruption following ischemic insult. Edema volumes and Cav-1 expression levels were measured following photothrombosis and middle cerebral artery occlusion (MCAO). Endothelial cells that were transduced with a Cav-1 lentiviral expression vector were transplanted into rats. BBB permeability was quantified with Evans blue extravasation. Edema volume was determined from measures of the extravasation area, brain water content, and average fluorescence intensity after Cy5.5 injections. Tight junction (TJ) protein expression was measured with immunoblotting. Cav-1 expression levels and vasogenic brain edema correlated strongly after ischemic insult. Cav-1 expression and BBB disruption peaked 3 d after the MCAO. In addition, intravenous administration of endothelial cells expressing Cav-1 effectively increased the Cav-1 levels 3 d after the MCAO ischemic insult. Importantly, Cav-1 OE ameliorated the vasogenic edema by inhibiting the degradation of TJ protein expression in the acute phase of ischemic stroke. These results suggested that Cav-1 OE protected the integrity of the BBB mainly by preventing the degradation of TJ proteins in rats. These findings need to be confirmed in a clinical setting in human subjects.

Dose- and time-dependent expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in PCB-, B[a]P-, and TBT-exposed intertidal copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Rhee, Jae-Sung; Hwang, Un-Ki; Seo, Jung Soo; Shin, Kyung-Hoon; Lee, Jae-Seong

2015-02-01

The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (ARNT) genes from the copepod Tigriopus japonicus (Tj) were cloned to examine their potential functions in the invertebrate putative AhR-CYP signaling pathway. The amino acid sequences encoded by the Tj-AhR and Tj-ARNT genes showed high similarity to homologs of Daphnia and Drosophila, ranging from 68% and 70% similarity for the AhR genes to 56% for the ARNT genes. To determine whether Tj-AhR and Tj-ARNT are modulated by environmental pollutants, transcriptional expression of Tj-AhR and Tj-ARNT was analyzed in response to exposure to five concentrations of polychlorinated biphenyl (PCB 126) (control, 10, 50, 100, 500 μg L(-1)), benzo[a]pyrene (B[a]P) (control, 5, 10, 50, 100 μg L(-1)), and tributyltin (TBT) (control, 1, 5, 10, 20 μg L(-1)) 24h after exposure. A time-course experiment (0, 3, 6, 12, 24h) was performed to analyze mRNA expression patterns after exposure to PCB, B[a]P, and TBT. T. japonicus exhibited dose-dependent and time-dependent upregulation of Tj-AhR and Tj-ARNT in response to pollutant exposure, and the degree of expression was dependent on the pollutant, suggesting that pollutants such as PCB, B[a]P, and TBT modulate expression of Tj-AhR and Tj-ARNT genes in the putative AhR-CYP signaling pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary salt loading and ion-poor water exposure provide insight into the molecular physiology of the rainbow trout gill epithelium tight junction complex.

PubMed

Kolosov, Dennis; Kelly, Scott P

2016-08-01

This study utilized dietary salt loading and ion-poor water (IPW) exposure of rainbow trout (Oncorhynchus mykiss) to further understand the role of fish gill epithelium tight junction (TJ) physiology in salt and water balance. Gill morphology, biochemistry and molecular physiology were examined, with an emphasis on genes encoding TJ proteins. Fish were either fed a control or salt-enriched diet (~10 % NaCl) for 4 weeks prior to IPW exposure for 24 h. Serum [Na(+)], [Cl(-)] and muscle moisture content were unaltered by salt feeding, but changed in response to IPW irrespective of diet. Dietary salt loading altered the morphology (reduced Na(+)-K(+)-ATPase-immunoreactive cell numbers and surface exposure of mitochondrion-rich cells), biochemistry (decreased vacuolar-type H(+)-ATPase activity) and molecular physiology (decreased nkaα1a and cftrII mRNA abundance) of the gill in a manner indicative of reduced active ion uptake activity. But in control fish and not salt-fed fish, gill mRNA abundance of nkaα1c increased and nbc decreased after IPW exposure. Genes encoding TJ proteins were typically either responsive to salt feeding or IPW, but select genes responded to combined experimental treatment (e.g. IPW responsive but only if fish were salt-fed). Therefore, using salt feeding and IPW exposure, new insights into what factors influence gill TJ proteins and the role that specific TJ proteins might play in regulating the barrier properties of the gill epithelium have been acquired. In particular, evidence suggests that TJ proteins in the gill epithelium, or the regulatory networks that control them, respond independently to external or internal stimuli.

Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis.

PubMed

Li, H; Sun, J; Du, J; Wang, F; Fang, R; Yu, C; Xiong, J; Chen, W; Lu, Z; Liu, J

2018-05-01

Traumatic brain injury (TBI) is a common occurrence following gastrointestinal dysfunction. Recently, more and more attentions are being focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1) is considered as a mediator that links the gut-brain axis. The aim of this study was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain damage in a mouse model of TBI. Male C57BL/6 mice were subjected to a model of TBI-induced by weight-drop impact head injury and were treated intragastrically with Cb. The cognitive deficits, brain water content, neuronal death, and blood-brain barrier (BBB) permeability were evaluated. The expression of tight junction (TJ) proteins, Bcl-2, Bax, GLP-1 receptor (GLP-1R), and phosphorylation of Akt (p-Akt) in the brain were also measured. Moreover, the intestinal barrier permeability, the expression of TJ protein and GLP-1, and IL-6 level in the intestine were detected. Cb treatment significantly improved neurological dysfunction, brain edema, neurodegeneration, and BBB impairment. Meanwhile, Cb treatment also significantly increased the expression of TJ proteins (occludin and zonula occluden-1), p-Akt and Bcl-2, but decreased expression of Bax. Moreover, Cb treatment exhibited more prominent effects on decreasing the levels of plasma d-lactate and colonic IL-6, upregulating expression of Occludin, and protecting intestinal barrier integrity. Furthermore, Cb-treated mice showed increased the secretion of intestinal GLP-1 and upregulated expression of cerebral GLP-1R. Our findings demonstrated the neuroprotective effect of Cb in TBI mice and the involved mechanisms were partially attributed to the elevating GLP-1 secretion through the gut-brain axis. © 2017 John Wiley & Sons Ltd.

Zinc ions regulate opening of tight junction favouring efflux of macromolecules via the GSK3β/snail-mediated pathway.

PubMed

Xiao, Ruyue; Yuan, Lan; He, Weijiang; Yang, Xiaoda

2018-01-24

Zinc is an essential trace element presenting in particularly high concentration in the brain. In some regions, e.g. lateral amygdala, subiculum and hippocampus, rapidly-exchangeable zinc may transiently reach even up to 600 μM. To explore the possible roles of high-concentration Zn 2+ in regulating the blood-brain barrier (BBB), we investigated the effects of Zn 2+ on the functions and structures of the tight junction (TJ) with an in vitro model of a Madin-Darby canine kidney (MDCK) cell monolayer. The experimental results indicated that high concentrations (>200 μM) of Zn 2+ can affect the TJ integrity in a polarized manner. Basolateral addition of Zn 2+ led to reversible TJ opening with pore paths of r ∼ 2 nm or more depending on Zn 2+ concentration. The efflux/influx ratios of different sized probes were found to be ∼4.6 for FD4 (M W 4000) and ∼1.8 for Eu-DTPA (M W 560), suggesting that the Zn 2+ -induced paracelluar channels favour efflux especially for macromolecules. Further mechanistic studies revealed that the elevated intracellular Zn 2+ taken from the basolateral side can increase phosphorylation of glycogen synthase kinase (GSK) 3β, primarily due to the inhibition of calcineurin (CaN), thus resulting in the elevation of the snail transcriptional repressors. Subsequently, Zn 2+ can cause the down-regulation of claudin-1, breakage of occludin and ZO-1 rings, and collapse of basolateral F-actin structures. These overall factors result in the formation of a trumpet-like paracellular channel, which allows asymmetric solute permeation. The ERK1/2 and JNK1/2 pathways may also be involved in the Zn 2+ -induced TJ opening process, while the activation of matrix metalloproteinase was not observed. Our results may suggest a potential role of zinc in regulation of BBB permeability associated with brain clearance of metabolites through the glymphatic system.

Role of claudin species-specific dynamics in reconstitution and remodeling of the zonula occludens.

PubMed

Yamazaki, Yuji; Tokumasu, Reitaro; Kimura, Hiroshi; Tsukita, Sachiko

2011-05-01

Tight-junction strands, which are organized into the beltlike cell-cell adhesive structure called the zonula occludens (TJ), create the paracellular permselective barrier in epithelial cells. The TJ is constructed on the basis of the zonula adherens (AJ) by polymerized claudins in a process mediated by ZO-1/2, but whether the 24 individual claudin family members play different roles at the TJ is unclear. Here we established a cell system for examining the polymerization of individual claudins in the presence of ZO-1/2 using an epithelial-like cell line, SF7, which lacked endogenous TJs and expressed no claudin but claudin-12 in immunofluorescence and real-time PCR assays. In stable SF7-derived lines, exogenous claudin-7, -14, or -19, but no other claudins, individually reconstituted TJs, each with a distinct TJ-strand pattern, as revealed by freeze-fracture analyses. Fluorescence recovery after photobleaching (FRAP) analyses of the claudin dynamics in these and other epithelial cells suggested that slow FRAP-recovery dynamics of claudins play a critical role in regulating their polymerization around AJs, which are loosely coupled with ZO-1/2, to form TJs. Furthermore, the distinct claudin stabilities in different cell types may help to understand how TJs regulate paracellular permeability by altering the paracellular flux and the paracellular ion permeability.

Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex

PubMed Central

Nunbhakdi-Craig, Viyada; Machleidt, Thomas; Ogris, Egon; Bellotto, Dennis; White, Charles L.; Sontag, Estelle

2002-01-01

Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABαC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with the TJ complex. Enhanced PP2A activity induces dephosphorylation of the TJ proteins, ZO-1, occludin, and claudin-1, and is associated with increased paracellular permeability. Expression of PP2A catalytic subunit severely prevents TJ assembly. Conversely, inhibition of PP2A by okadaic acid promotes the phosphorylation and recruitment of ZO-1, occludin, and claudin-1 to the TJ during junctional biogenesis. PP2A negatively regulates TJ assembly without appreciably affecting the organization of F-actin and E-cadherin. Significantly, inhibition of atypical PKC (aPKC) blocks the calcium- and serum-independent membrane redistribution of TJ proteins induced by okadaic acid. Indeed, PP2A associates with and critically regulates the activity and distribution of aPKC during TJ formation. Thus, we provide the first evidence for calcium-dependent targeting of PP2A in epithelial cells, we identify PP2A as the first serine/threonine phosphatase associated with the multiprotein TJ complex, and we unveil a novel role for PP2A in the regulation of epithelial aPKC and TJ assembly and function. PMID:12196510

Hydrostatic pressure incubation affects barrier properties of mammary epithelial cell monolayers, in vitro.

PubMed

Mießler, Katharina S; Markov, Alexander G; Amasheh, Salah

2018-01-01

During lactation, accumulation of milk in mammary glands (MG) causes hydrostatic pressure (HP) and concentration of bioactive compounds. Previously, a changed expression of tight junction (TJ) proteins was observed in mice MGs by accumulation of milk, in vivo. The TJ primarily determines the integrity of the MG epithelium. The present study questioned whether HP alone can affect the TJ in a mammary epithelial cell model, in vitro. Therefore, monolayers of HC11, a mammary epithelial cell line, were mounted into modified Ussing chambers and incubated with 10 kPa bilateral HP for 4 h. Short circuit current and transepithelial resistance were recorded and compared to controls, and TJ proteins were analyzed by Western blotting and immunofluorescent staining. In our first approach HC11 cells could withstand the pressure incubation and a downregulation of occludin was observed. In a second approach, using prolactin- and dexamethasone-induced cells, a decrease of short circuit current was observed, beginning after 2 h of incubation. With the addition of 1 mM barium chloride to the bathing solution the decrease could be blocked temporarily. On molecular level an upregulation of ZO-1 could be observed in hormone-induced cells, which was downregulated after the incubation with barium chloride. In conclusion, bilateral HP incubation affects mammary epithelial monolayers, in vitro. Both, the reduction of short circuit current and the change in TJ proteins may be interpreted as physiological requirements for lactation. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation

PubMed Central

Li, Jiebin; Li, Chunsheng; Yuan, Wei; Wu, Junyuan; Li, Jie; Li, Zhenhua; Zhao, Yongzhen

2017-01-01

Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood–brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression. PMID:28355299

The urothelium of a hibernator: the American black bear

PubMed Central

Spector, David A; Deng, Jie; Coleman, Richard; Wade, James B

2015-01-01

The American black bear undergoes a 3–5 month winter hibernation during which time bears do not eat, drink, defecate, or urinate. During hibernation renal function (GFR) is 16–50% of normal but urine is reabsorbed across the urinary bladder (UB) urothelium thus enabling metabolic recycling of all urinary constituents. To elucidate the mechanism(s) whereby urine is reabsorbed, we examined the UBs of five nonhibernating wild bears using light, electron (EM), and confocal immunofluorescent (IF) microscopy–concentrating on two components of the urothelial permeability barrier – the umbrella cell apical membranes and tight junctions (TJ). Bear UB has the same tissue layers (serosa, muscularis, lamina propria, urothelia) and its urothelia has the same cell layers (basal, intermediate, umbrella cells) as other mammalians. By EM, the bear apical membrane demonstrated a typical mammalian scalloped appearance with hinge and plaque regions – the latter containing an asymmetric trilaminar membrane and, on IF, uroplakins Ia, IIIa, and IIIb. The umbrella cell TJs appeared similar to those in other mammals and also contained TJ proteins occludin and claudin - 4, and not claudin –2. Thus, we were unable to demonstrate urothelial apical membrane or TJ differences between active black bears and other mammals. Expression and localization of UT-B, AQP-1 and -3, and Na+, K+-ATPase on bear urothelial membranes was similar to that of other mammals. Similar studies of urothelia of hibernating bears, including evaluation of the apical membrane lipid bilayer and GAGs layer are warranted to elucidate the mechanism(s) whereby hibernating bears reabsorb their daily urine output and thus ensure successful hibernation. PMID:26109187

Glucocorticoid Induction of Occludin Expression and Endothelial Barrier Requires Transcription Factor p54 NONO

PubMed Central

Keil, Jason M.; Liu, Xuwen; Antonetti, David A.

2013-01-01

Purpose. Glucocorticoids (GCs) effectively reduce retinal edema and induce vascular barrier properties but possess unwanted side effects. Understanding GC induction of barrier properties may lead to more effective and specific therapies. Previous work identified the occludin enhancer element (OEE) as a GC-responsive cis-element in the promoters of multiple junctional genes, including occludin, claudin-5, and cadherin-9. Here, we identify two OEE-binding factors and determine their contribution to GC induction of tight junction (TJ) gene expression and endothelial barrier properties. Methods. OEE-binding factors were isolated from human retinal endothelial cells (HREC) using DNA affinity purification followed by MALDI-TOF MS/MS. Chromatin immunoprecipitation (ChIP) assays determined in situ binding. siRNA was used to evaluate the role of trans-acting factors in transcription of TJ genes in response to GC stimulation. Paracellular permeability was determined by quantifying flux through a cell monolayer, whereas transendothelial electrical resistance (TER) was measured using the ECIS system. Results. MS/MS analysis of HREC nuclear extracts identified the heterodimer of transcription factors p54/NONO (p54) and polypyrimidine tract-binding protein-associated splicing factor (PSF) as OEE-binding factors, which was confirmed by ChIP assay from GC-treated endothelial cells and rat retina. siRNA knockdown of p54 demonstrated that this factor is necessary for GC induction of occludin and claudin-5 expression. Further, p54 knockdown ablated the pro-barrier effects of GC treatment. Conclusions. p54 is essential for GC-mediated expression of occludin, claudin-5, and barrier induction, and the p54/PSF heterodimer may contribute to normal blood-retinal barrier (BRB) induction in vivo. Understanding the mechanism of GC induction of BRB properties may provide novel therapies for macular edema. PMID:23640037

Glucocorticoid induction of occludin expression and endothelial barrier requires transcription factor p54 NONO.

PubMed

Keil, Jason M; Liu, Xuwen; Antonetti, David A

2013-06-12

Glucocorticoids (GCs) effectively reduce retinal edema and induce vascular barrier properties but possess unwanted side effects. Understanding GC induction of barrier properties may lead to more effective and specific therapies. Previous work identified the occludin enhancer element (OEE) as a GC-responsive cis-element in the promoters of multiple junctional genes, including occludin, claudin-5, and cadherin-9. Here, we identify two OEE-binding factors and determine their contribution to GC induction of tight junction (TJ) gene expression and endothelial barrier properties. OEE-binding factors were isolated from human retinal endothelial cells (HREC) using DNA affinity purification followed by MALDI-TOF MS/MS. Chromatin immunoprecipitation (ChIP) assays determined in situ binding. siRNA was used to evaluate the role of trans-acting factors in transcription of TJ genes in response to GC stimulation. Paracellular permeability was determined by quantifying flux through a cell monolayer, whereas transendothelial electrical resistance (TER) was measured using the ECIS system. MS/MS analysis of HREC nuclear extracts identified the heterodimer of transcription factors p54/NONO (p54) and polypyrimidine tract-binding protein-associated splicing factor (PSF) as OEE-binding factors, which was confirmed by ChIP assay from GC-treated endothelial cells and rat retina. siRNA knockdown of p54 demonstrated that this factor is necessary for GC induction of occludin and claudin-5 expression. Further, p54 knockdown ablated the pro-barrier effects of GC treatment. p54 is essential for GC-mediated expression of occludin, claudin-5, and barrier induction, and the p54/PSF heterodimer may contribute to normal blood-retinal barrier (BRB) induction in vivo. Understanding the mechanism of GC induction of BRB properties may provide novel therapies for macular edema.

Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.

PubMed

Cresci, Gail A; Glueck, Bryan; McMullen, Megan R; Xin, Wei; Allende, Daniella; Nagy, Laura E

2017-09-01

Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll-like receptors, and tumor necrosis factor-alpha were assessed. Caco-2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic toll-like receptor mRNA expression and tumor necrosis factor-alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice. Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum.

PubMed

Benedicto, Ignacio; Molina-Jiménez, Francisca; Barreiro, Olga; Maldonado-Rodríguez, Alejandra; Prieto, Jesús; Moreno-Otero, Ricardo; Aldabe, Rafael; López-Cabrera, Manuel; Majano, Pedro L

2008-10-01

Hepatocyte tight junctions (TJ) play key roles in characteristic liver functions, including bile formation and secretion. Infection by hepatitis C virus (HCV) may cause alterations of the liver architecture and disruption of the bile duct, which ultimately can lead to cholestasis. Herein, we employed the HCV replicon system to analyze the effect of HCV on TJ organization. TJ-associated proteins occludin, claudin-1, and Zonula Occludens protein-1 (ZO-1) disappeared from their normal localization at the border of adjacent cells in Huh7 clones harboring genomic but not subgenomic replicons expressing only the nonstructural proteins. Furthermore, cells containing genomic replicons showed a cytoplasmic accumulation of occludin in the endoplasmic reticulum (ER). TJ-associated function, measured as FITC-dextran paracellular permeability, of genomic replicon-containing cells, was also altered. Interestingly, clearance of the HCV replicon by interferon-alpha (IFN-alpha) treatment and by short hairpin RNA (shRNA) significantly restored the localization of TJ-associated proteins. Transient expression of all HCV structural proteins, but not core protein alone, altered the localization of TJ-associated proteins in Huh7 cells and in clones with subgenomic replicons. Confocal analysis showed that accumulation of occludin in the ER partially co-localized with HCV envelope glycoprotein E2. E2/occludin association was further confirmed by co-immunoprecipitation and pull-down assays. Additionally, using a cell culture model of HCV infection, we observed the cytoplasmic dot-like accumulation of occludin in infected Huh7 cells. We propose that HCV structural proteins, most likely those of the viral envelope, promote alterations of TJ-associated proteins, which may provide new insights for HCV-related pathogenesis.

Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells.

PubMed

Egawa, M; Kamata, H; Kushiyama, A; Sakoda, H; Fujishiro, M; Horike, N; Yoneda, M; Nakatsu, Y; Ying, Guo; Jun, Zhang; Tsuchiya, Y; Takata, K; Kurihara, H; Asano, T

2008-12-01

BeWo cells, derived from human choriocarcinoma, have been known to respond to forskolin or cAMP analogues by differentiating into multinucleated cells- like syncytiotrophoblasts on the surfaces of chorionic villi of the human placenta. In this study, we demonstrated that long-term treatment with forskolin enhances the tight junction (TJ) formation in human placental BeWo cells. Interestingly, AMPK activation and phosphorylation of acetyl-CoA carboxylase (ACC), a molecule downstream from AMPK, were induced by long-term incubation (>12h) with forskolin, despite not being induced by acute stimulation with forskolin. In addition, co-incubation with an AMPK inhibitor, compound C, as well as overexpression of an AMPK dominant negative mutant inhibited forskolin-induced TJ formation. Thus, although the molecular mechanism underlying AMPK activation via the forskolin stimulation is unclear, the TJ formation induced by forskolin is likely to be mediated by the AMPK pathway. Taking into consideration that TJs are present in the normal human placenta, this mechanism may be important for forming the placental barrier system between the fetal and maternal circulations.

Zinc Supplementation, via GPR39, Upregulates PKCζ to Protect Intestinal Barrier Integrity in Caco-2 Cells Challenged by Salmonella enterica Serovar Typhimurium.

PubMed

Shao, Yu-Xin; Lei, Zhao; Wolf, Patricia G; Gao, Yan; Guo, Yu-Ming; Zhang, Bing-Kun

2017-07-01

Background: Zinc has been shown to improve intestinal barrier function against Salmonella enterica serovar Typhimurium ( S. typhimurium ) infection, but the mechanisms involved in this process remain undefined. Objective: We aimed to explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Cζ (PKCζ) in the regulation by zinc of intestinal barrier function. Methods: A Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 μM Zn and then incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small interfering RNA for GPR39 or PKCζ were pretreated with 100 μM Zn and incubated with S. typhimurium for 3 h. Finally, transepithelial electrical resistance (TEER), permeability, tight junction (TJ) proteins, and signaling molecules GPR39 and PKCζ were measured. Results: Compared with controls, S. typhimurium decreased TEER by 62.3-96.2% at 4-6 h ( P < 0.001), increased ( P < 0.001) permeability at 6 h, and downregulated ( P < 0.05) TJ protein zonula occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and PKCζ by 35.1% and 75.2%, respectively. Compared with S. typhimurium- challenged cells, 50 and 100 μM Zn improved TEER by 26.3-60.9% at 4-6 h ( P < 0.001) and decreased ( P < 0.001) permeability and bacterial invasion at 6 h. A total of 100 μM Zn increased ZO-1, occludin, GPR39, and PKCζ 0.72- to 1.34-fold ( P < 0.05); however, 50 μM Zn did not affect ZO-1 or occludin ( P > 0.1). Silencing GPR39 decreased ( P < 0.05) zinc-activated PKCζ and blocked ( P < 0.05) the promotion of zinc on epithelial integrity. Furthermore, silencing PKCζ counteracted the protective effect of zinc on epithelial integrity but did not inhibit GPR39 ( P = 0.138). Conclusion: We demonstrated that zinc upregulates PKCζ by activating GPR39 to enhance the abundance of ZO-1, thereby improving epithelial integrity in S. typhimurium- infected Caco-2 cells. © 2017 American Society for Nutrition.

Traffic jam functions in a branched pathway from Notch activation to niche cell fate.

PubMed

Wingert, Lindsey; DiNardo, Stephen

2015-07-01

The niche directs key behaviors of its resident stem cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide niche specification and development. The male germline stem cell niche in Drosophila houses two stem cell populations and is specified within the embryonic gonad, thus making it an excellent model for studying niche development. The hub cells that form the niche are specified early by Notch activation. Over the next few hours, these individual cells then cluster together and take up a defined position before expressing markers of hub cell differentiation. This timing suggests that there are other factors for niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub cells. Furthermore, Tj depletion is sufficient to generate ectopic hub cells that can recruit stem cells. Surprisingly, ectopic niche cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub cell assembly in parallel to Tj downregulation. © 2015. Published by The Company of Biologists Ltd.

Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain.

PubMed

Avraham, Hava Karsenty; Jiang, Shuxian; Fu, Yigong; Nakshatri, Harikrishna; Ovadia, Haim; Avraham, Shalom

2014-02-01

Although the incidence of breast cancer metastasis (BCM) in brain has increased significantly in triple-negative breast cancer (TNBC), the mechanisms remain elusive. Using in vivo mouse models for BCM in brain, we observed that TNBC cells crossed the blood-brain barrier (BBB), lodged in the brain microvasculature and remained adjacent to brain microvascular endothelial cells (BMECs). Breaching of the BBB in vivo by TNBCs resulted in increased BBB permeability and changes in ZO-1 and claudin-5 tight junction (TJ) protein structures. Angiopoietin-2 expression was elevated in BMECs and was correlated with BBB disruption. Secreted Ang-2 impaired TJ structures and increased BBB permeability. Treatment of mice with the neutralizing Ang-2 peptibody trebananib prevented changes in the BBB integrity and BMEC destabilization, resulting in inhibition of TNBC colonization in brain. Thus, Ang-2 is involved in initial steps of brain metastasis cascade, and inhibitors for Ang-2 may serve as potential therapeutics for brain metastasis. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice

PubMed Central

Huang, Yalan; Feng, Yanhai; Wang, Yu; Wang, Pei; Wang, Fengjun; Ren, Hui

2018-01-01

The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction. Mice received a 30% total body surface area (TBSA) full-thickness burn, and were sacrificed at 0, 1, 2, 6, 12 and 24 h postburn. The results showed that intestinal permeability was increased significantly after burn injury, accompanied by the damage of mucosa and the alteration of TJ proteins. Severe burn induced ER stress, as indicated by increased intraluminal chaperone binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP) and inositol-requiring enzyme 1(IRE1)/X-box binding protein 1 splicing (XBP1). Autophagy was activated after burn injury, as evidenced by the increase of autophagy related protein 5 (ATG5), Beclin 1 and LC3II/LC3I ratio and the decrease of p62. Besides, the number of autophagosomes was also increased after burn injury. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. PMID:29740349

Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of trout.

PubMed

Kolosov, Dennis; Kelly, Scott P

2017-10-01

The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol-mediated alterations in gill epithelium permeability was examined using a primary cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins ( cldn-8b, -8c and -8d ) have been identified in trout and all are expressed in the model gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated by increased transepithelial resistance (TER) and reduced paracellular [ 3 H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium tightening' effect of cortisol in association with increased paracellular PEG-400 flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD hindered a cortisol-mediated reduction in basolateral to apical Na + and Cl - flux (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD did not abolish the tightening effect of cortisol on the gill epithelium. This is likely due, in part, to the effect of cortisol on genes encoding other TJ proteins, which in some cases appeared to exhibit a compensatory response. Data support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that contributes significantly to corticosteroid-mediated alterations in gill epithelium permeability. © 2017 Society for Endocrinology.

The effects of electromagnetic pulse on the protein levels of tight junction associated-proteins in the cerebral cortex, hippocampus, heart, lung, and testis of rats.

PubMed

Qiu, LianBo; Chen, Chen; Ding, GuiRong; Zhou, Yan; Zhang, MengYao

2011-08-01

To investigate changes in the expression of tight junction (TJ) proteins in the cerebral cortex, hippocampus, heart, lung, and testes of rats after exposure to electromagnetic pulse (EMP). Eighteen adult male Sprague-Dawley rats were divided into sham and exposure groups. The exposure groups received EMP at 200 kV/m for 200 pulses with a repetition rate of 1 Hz. The expression of TJ proteins (ZO-1, occludin, actin) in the several organs was examined by western blotting. ZO-1 levels in the cerebral cortex decreased 1 h and 3 h after EMP exposure compared with sham group (P<0.05). No significant difference was observed for occludin and actin. ZO-1 levels in the hippocampus increased 1 h and 3 h post-exposure (P<0.05), and occludin decreased after 3 h (P<0.05); however, actin was unaffected. ZO-1 levels in the heart increased 3 h post-exposure (P<0.05), occludin decreased 3 h post-exposure (P<0.05), and actin increased 1 h and 3 h post-exposure (P<0.05). ZO-1, occludin and actin levels in the lung decreased compared with those in the sham group (P<0.05). ZO-1 and occludin levels in the testes decreased 1 h and 3 h post-exposure (P<0.05), but actin showed no significant change. Exposure to EMP altered the expression levels of TJ proteins, particularly ZO-1, in the organs of adult male rats, which may induce changes in barrier structure and function. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Occludin Is Involved in Adhesion, Apoptosis, Differentiation and Ca2+-Homeostasis of Human Keratinocytes: Implications for Tumorigenesis

PubMed Central

Ohnemus, Ulrich; Kirschner, Nina; Vidal-y-Sy, Sabine; von den Driesch, Peter; Börnchen, Christian; Eberle, Jürgen; Mildner, Michael; Vettorazzi, Eik; Rosenthal, Rita; Moll, Ingrid; Brandner, Johanna M.

2013-01-01

Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca2+-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention. PMID:23390516

Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents: a 12-week prospective, open-label study.

PubMed

Wake, Rei; Miyaoka, Tsuyoshi; Inagaki, Takuji; Furuya, Motohide; Ieda, Masa; Liaury, Kristian; Kishi, Kazuko; Horiguchi, Jun

2013-06-01

Autistic disorder is a neuropsychiatric syndrome characterized by deficits in social interaction; qualitative impairments in communication; and restricted, repetitive, and stereotyped patterns of behavior, interests, or activities. It is classified as a type of pervasive developmental disorder (PDD). All PDDs have a qualitative impairment in social relatedness. However, many individuals with PDDs have interfering symptoms, including irritability (aggression, self-injurious behavior, and severe tantrums). Behavioral therapy is often helpful in decreasing these behaviors; however, sometimes adjunctive medications are needed, because of the intensity and severity of irritability. Numerous medications have been tested on patients with PDDs. Although many of these medications have been demonstrated to be useful, no clear main treatment for PDD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to their use. Yokukansan (TJ-54), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situations for treating psychiatric disorders by acting mainly on the glutamatergic and serotonergic nervous system. Recent studies indicate that TJ-54 may be safe and useful in treating behavioral and psychological symptoms in dementia patients. We aimed at evaluating both the efficacy and the safety of TJ-54 in patients with PDDs. This was a 12 week prospective, open-label investigation of TJ-54 in 20 children and adolescents ages 6-17 years diagnosed with PDDs. Primary outcome measures included the Clinical Global Impressions-Improvement of Illness Scale (CGI-I), Children's Global Assessment Score (CGAS), and the Aberrant Behavior Checklist (ABC) irritability subscale. Twenty subjects, ages 6-17 years, received TJ-54 in the dosage range of 2.5-7.5 g/day. The CGI-I was significantly improved from 8 weeks (p<0.001). The mean CGAS was 31.92 at baseline, whereas the mean final score at 12 weeks was 54.52 (p<0.001). The ABC irritability/agitation subscale (subscale 1) was significantly improved from 8 weeks, and the hyperactivity/noncompliance subscale (subscale 4) was significantly improved in 12 weeks. TJ-54 was well tolerated. No subject left the study because of a drug-related adverse event. These preliminary data suggest that TJ-54 may be effective and well tolerated for the treatment of severe irritability/agitation and hyperactivity/noncompliance in children and adolescents ages 6-17 years with PDD. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.

Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder: a 12-week prospective, open-label study.

PubMed

Miyaoka, Tsuyoshi; Wake, Rei; Furuya, Motohide; Liaury, Kristian; Ieda, Masa; Kawakami, Kazunori; Tsuchie, Keiko; Inagaki, Takuji; Horiguchi, Jun

2012-11-29

Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger's disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger's disorder. This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger's disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I). Forty subjects, ages 8-40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event. These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger's disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.

Supplementation of direct-fed microbial as an alternative to antibiotic on growth performance, intestinal immune status and epithelial barrier integrity in broiler chicken

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate the effects of supplementation of broiler diets with Bacillus subtilis-based probiotics on growth performance, feed efficiency, intestinal cytokine and tight junction (TJ) protein mRNA expression. Day-old broiler chicks (n = 140) were randomly assigned...

Electron heat transport comparison in the Large Helical Device and TJ-II

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

Garcia, J.; Dies, J.; Castejon, F.

2007-10-15

The electron heat transport in the Large Helical Device (LHD) [K. Ida, T. Shimozuma, H. Funaba et al., Phys. Rev. Lett. 91, 085003 (2003)] and TJ-II [F. Castejon, V. Tribaldos, I. Garcia-Cortes, E. de la Luna, J. Herranz, I. Pastor, T. Estrada, and TJ-II Team, Nucl. Fusion 42, 271 (2002)] is analyzed by means of the TOTAL [K. Yamazaki and T. Amano, Nucl. Fusion 32, 4 (1992)] and PRETOR-Stellarator [J. Dies, F. Castejon, J. M. Fontdecaba, J. Fontanet, J. Izquierdo, G. Cortes, and C. Alejaldre, Proceedings of the 29th European Physical Society Conference on Plasma Physics and Controlled Fusion, Montreux,more » 2002, Europhysics Conference Abstracts, 2004, Vol. 26B, P-5.027] plasma simulation codes and assuming a global transport model mixing GyroBohm-like drift wave model and other drift wave model with shorter wavelength. The stabilization of the GyroBohm-like model by the ExB shear has been also taken into account. Results show how such kind of electron heat transport can simulate experimental evidence in both devices, leading to the electron internal transport barrier (eITB) formation in the LHD and to the so-called 'enhanced heat confinement regimes' in TJ-II when electron density is low enough. Therefore, two sources for the anomalous electron heat transport can coexist in plasmas with eITB; however, for each device the relative importance of anomalous and neoclassical transport can be different.« less

Indigo naturalis upregulates claudin-1 expression in human keratinocytes and psoriatic lesions.

PubMed

Lin, Yin-Ku; Chen, Hsiao-Wen; Leu, Yann-Lii; Yang, Yueh-Lung; Fang, Yu; Su Pang, Jong-Hwei; Hwang, Tsong-Long

2013-01-30

Indigo naturalis is used in traditional Chinese medicine to treat various dermatoses. Our previous clinical studies showed that indigo naturalis is an effective treatment for psoriasis. Herein, the capabilities of indigo naturalis extract and its derivatives to increase claudin-1 expression and tight junction (TJ) function in human keratinocytes and psoriatic lesions were further studied. Claudin-1 expression in psoriatic plaques with or without indigo naturalis treatment was analyzed by immunohistochemical methods. In primary human keratinocytes, the expression of claudin-1 was analyzed by fluorescent immunostaining, a real-time RT-PCR, and Western blot analysis. The effect of indigo naturalis on TJs was evaluated by measuring the transepithelial electrical resistance (TEER) and paracellular tracer flux. The indigo naturalis extract upregulated mRNA and protein expressions of claudin-1 and function of TJs in primary human keratinocytes in concentration-dependent manners. Its main components, indirubin, indigo, and tryptanthrin, exerted synergistic effects on upregulating TJ functions in primary human keratinocytes. In addition, indigo naturalis increased the activity of protein kinase C (PKC), and a known potent PKC inhibitor, Ro318220, attenuated the indigo naturalis-induced claudin-1 expression. Significantly, restoration of claudin-1 was observed in healed psoriatic lesions after indigo naturalis treatment. Indigo naturalis upregulates claudin-1 expression and restores TJ function in keratinocytes. Our data also suggest that indirubin, indigo, and tryptanthrin have a synergistic effect on TJ function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.

PubMed

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L

2015-01-01

Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. Copyright © 2015 International Society for Peritoneal Dialysis.

Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

PubMed Central

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L.

2015-01-01

♦ Background: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. ♦ Methods: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. ♦ Results: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. ♦ Conclusions: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. PMID:24584604

Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions

PubMed Central

Baranwal, Somesh

2015-01-01

Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. PMID:25792565

Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

PubMed

Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

2015-05-01

Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. Copyright © 2015 the American Physiological Society.

Overview of TJ-II experiments

NASA Astrophysics Data System (ADS)

Sánchez, J.; Acedo, M.; Alonso, A.; Alonso, J.; Alvarez, P.; de Aragón, F.; Ascasíbar, E.; Baciero, A.; Balbín, R.; Barrera, L.; Blanco, E.; Botija, J.; Brañas, B.; de la Cal, E.; Calderón, E.; Calvo, I.; Cappa, A.; Carmona, J. A.; Carreras, B. A.; Carrasco, R.; Castejón, F.; Catalán, G.; Chmyga, A. A.; Dreval, N. B.; Chamorro, M.; Eguilior, S.; Encabo, J.; Eliseev, L.; Estrada, T.; Fernández, A.; Fernández, R.; Ferreira, J. A.; Fontdecaba, J. M.; Fuentes, C.; de la Gama, J.; García, A.; García, L.; García-Cortés, I.; García-Regaña, J. M.; Gonçalves, B.; Guasp, J.; Herranz, J.; Hidalgo, A.; Hidalgo, C.; Jiménez-Gómez, R.; Jiménez, J. A.; Jiménez, D.; Kirpitchev, I.; Komarov, A. D.; Kozachok, A. S.; Krupnik, L.; Lapayese, F.; Liniers, M.; López-Bruna, D.; López-Fraguas, A.; López-Rázola, J.; López-Sánchez, A.; de la Luna, E.; Marcon, G.; Martín, F.; Martínez-Fresno, L.; McCarthy, K. J.; Medina, F.; Medrano, M.; Melnikov, A. V.; Méndez, P.; Mirones, E.; van Milligen, B.; Nedzelskiy, I. S.; Ochando, M.; Olivares, J.; Orozco, R.; Ortiz, P.; de Pablos, J. L.; Pacios, L.; Pastor, I.; Pedrosa, M. A.; de la Peña, A.; Pereira, A.; Pérez-Risco, D.; Petrov, A.; Petrov, S.; Portas, A.; Rapisarda, D.; Ríos, L.; Rodríguez, C.; Rodríguez-Rodrigo, L.; Rodríguez-Solano, E.; Romero, J.; Ros, A.; Salas, A.; Sánchez, E.; Sánchez, M.; Sánchez-Sarabia, E.; Sarasola, X.; Sarksian, K.; Silva, C.; Schchepetov, S.; Skvortsova, N.; Soleto, A.; Tabarés, F.; Tafalla, D.; Tera, J.; Tolkachev, A.; Tribaldos, V.; Vargas, V. I.; Vega, J.; Velasco, G.; Weber, M.; Wolfers, G.; Zweben, S. J.; Zurro, B.

2007-10-01

This paper presents an overview of experimental results and progress made in investigating the link between magnetic topology, electric fields and transport in the TJ-II stellarator. The smooth change from positive to negative electric field observed in the core region as the density is raised is correlated with global and local transport data. A statistical description of transport is emerging as a new way to describe the coupling between profiles, plasma flows and turbulence. TJ-II experiments show that the location of rational surfaces inside the plasma can, in some circumstances, provide a trigger for the development of core transitions, providing a critical test for the various models that have been proposed to explain the appearance of transport barriers in relation to magnetic topology. In the plasma core, perpendicular rotation is strongly coupled to plasma density, showing a reversal consistent with neoclassical expectations. In contrast, spontaneous sheared flows in the plasma edge appear to be coupled strongly to plasma turbulence, consistent with the expectation for turbulent driven flows. The local injection of hydrocarbons through a mobile limiter and the erosion produced by plasmas with well-known edge parameters opens the possibility of performing carbon transport studies, relevant for understanding co-deposit formation in fusion devices.

Spinon-Holon Attraction in the Supersymmetric t-J Model with 1/r

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

Bernevig, B. A.; Giuliano, D.; Laughlin, R. B.

2001-10-22

We derive the coordinate representation of the one-spinon one-holon wave function for the supersymmetric t-J model with 1/r{sup 2} interaction. This result allows us to show that a spinon and a holon attract each other at short distance. The attraction gets stronger as the size of the system is increased and, in the thermodynamic limit, it is responsible for the square-root singularity in the hole spectral function [Y. Kato, Phys.Rev.Lett.81, 5402 (1998)].

Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton.

PubMed

Liu, Li-Bo; Xue, Yi-Xue; Liu, Yun-Hui; Wang, Yi-Bao

2008-04-01

Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and claudin-5 are attenuated by BK induction. Immunohistochemistry and immunofluorescence assays show that the attenuated expression of ZO-1, occludin, and claudin-5 and F-actin is most obvious in the smaller tumor capillaries (<20 microm) after BK infusion, and there is no change in the larger tumor capillaries (>20 microm). The redistribution of ZO-1, occludin, and claudin-5 and rearrangement of F-actin in brain microvascular endothelial cells are observed at the same time. Meanwhile, Evans blue assay shows that the permeability of BTB increases after BK infusion. Transmission electron microscopy indicates that TJ is opened and that pinocytotic vesicular density is increased. Transendothelial electrical resistance (TEER) and horseradish peroxidase flux assays also reveal that TJ is opened by BK induction. In addition, radioimmunity and Western blot assay reveal a significant decrease in expression levels of cAMP and catalytic subunit of protien kinase A (PKAcs) of tumor tissue. This study demonstrates that the increase of BK-mediated BTB permeability is associated with the down-regulation of ZO-1, occludin, and claudin-5 and the rearrangement of F-actin and that cAMP/PKA signal transduction system might be involved in the modulating process.

Antioxidant protects blood-testis barrier against synchrotron radiation X-ray-induced disruption

PubMed Central

Zhang, Tingting; Liu, Tengyuan; Shao, Jiaxiang; Sheng, Caibin; Hong, Yunyi; Ying, Weihai; Xia, Weiliang

2015-01-01

Synchrotron radiation (SR) X-ray has wide biomedical applications including high resolution imaging and brain tumor therapy due to its special properties of high coherence, monochromaticity and high intensity. However, its interaction with biological tissues remains poorly understood. In this study, we used the rat testis as a model to investigate how SR X-ray would induce tissue responses, especially the blood-testis barrier (BTB) because BTB dynamics are critical for spermatogenesis. We irradiated the male gonad with increasing doses of SR X-ray and obtained the testicles 1, 10 and 20 d after the exposures. The testicle weight and seminiferous tubule diameter reduced in a dose- and time-dependent manner. Cryosections of testes were stained with tight junction (TJ) component proteins such as occludin, claudin-11, JAM-A and ZO-1. Morphologically, increasing doses of SR X-ray consistently induced developing germ cell sloughing from the seminiferous tubules, accompanied by shrinkage of the tubules. Interestingly, TJ constituent proteins appeared to be induced by the increasing doses of SR X-ray. Up to 20 d after SR X-ray irradiation, there also appeared to be time-dependent changes on the steady-state level of these protein exhibiting differential patterns at 20-day after exposure, with JAM-A/claudin-11 still being up-regulated whereas occludin/ZO-1 being down-regulated. More importantly, the BTB damage induced by 40 Gy of SR X-ray could be significantly attenuated by antioxidant N-Acetyl-L-Cysteine (NAC) at a dose of 125 mg/kg. Taken together, our studies characterized the changes of TJ component proteins after SR X-ray irradiation, illustrating the possible protective effects of antioxidant NAC to BTB integrity. PMID:26413412

The effect of direct-fed microbial supplementation, as an alternative to antibiotics, on growth performance, intestinal immune status and epithelial barrier protein expression in broiler chickens

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate the effects of Bacillus subtilis-based probiotic supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine and tight junction (TJ) protein mRNA expression. Day-old broiler chicks (n = 140) were randomly assigne...

The effects of direct-fed microbial supplementation, as alternative to antibiotics, on growth performance, intestinal immune status and epithelial barrier protein expression in broiler chickens

USDA-ARS?s Scientific Manuscript database

This study was conducted to investigate the effects of Bacillus subtilis supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine and tight junction (TJ) protein mRNA expression. Day-old broiler chicks (n = 140) were assigned five dietary treatments: basal...

Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.

PubMed

Pelegrino, F S A; Pflugfelder, S C; De Paiva, C S

2012-01-01

Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity <30%RH. Nonstressed (NS) mice were used as controls. Oregon-green-dextran uptake was used to measure corneal barrier function. Levels of small proline-rich protein (SPRR)-2, involucrin, occludin, and MMP-9 were evaluated by immunofluorescent staining in cornea sections. Wholemount corneas immunostained for occludin were used to measure mean apical cell area. Gelatinase activity was evaluated by in situ zymography. Expression of MMP, CE and inflammatory cytokine genes was evaluated by qPCR. C57BL/6 mice exposed to LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Single-hole spectral function and spin-charge separation in the t-J model

NASA Astrophysics Data System (ADS)

Mishchenko, A. S.; Prokof'ev, N. V.; Svistunov, B. V.

2001-07-01

Worm algorithm Monte Carlo simulations of the hole Green function with subsequent spectral analysis were performed for 0.1<=J/t<=0.4 on lattices with up to L×L=32×32 sites at a temperature as low as T=J/40, and present, apparently, the hole spectral function in the thermodynamic limit. Spectral analysis reveals a δ-function-sharp quasiparticle peak at the lower edge of the spectrum that is incompatible with the power-law singularity and thus rules out the possibility of spin-charge separation in this parameter range. Spectral continuum features two peaks separated by a gap ~4÷5 t.

Simultaneous cell death and desquamation of the embryonic diffusion barrier during epidermal development.

PubMed

Saathoff, Manuela; Blum, Barbara; Quast, Thomas; Kirfel, Gregor; Herzog, Volker

2004-10-01

The periderm is an epithelial layer covering the emerging epidermis in early embryogenesis of vertebrates. In the chicken embryo, an additional cellular layer, the subperiderm, occurs at later embryonic stages underneath the periderm. The questions arose what is the function of both epithelial layers and, as they are transitory structures, by which mechanism are they removed. By immunocytochemistry, the tight junction (TJ) proteins occludin and claudin-1 were localized in the periderm and in the subperiderm, and sites of close contact between adjacent cells were detected by electron microscopy. Using horseradish peroxidase (HRP) as tracer, these contacts were identified as tight junctions involved in the formation of the embryonic diffusion barrier. This barrier was lost by desquamation at the end of the embryonic period, when the cornified envelope of the emerging epidermis was formed. By TUNEL and DNA ladder assays, we detected simultaneous cell death in the periderm and the subperiderm shortly before hatching. The absence of caspases-3, -6, and -7 activity, key enzymes of apoptosis, and the lack of typical morphological criteria of apoptosis such as cell fragmentation or membrane blebbing point to a special form of programmed cell death (PCD) leading to the desquamation of the embryonic diffusion barrier. Copyright 2004 Elsevier Inc.

Effects of Hange-shashin-to (TJ-14) and Keishi-ka-shakuyaku-to (TJ-60) on contractile activity of circular smooth muscle of the rat distal colon.

PubMed

Kito, Yoshihiko; Teramoto, Noriyoshi

2012-11-01

The Japanese Kampo medicines Hange-shashin-to (TJ-14) and Keishi-ka-shakuyaku-to (TJ-60) have been used to treat symptoms of human diarrhea on an empirical basis as Japanese traditional medicines. However, it remains unclear how these drugs affect smooth muscle tissues in the distal colon. The aim of the present study was to investigate the effects of TJ-14 and TJ-60 on the contractile activity of circular smooth muscle from the rat distal colon. TJ-14 and TJ-60 (both 1 mg/ml) inhibited spontaneous contractions of circumferentially cut preparations with the mucosa intact. Blockade of nitric oxide (NO) synthase or soluble guanylate cyclase activity abolished the inhibitory effects of TJ-60 but only attenuated the inhibitory effects of TJ-14. Apamin (1 μM), a blocker of small-conductance Ca(2+)-activated K(+) channels (SK channels), attenuated the inhibitory effects of 5 mg/ml TJ-60 but not those of 5 mg/ml TJ-14. TJ-14 suppressed contractile responses (phasic contractions and off-contractions) evoked by transmural nerve stimulation and increased basal tone, whereas TJ-60 had little effect on these parameters. These results suggest that 1 mg/ml TJ-14 or TJ-60 likely inhibits spontaneous contractions of the rat distal colon through the production of NO. Activation of SK channels seems to be involved in the inhibitory effects of 5 mg/ml TJ-60. Since TJ-14 has potent inhibitory effects on myogenic and neurogenic contractile activity, TJ-14 may be useful in suppressing gastrointestinal motility.

Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 12-week prospective, open-label study

PubMed Central

2012-01-01

Background Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger’s disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger’s disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger’s disorder. Methods This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger’s disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I). Results Forty subjects, ages 8–40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event. Conclusions These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger’s disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population. PMID:23194148

Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and modulation of zebrafish epidermal barrier.

PubMed

Zhang, Jingjing; Ni, Chen; Yang, Zhenguo; Piontek, Anna; Chen, Huapu; Wang, Sijie; Fan, Yiming; Qin, Zhihai; Piontek, Joerg

2015-08-01

Claudins (Cldn) are the major components of tight junctions (TJs) sealing the paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the homolog of mammalian Cldn4, is expressed at epithelial cell-cell contacts and is important for regulating epidermal permeability. The bacterial toxin Clostridium perfringens enterotoxin (CPE) has been shown to bind to a subset of mammalian Cldns. In this study, we used the Cldn-binding C-terminal domain of CPE (194-319 amino acids, cCPE 194-319 ) to investigate its functional role in modulating zebrafish larval epidermal barriers. In vitro analyses show that cCPE 194-319 removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which could be rescued by the removal of cCPE 194-319. Incubation of zebrafish larvae with cCPE 194-319 removed Cldnb specifically from the epidermal cell membrane. Dye diffusion analysis with 4-kDa fluorescent dextran indicated that the permeability of the epidermal barrier increased due to cCPE 194-319 incubation. Electron microscopic investigation revealed reversible loss of TJ integrity by Cldnb removal. Collectively, these results suggest that cCPE 194-319 could be used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish. In addition, zebrafish might be used as an in vivo system to investigate the capability of cCPE to enhance drug delivery across tissue barriers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway

PubMed Central

Caraballo, Juan Carlos; Yshii, Cecilia; Butti, Maria L.; Westphal, Whitney; Borcherding, Jennifer A.; Allamargot, Chantal

2011-01-01

During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of the alveolar epithelial barrier is required for the reabsorption of alveolar fluid. Tight junctions (TJ) maintain the integrity of this barrier. We set out to determine whether hypoxia creates a dysfunctional alveolar epithelial barrier, evidenced by an increase in transepithelial electrical conductance (Gt), due to a decrease in the abundance of TJ proteins at the plasma membrane. Alveolar epithelial cells (AEC) exposed to mild hypoxia (Po2 = 50 mmHg) for 30 and 60 min decreased occludin abundance at the plasma membrane and significantly increased Gt. Other cell adhesion molecules such as E-cadherin and claudins were not affected by hypoxia. AEC exposed to hypoxia increased superoxide, but not hydrogen peroxide (H2O2). Overexpression of superoxide dismutase 1 (SOD1) but not SOD2 prevented the hypoxia-induced Gt increase and occludin reduction in AEC. Also, overexpression of catalase had a similar effect as SOD1, despite not detecting any increase in H2O2 during hypoxia. Blocking PKC-ζ and protein phosphatase 2A (PP2A) prevented the hypoxia-induced occludin reduction at the plasma membrane and increase in Gt. In summary, we show that superoxide, PKC-ζ, and PP2A are involved in the hypoxia-induced increase in Gt and occludin reduction at the plasma membrane in AEC. PMID:21257729

Mechanisms and pathways of Toxoplasma gondii transepithelial migration

PubMed Central

Jones, Emily J.; Carding, Simon R.

2017-01-01

ABSTRACT Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite. PMID:28452683

Mechanisms and pathways of Toxoplasma gondii transepithelial migration.

PubMed

Jones, Emily J; Korcsmaros, Tamas; Carding, Simon R

2017-01-02

Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite.

Hole spectral functions in lightly doped quantum antiferromagnets

NASA Astrophysics Data System (ADS)

Kar, Satyaki; Manousakis, Efstratios

2011-11-01

We study the hole and magnon spectral functions as a function of hole doping in the two-dimensional t-J and t-t'-t''-J models working within the limits of spin-wave theory by linearizing the hole-spin-deviation interaction and by adapting the noncrossing approximation. We find that the staggered magnetization decreases rather rapidly with doping and it goes to zero at a few percent of hole concentration in both t-J and t-t'-t''-J models. Furthermore, our results show that the residue of the quasiparticle peak at G⃗=(±π/2,±π/2) decreases very rapidly with doping. We also find pockets centered at G⃗, (i) with an elliptical shape with large eccentricity along the antinodal direction in the case of the t-J model and (ii) with an almost circular shape in the case of the t-t'-t''-J model. Last, we show that the spectral intensity distribution in the doped antiferromagnet has a waterfall-like pattern along the nodal direction of the Brillouin zone, a feature that is also seen in angle-resolved photoemission spectroscopy measurements.

Self consistent solution of the tJ model in the overdoped regime

NASA Astrophysics Data System (ADS)

Shastry, B. Sriram; Hansen, Daniel

2013-03-01

Detailed results from a recent microscopic theory of extremely correlated Fermi liquids, applied to the t-J model in two dimensions, are presented. The theory is to second order in a parameter λ, and is valid in the overdoped regime of the tJ model. The solution reported here is from Ref, where relevant equations given in Ref are self consistently solved for the square lattice. Thermodynamic variables and the resistivity are displayed at various densities and T for two sets of band parameters. The momentum distribution function and the renormalized electronic dispersion, its width and asymmetry are reported along principal directions of the zone. The optical conductivity is calculated. The electronic spectral function A (k , ω) probed in ARPES, is detailed with different elastic scattering parameters to account for the distinction between LASER and synchrotron ARPES. A high (binding) energy waterfall feature, sensitively dependent on the band hopping parameter t' is noted. This work was supported by DOE under Grant No. FG02-06ER46319.

Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.

PubMed

Sivagurunathan, Suganya; Palanisamy, Karthikka; Arunachalam, Jayamuruga Pandian; Chidambaram, Subbulakshmi

2017-03-01

PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

NHERF1 and CFTR restore tight junction organisation and function in cystic fibrosis airway epithelial cells: role of ezrin and the RhoA/ROCK pathway.

PubMed

Castellani, Stefano; Guerra, Lorenzo; Favia, Maria; Di Gioia, Sante; Casavola, Valeria; Conese, Massimo

2012-11-01

Tight junctions (TJs) restrict the transit of ions and molecules through the paracellular route and act as a barrier to regulate access of inflammatory cells into the airway lumen. The pathophysiology of cystic fibrosis (CF) lung disease is characterised by abnormal ion and fluid transport across the epithelium and polymorphonuclear (PMN) leukocyte-dominated inflammatory response. Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) is a protein involved in PKA-dependent activation of CFTR by interacting with CFTR via its PDZ domains and with ezrin via its C-terminal domain. We have previously found that the NHERF1-overexpression dependent rescue CFTR-dependent chloride secretion is due to the re-organisation of the actin cytoskeleton network induced by the formation of the multiprotein complex NHERF1-RhoA-ezrin-actin. In this context, we here studied whether NHERF1 and CFTR are involved in the organisation and function of TJs. F508del CFBE41o⁻ monolayers presented nuclear localisation of zonula occludens (ZO-1) and occludin as well as disorganisation of claudin 1 and junction-associated adhesion molecule 1 as compared with wild-type 16HBE14o⁻ monolayers, paralleled by increased permeability to dextrans and PMN transmigration. Overexpression of either NHERF1 or CFTR in CFBE41o⁻ cells rescued TJ proteins to their proper intercellular location and decreased permeability and PMN transmigration, while this effect was not achieved by overexpressing either NHERF1 deprived of ezrin-binding domain. Further, expression of a phospho-dead ezrin mutant, T567A, increased permeability in both 16HBE14o⁻ cells and in a CFBE clone stably overexpressing NHERF1 (CFBE/sNHERF1), whereas a constitutively active form of ezrin, T567D, achieved the opposite effect in CFBE41o⁻ cells. A dominant-negative form of RhoA (RhoA-N19) also disrupted ZO-1 localisation at the intercellular contacts dislodging it to the nucleus and increased permeability in CFBE/sNHERF1. The inhibitor Y27632 of Rho kinase (ROCK) increased permeability as well. Overall, these data suggest a significant role for the multiprotein complex CFTR-NHERF1-ezrin-actin in maintaining TJ organisation and barrier function, and suggest that the RhoA/ROCK pathway is involved.

Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

PubMed

Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

2017-07-01

A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

Zonula Occludens-1, Occludin and E-cadherin Expression and Organization in Salivary Glands with Sjögren’s Syndrome

PubMed Central

Mellas, Rachel E.; Leigh, Noel J.; Nelson, Joel W.; McCall, Andrew D.

2015-01-01

Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disorder that causes secretory dysfunction of the salivary glands leading to dry mouth. Previous studies reported that tight junction (TJ) proteins are down-regulated and lose polarity in human minor salivary glands with SS, suggesting that TJ structure is compromised in SS patients. In this paper, we utilized the NOD/ShiLtJ mouse with the main goal of evaluating this model for future TJ research. We found that the organization of apical proteins in areas proximal and distal to lymphocytic infiltration remained intact in mouse and human salivary glands with SS. These areas looked comparable to control glands (i.e., with no lymphocytic infiltration). TJ staining was absent in areas of lymphocytic infiltration coinciding with the loss of salivary epithelium. Gene expression studies show that most TJs are not significantly altered in 20-week-old NOD/ShiLtJ mice as compared with age-matched C57BL/6 controls. Protein expression studies revealed that the TJ proteins, zonula occludens-1 (ZO-1), occludin, claudin-12, as well as E-cadherin, do not significantly change in NOD/ShiLtJ mice. Our results suggest that ZO-1, occludin and E-cadherin are not altered in areas without lymphocytic infiltration. However, future studies will be necessary to test the functional aspect of these results. PMID:25248927

Zonula occludens-1, occludin and E-cadherin expression and organization in salivary glands with Sjögren's syndrome.

PubMed

Mellas, Rachel E; Leigh, Noel J; Nelson, Joel W; McCall, Andrew D; Baker, Olga J

2015-01-01

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that causes secretory dysfunction of the salivary glands leading to dry mouth. Previous studies reported that tight junction (TJ) proteins are down-regulated and lose polarity in human minor salivary glands with SS, suggesting that TJ structure is compromised in SS patients. In this paper, we utilized the NOD/ShiLtJ mouse with the main goal of evaluating this model for future TJ research. We found that the organization of apical proteins in areas proximal and distal to lymphocytic infiltration remained intact in mouse and human salivary glands with SS. These areas looked comparable to control glands (i.e., with no lymphocytic infiltration). TJ staining was absent in areas of lymphocytic infiltration coinciding with the loss of salivary epithelium. Gene expression studies show that most TJs are not significantly altered in 20-week-old NOD/ShiLtJ mice as compared with age-matched C57BL/6 controls. Protein expression studies revealed that the TJ proteins, zonula occludens-1 (ZO-1), occludin, claudin-12, as well as E-cadherin, do not significantly change in NOD/ShiLtJ mice. Our results suggest that ZO-1, occludin and E-cadherin are not altered in areas without lymphocytic infiltration. However, future studies will be necessary to test the functional aspect of these results. © The Author(s) 2014.

Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

PubMed

Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

2011-09-09

Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. Copyright © 2011 Elsevier B.V. All rights reserved.

Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.

PubMed

Jin, Xiangyuan; Uchiyama, Masateru; Zhang, Qi; Niimi, Masanori

2014-05-09

Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated. Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival. Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.

Electromagnetic-pulse-induced activation of p38 MAPK pathway and disruption of blood-retinal barrier.

PubMed

Li, Hai-Juan; Guo, Liang-Mei; Yang, Long-Long; Zhou, Yong-Chun; Zhang, Yan-Jun; Guo, Juan; Xie, Xue-Jun; Guo, Guo-Zhen

2013-06-20

The blood-retinal barrier (BRB) is critical for maintaining retina homeostasis and low permeability. In this study, we evaluated the effects of electromagnetic pulse (EMP) exposure on the permeability of BRB, alterations of tight junction (TJ) proteins of BRB and if any, involvement of mitogen-activated protein kinase (MAPK) pathway. Male Sprague-Dawley (SD) rats and RF/6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV/m for 200 pulses. The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue (EB) and endogenous albumin as tracers. The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots. The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin-5, which were correlated with the increased expressions of phospho-p38, phospho-JNK and phospho-ERK and could be blocked when pretreated with p38 MAPK inhibitor. Thus, the results suggested that the alterations of occludin and claudin-5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

PubMed

Sakaida, Isao; Tsuchiya, Masako; Kawaguchi, Kotarou; Kimura, Teruaki; Terai, Shuji; Okita, Kiwamu

2003-06-01

The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis. The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined. TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner. These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.

Environmental toxicants and male reproductive function

PubMed Central

Wong, Elissa W.P; Lie, Pearl P.Y; Li, Michelle W.M; Su, Linlin; Siu, Erica R; Yan, Helen H.N; Mannu, Jayakanthan; Mathur, Premendu P; Bonanomi, Michele; Silvestrini, Bruno; Mruk, Dolores D

2011-01-01

Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or Erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to “manage” the illnesses caused by these toxicants and/or “protect” industrial workers being exposed to high levels of these toxicants in their work environment. PMID:21866273

Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C.

PubMed

Cario, Elke; Gerken, Guido; Podolsky, Daniel K

2004-07-01

Protein kinase C (PKC) has been implicated in regulation of intestinal epithelial integrity in response to lumenal bacteria. Intestinal epithelial cells (IECs) constitutively express Toll-like receptor (TLR)2, which contains multiple potential PKC binding sites. The aim of this study was to determine whether TLR2 may activate PKC in response to specific ligands, thus potentially modulating barrier function in IECs. TLR2 agonist (synthetic bacterial lipopeptide Pam(3)CysSK4, peptidoglycan)-induced activation of PKC-related signaling cascades were assessed by immunoprecipitation, Western blotting, immunofluorescence, and kinase assays-combined with functional transfection studies in the human model IEC lines HT-29 and Caco-2. Transepithelial electrical resistance characterized intestinal epithelial barrier function. Stimulation with TLR2 ligands led to activation (phosphorylation, enzymatic activity, translocation) of specific PKC isoforms (PKCalpha and PKCdelta). Phosphorylation of PKC by TLR2 ligands was blocked specifically by transfection with a TLR2 deletion mutant. Ligand-induced activation of TLR2 greatly enhanced transepithelial resistance in IECs, which was prevented by pretreatment with PKC-selective antagonists. This effect correlated with apical tightening and sealing of tight junction (TJ)-associated ZO-1, which was mediated via PKC in response to TLR2 ligands, whereas morphologic changes of occludin, claudin-1, or actin cytoskeleton were not evident. Downstream the endogenous PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS), but not transcriptional factor activator protein-1 (AP-1), was activated significantly on stimulation. The present study provides evidence that PKC is an essential component of the TLR2 signaling pathway with the physiologic consequence of directly enhancing intestinal epithelial integrity through translocation of ZO-1 on activation.

Differential protection by cell wall components of Lactobacillus amylovorus DSM 16698Tagainst alterations of membrane barrier and NF-kB activation induced by enterotoxigenic F4+ Escherichia coli on intestinal cells.

PubMed

Roselli, Marianna; Finamore, Alberto; Hynönen, Ulla; Palva, Airi; Mengheri, Elena

2016-09-29

The role of Lactobacillus cell wall components in the protection against pathogen infection in the gut is still largely unexplored. We have previously shown that L. amylovorus DSM 16698 T is able to reduce the enterotoxigenic F4 + Escherichia coli (ETEC) adhesion and prevent the pathogen-induced membrane barrier disruption through the regulation of IL-10 and IL-8 expression in intestinal cells. We have also demonstrated that L. amylovorus DSM 16698 T protects host cells through the inhibition of NF-kB signaling. In the present study, we investigated the role of L. amylovorus DSM 16698 T cell wall components in the protection against F4 + ETEC infection using the intestinal Caco-2 cell line. Purified cell wall fragments (CWF) from L. amylovorus DSM 16698 T were used either as such (uncoated, U-CWF) or coated with S-layer proteins (S-CWF). Differentiated Caco-2/TC7 cells on Transwell filters were infected with F4 + ETEC, treated with S-CWF or U-CWF, co-treated with S-CWF or U-CWF and F4 + ETEC for 2.5 h, or pre-treated with S-CWF or U-CWF for 1 h before F4 + ETEC addition. Tight junction (TJ) and adherens junction (AJ) proteins were analyzed by immunofluorescence and Western blot. Membrane permeability was determined by phenol red passage. Phosphorylated p65-NF-kB was measured by Western blot. We showed that both the pre-treatment with S-CWF and the co- treatment of S-CWF with the pathogen protected the cells from F4 + ETEC induced TJ and AJ injury, increased membrane permeability and activation of NF-kB expression. Moreover, the U-CWF pre-treatment, but not the co-treatment with F4 + ETEC, inhibited membrane damage and prevented NF-kB activation. The results indicate that the various components of L. amylovorus DSM 16698 T cell wall may counteract the damage caused by F4 + ETEC through different mechanisms. S-layer proteins are essential for maintaining membrane barrier function and for mounting an anti-inflammatory response against F4 + ETEC infection. U-CWF are not able to defend the cells when they are infected with F4 + ETEC but may activate protective mechanisms before pathogen infection.

Tight Junction–Associated Signaling Pathways Modulate Cell Proliferation in Uveal Melanoma

PubMed Central

Jayagopal, Ashwath; Yang, Jin-Long; Haselton, Frederick R.; Chang, Min S.

2011-01-01

Purpose. To investigate the role of tight junction (TJ)–associated signaling pathways in the proliferation of uveal melanoma. Methods. Human uveal melanoma cell lines overexpressing the TJ molecule blood vessel epicardial substance (Bves) were generated. The effects of Bves overexpression on TJ protein expression, cell proliferation, and cell cycle distribution were quantified. In addition, localization and transcription activity of the TJ-associated protein ZO-1–associated nucleic acid binding protein (ZONAB) were evaluated using immunofluorescence and bioluminescence reporter assays to study the involvement of Bves signaling in cell proliferation-associated pathways. Results. Bves overexpression in uveal melanoma cell lines resulted in increased expression of the TJ proteins occludin and ZO-1, reduced cell proliferation, and increased sequestration of ZONAB at TJs and reduced ZONAB transcriptional activity. Conclusions. TJ proteins are present in uveal melanoma, and TJ-associated signaling pathways modulate cell signaling pathways relevant to proliferation in uveal melanoma. PMID:20861479

Development of enzyme-linked immunosorbent assay (ELISA) for glutathione S-transferase (GST-S) protein in the intertidal copepod Tigriopus japonicus and its application for environmental monitoring.

PubMed

Rhee, Jae-Sung; Kim, Bo-Mi; Jeong, Chang-Bum; Leung, Kenneth Mei Yee; Park, Gyung Soo; Lee, Jae-Seong

2013-11-01

To utilize the GST-S protein as a useful biomarker for environmental contamination, we developed a polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) in the intertidal copepod Tigriopus japonicus. Two polyclonal antibodies, TJ-GST-S1 and TJ-GST-S2, were raised against two TJ-GST-S synthetic peptides. Also a recombinant TJ-GST-S protein was purified as a standard for ELISA development. Each polyclonal antibody was tested by Western blot analysis and indirect ELISA. Of two polyclonal antibodies, TJ-GST-S2 ELISA was further employed due to its wide range of detection and the limit of specificity compared to those of TJ-GST-S1 ELISA system. After exposure to 4 metals (Ag, As, Cd, and Cu) to T. japonicus, the amount of TJ-GST-S protein was significantly elevated in a concentration-dependent manner. Also, TJ-GST-S protein was upregulated at relative high concentrations of B[α]P, PCB, and TBT. In this paper, we suggest that T. japonicas ELISA for TJ-GST-S2 is useful as a potential indicator system for marine contaminants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Claudin-31 contributes to corticosteroid-induced alterations in the barrier properties of the gill epithelium.

PubMed

Kolosov, Dennis; Donini, Andrew; Kelly, Scott P

2017-01-05

The contribution of Claudin-31 (Cldn-31) to corticosteroid-induced tightening of the trout gill epithelium was examined using a primary cultured model preparation. Cldn-31 is a ∼23 kDa protein that localizes to the periphery of gill epithelial cells and diffusely in select gill cells that are Na + -K + -ATPase-immunoreactive. Transcriptional knockdown (KD) of cldn-31 reduced Cldn-31 abundance and increased epithelium permeability. Under simulated in vivo conditions (apical freshwater), cldn-31 KD increased net ion flux rates (≡ efflux). Cortisol treatment increased Cldn-31 abundance and decreased epithelium permeability. This tightening effect was diminished, but not eliminated, by cldn-31 KD, most likely due to other cortisol-sensitive TJ proteins that were transcriptionally unperturbed or enhanced in cortisol-treated cldn-31 KD preparations. However, cldn-31 KD abolished a cortisol-induced increase in Cldn-8d abundance, which may contribute to compromised cldn-31 KD epithelium permeability. Data suggest an important barrier function for Cldn-31 and an integral role for Cldn-31 in corticosteroid-induced gill epithelium tightening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of crustacean hyperglycemic hormone (CHH) in the environmental stressor-exposed intertidal copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Jeong, Chang-Bum; Han, Jeonghoon; Kim, Il-Chan; Rhee, Jae-Sung; Lee, Jae-Seong

2013-09-01

To identify and characterize CHH (TJ-CHH) gene in the copepod Tigriopus japonicus, we analyzed the full-length cDNA sequence, genomic structure, and promoter region. The full-length TJ-CHH cDNA was 716 bp in length, encoding 136 amino acid residues. The deduced amino acid sequences of TJ-CHH showed a high similarity of the CHH mature domain to other crustaceans. Six conserved cysteine residues and five conserved structural motifs in the CHH mature peptide domain were also observed. The genomic structure of the TJ-CHH gene contained three exons and two introns in its open reading frame (ORF), and several transcriptional elements were detected in the promoter region of the TJ-CHH gene. To investigate transcriptional change of TJ-CHH under environmental stress, T. japonicus were exposed to heat treatment, UV-B radiation, heavy metals, and water-accommodated fractions (WAFs) of Iranian crude oil. Upon heat stress, TJ-CHH transcripts were elevated at 30 °C and 35 °C for 96 h in a time-course experiment. UV-B radiation led to a decreased pattern of the TJ-CHH transcript 48 h and more after radiation (12 kJ/m(2)). After exposure of a fixed dose (12 kJ/m(2)) in a time-course experiment, TJ-CHH transcript was down-regulated in time-dependent manner with a lowest value at 12h. However, the TJ-CHH transcript level was increased in response to five heavy metal exposures for 96 h. Also, the level of the TJ-CHH transcript was significantly up-regulated at 20% of WAFs after exposure to WAFs for 48 h and then remarkably reduced in a dose-dependent manner. These findings suggest that the enhanced TJ-CHH transcript level is associated with a cellular stress response of the TJ-CHH gene as shown in decapod crustaceans. This study is also helpful for a better understanding of the detrimental effects of environmental changes on the CHH-triggered copepod metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex

PubMed Central

Hou, Jianghui; Renigunta, Aparna; Konrad, Martin; Gomes, Antonio S.; Schneeberger, Eveline E.; Paul, David L.; Waldegger, Siegfried; Goodenough, Daniel A.

2008-01-01

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an inherited disorder caused by mutations in the genes encoding the TJ proteins claudin-16 (CLDN16) and CLDN19; however, the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney are not understood. Here we showed that in pig kidney epithelial cells, CLDN19 functioned as a Cl– blocker, whereas CLDN16 functioned as a Na+ channel. Mutant forms of CLDN19 that are associated with FHHNC were unable to block Cl– permeation. Coexpression of CLDN16 and CLDN19 generated cation selectivity of the TJ in a synergistic manner, and CLDN16 and CLDN19 were observed to interact using several criteria. In addition, disruption of this interaction by introduction of FHHNC-causing mutant forms of either CLDN16 or CLDN19 abolished their synergistic effect. Our data show that CLDN16 interacts with CLDN19 and that their association confers a TJ with cation selectivity, suggesting a mechanism for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC. PMID:18188451

Anxiolytic effect of Kami-Shoyo-San (TJ-24) in mice: possible mediation of neurosteroid synthesis.

PubMed

Mizowaki, M; Toriizuka, K; Hanawa, T

2001-09-21

We assessed the anxiolytic effect of Kami-Shoyo-San (Jia-wei-xiao-yao-san; TJ-24), one of a traditional Chinese herbal medicine used for the treatment of menopausal anxiety, by the social interaction (SI) test in male mice. Acute administration of TJ-24 (25-100 mg/kg, p.o.), as well as the gamma-amino-butyric acidA/benzodiazepine (GABA(A)/BZP) receptor agonist diazepam (1-3 mg/kg, i.p.), dose dependently increased the SI time, respectively. The GABA(A) receptor antagonist picrotoxin blocked the effects of TJ-24 and diazepam. TJ-24-induced SI behavior was significantly blocked by the GABA(A)/BZP receptor inverse agonist Ro 15-4513 and the GABA(A)/BZP receptor antagonist flumazenil. In addition, 5alpha-reductase inhibitor finasteride potently blocked the effect of TJ-24 without attenuating the basal level by itself. These findings suggest that TJ-24 shows the anxiolytic effect through the neurosteroid synthesis followed by GABA(A)/BDZ receptor stimulations.

Redox Regulation of Cell Contacts by Tricellulin and Occludin: Redox-Sensitive Cysteine Sites in Tricellulin Regulate Both Tri- and Bicellular Junctions in Tissue Barriers as Shown in Hypoxia and Ischemia.

PubMed

Cording, Jimmi; Günther, Ramona; Vigolo, Emilia; Tscheik, Christian; Winkler, Lars; Schlattner, Isabella; Lorenz, Dorothea; Haseloff, Reiner F; Schmidt-Ott, Kai M; Wolburg, Hartwig; Blasig, Ingolf E

2015-11-01

Tight junctions (TJs) seal paracellular clefts in epithelia/endothelia and form tissue barriers for proper organ function. TJ-associated marvel proteins (TAMPs; tricellulin, occludin, marvelD3) are thought to be relevant to regulation. Under normal conditions, tricellulin tightens tricellular junctions against macromolecules. Traces of tricellulin occur in bicellular junctions. As pathological disturbances have not been analyzed, the structure and function of human tricellulin, including potentially redox-sensitive Cys sites, were investigated under reducing/oxidizing conditions at 3- and 2-cell contacts. Ischemia, hypoxia, and reductants redistributed tricellulin from 3- to 2-cell contacts. The extracellular loop 2 (ECL2; conserved Cys321, Cys335) trans-oligomerized between three opposing cells. Substitutions of these residues caused bicellular localization. Cys362 in transmembrane domain 4 contributed to bicellular heterophilic cis-interactions along the cell membrane with claudin-1 and marvelD3, while Cys395 in the cytosolic C-terminal tail promoted homophilic tricellullar cis-interactions. The Cys sites included in homo-/heterophilic bi-/tricellular cis-/trans-interactions contributed to cell barrier tightness for small/large molecules. Tricellulin forms TJs via trans- and cis-association in 3-cell contacts, as demonstrated electron and quantified fluorescence microscopically; it tightens 3- and 2-cell contacts. Tricellulin's ECL2 specifically seals 3-cell contacts redox dependently; a structural model is proposed. TAMP ECL2 and claudins' ECL1 share functionally and structurally similar features involved in homo-/heterophilic tightening of cell-cell contacts. Tricellulin is a specific redox sensor and sealing element at 3-cell contacts and may compensate as a redox mediator for occludin loss at 2-cell contacts in vivo and in vitro. Molecular interaction mechanisms were proposed that contribute to tricellulin's function. In conclusion, tricellulin is a junctional redox regulator for ischemia-related alterations.

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

Comparison of online and offline tests in LED accelerated reliability tests under temperature stress.

PubMed

Ke, Hong-Liang; Jing, Lei; Gao, Qun; Wang, Yao; Hao, Jian; Sun, Qiang; Xu, Zhi-Jun

2015-11-20

Accelerated aging tests are the main method used in the evaluation of LED reliability, and can be performed in either online or offline modes. The goal of this study is to provide the difference between the two test modes. In the experiments, the sample is attached to different heat sinks to acquire the optical parameters under different junction temperatures of LEDs. By measuring the junction temperature in the aging process (Tj1), and the junction temperature in the testing process (Tj2), we achieve consistency with an online test of Tj1 and Tj2 and a difference with an offline test of Tj1 and Tj2. Experimental results show that the degradation rate of the luminous flux rises as Tj2 increases, which yields a difference of projected life L(70%) of 8% to 13%. For color shifts over 5000 h of aging, the online test shows a larger variation of the distance from the Planckian locus, about 40% to 50% more than the normal test at an ambient temperature of 25°C.

Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood–brain barrier model for drug permeability studies

PubMed Central

2013-01-01

Background Reliable human in vitro blood–brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellular permeability. Co-culture systems using immortalized human astrocytes (SVG-A cell line) and immortalized human pericytes (HBPCT cell line) were designed with the aim of positively influencing barrier tightness. Methods Tight junction (TJ) formation was assessed by transendothelial electrical resistance (TEER) measurements using a conventional epithelial voltohmmeter (EVOM) and an automated CellZscope system which records TEER and cell layer capacitance (CCL) in real-time. Paracellular permeability was assessed using two fluorescent marker compounds with low BBB penetration (sodium fluorescein (Na-F) and lucifer yellow (LY)). Conditions were optimized for each endothelial cell line by screening a series of 24-well tissue culture inserts from different providers. For hBMEC cells, further optimization was carried out by varying coating material, coating procedure, cell seeding density, and growth media composition. Biochemical characterization of cell type-specific transmembrane adherens junction protein VE-cadherin and of TJ proteins ZO-1 and claudin-5 were carried out for each endothelial cell line. In addition, immunostaining for ZO-1 in hBMEC cell line was performed. Results The four cell lines all expressed the endothelial cell type-specific adherens junction protein VE-cadherin. The TJ protein ZO-1 was expressed in hCMEC/D3 and in hBMEC cells. ZO-1 expression could be confirmed in hBMEC cells by immunocytochemical staining. Claudin-5 expression was detected in hCMEC/D3, TY10, and at a very low level in hBMEC cells. Highest TEER values and lowest paracellular permeability for Na-F and LY were obtained with mono-cultures of hBMEC cell line when cultivated on 24-well tissue culture inserts from Greiner Bio-one® (transparent PET membrane, 3.0 μm pore size). In co-culture models with SVG-A and HBPCT cells, no increase of TEER could be observed, suggesting that none of the investigated endothelial cell lines responded positively to stimuli from immortalized astrocytic or pericytic cells. Conclusions Under the conditions examined in our experiments, hBMEC proved to be the most suitable human cell line for an in vitro BBB model concerning barrier tightness in a 24-well mono-culture system intended for higher throughput. This BBB model is being validated with several compounds (known to cross or not to cross the BBB), and will potentially be selected for the assessment of BBB permeation of bioactive natural products. PMID:24262108

Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood-brain barrier model for drug permeability studies.

PubMed

Eigenmann, Daniela E; Xue, Gongda; Kim, Kwang S; Moses, Ashlee V; Hamburger, Matthias; Oufir, Mouhssin

2013-11-22

Reliable human in vitro blood-brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellular permeability. Co-culture systems using immortalized human astrocytes (SVG-A cell line) and immortalized human pericytes (HBPCT cell line) were designed with the aim of positively influencing barrier tightness. Tight junction (TJ) formation was assessed by transendothelial electrical resistance (TEER) measurements using a conventional epithelial voltohmmeter (EVOM) and an automated CellZscope system which records TEER and cell layer capacitance (CCL) in real-time.Paracellular permeability was assessed using two fluorescent marker compounds with low BBB penetration (sodium fluorescein (Na-F) and lucifer yellow (LY)). Conditions were optimized for each endothelial cell line by screening a series of 24-well tissue culture inserts from different providers. For hBMEC cells, further optimization was carried out by varying coating material, coating procedure, cell seeding density, and growth media composition. Biochemical characterization of cell type-specific transmembrane adherens junction protein VE-cadherin and of TJ proteins ZO-1 and claudin-5 were carried out for each endothelial cell line. In addition, immunostaining for ZO-1 in hBMEC cell line was performed. The four cell lines all expressed the endothelial cell type-specific adherens junction protein VE-cadherin. The TJ protein ZO-1 was expressed in hCMEC/D3 and in hBMEC cells. ZO-1 expression could be confirmed in hBMEC cells by immunocytochemical staining. Claudin-5 expression was detected in hCMEC/D3, TY10, and at a very low level in hBMEC cells. Highest TEER values and lowest paracellular permeability for Na-F and LY were obtained with mono-cultures of hBMEC cell line when cultivated on 24-well tissue culture inserts from Greiner Bio-one® (transparent PET membrane, 3.0 μm pore size). In co-culture models with SVG-A and HBPCT cells, no increase of TEER could be observed, suggesting that none of the investigated endothelial cell lines responded positively to stimuli from immortalized astrocytic or pericytic cells. Under the conditions examined in our experiments, hBMEC proved to be the most suitable human cell line for an in vitro BBB model concerning barrier tightness in a 24-well mono-culture system intended for higher throughput. This BBB model is being validated with several compounds (known to cross or not to cross the BBB), and will potentially be selected for the assessment of BBB permeation of bioactive natural products.

The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

PubMed

Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

2003-11-01

Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

Reduced-droop green III-nitride light-emitting diodes utilizing GaN tunnel junction

NASA Astrophysics Data System (ADS)

Alhassan, Abdullah I.; Young, Erin C.; Alyamani, Ahmed Y.; Albadri, Abdulrahman; Nakamura, Shuji; DenBaars, Steven P.; Speck, James S.

2018-04-01

We report the fabrication of low-droop high-efficiency green c-plane light-emitting diodes (LEDs) utilizing GaN tunnel junction (TJ) contacts. The LED epitaxial layers with a top p-GaN layer were grown by metal organic chemical vapor deposition and an n++-GaN layer was deposited by molecular beam epitaxy to form a TJ. The TJ LEDs were then compared with equivalent LEDs having a tin-doped indium oxide (ITO) contact. The TJ LEDs exhibited a higher performance and a lower efficiency droop than did the ITO LEDs. At 35 A/cm2, the external quantum efficiencies for the TJ and ITO LEDs were 31.2 and 27%, respectively.

Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction.

PubMed

McCabe, M J; Tarulli, G A; Laven-Law, G; Matthiesson, K L; Meachem, S J; McLachlan, R I; Dinger, M E; Stanton, P G

2016-04-01

Are Sertoli cell tight junctions (TJs) disrupted in men undergoing hormonal contraception? Localization of the key Sertoli cell TJ protein, claudin-11, was markedly disrupted by 8 weeks of gonadotropin suppression, the degree of which was related to the extent of adluminal germ cell suppression. Sertoli cell TJs are vital components of the blood-testis barrier (BTB) that sequester developing adluminal meiotic germ cells and spermatids from the vascular compartment. Claudin-11 knockout mice are infertile; additionally claudin-11 is spatially disrupted in chronically gonadotropin-suppressed rats coincident with a loss of BTB function, and claudin-11 is disorganized in various human testicular disorders. These data support the Sertoli cell TJ as a potential site of hormonal contraceptive action. BTB proteins were assessed by immunohistochemistry (n = 16 samples) and mRNA (n = 18 samples) expression levels in available archived testis tissue from a previous study of 22 men who had undergone 8 weeks of gonadotropin suppression and for whom meiotic and post-meiotic germ cell numbers were available. The gonadotropin suppression regimens were (i) testosterone enanthate (TE) plus the GnRH antagonist, acyline (A); (ii) TE + the progestin, levonorgestrel, (LNG); (iii) TE + LNG + A or (iv) TE + LNG + the 5α-reductase inhibitor, dutasteride (D). A control group consisted of seven additional men, with three archived samples available for this study. Immunohistochemical localization of claudin-11 (TJ) and other junctional type markers [ZO-1 (cytoplasmic plaque), β-catenin (adherens junction), connexin-43 (gap junction), vinculin (ectoplasmic specialization) and β-actin (cytoskeleton)] and quantitative PCR was conducted using matched frozen testis tissue. Claudin-11 formed a continuous staining pattern at the BTB in control men. Regardless of gonadotropin suppression treatment, claudin-11 localization was markedly disrupted and was broadly associated with the extent of meiotic/post-meiotic germ cell suppression; claudin-11 staining was (i) punctate (i.e. 'spotty' appearance) at the basal aspect of tubules when the average numbers of adluminal germ cells were <15% of control, (ii) presented as short fragments with cytoplasmic extensions when numbers were 15-25% of control or (iii) remained continuous when numbers were >40% of control. Changes in localization of connexin-43 and vinculin were also observed (smaller effects than for claudin-11) but ZO-1, β-catenin and β-actin did not differ, compared with control. Claudin-11 was the only Sertoli cell TJ protein investigated, but it is considered to be the most pivotal of constituent proteins given its known implication in infertility and BTB function. We were limited to testis samples which had been gonadotropin-suppressed for 8 weeks, shorter than the 74-day spermatogenic wave, which may account for the heterogeneity in claudin-11 and germ cell response observed among the men. Longer suppression (12-24 weeks) is known to suppress germ cells further and claudin-11 disruption may be more uniform, although we could not access such samples. These findings are important for our understanding of the sites of action of male hormonal contraception, because they suggest that BTB function could be ablated following long-term hormone suppression treatment. National Health and Medical Research Council (Australia) Program Grants 241000 and 494802; Research Fellowship 1022327 (to R.I.M.) and the Victorian Government's Operational Infrastructure Support Program. None of the authors have any conflicts to disclose. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin

PubMed Central

Chen, Haiqi; Mruk, Dolores D.; Xia, Weiliang; Bonanomi, Michele; Silvestrini, Bruno; Cheng, Chuen-Yan

2016-01-01

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men. PMID:26758796

Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) - Lesson from Adjudin.

PubMed

Chen, Haiqi; Mruk, Dolores D; Xia, Weiliang; Bonanomi, Michele; Silvestrini, Bruno; Cheng, Chuen-Yan

2016-01-01

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men.

A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila.

PubMed

Saito, Kuniaki; Inagaki, Sachi; Mituyama, Toutai; Kawamura, Yoshinori; Ono, Yukiteru; Sakota, Eri; Kotani, Hazuki; Asai, Kiyoshi; Siomi, Haruhiko; Siomi, Mikiko C

2009-10-29

PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi. piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster, traffic jam (tj), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini, a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.

Cingulin Contains Globular and Coiled-Coil Domains and Interacts with Zo-1, Zo-2, Zo-3, and Myosin

PubMed Central

Cordenonsi, Michelangelo; D'Atri, Fabio; Hammar, Eva; Parry, David A.D.; Kendrick-Jones, John; Shore, David; Citi, Sandra

1999-01-01

We characterized the sequence and protein interactions of cingulin, an M r 140–160-kD phosphoprotein localized on the cytoplasmic surface of epithelial tight junctions (TJ). The derived amino acid sequence of a full-length Xenopus laevis cingulin cDNA shows globular head (residues 1–439) and tail (1,326–1,368) domains and a central α-helical rod domain (440–1,325). Sequence analysis, electron microscopy, and pull-down assays indicate that the cingulin rod is responsible for the formation of coiled-coil parallel dimers, which can further aggregate through intermolecular interactions. Pull-down assays from epithelial, insect cell, and reticulocyte lysates show that an NH2-terminal fragment of cingulin (1–378) interacts in vitro with ZO-1 (K d ∼5 nM), ZO-2, ZO-3, myosin, and AF-6, but not with symplekin, and a COOH-terminal fragment (377–1,368) interacts with myosin and ZO-3. ZO-1 and ZO-2 immunoprecipitates contain cingulin, suggesting in vivo interactions. Full-length cingulin, but not NH2-terminal and COOH-terminal fragments, colocalizes with endogenous cingulin in transfected MDCK cells, indicating that sequences within both head and rod domains are required for TJ localization. We propose that cingulin is a functionally important component of TJ, linking the submembrane plaque domain of TJ to the actomyosin cytoskeleton. PMID:10613913

Tracer-Encapsulated Solid Pellet (TESPEL) Injection System for the TJ-II Stellarator

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

Tamura, N.; McCarthy, K. J.; Hayashi, H.

2016-01-01

A tracer-encapsulated solid pellet (TESPEL) injection system for the TJ-II stellarator was recently developed. In order to reduce the time and cost for the development, we combined a TESPEL injector provided by National Institute for Fusion Science with an existing TJ-II cryogenic pellet injection system. Consequently, the TESPEL injection into the TJ-II plasma was successfully achieved, which was confirmed by several pellet diagnostics including a normal-incidence spectrometer for monitoring a tracer impurity behavior.

Acceleration of small bowel motility after oral administration of dai-kenchu-to (TJ-100) assessed by cine magnetic resonance imaging

PubMed Central

Furukawa, Akira; Yamamoto, Hiroshi; Ohta, Shinichi; Linh, Nguyen Dai Hung; Syerikjan, Tulyeubai; Kaida, Sachiko; Yamaguchi, Tsuyoshi; Murata, Satoshi; Obata, Toru; Tani, Masaji; Murata, Kiyoshi

2018-01-01

Dai-kenchu-to (TJ-100) is an herbal medicine used to shorten the duration of intestinal transit by accelerating intestinal movement. However, intestinal movement in itself has not been evaluated in healthy volunteers using radiography, fluoroscopy, and radioisotopes because of exposure to ionizing radiation. The purpose of this study was to evaluate the effect of TJ-100 on intestinal motility using cinematic magnetic resonance imaging (cine MRI) with a steady-state free precession sequence. Ten healthy male volunteers received 5 g of either TJ-100 or lactose without disclosure of the identity of the substance. Each volunteer underwent two MRI examinations after taking the substances (TJ-100 and lactose) on separate days. They drank 1200 mL of tap water and underwent cine MRI after 10 min. A steady-state free precession sequence was used for imaging, which was performed thrice at 0, 10, 20, 30, 40, and 50 min. The bowel contraction frequency and distention score were assessed. Wilcoxon signed-rank test was used, and differences were considered significant at a P-value <0.05. The bowel contraction frequency tended to be greater in the TJ-100 group and was significantly different in the ileum at 20 (TJ-100, 8.95 ± 2.88; lactose, 4.80 ± 2.92; P < 0.05) and 50 min (TJ-100, 9.45 ± 4.49; lactose, 4.45 ± 2.65; P < 0.05) between the groups. No significant differences were observed in the bowel distention scores. Cine MRI demonstrated that TJ-100 activated intestinal motility without dependence on ileum distention. PMID:29320574

Micro-light-emitting diodes with III-nitride tunnel junction contacts grown by metalorganic chemical vapor deposition

NASA Astrophysics Data System (ADS)

Hwang, David; Mughal, Asad J.; Wong, Matthew S.; Alhassan, Abdullah I.; Nakamura, Shuji; DenBaars, Steven P.

2018-01-01

Micro-light-emitting diodes (µLEDs) with tunnel junction (TJ) contacts were grown entirely by metalorganic chemical vapor deposition. A LED structure was grown, treated with UV ozone and hydrofluoric acid, and reloaded into the reactor for TJ regrowth. The silicon doping level of the n++-GaN TJ was varied to examine its effect on voltage. µLEDs from 2.5 × 10-5 to 0.01 mm2 in area were processed, and the voltage penalty of the TJ for the smallest µLED at 20 A/cm2 was 0.60 V relative to that for a standard LED with indium tin oxide. The peak external quantum efficiency of the TJ LED was 34%.

RAI14 (retinoic acid induced protein 14) is an F-actin regulator

PubMed Central

Qian, Xiaojing; Mruk, Dolores D.; Cheng, Yan-ho; Cheng, C. Yan

2013-01-01

RAI14 (retinoic acid induced protein 14) is an actin-binding protein first identified in the liver. In the testis, RAI14 is expressed by both Sertoli and germ cells in the seminiferous epithelium. Besides binding to actin in the testis, RAI14 is also a binding protein for palladin, an actin cross-linking and bundling protein. A recent report has shown that RAI14 displays stage-specific and spatiotemporal expression at the ES [ectoplasmic specialization, a testis-specific filamentous (F)-actin-rich adherens junction] in the seminiferous epithelium of adult rat testes during the epithelial cycle of spermatogenesis, illustrating its likely involvement in F-actin organization at the ES. Functional studies in which RAI14 was knocked down by RNAi in Sertoli cells in vitro and also in testicular cells in vivo have illustrated its role in conferring the integrity of actin filament bundles at the ES, perturbing the Sertoli cell tight junction (TJ)-pemeability barrier function in vitro, and also spermatid polarity and adhesion in vivo, thereby regulating spermatid transport at spermiation. Herein, we critically evaluate these earlier findings and also provide a likely hypothetic model based on the functional role of RAI14 at the ES, and how RAI14 is working with palladin and other actin regulatory proteins in the testis to regulate the transport of (1) spermatids and (2) preleptotene spermatocytes across the seminiferous epithelium and the blood-testis barrier (BTB), respectively, during spermatogenesis. This model should serve as a framework upon which functional experiments can be designed to better understand the biology of RAI14 and other actin-binding and regulatory proteins in the testis. PMID:23885305

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.

PubMed

Fiorentino, Maria; Sapone, Anna; Senger, Stefania; Camhi, Stephanie S; Kadzielski, Sarah M; Buie, Timothy M; Kelly, Deanna L; Cascella, Nicola; Fasano, Alessio

2016-01-01

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin ( CLDN )-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3 , tricellulin , and MMP-9 were higher in the ASD cortex. IL-8 , tPA , and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components ( CLDN-1 , OCLN , TRIC ), whereas 66% had increased pore-forming CLDNs ( CLDN-2 , -10 , -15 ) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Creamer uses communication equipment in the FGB during Expedition 22

NASA Image and Video Library

2010-01-14

ISS022-E-025400 (14 Jan. 2010) --- NASA astronaut T.J. Creamer, Expedition 22 flight engineer, uses a communication system in the Zarya Functional Cargo Block (FGB) of the International Space Station.

Development of methane and nitrous oxide emission factors for the biomass fired circulating fluidized bed combustion power plant.

PubMed

Cho, Chang-Sang; Sa, Jae-Hwan; Lim, Ki-Kyo; Youk, Tae-Mi; Kim, Seung-Jin; Lee, Seul-Ki; Jeon, Eui-Chan

2012-01-01

This study makes use of this distinction to analyze the exhaust gas concentration and fuel of the circulating fluidized bed (CFB) boiler that mainly uses wood biomass, and to develop the emission factors of Methane (CH(4)), Nitrous oxide (N(2)O). The fuels used as energy sources in the subject working sites are Wood Chip Fuel (WCF), RDF and Refused Plastic Fuel (RPF) of which heating values are 11.9 TJ/Gg, 17.1 TJ/Gg, and 31.2 TJ/Gg, respectively. The average concentrations of CH(4) and N(2)O were measured to be 2.78 ppm and 7.68 ppm, respectively. The analyzed values and data collected from the field survey were used to calculate the emission factor of CH(4) and N(2)O exhausted from the CFB boiler. As a result, the emission factors of CH(4) and N(2)O are 1.4 kg/TJ (0.9-1.9 kg/TJ) and 4.0 kg/TJ (2.9-5.3 kg/TJ) within a 95% confidence interval. Biomass combined with the combustion technology for the CFB boiler proved to be more effective in reducing the N(2)O emission, compared to the emission factor of the CFB boiler using fossil fuel.

Demonstration of a III-nitride vertical-cavity surface-emitting laser with a III-nitride tunnel junction intracavity contact

NASA Astrophysics Data System (ADS)

Leonard, J. T.; Young, E. C.; Yonkee, B. P.; Cohen, D. A.; Margalith, T.; DenBaars, S. P.; Speck, J. S.; Nakamura, S.

2015-08-01

We report on a III-nitride vertical-cavity surface-emitting laser (VCSEL) with a III-nitride tunnel junction (TJ) intracavity contact. The violet nonpolar VCSEL employing the TJ is compared to an equivalent VCSEL with a tin-doped indium oxide (ITO) intracavity contact. The TJ VCSEL shows a threshold current density (Jth) of ˜3.5 kA/cm2, compared to the ITO VCSEL Jth of 8 kA/cm2. The differential efficiency of the TJ VCSEL is also observed to be significantly higher than that of the ITO VCSEL, reaching a peak power of ˜550 μW, compared to ˜80 μW for the ITO VCSEL. Both VCSELs display filamentary lasing in the current aperture, which we believe to be predominantly a result of local variations in contact resistance, which may induce local variations in refractive index and free carrier absorption. Beyond the analyses of the lasing characteristics, we discuss the molecular-beam epitaxy (MBE) regrowth of the TJ, as well as its unexpected performance based on band-diagram simulations. Furthermore, we investigate the intrinsic advantages of using a TJ intracavity contact in a VCSEL using a 1D mode profile analysis to approximate the threshold modal gain and general loss contributions in the TJ and ITO VCSEL.

The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.

PubMed

Xue, Meilan; Ji, Xinqiang; Liang, Hui; Liu, Ying; Wang, Bing; Sun, Lingling; Li, Weiwei

2018-02-21

Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.

Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.

PubMed

Zhu, Jing-Cheng; Si, Meng-Ya; Li, Ya-Zhen; Chen, Huan-Zhu; Fan, Zhi-Cheng; Xie, Qing-Dong; Jiao, Xiao-Yang

2017-09-01

The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBC CSF , ALB CSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5 CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Performance improvement in novel germanium-tin/germanium heterojunction-enhanced p-channel tunneling field-effect transistor

NASA Astrophysics Data System (ADS)

Wang, Hongjuan; Liu, Yan; Liu, Mingshan; Zhang, Qingfang; Zhang, Chunfu; Ma, Xiaohua; Zhang, Jincheng; Hao, Yue; Han, Genquan

2015-07-01

We design a novel GeSn-based heterojunction-enhanced p-channel tunneling field-effect transistor (HE-PTFET) with a Ge0.92Sn0.08/Ge heterojunction located in channel region, at a distance of LT-H from the Ge0.92Sn0.08 source-channel tunneling junction (TJ). HE-PTFETs demonstrate the negative shift of onset voltage VONSET, the steeper subthreshold swing S, and the improved on-state current ION compared to Ge0.92Sn0.08 homo-PTFET. At low VGS, the suppression of BTBT due to the widening of the tunneling barrier caused by the heterojunction leads to a negative shift of VONSET in HE-PTFETs. At high VGS, ION enhancement in HE-PTFETs is achieved over the homo device, which is attributed to the confinement of BTBT in Ge0.92Sn0.08 source-channel TJ region by the heterojunction, where the short tunneling paths lead to a high tunneling probability. Due to the steeper average S, HE-PTFET with a 6 nm LT-H achieves a 4 times higher ION compared to homo device at a VDD of -0.3 V.

Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.

PubMed

Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

2016-11-01

We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Methyl-beta-cyclodextrin increases permeability of Caco-2 cell monolayers by displacing specific claudins from cholesterol rich domains associated with tight junctions.

PubMed

Lambert, Daniel; O'Neill, Catherine A; Padfield, Philip J

2007-01-01

In a previous study we demonstrated that depletion of Caco-2 cell cholesterol results in the loss of tight junction (TJ) integrity through the movement of claudins 3 and 4 and occludin, but not claudin 1, out of the TJs [1]. The aims of this study were to determine whether the major tight junction (TJ) proteins in Caco-2 cells are associated with cholesterol rich, membrane raft-like domains and if the loss of TJ integrity produced by the extraction of cholesterol reflects the dissolution of these domains resulting in the loss of TJ organisation. We have demonstrated that in Caco-2 cells claudins 1, 3, 4 and 7, JAM-A and occludin, are associated with cholesterol rich membrane domains that are insoluble in Lubrol WX. Co-immunoprecipitation studies demonstrated that there is no apparent restriction on the combination of claudins present in the rafts and that interaction between the proteins is dependent on cholesterol. JAM-A was not co-immunoprecipitated with the other TJ proteins indicating that it is resident within in a distinct population of rafts and therefore is likely not directly associated with the claudins/occludin present in the TJ complexes. Depletion of Caco-2 cell cholesterol with methyl-beta-cyclodextrin resulted in the displacement of claudins 3, 4 and 7, JAM-A and occludin, but not claudin 1, out of the cholesterol rich domains. Our data indicate that depletion of cholesterol does not result in the loss of the TJ-associated membrane rafts. However, the sterol is required to maintain the association of key proteins with the TJ associated membrane rafts and therefore the TJs. Furthermore, the data suggest that cholesterol may actually directly stabilise the multi-protein complexes that form the TJ strands. Copyright (c) 2007 S. Karger AG, Basel.

Spectral properties near the Mott transition in the two-dimensional t-J model with next-nearest-neighbor hopping

NASA Astrophysics Data System (ADS)

Kohno, Masanori

2018-05-01

The single-particle spectral properties of the two-dimensional t-J model with next-nearest-neighbor hopping are investigated near the Mott transition by using cluster perturbation theory. The spectral features are interpreted by considering the effects of the next-nearest-neighbor hopping on the shift of the spectral-weight distribution of the two-dimensional t-J model. Various anomalous features observed in hole-doped and electron-doped high-temperature cuprate superconductors are collectively explained in the two-dimensional t-J model with next-nearest-neighbor hopping near the Mott transition.

Demonstration of a III-nitride vertical-cavity surface-emitting laser with a III-nitride tunnel junction intracavity contact

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

Leonard, J. T., E-mail: jtleona01@gmail.com; Young, E. C.; Yonkee, B. P.

2015-08-31

We report on a III-nitride vertical-cavity surface-emitting laser (VCSEL) with a III-nitride tunnel junction (TJ) intracavity contact. The violet nonpolar VCSEL employing the TJ is compared to an equivalent VCSEL with a tin-doped indium oxide (ITO) intracavity contact. The TJ VCSEL shows a threshold current density (J{sub th}) of ∼3.5 kA/cm{sup 2}, compared to the ITO VCSEL J{sub th} of 8 kA/cm{sup 2}. The differential efficiency of the TJ VCSEL is also observed to be significantly higher than that of the ITO VCSEL, reaching a peak power of ∼550 μW, compared to ∼80 μW for the ITO VCSEL. Both VCSELs display filamentary lasing inmore » the current aperture, which we believe to be predominantly a result of local variations in contact resistance, which may induce local variations in refractive index and free carrier absorption. Beyond the analyses of the lasing characteristics, we discuss the molecular-beam epitaxy (MBE) regrowth of the TJ, as well as its unexpected performance based on band-diagram simulations. Furthermore, we investigate the intrinsic advantages of using a TJ intracavity contact in a VCSEL using a 1D mode profile analysis to approximate the threshold modal gain and general loss contributions in the TJ and ITO VCSEL.« less

Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial.

PubMed

Urata, Y; Yoshida, S; Irie, Y; Tanigawa, T; Amayasu, H; Nakabayashi, M; Akahori, K

2002-06-01

Alternative medicine use has increased at a remarkable pace all over the world in recent years. Although herbal medicine for the treatment of asthma is becoming the focus of public attention, randomized studies had not been performed, even in Eastern countries including Japan. This study was designed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to (TJ-96) is effective for the treatment of atopic asthma, and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation. A double-blind, randomized, crossover design was used. Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine. Furthermore, eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. After 4 weeks of treatment with TJ-96, values of PC20 -methacholine significantly improved in the treatment with TJ-96. Also, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma.

Development of Methane and Nitrous Oxide Emission Factors for the Biomass Fired Circulating Fluidized Bed Combustion Power Plant

PubMed Central

Cho, Chang-Sang; Sa, Jae-Hwan; Lim, Ki-Kyo; Youk, Tae-Mi; Kim, Seung-Jin; Lee, Seul-Ki; Jeon, Eui-Chan

2012-01-01

This study makes use of this distinction to analyze the exhaust gas concentration and fuel of the circulating fluidized bed (CFB) boiler that mainly uses wood biomass, and to develop the emission factors of Methane (CH4), Nitrous oxide (N2O). The fuels used as energy sources in the subject working sites are Wood Chip Fuel (WCF), RDF and Refused Plastic Fuel (RPF) of which heating values are 11.9 TJ/Gg, 17.1 TJ/Gg, and 31.2 TJ/Gg, respectively. The average concentrations of CH4 and N2O were measured to be 2.78 ppm and 7.68 ppm, respectively. The analyzed values and data collected from the field survey were used to calculate the emission factor of CH4 and N2O exhausted from the CFB boiler. As a result, the emission factors of CH4 and N2O are 1.4 kg/TJ (0.9–1.9 kg/TJ) and 4.0 kg/TJ (2.9–5.3 kg/TJ) within a 95% confidence interval. Biomass combined with the combustion technology for the CFB boiler proved to be more effective in reducing the N2O emission, compared to the emission factor of the CFB boiler using fossil fuel. PMID:23365540

A mechanism enhancing macromolecule transport through paracellular spaces induced by Poly-L-Arginine: Poly-L-Arginine induces the internalization of tight junction proteins via clathrin-mediated endocytosis.

PubMed

Yamaki, Tsutomu; Kamiya, Yusuke; Ohtake, Kazuo; Uchida, Masaki; Seki, Toshinobu; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

2014-09-01

Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we investigated the mechanism of disappearance of TJ proteins from cell-cell junctions after the application of PLA to Caco-2 cell monolayers. The membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA in the presence of various endocytosis inhibitors. In addition, the localization of endosome marker proteins was also observed. Clathrin-mediated endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by PLA, and also significantly suppressed the disappearance of TJ proteins induced by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early endosome and recycling endosomes after the internalization of occludin induced by PLA, and then was recycled to the cell-cell junctions. PLA induced the transient internalization of TJ proteins in cell-cell junctions via clathrin-mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.

Tetramethylpyrazine-2'-O-sodium ferulate attenuates blood-brain barrier disruption and brain oedema after cerebral ischemia/reperfusion.

PubMed

Xu, S-H; Yin, M-S; Liu, B; Chen, M-L; He, G-W; Zhou, P-P; Cui, Y-J; Yang, D; Wu, Y-L

2017-07-01

Disruption of blood-brain barrier (BBB) and subsequent oedema are major causes of the pathogenesis in ischaemic stroke with which the current clinical therapy remains unsatisfied. In this study, we examined the therapeutic effect of tetramethylpyrazine-2'-O-sodium ferulate (TSF)-a novel analogue of tetramethylpyrazine in alleviating BBB breakdown and brain oedema after cerebral ischaemia/reperfusion (I/R). Then, we explored the potential mechanism of the protection on BBB disruption in cerebral I/R rat models. Male Sprague-Dawley rats (250-300 g) were subjected to 120 min middle cerebral artery occlusion (MCAO), followed by 48 h reperfusion. TSF (10.8, 18 and 30 mg kg -1 ) and ozagrel (18 mg kg -1 ) were administrated by intravenous injection immediately for the first time and then received the same dose every 24 h for 2 days. We found that TSF treatment significantly attenuated the cerebral water content, infarction volume and improved neurological outcomes in MCAO rats compared to I/R models. Moreover, we investigated the effect of TSF on the BBB for that cerebral oedema is closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in TSF groups compared to I/R model group by Evans blue leakage testing. Furthermore, the expressions of tight junction (TJ) proteins junction adhesion molecule-1 and occludin significantly decreased, but the protein expression of matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) increased after cerebral I/R, all of which were alleviated by TSF treatment. In conclusion, TSF significantly reduced BBB permeability and brain oedema, which were correlated with regulating the expression of TJ proteins, MMP-9 and AQP4. These findings provide a novel approach to the treatment of ischaemic stroke.

Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

PubMed

Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

2013-07-21

It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

Dinoflagellate cysts and pollen from the Tjörnes / Breidavik section: a biostratigraphical and palaeoclimatological study of Plio-Pleistocene sediments from northern Iceland.

NASA Astrophysics Data System (ADS)

Verhoeven, Koen; Louwye, Stephen; Eiríksson, Jon

2010-05-01

On the Tjörnes peninsula in northern Iceland, a unique sequence of Plio-Pleistocene shallow marine, continental and glacial sediments is exposed in cliffs near the Tjörnes Fracture Zone. The lowest part of the sequence consists of the more than 500 m thick Tjörnes beds of Pliocene age. In the overlying Breidavik Group, marine interglacial sediments are present together with lava flows and glacial deposits. In this unit, cycles 3, 4, 5 and 7 of the 14 glacial/interglacial cycles were examined for palynomorphs. Sixty eight samples from the sedimentary succession of the Tjörnes beds and 20 samples from the overlying Breidavik Group were palynologicaly investigated for dinoflagellate cysts, pollen and spores. Despite the fact that half of the samples were barren or yielded a very low dinoflagellate cyst concentration (<25 cysts/g), the recovered assemblage holds valuable palaeoecological and biostratigraphical information. The dinoflagellate cyst assemblage from the Tjörnes section reflects a Pliocene flora. Typical Miocene species disappearing at the Miocene - Pliocene boundary (5.33 Ma) such as Selenopemphix armageddonensis are not observed. The combination of the Pliocene record and the lack of typical Miocene species sets a maximum age for the base of the Tjörnes Beds at 5.33 Ma. The nearly continuous occurrence of Batiacasphaera minuta (highest occurrence at 3.8 Ma) and Operculodinium tegillatum (HO at 3.7 Ma) in the upper part of the Tjörnes beds (the Serripes mollusc zone) gives a minimum age of about 3.7 Ma for the top of this zone. These results indicate that the sediments of the Tjörnes beds are older and were deposited faster than previously thought, based on a K/Ar dating of the overlying basalt flows (Albertsson, 1976). In the Serripes zone, the new species Selenopemphix islandicus was recorded. Observations of fragile heterotrophic cysts such as Barssidinium pliocenicum (HO at 2.66 Ma), Echinidinium euaxum (HO at 2.66 Ma), Selenopemphix dionaeacysta (HO at 2.4 to 2.6 Ma) and Trinovantedinium glorianum (HO 2.4 to 2.6 Ma) in the Hörgi Formation sets a minimum age of 2.7 Ma for the third glacial/interglacial cycle. In accordance to the age of the upper Tjörnes beds, this formation has to be older than thought in the present age model of the outcrop. (Símonarson and Eiríksson, 2008). The biostratigraphical analysis indicates an upper Piacenzian age for the Hörgi Formation, instead of the previous Gelasian age. The K/Ar dates of the Höskuldsvik lavas between the Tjörnes beds and the Breidavik Group (2.55+/-0.27Ma; 2.36+/-0.16Ma) appears to be too young. Sea surface temperature reconstruction of the ocean water based on the warm/cold ratio of dinoflagellate cysts indicates higher values for the Tjörnes beds and the Hörgi Formation (3), compared to the colder water of the Svarthamar (5) and Torfhóll (7) Members. The appearance of pollen of temperate plants such as Ilex, Juglans and Tilia in the Tjörnes beds ánd the Hörgi Formation confirms the Pliocene age, and is in agreement with the dinoflagellate cyst biostratigraphy. References: Albertsson, K.J. 1976: K/Ar ages of Pliocene-Pleistocene glaciations in Iceland with special reference to the Tjörnes sequence, northern Iceland. PhD thesis University of Cambridge, 268pp. Símonarson, L.A. and Eiríksson, J. 2008: Tjörnes - Pliocene and Pleistocene sediments and fauna. Jökull 58, 331-342.

Study of the in vitro metabolism of TJ0711 using ultra high performance liquid chromatography with quadrupole time-of-flight and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry.

PubMed

Hu, Lei; Lv, Zhenhua; Li, Gao; Xu, Xiaolong; Zhang, Chenghao; Cao, Peng; Huang, Jiangeng; Si, Luqin

2015-06-01

TJ0711 (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol) is a novel β-adrenoreceptor blocker with vasodilating activity. The aim of this study was to investigate the in vitro metabolic properties of TJ0711 from both qualitative and quantitative aspects using mouse, rat, dog, and human liver microsomes as well as rat hepatocytes. Two modern liquid chromatography with tandem mass spectrometry systems, ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry, were utilized for the analysis. To better characterize the metabolic pathways of TJ0711, two major metabolites were incubated under the same conditions as that for TJ0711. TJ0711 was extensively metabolized in vitro, and a total of 34 metabolites, including 19 phase I and 15 phase II metabolites, were identified. Similar metabolite profiles were observed among species, and demethylation, hydroxylation, carboxylic acid formation, and glucuronidation were proposed as the major metabolic routes. Significant interspecies differences were observed in the metabolic stability studies of TJ0711. Furthermore, gender differences were significant in mice, rats, and dogs, but were negligible in humans. The valuable information provided in this work will be useful in planning and interpreting further pharmacokinetic, in vivo metabolism and toxicological studies of this novel β-blocker. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model: a pilot study

PubMed Central

Gu, Guo-Sheng; Ren, Jian-An; Li, Guan-Wei; Yuan, Yu-Jie; Li, Ning; Li, Jie-Shou

2015-01-01

Background: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. Methods: A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). Results: C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. Conclusion: These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis. PMID:26221273

Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model: a pilot study.

PubMed

Gu, Guo-Sheng; Ren, Jian-An; Li, Guan-Wei; Yuan, Yu-Jie; Li, Ning; Li, Jie-Shou

2015-01-01

Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis.

Effect of low and staggered gap quantum wells inserted in GaAs tunnel junctions

NASA Astrophysics Data System (ADS)

Louarn, K.; Claveau, Y.; Marigo-Lombart, L.; Fontaine, C.; Arnoult, A.; Piquemal, F.; Bounouh, A.; Cavassilas, N.; Almuneau, G.

2018-04-01

In this article, we investigate the impact of the insertion of either a type I InGaAs or a type II InGaAs/GaAsSb quantum well on the performances of MBE-grown GaAs tunnel junctions (TJs). The devices are designed and simulated using a quantum transport model based on the non-equilibrium Green’s function formalism and a 6-band k.p Hamiltonian. We experimentally observe significant improvements of the peak tunneling current density on both heterostructures with a 460-fold increase for a moderately doped GaAs TJ when the InGaAs QW is inserted at the junction interface, and a 3-fold improvement on a highly doped GaAs TJ integrating a type II InGaAs/GaAsSb QW. Thus, the simple insertion of staggered band lineup heterostructures enables us to reach a tunneling current well above the kA cm‑2 range, equivalent to the best achieved results for Si-doped GaAs TJs, implying very interesting potential for TJ-based components, such as multi-junction solar cells, vertical cavity surface emitting lasers and tunnel-field effect transistors.

Endophilin-1 regulates blood-brain barrier permeability via EGFR-JNK signaling pathway.

PubMed

Chen, Lin; Liu, Wenjing; Wang, Ping; Xue, Yixue; Su, Qingjie; Zeng, Chaosheng; Shang, Xiuli

2015-05-05

Endophilin-1 (Endo1), a multifunctional protein, is essential for synaptic vesicle endocytosis. However, the role and mechanism of endophilin-1 in blood-brain barrier (BBB) function are still unclear. This study was performed to determine whether endophilin-1 regulated BBB permeability via the EGFR-JNK signaling pathway. In the present study, we found that endophilin-1 over-expression in human cerebral microvascular endothelial cell (hCMEC/D3) increased BBB permeability and meanwhile reduced the expression levels of epidermal growth factor receptor (EGFR), phosphorylated c-Jun N-terminal kinase (p-JNK). While endophilin-1 knockdown led to the contrary results. After JNK inhibitor SP600125 was administered to the endophilin-1 silenced hCMEC/D3 cells, the transendothelial electrical resistance (TEER) value was decreased and the permeability coefficient values to 4kDa and 40kDa FITC-dextran were increased. Results observed by Transmission electron microscopy (TEM) showed that tight junctions (TJs) were opened. Moreover, immunofluorescence and Western blot assays revealed the discontinuous distribution of TJ-associated proteins ZO-1, occludin on cell-cell boundaries and a significant decrease in protein expressing levels. Therefore, these results indicated that endophilin-1 positively regulated BBB permeability via the EGFR-JNK signaling pathway in hCMEC/D3 cells, which would provide an experimental basis for further research on endophilin-1 mediated the opening of BBB. Copyright © 2015 Elsevier B.V. All rights reserved.

Two-loop beam and soft functions for rapidity-dependent jet vetoes

NASA Astrophysics Data System (ADS)

Gangal, Shireen; Gaunt, Jonathan R.; Stahlhofen, Maximilian; Tackmann, Frank J.

2017-02-01

Jet vetoes play an important role in many analyses at the LHC. Traditionally, jet vetoes have been imposed using a restriction on the transverse momentum p Tj of jets. Alternatively, one can also consider jet observables for which p Tj is weighted by a smooth function of the jet rapidity y j that vanishes as | y j | → ∞. Such observables are useful as they provide a natural way to impose a tight veto on central jets but a looser one at forward rapidities. We consider two such rapidity-dependent jet veto observables, T_{Bj} and {T_{Cj} , and compute the required beam and dijet soft functions for the jet-vetoed color-singlet production cross section at two loops. At this order, clustering effects from the jet algorithm become important. The dominant contributions are computed fully analytically while corrections that are subleading in the limit of small jet radii are expressed in terms of finite numerical integrals. Our results enable the full NNLL' resummation and are an important step towards N3LL resummation for cross sections with a T_{Bj} or T_{Cj} jet veto.

Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components.

PubMed

Kase, Y; Saitoh, K; Makino, B; Hashimoto, K; Ishige, A; Komatsu, Y

1999-09-01

This study was designed to examine the relationship between the antidiarrhoeal effects of Hange-Shashin-To (TJ-14) and its active components. Oral treatment with TJ-14 at 1000 mg/kg significantly inhibited castor oil-induced diarrhoea. Both the 50% methanol eluate fraction (fraction III) and the methanol eluate fraction (fraction IV) showed antidiarrhoeal effects at oral doses of 68 mg/kg and 63 mg/kg, respectively, corresponding to 1000 mg/kg of TJ-14. TJ-14 (1000 mg/kg, p.o.) showed a significant increase in blood corticosterone levels. Increased blood corticosterone was noted after the oral administration of 63 mg/kg of fraction IV. The inhibitory activity of TJ-14 on cyclooxygenase-2 (COX-2) was also observed in fractions III and IV. The main component of fraction III was Scutellariae Radix-derived baicalin. Fraction IV contained Glycyrrhizae Radix-derived glycyrrhizin and isoliquiritin, Coptidis Rhizoma-derived berberine, coptisine and palmitine. Ginseng Radix-derived saponins were also present in fraction IV. These compounds inhibited castor-oil induced diarrhoea at oral doses of 10 or 30 mg/kg. Thus, the present results indicate that Scutellariae Radix, Glycyrrhizae Radix, Ginseng radix and Coptidis Rhizoma-derived components are involved in the antidiarrhoeal action of TJ-14. Copyright 1999 John Wiley & Sons, Ltd.

PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced in MMP-9-deficient mice

PubMed Central

Huang, Wen; Chen, Lei; Zhang, Bei; Park, Minseon; Toborek, Michal

2014-01-01

The strategies to protect against the disrupted blood–brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPARα agonist) or rosiglitazone (PPARγ agonist). In contrast, exposure to GW9662 (PPARγ antagonist) exacerbated Tat-induced disruption of the BBB integrity. Increased BBB permeability was associated with decreased tight junction (TJ) protein expression and activation of ERK1/2 and Akt in brain microvessels; these effects were attenuated by cotreatment with fenofibrate but not with rosiglitazone. Importantly, both PPAR agonists also protected against Tat-induced astrogliosis and neuronal loss. Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1. PMID:24424383

Comparison of nonpolar III-nitride vertical-cavity surface-emitting lasers with tunnel junction and ITO intracavity contacts

NASA Astrophysics Data System (ADS)

Leonard, J. T.; Young, E. C.; Yonkee, B. P.; Cohen, D. A.; Shen, C.; Margalith, T.; Ng, T. K.; DenBaars, S. P.; Ooi, B. S.; Speck, J. S.; Nakamura, S.

2016-02-01

We report on the lasing of III-nitride nonpolar, violet, vertical-cavity surface-emitting lasers (VCSELs) with IIInitride tunnel-junction (TJ) intracavity contacts and ion implanted apertures (IIAs). The TJ VCSELs are compared to similar VCSELs with tin-doped indium oxide (ITO) intracavity contacts. Prior to analyzing device results, we consider the relative advantages of III-nitride TJs for blue and green emitting VCSELs. The TJs are shown to be most advantageous for violet and UV VCSELs, operating near or above the absorption edge for ITO, as they significantly reduce the total internal loss in the cavity. However, for longer wavelength III-nitride VCSELs, TJs primarily offer the advantage of improved cavity design flexibility, allowing one to make the p-side thicker using a thick n-type III-nitride TJ intracavity contact. This offers improved lateral current spreading and lower loss, compare to using ITO and p-GaN, respectively. These aspects are particularly important for achieving high-power CW VCSELs, making TJs the ideal intracavity contact for any III-nitride VCSEL. A brief overview of III-nitride TJ growth methods is also given, highlighting the molecular-beam epitaxy (MBE) technique used here. Following this overview, we compare 12 μm aperture diameter, violet emitting, TJ and ITO VCSEL experimental results, which demonstrate the significant improvement in differential efficiency and peak power resulting from the reduced loss in the TJ design. Specifically, the TJ VCSEL shows a peak power of ~550 μW with a threshold current density of ~3.5 kA/cm2, while the ITO VCSELs show peak powers of ~80 μW and threshold current densities of ~7 kA/cm2.

Comparison of properties of new sources of partially purified inulin to those of commercially pure chicory inulin.

PubMed

Mudannayake, Deshani C; Wimalasiri, Kuruppu M S; Silva, Kahandage F S T; Ajlouni, Said

2015-05-01

Newly developed inulin powders were prepared from roots of Asparagus falcatus (AF) and Taraxacum javanicum (TJ) plants grown in Sri Lanka. Inulin content, analyzed by enzymatic spectrophotometric as well as high-performance liquid chromatographic methods, showed that AF and TJ inulin powders contain 65.5% and 45.4% (dry wt) inulin, respectively, compared with 72% dry wt in the commercially available chicory inulin. Treating the AF and TJ inulin powders using ion exchange techniques significantly (P < 0.05) reduced their contents of micro (Zn, Cu, Mn, Fe) and macro (Na, K, Ca, Mg) elements. Enzymatic hydrolysis of inulin into fructose and glucose by fructanase, and FT-IR analyses proved that the developed AF and TJ inulins have characteristic molecular composition similar to commercial inulin. TJ inulin contained significantly (P < 0.05) greater amounts of total phenolics (4.37 mg GAE/g), total flavonoids (2.79 mg QE/g), and antioxidant capacity (833.11 mM TE/g) than AF inulin, which contained 1.33 mg GAE/g of total phenolics, 0.43 mg QE/g of total flavonoids, and 406.26 mM TE/g antioxidant capacity. The current study suggests that the newly developed inulin from AF and TJ roots could be used as an alternative commercial source of inulin for the food industry. © 2015 Institute of Food Technologists®

A novel totivirus-like virus isolated from bat guano.

PubMed

Yang, Xinglou; Zhang, Yunzhi; Ge, Xingyi; Yuan, Junfa; Shi, Zhengli

2012-06-01

Previous metagenomic analysis indicated that numerous insect viruses exist in bat guano. In this study, we isolated a novel double-stranded RNA virus, a tentative member of the family Totiviridae, designated Tianjin totivirus (ToV-TJ), from bat feces. The virus is an icosahedral particle with a diameter of 40-43 nm, and it causes cytopathic effect in Sf9, Hz, and C6/36 cell lines. Full-length genomic sequence analysis showed that ToV-TJ shares high similarity with the totivirus OMRV-AK4, which was recently isolated from mosquitoes in Japan. The full-length genome of the ToV-TJ was 7611 bp and contained two predicted non-overlapping open reading frames (ORFs): ORF1, encoding the capsid protein (CP), and ORF2, encoding an RNA-dependent RNA polymerase. Bioassay of ToV-TJ by feeding on the larvae of Spodoptera exigua and Helicoverpa armigera (Hubner) suggests that this virus is not infectious for these two larvae in vivo. Sequences similar to that of ToV-TJ have been detected in bat feces sampled in Yunnan and Hainan Provinces, suggesting that this virus is widely distributed.

Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.

PubMed

Almansour, Khaled; Taverner, Alistair; Eggleston, Ian M; Mrsny, Randall J

2018-06-10

Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS 19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH 2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character. Here, we examine compositional requirements of PIP 640 with regard to its actions on MLC phosphorylation, its intracellular localization to TJ structures, and its interactions with MLC phosphatase (MLCP) elements that correlate with enhanced solute uptake. These studies showed that a glutamic acid and tyrosine within this peptide are critical for PIP 640 to retain its ability to increase MLC-pS 19 levels and enhance the permeability of macromolecular solutes of the size range of therapeutic peptides without detectable cytotoxicity. On the other hand, exchange of the aspartic acid for alanine and then arginine resulted in an increasingly greater bias toward protein phosphatase-1 (PP1) relative to MLCP inhibition, an outcome that resulted in increased paracellular permeability for solutes in the size range of therapeutic peptides, but with a significant increase in cytotoxicity. Together, these data further our understanding of the composition requirements of PIP 640 with respect to the desired goal of transiently altering the intestinal epithelial cell paracellular barrier properties through an endogenous mechanism, providing a novel approach to enhance the oral bioavailability of poorly absorbed therapeutic agents of < ~ 5 kDa. Copyright © 2018 Elsevier B.V. All rights reserved.

Indigenous lactobacilli strains of food and human sources reverse enteropathogenic E. coli O26:H11-induced damage in intestinal epithelial cell lines: effect on redistribution of tight junction proteins.

PubMed

Jariwala, Ruchi; Mandal, Hemanti; Bagchi, Tamishraha

2017-09-01

The aim of the study was to investigate the neutralizing effect of lactobacilli isolated from indigenous food and human sources on enteropathogenic Escherichia coli (EPEC) O26 : H11-induced epithelial barrier dysfunction in vitro. This was assessed by transepithelial electrical resistance (TEER) and permeability assays using intestinal cell lines, HT-29 and Caco-2. Furthermore, the expression and distribution of tight junction (TJ) proteins were analysed by qRT-PCR and immunofluorescence assay, respectively. The nine strains used in the study were from different species viz. Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus salivarius and Lactobacillus plantarum. All strains were able to reverse the decrease in TEER and corresponding increase in permeability across E. coli-infected monolayers. Maximum reversal was observed after 18 h [up to 93.8±2.0 % by L. rhamnosus GG followed by L. fermentum IIs11.2 (92.6±2.2 %) and L. plantarum GRI-2 (91.9±0.9 %)] of lactobacilli exposure following EPEC O26 : H11 infection. All strains were able to redistribute the TJ proteins to the cell periphery either partially or completely. Moreover, L. helveticus FA-7 was also able to significantly increase the mRNA expression of ZO-1 and claudin-1 (2.5-fold and 3.0-fold, respectively; P<0.05). The rapid reversal observed by these strains could be mostly because of the redistribution rather than increased mRNA expression of TJ proteins. In conclusion, L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 were good in all the aspects studied, and the other strains were good in some aspects. L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 can therefore be used for potential therapeutic purpose against intestinal epithelial dysfunction.

Genetics Home Reference: phosphoglycerate dehydrogenase deficiency

MedlinePlus

... on PubMed Tabatabaie L, Klomp LW, Berger R, de Koning TJ. L-serine synthesis in the central ... Gozalbo ME, Spaapen LJ, Haagen AA, Dorland L, de Koning TJ. Expanding the clinical spectrum of 3- ...

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

PubMed Central

2004-01-01

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection. PMID:15480446

Structural stability and energetics of grain boundary triple junctions in face centered cubic materials

NASA Astrophysics Data System (ADS)

Adlakha, I.; Solanki, K. N.

2015-03-01

We present a systematic study to elucidate the role of triple junctions (TJs) and their constituent grain boundaries on the structural stability of nanocrystalline materials. Using atomistic simulations along with the nudge elastic band calculations, we explored the atomic structural and thermodynamic properties of TJs in three different fcc materials. We found that the magnitude of excess energy at a TJ was directly related to the atomic density of the metal. Further, the vacancy binding and migration energetics in the vicinity of the TJ were examined as they play a crucial role in the structural stability of NC materials. The resolved line tension which takes into account the stress buildup at the TJ was found to be a good measure in predicting the vacancy binding tendency near the TJ. The activation energy for vacancy migration along the TJ was directly correlated with the measured excess energy. Finally, we show that the resistance for vacancy diffusion increased for TJs with larger excess stored energy and the defect mobility at some TJs is slower than their constituent GBs. Hence, our results have general implications on the diffusional process in NC materials and provide new insight into stabilizing NC materials with tailored TJs.

The response of a fast scintillator screen (YAP:Ce) to low energy ions (0-40 keV) and its use to detect fast-ion-loss in stellarator TJ-II

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

Martínez, M., E-mail: marcos.martinez@externos.ciemat.es; Zurro, B.; Baciero, A.

2016-11-15

A systematic study of scintillation materials was undertaken to improve the time resolution of the fast ion diagnostic currently installed at TJ-II stellarator. It was found that YAP:Ce (formula YAlO{sub 3}:Ce, Yttrium Aluminum Perovskite doped with Cerium) ionoluminescence offers better sensitivity and time response compared to the standard detector material, SrGa{sub 2}S{sub 4}:Eu (TG-Green), currently used in TJ-II. A comparison between both materials was carried out by irradiating them with H{sup +} ions of up to 40 keV using a dedicated laboratory setup. It is found that for the low energy ions of interest at TJ-II, YAP:Ce offers 20 timesmore » higher sensitivity than TG-Green and much faster decay time, 27 ns versus 540 ns. It is expected that the use of YAP:Ce in combination with a faster data acquisition and an ion counting software as part of the TJ-II ion luminescent probe will provide 20 times faster data on ion loss.« less

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-κβ and myosin light-chain kinase pathways.

PubMed

Zhang, Ying; Li, Jianguo

2012-11-16

Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-κβ) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the α7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-κβ and MLCK pathways in an α7nAchR-dependent manner. Copyright © 2012 Elsevier Inc. All rights reserved.

Nociceptive inhibition prevents inflammatory pain induced changes in the blood-brain barrier

PubMed Central

Campos, Christopher R.; Ocheltree, Scott M.; Hom, Sharon; Egleton, Richard D.; Davis, Thomas P.

2008-01-01

Previous studies by our group have shown that peripheral inflammatory insult, using the λ-carrageenan inflammatory pain (CIP) model, induced alterations in the molecular and functional properties of the blood-brain barrier (BBB). The question remained whether these changes were mediated via an inflammatory and/or neuronal mechanism. In this study, we investigated the involvement of neuronal input from pain activity on alterations in BBB integrity by peripheral inhibition of nociceptive input. A perineural injection of 0.75% bupivacaine into the right hind leg prior to CIP was used for peripheral nerve block. Upon nerve block, there was a significant decrease in thermal allodynia induced by CIP, but no effect on edema formation 1 h post CIP. BBB permeability was increased 1 h post CIP treatment as determined by in situ brain perfusion of [14C] sucrose; bupivacaine nerve block of CIP caused an attenuation of [14C] sucrose permeability, back to saline control levels. Paralleling the changes in [14C] sucrose permeability, we also report increased expression of three tight junction (TJ) proteins, zonula occluden-1 (ZO-1), occludin and claudin-5 with CIP. Upon bupivacaine nerve block, changes in expression were prevented. These data show that the λ-carrageenan induced changes in [14C] sucrose permeability and protein expression of ZO-1, occludin and claudin-5 are prevented with inhibition of nociceptive input. Therefore, we suggest that nociceptive signaling is in part responsible for the alteration in BBB integrity under CIP. PMID:18554577

Causal impact of magnetic fluctuations in slow and fast L–H transitions at TJ-II

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

Milligen, B. Ph. van; Estrada, T.; Ascasíbar, E.

2016-07-15

This work focuses on the relationship between L–H (or L–I) transitions and MHD activity in the low magnetic shear TJ-II stellarator. It is shown that the presence of a low order rational surface in the plasma edge (gradient) region lowers the threshold density for H-mode access. MHD activity is systematically suppressed near the confinement transition. We apply a causality detection technique (based on the Transfer Entropy) to study the relation between magnetic oscillations and locally measured plasma rotation velocity (related to Zonal Flows). For this purpose, we study a large number of discharges in two magnetic configurations, corresponding to “fast”more » and “slow” transitions. With the “slow” transitions, the developing Zonal Flow prior to the transition is associated with the gradual reduction of magnetic oscillations. The transition itself is marked by a strong spike of “information transfer” from magnetic to velocity oscillations, suggesting that the magnetic drive may play a role in setting up the final sheared flow responsible for the H-mode transport barrier. Similar observations were made for the “fast” transitions. Thus, it is shown that magnetic oscillations associated with rational surfaces play an important and active role in confinement transitions, so that electromagnetic effects should be included in any complete transition model.« less

Effects of trimethoprim on life history parameters, oxidative stress, and the expression of cytochrome P450 genes in the copepod Tigriopus japonicus.

PubMed

Han, Jeonghoon; Lee, Min-Chul; Kim, Duck-Hyun; Lee, Young Hwan; Park, Jun Chul; Lee, Jae-Seong

2016-09-01

Trimethoprim (TMP) is an antibiotic that has been detected in various environments including marine habitats; however, the toxic effects of TMP are poorly understood in non-target marine organisms. In this study, the effects of TMP on mortality, development, reproduction, intracellular reactive oxygen species (ROS) levels, and transcription levels of antioxidant and xenobiotic detoxification-related enzyme genes were investigated in the copepod Tigriopus japonicus. The TMP half lethal dose at 48 h (LC50-48 h) in nauplius and TMP LC50-96 h in adult T. japonicus copepods was determined as 156 mg/L and 200 mg/L, respectively. In TMP-exposed T. japonicus, delayed developmental time and impaired reproduction were observed as harmful effects on the life history parameters. Increased ROS levels were also shown in response to TMP exposure at the highest concentration (100 mg/L TMP) and the expression of antioxidant- (e.g. GST-kappa, GST-sigma) and xenobiotic detoxification (e.g. CYPs)-related genes were upregulated in a time and/or dose-dependent manner in response to TMP. Particularly, significant upregulation of three CYP genes (Tj-CYP3024A2, Tj-CYP3024A3 and Tj-CYP3027C2) were examined, suggesting that these CYP genes are likely playing an important role in the TMP detoxification metabolism in T. japonicus. In summary, we found that TMP induced oxidative stress via the transcriptional regulation of antioxidant- and xenobiotic detoxification-related genes, leading to changes in life history parameters such as developmental delay and reproduction impairment. Three Tj-CYP genes (Tj-CYP3024A2, Tj-CYP3024A3 and Tj-CYP3027C2) could be useful as potential T. japonicus biomarkers in response to antibiotics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetics Home Reference: North American Indian childhood cirrhosis

MedlinePlus

... Chagnon P, Fujiwara TM, Morgan K, Richter A, Hudson TJ, Mitchell GA. Localization of a recessive gene ... J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A. A missense mutation (R565W) in ...

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. PMID:29538417

Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.

PubMed

Gu, Yan-ting; Xue, Yi-xue; Wang, Yan-feng; Wang, Jin-hui; Chen, Xia; ShangGuan, Qian-ru; Lian, Yan; Zhong, Lei; Meng, Ying-nan

2013-12-01

Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion. Based on these findings, we then used an in vitro BTB model and selective inhibitors of diverse signaling pathways to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a key role in the process of the increase of BTB permeability induced by MS. The inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression of tight junction (TJ) protein and the increase of the BTB permeability after 2 h of MS treatment. In addition, the significant increases in RhoA activity and PKB phosphorylation after MS administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002 pretreatment. The present study indicates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB permeability induced by MS. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR-4 signal transduction pathway activation of FAK and MyD88

PubMed Central

Guo, Shuhong; Nighot, Meghali; Al-Sadi, Rana; Alhmoud, Tarik; Nighot, Prashant; Ma, Thomas Y.

2015-01-01

Gut-derived bacterial lipopolysaccharides (LPS) play an essential role in inducing intestinal and systemic inflammatory responses and have been implicated as a pathogenic factor of necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). The defective intestinal tight junction (TJ) barrier has been shown to be an important factor contributing to the development of intestinal inflammation. LPS, at physiological concentrations, cause an increase in intestinal tight junction permeability (TJP) via a TLR-4 dependent process; however the intracellular mechanisms that mediate LPS regulation of intestinal TJP remain unclear. The aim of this study was to investigate the adaptor proteins and the signaling interactions that mediate LPS modulation of intestinal TJ barrier using an in-vitro and in-vivo model system. LPS caused a TLR-4 dependent activation of membrane-associated adaptor protein FAK in Caco-2 monolayers. LPS caused an activation of both MyD88-dependent and –independent pathways. SiRNA silencing of MyD88 prevented LPS-induced increase in TJP. LPS caused a MyD88-dependent activation of IRAK4. TLR-4, FAK and MyD88 were co-localized. SiRNA silencing of TLR-4 inhibited TLR-4 associated FAK activation; and FAK knockdown prevented MyD88 activation. In-vivo studies also confirmed that LPS-induced increase in mouse intestinal permeability was associated with FAK and MyD88 activation; knockdown of intestinal epithelial FAK prevented LPS-induced increase in intestinal permeability. Additionally, high dose LPS-induced intestinal inflammation was also dependent on TLR-4/FAK/MyD88 signal-transduction axis. Our data show for the first time that LPS-induced increase in intestinal TJP and intestinal inflammation was regulated by TLR-4 dependent activation of FAK-MyD88-IRAK4 signaling pathway. PMID:26466961

Generalized One-Band Model Based on Zhang-Rice Singlets for Tetragonal CuO.

PubMed

Hamad, I J; Manuel, L O; Aligia, A A

2018-04-27

Tetragonal CuO (T-CuO) has attracted attention because of its structure similar to that of the cuprates. It has been recently proposed as a compound whose study can give an end to the long debate about the proper microscopic modeling for cuprates. In this work, we rigorously derive an effective one-band generalized t-J model for T-CuO, based on orthogonalized Zhang-Rice singlets, and make an estimative calculation of its parameters, based on previous ab initio calculations. By means of the self-consistent Born approximation, we then evaluate the spectral function and the quasiparticle dispersion for a single hole doped in antiferromagnetically ordered half filled T-CuO. Our predictions show very good agreement with angle-resolved photoemission spectra and with theoretical multiband results. We conclude that a generalized t-J model remains the minimal Hamiltonian for a correct description of single-hole dynamics in cuprates.

Anderson localization on the Cayley tree: multifractal statistics of the transmission at criticality and off criticality

NASA Astrophysics Data System (ADS)

Monthus, Cécile; Garel, Thomas

2011-04-01

In contrast to finite dimensions where disordered systems display multifractal statistics only at criticality, the tree geometry induces multifractal statistics for disordered systems also off criticality. For the Anderson tight-binding localization model defined on a tree of branching ratio K = 2 with N generations, we consider the Miller-Derrida scattering geometry (1994 J. Stat. Phys. 75 357), where an incoming wire is attached to the root of the tree, and where KN outcoming wires are attached to the leaves of the tree. In terms of the KN transmission amplitudes tj, the total Landauer transmission is T ≡ ∑j|tj|2, so that each channel j is characterized by the weight wj = |tj|2/T. We numerically measure the typical multifractal singularity spectrum f(α) of these weights as a function of the disorder strength W and we obtain the following conclusions for its left termination point α+(W). In the delocalized phase W < Wc, α+(W) is strictly positive α+(W) > 0 and is associated with a moment index q+(W) > 1. At criticality, it vanishes α+(Wc) = 0 and is associated with the moment index q+(Wc) = 1. In the localized phase W > Wc, α+(W) = 0 is associated with some moment index q+(W) < 1. We discuss the similarities with the exact results concerning the multifractal properties of the directed polymer on the Cayley tree.

Evaluation of the proximate quality of the combination of Tuna (Thunnus albacares) and white oyster mushroom (Pleurotus ostreatus) nuggets

NASA Astrophysics Data System (ADS)

Yufidasari, H. S.; Prihanto, A. A.; Nurdiani, R.; Jaziri, A. A.

2018-04-01

Nugget is a processed meat product which has great market demand but need variations to increase its nutritional content. Tuna is rich in omega-3 protein, vitamins, and minerals. White oyster mushrooms have high nutritional content which are about 23-33% protein, 36-68 % carbohydrates and 12-22 % amino acids. The purpose of this research is to evaluate the chemical quality of Tuna nugget (Thunnus albacores) with combination of white oyster mushroom (Pleurotus ostreatus). Complete Randomized Design (RAL) with parameters of Tuna and white oyster mushroom formulation, TJ1 (70 % Tuna: 30 % white oyster mushroom), TJ2 (50 % Tuna: 50 % white oyster mushroom), TJ3 (30 % Tuna: 70 % white oyster mushroom), and Control or K Treatment (100 % Tuna) is used. Results of Tuna nuggets with white oyster mushroom combination showed the highest value of water content in TJ3 50.14 %, protein K 19.6 %, fat TJ3 22.98 %, ash K 3.99 % and 2.47 % crude fiber. From these results, there is a need for further research on fat, ash and coarse fiber content that is used in the manufacture of fish nuggets combined with oyster mushrooms because it failed to meet Indonesian National Standard (SNI).

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

Zhang, Ying; Li, Jianguo, E-mail: 2010lijianguo@sina.cn

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption ofmore » tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.« less

Integrated Bioenvironmental Hazards Research Program

DTIC Science & Technology

2004-01-01

Elliott S, ZhaoW, Curiel TJ, Beckman BS, Burow ME. Epigallocatechin gallate ( EGCG ) induces growth inhibition and apoptosis in human breast cancer...Zhao DY, Elliott S, ZhaoW, Curiel TJ, Beckman BS, Burow ME. " Epigallocatechin gallate ( EGCG ) induces growth inhibition and apoptosis in human breast

QuartetS-DB: A Large-Scale Orthology Database for Prokaryotes and Eukaryotes Inferred by Evolutionary Evidence

DTIC Science & Technology

2012-01-01

particular functions and identify species that contain these proteins. For example, if users select two species, Homo sapiens and Mus musculus, and...Kerr AR, McCormack TJ, Riley M: Evolution by leaps: gene duplication in bacteria. Biol Direct 2009, 4:46. 12. Remm M, Storm CE, Sonnhammer EL

Examining the links between therapeutic jurisprudence and mental health court completion.

PubMed

Redlich, Allison D; Han, Woojae

2014-04-01

Research demonstrates that mental health courts (MHCs) lead to improved outcomes compared to traditional criminal court processes. An underlying premise of MHCs is therapeutic jurisprudence (TJ). However, no research, to our knowledge, has examined whether MHC outcomes are predicted by TJ principles as theorized. In the present study, we examined whether principles measured at the onset of MHC enrollment (knowledge, perceived voluntariness, and procedural justice) predicted MHC completion (graduation). Using structural equation modeling with MHC participants from four courts, a significant, direct relationship between TJ and MHC completion was found, such that higher levels of TJ were associated with higher rates of success. Although this direct effect became nonsignificant when mediator variables were included, a significant indirect path remained, such that increased levels of initial perceived voluntariness and procedural justice, and MHC knowledge, led to decreased rates of new arrests, prison, MHC bench warrants, and increased court compliance, which, in turn, led to a higher likelihood of MHC graduation. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Triassic–Jurassic mass extinction as trigger for the Mesozoic radiation of crocodylomorphs

PubMed Central

Toljagić, Olja; Butler, Richard J.

2013-01-01

Pseudosuchia, one of the two main clades of Archosauria (Reptilia: Diapsida), suffered a major decline in lineage diversity during the Triassic–Jurassic (TJ) mass extinction (approx. 201 Ma). Crocodylomorpha, including living crocodilians and their extinct relatives, is the only group of pseudosuchians that survived into the Jurassic. We reassess changes in pseudosuchian morphological diversity (disparity) across this time interval, using considerably larger sample sizes than in previous analyses. Our results show that metrics of pseudosuchian disparity did not change significantly across the TJ boundary, contrasting with previous work suggesting low pseudosuchian disparity in the Early Jurassic following the TJ mass extinction. However, a significant shift in morphospace occupation between Late Triassic and Early Jurassic taxa is recognized, suggesting that the TJ extinction of many pseudosuchian lineages was followed by a major and geologically rapid adaptive radiation of crocodylomorphs. This marks the onset of the spectacularly successful evolutionary history of crocodylomorphs in Jurassic and Cretaceous ecosystems. PMID:23536443

Role of isotope mass and evidence of fluctuating zonal flows during the L–H transition in the TJ-II stellarator

NASA Astrophysics Data System (ADS)

Losada, U.; Estrada, T.; Liu, B.; van Milligen, B.; Cheng, J.; Silva, C.; Pastor, I.; Fontdecaba, J. M.; Hidalgo, C.; TJ-II team1, the

2018-07-01

Mean radial electric fields as well as low frequency Zonal Flow-like global oscillations in radial electric field have been identified during the low to high (L–H) transition in Hydrogen and Deuterium dominated plasmas in the stellarator TJ-II. No evidence of isotope effect on the L–H transition dynamics was observed in the investigated TJ-II plasma scenarios. These observations emphasize the critical role of both zero frequency (equilibrium) and low frequency varying large-scale flows for stabilizing turbulence during the triggering of the L–H transition in magnetically confined toroidal plasmas.

Hazardous Waste Cleanup: IBM Corporation-TJ Watson Research Center in Yorktown Heights, New York

EPA Pesticide Factsheets

IBM Corporation -TJ Watson Research Center is located in southern Yorktown near the boundary separating the Town of Yorktown from the Town of New Castle. The site occupies an area of approximately 217 acres and adjoins land uses are predominantly residenti

Comparison of lower limb kinetics during vertical jumps in turnout and neutral foot positions by classical ballet dancers.

PubMed

Imura, Akiko; Iino, Yoichi

2017-03-01

The purpose of this study was to investigate the effect of hip external rotation (turnout) on lower limb kinetics during vertical jumps by classical ballet dancers. Vertical jumps in a turnout (TJ) and a neutral hip position (NJ) performed by 12 classical female ballet dancers were analysed through motion capture, recording of the ground reaction forces, and inverse dynamics analysis. At push-off, the lower trunk leaned forward 18.2° and 20.1° in the TJ and NJ, respectively. The dancers jumped lower in the TJ than in the NJ. The knee extensor and hip abductor torques were smaller, whereas the hip external rotator torque was larger in the TJ than in the NJ. The work done by the hip joint moments in the sagittal plane was 0.28 J/(Body mass*Height) and 0.33 J/(Body mass*Height) in the TJ and NJ, respectively. The joint work done by the lower limbs were not different between the two jumps. These differences resulted from different planes in which the lower limb flexion-extension occurred, i.e. in the sagittal or frontal plane. This would prevent the forward lean of the trunk by decreasing the hip joint work in the sagittal plane and reduce the knee extensor torque in the jump.

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia.

PubMed

Hirako, Shima; Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Mano, Yukio; Nakano, Tomoko; Imai, Kenji; Li, Hua; Toyokuni, Shinya; Kikkawa, Fumitaka

2016-09-01

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2 ; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

East Europe Report, Economic and Industrial Affairs, No. 2429

DTIC Science & Technology

1983-08-02

Draft Version of Controversial New Income Tax Law Summarized (T.J.; ZYCIE GOSPODARCZE, No 20, 15 May 83) 32 Utilization of Polish Specialists... INCOME TAX LAW SUMMARIZED Warsaw ZYCIE GOSPODARCZE in Polish No 20, 15 May 83 p 11 [Article by T.J.] [Text] The Ministry of Finance has prepared a

Publications and Presentations of the Opthalmology Branch, USAF School of Aerospace Medicine 1981-1990

DTIC Science & Technology

1990-12-01

Meeting CORNEAL OPACIFICATION AND LECITHIN -CHOLESTEROL ACETYLTRANSFERASE (LCAT) DEFICIENCY: A CASE REPORT Hesterberg RC Jr and TJ Tredici Annals of...Pittsburgh PA, 14 May 1987 OCULAR SIDE EFFECTS OF HYPERBARIC OXYGEN THERAPY Tredici TJ, LL Tredici, DJ Ivan, and PS O’Connor Baylor College of Medicine

Dirk Jordan | NREL

Science.gov Websites

quantify module degradation rates. Statistical analysis of reported degradation rates of PV modules degradation rates," Prog. in PV 24(7), 2016, DOI: 10.1002/pip.2744 Jordan D.C., Silverman T.J PV, 2017, DOI: 10.1002/pip.2866 Jordan D.C., Silverman T.J., Sekulic B., Kurtz S.R., "PV

Educator Market Research: In-depth Interviews

DTIC Science & Technology

2001-11-01

Journal of Advertising Research , February...March 1988. Reynolds, T.J. and Whitlark, D. “Applying Laddering Data to Communications Strategy and Advertising Practice.” Journal of Advertising Research , February...Advertising Strategy.” Journal of Advertising Research , April/May 1988. Reynolds, T.J. and Rochon, J.P. “Means-End Based Advertising Research.” Journal

NSSEFF COMPUTATIONAL AND THEORETICAL DESIGN OF PHOTO AND MECHANORESPONSIVE MOLECULAR DEVICES

DTIC Science & Technology

2016-11-10

R. McGibbon, F. Liu, V.S. Pande and T.J. Martinez, "Discovering Chemistry with an Ab Initio Nanoreactor," Nature Chem. 6, 1044 (2014...Pande and T.J. Martinez, "Discovering Chemistry with an Ab Initio Nanoreactor," Nature Chem. 6, 1044 (2014). New discoveries, inventions, or patent

Mercury in Bituminous Coal Used in Polish Power Plants

NASA Astrophysics Data System (ADS)

Burmistrz, Piotr; Kogut, Krzysztof

2016-09-01

Poland is a country with the highest anthropogenic mercury emission in the European Union. According to the National Centre for Emissions Management (NCEM) estimation yearly emission exceeds 10 Mg. Within that approximately 56% is a result of energetic coal combustion. In 121 studied coal samples from 30 coal mines an average mercury content was 112.9 ppb with variation between 30 and 321 ppb. These coals have relatively large contents of chlorine and bromine. Such chemical composition is benefitial to formation of oxidized mercury Hg2+, which is easier to remove in Air Pollution Control Devices. The Hgr/Qir (mercury content to net calorific value in working state) ratio varied between 1.187 and 13.758 g Hg · TJ-1, and arithmetic mean was 4.713 g Hg · TJ-1. Obtained results are close to the most recent NCEM mercury emission factor of 1.498 g Hg · TJ-1. Value obtained by us is more reliable that emission factor from 2011 (6.4 g Hg · TJ-1), which caused overestimation of mercury emission from energetic coal combustion.

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

Nakano, Yuki; Matsui, Tetsuo; Ishima, Takumi

We study the three-dimensional bosonic t-J model, that is, the t-J model of 'bosonic electrons' at finite temperatures. This model describes a system of an isotropic antiferromagnet with doped bosonic holes and is closely related to systems of two-component bosons in an optical lattice. The bosonic 'electron' operator B{sub x{sigma}} at the site x with a two-component spin {sigma}(=1,2) is treated as a hard-core boson operator and represented by a composite of two slave particles: a spinon described by a Schwinger boson (CP{sup 1} boson) z{sub x}{sigma} and a holon described by a hard-core-boson field {phi}{sub x} as B{sub x}{sigma}={phi}{submore » x}{sup {dagger}}z{sub x}{sigma}. By means of Monte Carlo simulations of this bosonic t-J model, we study its phase structure and the possible phenomena like appearance of antiferromagnetic long-range order, Bose-Einstein condensation, phase separation, etc. Obtained results show that the bosonic t-J model has a phase diagram that suggests some interesting implications for high-temperature superconducting materials.« less

High performance as-grown and annealed high band gap tunnel junctions: Te behavior at the interface

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

Bedair, S. M., E-mail: bedair@ncsu.edu; Harmon, Jeffrey L.; Carlin, C. Zachary

2016-05-16

The performance of n{sup +}-InGaP(Te)/p{sup +}-AlGaAs(C) high band gap tunnel junctions (TJ) is critical for achieving high efficiency in multijunction photovoltaics. Several limitations for as grown and annealed TJ can be attributed to the Te doping of InGaP and its behavior at the junction interface. Te atoms in InGaP tend to get attached at step edges, resulting in a Te memory effect. In this work, we use the peak tunneling current (J{sub pk}) in this TJ as a diagnostic tool to study the behavior of the Te dopant at the TJ interface. Additionally, we used our understanding of Te behaviormore » at the interface, guided by device modeling, to modify the Te source shut-off procedure and the growth rate. These modifications lead to a record performance for both the as-grown (2000 A/cm{sup 2}) and annealed (1000 A/cm{sup 2}) high band gap tunnel junction.« less

A New Four-Barrel Pellet Injection System for the TJ-II Stellarator

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

Combs, Stephen Kirk; Foust, Charles R; McGill, James M

2011-01-01

A new pellet injection system for the TJ-II stellarator has been developed/constructed as part of a collaboration between the Oak Ridge National Laboratory (ORNL) and the Centro de Investigaciones Energ ticas, Medioambientales y Tecnol gicas (CIEMAT). ORNL is providing most of the injector hardware and instrumentation, the pellet diagnostics, and the pellet transport tubes; CIEMAT is responsible for the injector stand/interface to the stellarator, cryogenic refrigerator, vacuum pumps/ballast volumes, gas manifolds, remote operations, plasma diagnostics, and data acquisition. The pellet injector design is an upgraded version of that used for the ORNL injector installed on the Madison Symmetric Torus (MST).more » It is a four-barrel system equipped with a cryogenic refrigerator for in situ hydrogen pellet formation and a combined mechanical punch/propellant valve system for pellet acceleration (speeds ~100 to 1000 m/s). On TJ-II, it will be used as an active diagnostic and for fueling. To accommodate the plasma experiments planned for TJ-II, pellet sizes significantly smaller than those typically used for the MST application are required. The system will initially be equipped with four different pellet sizes, with the gun barrel bores ranging between ~0.5 to 1.0 mm. The new system is almost complete and is described briefly here, highlighting the new features added since the original MST injector was constructed. Also, the future installation on TJ-II is reviewed.« less

"The ladder of the law has no top and no bottom": how therapeutic jurisprudence can give life to international human rights.

PubMed

Perlin, Michael L

2014-01-01

In the past two decades, therapeutic jurisprudence (TJ) has become one of the most important theoretical approaches to the law. But, there has, as of yet, been puzzlingly little written about the relationship between TJ and international human rights law. To be sure, there has been some preliminary and exploratory work on the relationship between TJ and international law in general, but virtually nothing on its relationship to international human rights law in a mental disability law context. This paper seeks to focus on this lack of consideration, to speculate as to why that might be, and to offer some suggestions as to how to infuse some new vitality and vigor into this important area of law and social policy. In this article, first, I offer a brief explanation of TJ. Next, I discuss, also briefly, the impact (and the potential future greater impact) of the recently-ratified United Nations Convention on the Rights of Persons with Disabilities (CRPD) on this area. Then, I consider the sparse commentary currently available on the intersection between TJ and international law in general, and will speculate as to why this is so sparse. Then, I offer some thoughts as to the TJ/international human rights law connection, looking specifically at three questions that require far more attention from this perspective (access to counsel, the use of state-sanctioned psychiatry as a tool of political oppression, and the potential redemptive power of the CRPD), and describe a research agenda that scholars might turn to in furtherance of the investigation of the relationships between therapeutic jurisprudence, international human rights law and mental disability law. I conclude by calling on scholars, activists, advocates and practitioners to begin to take this connection seriously in their future work. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency.

PubMed

Loma, Patricia; Guzman-Aranguez, Ana; Perez de Lara, Maria Jesus; Pintor, Jesus

2015-05-01

The effect of the dinucleotide P(1), P(4)-Di (adenosine-5') tetraphosphate (Ap4A) in improving adrenergic anti-glaucomatous delivery by modifying the tight junction proteins of the corneal epithelium was evaluated. Stratified human corneal epithelial cells (HCLE) were treated with Ap4A (100 μM) for 5 min and TJ protein levels and barrier function were analysed by western blotting and transepithelial electrical resistance (TEER), respectively. Western blot experiments showed a significant reduction at 2 h (45% reduction of ZO-1 and 65% reduction of occludin protein levels) as compared to non-treated (control) cells. Two hours after Ap4A treatment, TEER values were significantly reduced (65% as compared to control levels (p < 0.001)), indicating an increase in corneal barrier permeability. Topical application of Ap4A in New Zealand white rabbits two hours before the instillation of the hypotensor compounds (the α2-adrenergic receptor agonist, brimonidine and the β-adrenergic receptor antagonist, timolol), improved the delivery of these compounds to the anterior chamber as well as their hypotensive action on the intraocular pressure. The results obtained showed that, when Ap4A was topically applied two hours before the adrenergic compounds, the concentration of brimonidine in the aqueous humour increased from 64.3 ± 5.3 nM to 240.6 ± 8.6 nM and from 58.9 ± 9.2 nM to 183.7 ± 6.8 nM in the case of timolol, which also produces a more profound effect on IOP. Therefore, Ap4A treatment results in a better entrance of adrenergic anti-glaucomatous compounds within the eye and consequently improved therapeutic efficiency by increasing corneal epithelial barrier permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome sequence of Clostridium tunisiense TJ, isolated from drain sediment from a pesticide factory.

PubMed

Sun, Lili; Wang, Yu; Yu, Chunyan; Zhao, Yongqin; Gan, Yinbo

2012-12-01

Clostridium tunisiense is a Gram-positive, obligate anaerobe that was first isolated in an anaerobic environment under eutrophication. Here we report the first genome sequence of the Clostridium tunisiense TJ isolated from drain sediment of a pesticide factory in Tianjin, China. The genome is of great importance for both basic and application research.

GaN-based vertical-cavity surface-emitting lasers with tunnel junction contacts grown by metal-organic chemical vapor deposition

NASA Astrophysics Data System (ADS)

Lee, SeungGeun; Forman, Charles A.; Lee, Changmin; Kearns, Jared; Young, Erin C.; Leonard, John T.; Cohen, Daniel A.; Speck, James S.; Nakamura, Shuji; DenBaars, Steven P.

2018-06-01

We report the first demonstration of III–nitride vertical-cavity surface-emitting lasers (VCSELs) with tunnel junction (TJ) intracavity contacts grown completely by metal–organic chemical vapor deposition (MOCVD). For the TJs, n++-GaN was grown on in-situ activated p++-GaN after buffered HF surface treatment. The electrical properties and epitaxial morphologies of the TJs were first investigated on TJ LED test samples. A VCSEL with a TJ intracavity contact showed a lasing wavelength of 408 nm, a threshold current of ∼15 mA (10 kA/cm2), a threshold voltage of 7.8 V, a maximum output power of 319 µW, and a differential efficiency of 0.28%.

True-blue laser diodes with tunnel junctions grown monolithically by plasma-assisted molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Skierbiszewski, Czeslaw; Muziol, Grzegorz; Nowakowski-Szkudlarek, Krzesimir; Turski, Henryk; Siekacz, Marcin; Feduniewicz-Zmuda, Anna; Nowakowska-Szkudlarek, Anna; Sawicka, Marta; Perlin, Piotr

2018-03-01

We demonstrate true-blue 450 nm tunnel junction (TJ) laser diodes (LDs) grown by plasma-assisted molecular beam epitaxy (PAMBE). The absence of hydrogen during PAMBE growth allows us to achieve TJs with low resistance. We compare TJ LDs with LDs of standard construction with p-type metal contact. For both types of LD, the threshold current density is around 3 kA/cm2 and the slope efficiency is 0.5 W/A. We do not observe any significant changes in optical losses and differential gain in TJ LDs compared with standard LDs. The differential resistivity of the TJs for current densities higher than 2 kA/cm2 is below 10-4 Ω·cm2.

Magainin 2a - Induced Permeabilization of Phospholipid Vesicles

DTIC Science & Technology

1991-01-02

flJ ə) fl) C rH -H 0) E M D e t e 1 0 0 % • 43 • fl) J3 0 C3...fl) +) ft-H to U4 EH RJ OP 43 o 4J H -H IS *M 0 0 fl) c to 0 • H O 4J O -H in 73 TJ h RJ 0 MH >t 43 fl) to TJ flj fl) fl) C...r H - H F r e t e r m O fl) VD TJ tp to G rt •rH r% f o l l o w : f 6 C F 1 O 43 0) to T J flJ fl) fl) C rH •H fl) E Ul

Adenovirus-delivered GFP-HO-1C[INCREMENT]23 attenuates blood-spinal cord barrier permeability after rat spinal cord contusion.

PubMed

Chang, Sheng; Bi, Yunlong; Meng, Xiangwei; Qu, Lin; Cao, Yang

2018-03-21

The blood-spinal cord barrier (BSCB) plays a key role in maintaining the microenvironment and is primarily composed of tight junction proteins and nonfenestrated capillary endothelial cells. After injury, BSCB damage results in increasing capillary permeability and release of inflammatory factors. Recent studies have reported that haem oxygenase-1 (HO-1) fragments lacking 23 amino acids at the C-terminus (HO-1C[INCREMENT]23) exert novel anti-inflammatory and antioxidative effects in vitro. However, no study has identified the role of HO-1C[INCREMENT]23 in vivo. We aimed to investigate the protective effects of HO-1C[INCREMENT]23 on the BSCB after spinal cord injury (SCI) in a rat model. Here, adenoviral HO-1C[INCREMENT]23 (Ad-GFP-HO-1C[INCREMENT]23) was intrathecally injected into the 10th thoracic spinal cord segment (T10) 7 days before SCI. In addition, nuclear and cytoplasmic extraction and immunofluorescence staining of HO-1 were used to examine the effect of Ad-GFP-HO-1C[INCREMENT]23 on HO-1 nuclear translocation. Evan's blue staining served as an index of capillary permeability and was detected by fluorescence microscopy at 633 nm. Western blotting was also performed to detect tight junction protein expression. The Basso, Beattie and Bresnahan score was used to evaluate kinematic functional recovery through the 28th day after SCI. In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.

Ionization equilibrium at the transition from valence-band to acceptor-band migration of holes in boron-doped diamond

NASA Astrophysics Data System (ADS)

Poklonski, N. A.; Vyrko, S. A.; Poklonskaya, O. N.; Kovalev, A. I.; Zabrodskii, A. G.

2016-06-01

A quasi-classical model of ionization equilibrium in the p-type diamond between hydrogen-like acceptors (boron atoms which substitute carbon atoms in the crystal lattice) and holes in the valence band (v-band) is proposed. The model is applicable on the insulator side of the insulator-metal concentration phase transition (Mott transition) in p-Dia:B crystals. The densities of the spatial distributions of impurity atoms (acceptors and donors) and of holes in the crystal are considered to be Poissonian, and the fluctuations of their electrostatic potential energy are considered to be Gaussian. The model accounts for the decrease in thermal ionization energy of boron atoms with increasing concentration, as well as for electrostatic fluctuations due to the Coulomb interaction limited to two nearest point charges (impurity ions and holes). The mobility edge of holes in the v-band is assumed to be equal to the sum of the threshold energy for diffusion percolation and the exchange energy of the holes. On the basis of the virial theorem, the temperature Tj is determined, in the vicinity of which the dc band-like conductivity of holes in the v-band is approximately equal to the hopping conductivity of holes via the boron atoms. For compensation ratio (hydrogen-like donor to acceptor concentration ratio) K ≈ 0.15 and temperature Tj, the concentration of "free" holes in the v-band and their jumping (turbulent) drift mobility are calculated. Dependence of the differential energy of thermal ionization of boron atoms (at the temperature 3Tj/2) as a function of their concentration N is calculated. The estimates of the extrapolated into the temperature region close to Tj hopping drift mobility of holes hopping from the boron atoms in the charge states (0) to the boron atoms in the charge states (-1) are given. Calculations based on the model show good agreement with electrical conductivity and Hall effect measurements for p-type diamond with boron atom concentrations in the range from 3 × 1017 to 3 × 1020 cm-3, i.e., up to the Mott transition. The model uses no fitting parameters.

Plasma fuelling with cryogenic pellets in the stellarator TJ-II

NASA Astrophysics Data System (ADS)

McCarthy, K. J.; Panadero, N.; Velasco, J. L.; Combs, S. K.; Caughman, J. B. O.; Fontdecaba, J. M.; Foust, C.; García, R.; Hernández Sánchez, J.; Navarro, M.; Pastor, I.; Soleto, A.; the TJ-II Team

2017-05-01

Cryogenic pellet injection is a widely used technique for delivering fuel to the core of magnetically confined plasmas. Indeed, such systems are currently functioning on many tokamak, reversed field pinch and stellarator devices. A pipe-gun-type pellet injector is now operated on the TJ-II, a low-magnetic shear stellarator of the heliac type. Cryogenic hydrogen pellets, containing between 3  ×  1018 and 4  ×  1019 atoms, are injected at velocities between 800 and 1200 m s-1 from its low-field side into plasmas created and/or maintained in this device by electron cyclotron resonance and/or neutral beam injection heating. In this paper, the first systematic study of pellet ablation, particle deposition and fuelling efficiency is presented for TJ-II. From this, light-emission profiles from ablating pellets are found to be in reasonable agreement with simulated pellet ablation profiles (created using a neutral gas shielding-based code) for both heating scenarios. In addition, radial offsets between recorded light-emission profiles and particle deposition profiles provide evidence for rapid outward drifting of ablated material that leads to pellet particle loss from the plasma. Finally, fuelling efficiencies are documented for a range of target plasma densities (~4  ×  1018-  ~2  ×  1019 m-3). These range from ~20%-  ~85% and are determined to be sensitive to pellet penetration depth. Additional observations, such as enhanced core ablation, are discussed and planned future work is outlined.

TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin.

PubMed

Kanda, Yusuke; Yamasaki, Youhei; Sasaki-Yamaguchi, Yoshie; Ida-Koga, Noriko; Kamisuki, Shinji; Sugawara, Fumio; Nagumo, Yoko; Usui, Takeo

2018-02-02

The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca 2+ influx, we first screened the compounds that induce Ca 2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca 2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

Production of a High Efficiency Microbial Flocculant by Proteus mirabilis TJ-1 Using Compound Organic Wastewater

NASA Astrophysics Data System (ADS)

Zhang, Zhiqiang; Xia, Siqing; Zhang, Jiao

2010-11-01

The production of a high efficiency microbial flocculant (MBF) by Proteus mirabilis TJ-1 using compound organic wastewater was investigated. To cut down the cost of the MBF production, several nutritive organic wastewaters were selected to replace glucose and peptone as the carbon source and the nitrogen source in the optimized medium of strain TJ-1, respectively. The compound wastewater of the milk candy and the soybean milk was found to be good carbon source and nitrogen source for this strain to produce MBF. The cost-effective culture medium consists of (per liter): 800 mL wastewater of milk candy, 200 mL wastewater of soybean milk, 0.3 g MgSO4ṡ7 H2O, 5 g K2HPO4, 2 g and KH2PO4, pH 7.0. The economic cost for the MBF production can be cut down over a half by using the developed culture medium. Furthermore, the utilization of the two wastewaters in the preparation of culture medium of strain TJ-1 can not only save their big treatment cost, but also realize their resource reuse.

Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F1 progeny rats.

PubMed

Kumar, Kathiresh M; Aruldhas, Mariajoseph Michael; Banu, Sheerin L; Sadasivam, Balaji; Vengatesh, Ganapathy; Ganesh, Karthik M; Navaneethabalakrishnan, Shobana; Navin, Ajith Kumar; Michael, Felicia Mary; Venkatachalam, Sankar; Stanley, Jone A; Ramachandran, Ilangovan; Banu, Sakhila K; Akbarsha, Mohammad Abdulkader

2017-04-01

The effect of gestational exposure to CrVI (occupational/environmental pollutant and target to Sertoli cells(SC)) was tested in a rat model during the testicular differentiation from the bipotential gonad may interrupt spermatogenesis by disrupting SC tight junctions(TJ) and it's proteins and hormone receptors. Pregnant Wistar rats were exposed to 50/100/200ppm CrVI through drinking water during embryonic days 9-14. On Postnatal day 120, testes were subjected to ion exchange chromatographic analysis and revealed increased level of CrIII in SCs and germ cells, serum and testicular interstitial fluid(TIF). Microscopic analyses showed seminiferous tubules atrophy and disruption of SC TJ, which also recorded decreased testosterone in TIF. mRNA and Protein expression analyses attested decreased level of Fshr, Ar, occludin and claudin-11 in SCs. Immunofluorescent detection revealed weak signal of TJ proteins. Taken together, we concluded that gestational exposure to CrVI interferes with the expression of SC TJ proteins due to attenuated expression of hormone receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Tidal Channel Dynamics and Muddy Substrates: a Comparison Between a Wave Dominated and a Tidal Dominated System

DTIC Science & Technology

2011-09-30

McGlathery, J.T. Morris, T.J. Tolhurst, L.A. Deegan , D.S. Johnson, Ecogeomorphology of Salt Marshes (in press) Fagherazzi S., D.M. FitzGerald, R.W...Fulweiler, Z. Hughes, P.L. Wiberg, K.J. McGlathery, J.T. Morris, T.J. Tolhurst, L.A. Deegan , D.S. Johnson, Ecogeomorphology of Tidal Flats (in press

Sorbents and Mechanisms of Removal

DTIC Science & Technology

2010-08-21

Interactions of Ammonia with Pillared Graphite Oxide Intercalated with Aluminium and Zirconium Polyoxycations Mykola Seredych and T. J. Bandosz ,J...Adsorbents Containing Silver Nanoparticles M. Seredych, S. Bashkova, R. Pietrzak, T.J. Bandosz Langmuir, 26 (2010) 9457-9464 35. Graphite Oxide /Zr(OH)4...Small Molecule Toxic Gases on Graphite Oxide Based Adsorbents Adorbent Wokshop Camille Petit, Roberts Pietrzak and T.J. Bandosz Seattle, WA, July 12-14

Biodegradation of 2-methylquinoline by Enterobacter aerogenes TJ-D isolated from activated sludge.

PubMed

Wang, Lin; Li, Yongmei; Duan, Jingyuan

2013-07-01

Bacterial strain Enterobacter aerogenes TJ-D capable of utilizing 2-methylquinoline as the sole carbon and energy source was isolated from acclimated activated sludge under denitrifying conditions. The ability to degrade 2-methylquinoline by E. aerogenes TJ-D was investigated under denitrifying conditions. Under optimal conditions of temperature (35 degrees C) and initial pH 7, 2-methylquinoline of 100 mg/L was degraded within 176 hr. The degradation of 2-methylquinoline by E. aerogenes TJ-D could be well described by the Haldane model (R2 > 0.91). During the degradation period of 2-methylquinoline (initial concentration 100 mg/L), nitrate was almost completely consumed (the removal efficiency was 98.5%), while nitrite remained at low concentration (< 0.62 mg/L) during the whole denitrification period. 1,2,3,4-Tetrahydro-2-methylquinoline, 4-ethyl-benzenamine, N-butyl-benzenamine, N-ethyl-benzenamine and 2,6-diethyl-benzenamine were metabolites produced during the degradation. The degradation pathway of 2-methylquinoline by E. aerogenes TJ-D was proposed. 2-Methylquinoline is initially hydroxylated at C-4 to form 2-methyl-4-hydroxy-quinoline, and then forms 2-methyl-4-quinolinol as a result of tautomerism. Hydrogenation of the heterocyclic ring at positions 2 and 3 produces 2,3-dihydro-2-methyl-4-quinolinol. The carbon-carbon bond at position 2 and 3 in the heterocyclic ring may cleave and form 2-ethyl-N-ethyl-benzenamine. Tautomerism may result in the formation of 2,6-diethyl-benzenamine and N-butyl-benzenamine. 4-Ethyl-benzenamine and N-ethyl-benzenamine were produced as a result of losing one ethyl group from the above molecules.

Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice.

PubMed

Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

2018-01-12

To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.

Effect of fast electrons on the stability of resistive interchange modes in the TJ-II stellarator

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

García, L.; Ochando, M. A.; Hidalgo, C.

2016-06-15

In this paper, we report on electromagnetic phenomena in low-β plasmas at the TJ-II stellarator, controlled by external heating. To understand the observations qualitatively, we introduce a simple modification of the standard resistive MHD equations, to include the potential impact of fast electrons on instabilities. The dominant instabilities of the modeling regime are resistive interchange modes, and calculations are performed in a configuration with similar characteristics as the TJ-II stellarator. The main effect of the trapping of fast electrons by magnetic islands induced by MHD instabilities is to increase the magnetic component of the fluctuations, changing the character of themore » instability to tearing-like and modifying the frequency of the modes. These effects seem to be consistent with some of the experimental observations.« less

Collisionless damping of flows in the TJ-II stellarator

NASA Astrophysics Data System (ADS)

Sánchez, E.; Kleiber, R.; Hatzky, R.; Borchardt, M.; Monreal, P.; Castejón, F.; López-Fraguas, A.; Sáez, X.; Velasco, J. L.; Calvo, I.; Alonso, A.; López-Bruna, D.

2013-01-01

The results of global linear gyrokinetic simulations of residual flows carried out with the code EUTERPE in the TJ-II three-dimensional geometry are reported. The linear response of the plasma to potential perturbations homogeneous in a magnetic surface shows several oscillation frequencies: a Geodesic-acoustic-mode-like frequency, in qualitative agreement with the formula given by Sugama and Watanabe (2006 Plasma Phys. 72 825), and a much lower frequency oscillation in agreement with the predictions of Mishchenko et al (2008 Phys. Plasmas 15 072309) and Helander et al (2011 Plasma Phys. Control. Fusion 53 054006) for stellarators. The dependence of both oscillations on ion and electron temperatures and the magnetic configuration is studied. The low-frequency oscillations are in the frequency range supporting the long-range correlations between potential signals experimentally observed in TJ-II.

Upgrade of the neutral particle analyzers for the TJ-II stellarator

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

Fontdecaba, J. M., E-mail: josepmaria.fontdecaba@ciemat.es; Ros, A.; McCarthy, K. J.

2014-11-15

The TJ-II stellarator, a magnetically confined plasma device, is equipped with a broad range of diagnostics for plasma characterization. These include 4 neutral particle analyzers (NPAs), consisting of two Acord-12's, to perform poloidal measurements, plus a compact NPA, and an Acord-24, these in tangential viewing positions. The Acord-12's were originally equipped with two rows of 6 channels each, one for hydrogen neutrals and the other for deuterium neutrals but were changed to a single row of 12 detectors for hydrogen, the principal working gas in TJ-II. With this upgrade the resultant improved energy resolution spectrum has allowed more reliable ionmore » temperature estimates to be obtained. Here we present the upgrades undertaken and present results to demonstrate the improved performance of this diagnostic.« less

VizieR Online Data Catalog: Methods for CIP and CIO localisation (Capitaine+, 2006)

NASA Astrophysics Data System (ADS)

Capitaine, N.; Wallace, P. T.

2006-04-01

Various implementations are described, their theoretical bases compared and the relationships between the expressions for the relevant parameters are provided. Semi-analytical and numerical comparisons have been made, based on the P03 precession and the IAU 2000A nutation, with slight modifications to the latter to make it consistent with P03. Methods based on the recent P03 precession model can be found in Capitaine et al. (2003A&A...412..567C, 2005A&A...432..355C). Tables 5-11 contain the coefficients in microarcseconds (uas) of the series developments (i.e. Fourier and Poisson terms) as functions of (terrestrial) time t (expressed in centuries since J2000.0) for the quantities s (Eq. (53)), s+XY/2 (Eq. (58)), s+XY/2+D (Eq. (60)), EO+Dpsi*cos(epsilonA) (where EO is given by Eq. (69)), x{CIO}, y{CIO}, z{CIO} (Eq. (70)), respectively, retaining all terms larger than 0.1 uas. The general formula is: S=Sum{on i}[Sum{j=0,5}[(S{j}i)*tj*sin(ARG)+(C{j}i*cos(ARG)]*tj

Balancing Value and Risk in Information Sharing Through Obfuscation

DTIC Science & Technology

2012-09-20

California, Los Angeles Chatschik Bisdikian IBM T.J. Watson Research Center Lance M. Kaplan US Army Research Laboratory Abstract—Fast-paced data-to...AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) IBM T.J. Watson Research...giving us annotations for both the white listed activity detection as well as the black listed activity recognition . We implemented five features

RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.

PubMed

Zihni, Ceniz; Terry, Stephen James

2015-07-01

The establishment and maintenance of epithelial polarity must be correctly controlled for normal development and homeostasis. Tight junctions (TJ) in vertebrates define apical and basolateral membrane domains in polarized epithelia via bi-directional, complex signalling pathways between TJ themselves and the cytoskeleton they are associated with. RhoGTPases are central to these processes and evidence suggests that their regulation is coordinated by interactions between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this InFocus review we determine that the expression, localization or stability of a variety of these adaptor proteins is altered in various cancers, potentially representing an important mechanistic link between loss of polarity and cancer. We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Scutellaria barbata attenuates diabetic retinopathy by preventing retinal inflammation and the decreased expression of tight junction protein

PubMed Central

Mei, Xi-Yu; Zhou, Ling-Yu; Zhang, Tian-Yu; Lu, Bin; Ji, Li-Li

2017-01-01

AIM To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. RESULTS SE (100, 200 mg/kg) reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ) proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1). SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB) p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1) demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19. PMID:28730076

The role of the lectin-like oxLDL receptor (LOX-1) in traffic-generated air pollution exposure-mediated alteration of the brain microvasculature in Apolipoprotein (Apo) E knockout mice.

PubMed

Lucero, JoAnn; Suwannasual, Usa; Herbert, Lindsay M; McDonald, Jacob D; Lund, Amie K

2017-05-01

Recent studies have shown a strong correlation between air pollution-exposure and detrimental outcomes in the central nervous system, including alterations in blood brain barrier (BBB) integrity, neuroinflammation, and neurodegeneration. However, the mechanisms mediating these pathologies have not yet been fully elucidated. We have previously reported that exposure to traffic-generated air pollution results in increased circulating oxidized low-density lipoprotein (oxLDL), associated with alterations in BBB integrity, in atherosclerotic Apolipoprotein E null (ApoE -/- ) mice. Thus, we investigated the role of the lectin-like oxLDL receptor (LOX)-1 in mediating these deleterious effects in ApoE -/- mice exposed to a mixture of gasoline and diesel engine exhaust (MVE: 100 PM µg/m 3 ) for 6 h/d, 7d/week, for 30 d by inhalation. Concurrent with exposures, a subset of mice were treated with neutralizing antibodies to LOX-1 (LOX-1 Ab) i.p., or IgG (control) i.p., every other day during exposures. Resulting brain microvascular integrity, tight junction (TJ) protein expression, matrix metalloproteinase (MMP)-9/-2 activity, ROS, and markers of cellular adhesion and monocyte/macrophage sequestration were assessed. MVE-exposure resulted in decreased BBB integrity and alterations in microvascular TJ protein expression, associated with increased LOX-1 expression, MMP-9/-2 activities, and lipid peroxidation, each of which was attenuated with LOX-1 Ab treatment. Furthermore, MVE-exposure induced cerebral microvascular ROS and adhesion molecules, expression of which was not normalized through LOX-1 Ab-treatment. Such findings suggest that alterations in brain microvascular structure and integrity observed with MVE-exposure may be mediated, at least in part, via LOX-1 signaling.

Cell polarity proteins and spermatogenesis.

PubMed

Gao, Ying; Xiao, Xiang; Lui, Wing-Yee; Lee, Will M; Mruk, Dolores; Cheng, C Yan

2016-11-01

When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

PubMed

Wilcz-Villega, E; McClean, S; O'Sullivan, M

2014-03-01

Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms. Junctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence. E-cadherin and ZO-1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1 expression was not significantly altered compared with controls. On subtype analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E-cadherin expression was associated with longer symptoms duration specifically in IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but this association was unrelated to IBS subtype. E-cadherin protein expression in the cecum was significantly lower in IBS-A compared with controls and associated with longstanding symptoms. E-cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E-cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS. © 2013 John Wiley & Sons Ltd.

Internet-Based Cognitive Behavioral Therapy Effects on Depressive Cognitions and Brain Function

DTIC Science & Technology

2014-03-01

differentiates deficit and nondeficit schizophrenia. Arch Gen Psychiatry 1999;56:1117-1123. 58. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras...Koneru VK, Garroway J, Stein N, Rauch SL, Herbert MR, Dietrich ME, Melrose R, Grant PE, Sohma M, Klaviness S, Cohen BM, Seidman LJ, Caviness V, Biederman...2005;57(9):1011-9. 116. Frazier JA, Breeze JL, Makris N, Giuliano AS, Herbert MR, Seidman L, Biederman J, Hodge SM, Dieterich ME, Gerstein E

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.

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

PubMed Central

Sankapal, Soni; Gupta, Phalguni; Ratner, Deena; Ding, Ming; Shen, Chengli; Sanyal, Anwesha; Stolz, Donna; Cu-Uvin, Susan; Ramratnam, Bharat

2016-01-01

Abstract Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction (TJ) and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model. After HIV exposure, the distribution patterns and quantities of epithelial TJ and adherens proteins were evaluated by immunofluorescence staining followed by confocal microscopy. Cytokine mRNA in the mucosal epithelia was also evaluated by real-time reverse transcription–polymerase chain reaction (RT-PCR). HIV transmission was evaluated by measuring p24 production in culture supernatant. Our results showed there were no significant changes in the distribution and quantities of epithelial TJ/adherens junction (AJ) proteins after exposure to HIV. However, higher levels of CXCL10 and CXCL11 mRNA expression were detected in HIV-exposed ectocervical epithelia. In case of colon mucosa, higher levels of CXCL10 and IL-6 mRNA expression were detected in HIV-exposed colon mucosa. Our study suggests that HIV induces cytokine production in epithelial cells, which may facilitate HIV transmission by recruiting HIV target cells in the submucosal region. Furthermore, HIV transmission may not occur through epithelial TJ/AJ disruption. PMID:27153934

Oxidative stress induced by potassium bromate exposure results in altered tight junction protein expression in renal proximal tubule cells.

PubMed

Limonciel, Alice; Wilmes, Anja; Aschauer, Lydia; Radford, Robert; Bloch, Katarzyna M; McMorrow, Tara; Pfaller, Walter; van Delft, Joost H; Slattery, Craig; Ryan, Michael P; Lock, Edward A; Jennings, Paul

2012-11-01

Potassium bromate (KBrO(3)) is an oxidising agent that has been widely used in the food and cosmetic industries. It has shown to be both a nephrotoxin and a renal carcinogen in in vivo and in vitro models. Here, we investigated the effects of KBrO(3) in the human and rat proximal tubular cell lines RPTEC/TERT1 and NRK-52E. A genome-wide transcriptomic screen was carried out from cells exposed to a sub-lethal concentration of KBrO(3) for 6, 24 and 72 h. Pathway analysis identified "glutathione metabolism", "Nrf2-mediated oxidative stress" and "tight junction (TJ) signalling" as the most enriched pathways. TJ signalling was less impacted in the rat model, and further studies revealed low transepithelial electrical resistance (TEER) and an absence of several TJ proteins in NRK-52E cells. In RPTEC/TERT1 cells, KBrO(3) exposure caused a decrease in TEER and resulted in altered expression of several TJ proteins. N-Acetylcysteine co-incubation prevented these effects. These results demonstrate that oxidative stress has, in conjunction with the activation of the cytoprotective Nrf2 pathway, a dramatic effect on the expression of tight junction proteins. The further understanding of the cross-talk between these two pathways could have major implications for epithelial repair, carcinogenesis and metastasis.

[Effects of electromagnetic pulse on blood-brain barrier permeability and tight junction proteins in rats].

PubMed

Qiu, Lian-bo; Ding, Gui-rong; Zhang, Ya-mei; Zhou, Yan; Wang, Xiao-wu; Li, Kang-chu; Xu, Sheng-long; Tan, Juan; Zhou, Jia-xing; Guo, Guo-zhen

2009-09-01

To study the effect of electromagnetic pulse (EMP) on the permeability of blood-brain barrier, tight junction (TJ)-associated protein expression and localization in rats. 66 male SD rats, weighing (200 approximately 250) g, were sham or whole-body exposed to EMP at 200 kV/m for 200 pulses. The repetition rate was 1 Hz. The permeability of the blood-brain barrier in rats was assessed by albumin immunohistochemistry. The expression of typical tight junction protein ZO-1 and occludin in both cerebral cortex homogenate and cerebral cortex microvessel homogenate was analyzed by the Western blotting and the distribution of ZO-1 and occludin was examined by immunofluorescence microscopy. In the sham exposure rats, no brain capillaries showed albumin leakage, at 0.5 h after 200 kV/m EMP exposure for 200 pulses; a few brain capillaries with extravasated serum albumin was found, with the time extended, the number of brain capillaries with extravasated serum albumin increased, and reached the peak at 3 h, then began to recover at 6 h. In addition, no change in the distribution of the occludin was found after EMP exposure. Total occludin expression had no significant change compared with the control. However, the expression level of ZO-1 significantly decreased at 1 h and 3 h after EMP exposure in both cerebral cortex homogenate and cerebral cortex microvessel homogenate. Furthermore, immunofluorescence studies also showed alterations in ZO-1 protein localization in cerebral cortex microvessel. The EMP exposure (200 kV/m, 200 pulses) could increase blood-brain barrier permeability in rat, and this change is associated with specific alterations in tight junction protein ZO-1.

Claudins and renal salt transport.

PubMed

Muto, Shigeaki; Furuse, Mikio; Kusano, Eiji

2012-02-01

Tight junctions (TJs) are the most apical component of junctional complexes and regulate the movement of electrolytes and solutes by the paracellular pathway across epithelia. The defining ultrastructural features of TJs are strands of transmembrane protein particles that adhere to similar strands on adjacent cells. These strands are mainly composed of linearly polymerized integral membrane proteins called claudins. Claudins comprise a multigene family consisting of more than 20 members in mammals. Recent work has shown that claudins form barriers, determined by the paracellular electrical resistance and charge selectivity, and pores in the TJ strands. The paracellular pathways in renal tubular epithelia such as the proximal tubule, which reabsorbs the largest fraction of filtered NaCl and water, are important routes for the transport of electrolytes and water. Their transport characteristics vary among different nephron segments. Multiple claudins are expressed at TJs of individual nephron segments in a nephron segment-specific manner. Among them, claudin-2 is highly expressed at TJs of proximal tubules, which are leaky epithelia. Overexpression and knockdown of claudin-2 in epithelial cell lines, and knockout of the claudin-2 gene in mice, have demonstrated that claudin-2 forms high-conductance cation-selective pores in the proximal tubule. Here, we review the renal physiology of paracellular transport and the physiological roles of claudins in kidney function, especially claudin-2 and proximal tubule paracellular NaCl transport.

The Validity of the Use of the Neutron Reduction Factor in Assessing Displacement Damage to Electronics in Armoured Vehicles

DTIC Science & Technology

1990-02-01

ELECTRONICS IN ARMOURED VEHICLES byo0 T. Cousins and TJ. Jamieson co N OTIC L , k .. •, ’" DEFENCE RESEARCH ESTABLISHMENT OTTAWA REPORT NO.1032 February...DISPLACEMENT DAMAGE TO ELECTRONICS IN ARMOURED VEHICLES by T. Cousins Nuclear Effects Section EAectronics Divsion and TJ. Jamkson Science Applications...The degree of protection from neutron irradiation afforded to electronics by armoured vehicles is most correctly defined by the outside-to-inside ratio

Experimental Analysis of Heat Transfer Characteristics and Pressure Drop through Screen Regenerative Heat Exchangers

DTIC Science & Technology

1993-12-01

of fluid T1 initial temperature of matrix and fluid Tf1 average inlet temperature after the step change Tii average inlet temperature before the step...respectively, of the regenerator. The horizontal distances shown with Tf1 , Tj, and T,2 illustrate the time interval for which the average values were...temperature was not a true step function, the investigator made an approximation. The approximation was based on an average temperature. Tf1 was the

Depleted fully monolithic CMOS pixel detectors using a column based readout architecture for the ATLAS Inner Tracker upgrade

NASA Astrophysics Data System (ADS)

Wang, T.; Barbero, M.; Berdalovic, I.; Bespin, C.; Bhat, S.; Breugnon, P.; Caicedo, I.; Cardella, R.; Chen, Z.; Degerli, Y.; Egidos, N.; Godiot, S.; Guilloux, F.; Hemperek, T.; Hirono, T.; Krüger, H.; Kugathasan, T.; Hügging, F.; Marin Tobon, C. A.; Moustakas, K.; Pangaud, P.; Schwemling, P.; Pernegger, H.; Pohl, D.-L.; Rozanov, A.; Rymaszewski, P.; Snoeys, W.; Wermes, N.

2018-03-01

Depleted monolithic active pixel sensors (DMAPS), which exploit high voltage and/or high resistivity add-ons of modern CMOS technologies to achieve substantial depletion in the sensing volume, have proven to have high radiation tolerance towards the requirements of ATLAS in the high-luminosity LHC era. DMAPS integrating fast readout architectures are currently being developed as promising candidates for the outer pixel layers of the future ATLAS Inner Tracker, which will be installed during the phase II upgrade of ATLAS around year 2025. In this work, two DMAPS prototype designs, named LF-Monopix and TJ-Monopix, are presented. LF-Monopix was fabricated in the LFoundry 150 nm CMOS technology, and TJ-Monopix has been designed in the TowerJazz 180 nm CMOS technology. Both chips employ the same readout architecture, i.e. the column drain architecture, whereas different sensor implementation concepts are pursued. The paper makes a joint description of the two prototypes, so that their technical differences and challenges can be addressed in direct comparison. First measurement results for LF-Monopix will also be shown, demonstrating for the first time a fully functional fast readout DMAPS prototype implemented in the LFoundry technology.

*C5a/CD88 signaling alters blood-brain barrier integrity in lupus through NFκb

PubMed Central

Jacob, Alexander; Hack, Bradley; Chen, Peili; Quigg, Richard J.; Alexander, Jessy J.

2011-01-01

Inflammation is a key factor in a number of neurodegenerative diseases including systemic lupus erythematosus (SLE). The complement system is an important mechanism in initiating and amplifying inflammation. Our recent studies demonstrate that C5a, a protein fragment generated during complement activation could alter the blood-brain barrier (BBB) integrity, and thereby disturb the brain microenvironment. To understand the mechanism by which this occurs, we examined the effects of C5a on apoptosis, translocation of nuclear factor-κB (NFκb) and the expression of Iκbα, MAPK, CREB and TJ protein, zona occludens (ZO-1) in mouse brain endothelial cells. Apoptosis was examined by DNA laddering and caspase-3 activity and the distribution of the ZO-1 and the p65 subunit of NFκB were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NFκb into the nucleus, altered ZO-1 at the interfaces of neighboring cells, decreased caspase-3 activity and prevented apoptosis in these cells. Our results indicate that signaling through CD88 regulates the BBB in a NFκb dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NFκb signaling cascades in inflammatory settings. PMID:21929539

Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice

PubMed Central

Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

2018-01-01

Objective To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. Results The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. Conclusions These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. Methods The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption. PMID:29435150

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and CNS Homeostasis

PubMed Central

Tran, Khiem A.; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F.; Göthert, Joachim R.; Malik, Asrar B.; Valyi-Nagy, Tibor; Zhao, You-Yang

2015-01-01

Background The blood-brain barrier (BBB) formed by brain endothelial cells (ECs) interconnected by tight junctions (TJs) is essential for the homeostasis of the central nervous system (CNS). Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Methods and Results Using a mouse model with tamoxifen-inducible EC-restricted disruption of ctnnb1 (iCKO), here we show that endothelial β-catenin signaling is essential for maintaining BBB integrity and CNS homeostasis in adult. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and CNS inflammation, and all died postictal. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of specific TJ proteins Claudin-1 and -3 in adult brain ECs. The clinical relevance of the data is indicated by the observation of decreased expression of Claudin-1 and nuclear β-catenin in brain ECs of hemorrhagic lesions of hemorrhagic stroke patients. Conclusion These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity and CNS inflammation. PMID:26538583

Signatures of a staggered-flux phase in the t-J model with two holes on a 32-site lattice

NASA Astrophysics Data System (ADS)

Leung, P. W.

2000-09-01

We study the relevance of the staggered-flux phase in the t-J model using a system with two holes on a 32-site lattice with periodic boundary conditions. We find a staggered-flux pattern in the current-current correlation in the lowest energy d-wave state where there is mutual attraction between the holes. This staggered correlation decays faster with distance when the hole binding becomes stronger. This is in complete agreement with a recent study by Ivanov, Lee, and Wen [Phys. Rev. Lett. 84, 3958 (2000)] based on the SU(2) theory, and strongly suggests that the staggered-flux phase is a key ingredient in the t-J model. We further show that this staggered-flux pattern does not exist in a state where the holes repel each other. Correlations of the chirality operator S1.(S2×S3) show that the staggered pattern of the chirality is closely tied to the holes.

Estimation of Electron Bernstein Emission in the TJ-II Stellarator

NASA Astrophysics Data System (ADS)

García-Rega\\ Na, J. M.; Cappa, A.; Castejón, F.; Tereshchenko, M.

2009-05-01

In order to study experimentally the viability of first harmonic EBW heating in the TJ-II stellarator by means of the O-X-B tecnique [1], an EBE diagnostic was recently installed [2]. In the present work a theoretical estimation of the EBW radiation in the TJ-II plasmas have been carried out making use of the ray tracing code TRUBA [3]. The line of sight of the EBE diagnostic may be modified using an internal movable mirror and therefore, for comparison with the experimental results, the theoretical O-X-B emission window has been determined. Experimental density and temperature profiles obtained in NBI discharges are considered in the simulations.References:[1] F. Castejon et al, Nucl. Fusion 48, 075011 (2008).[2] J. Caughman et al, Proc. 15th Joint Workshop on ECE and ECRH, Yosemite, USA (2008).[3] M. A. Tereshchenko et. al, Proc. 30th EPS Conference on Contr. Fusion and Plasma Phys., 27A, P-1.18 (2003).

Department of the Air Force Supporting Data for Fiscal Year 1986 Budget Estimates Submitted to Congress February 1985, Descriptive Summaries, Research, Development, Test and Evaluation

DTIC Science & Technology

1985-02-01

Wk B«U Oil &b 0 i »>BCbBB«00 fa s 0 0 0 0 * « •HR« i s fa •r* •T< 0 x:^>u0«to«-<-> -a fa to (J k kTJ<ri r...4J y <M •H JS o o U B 0 y 0 4J a w «M u b >n y b 0 1 0 « i o 0 •n o rH O y •P4 <M TJ 0 0 • a«M oil b •n TJ o B o 0 r^ o 4J 4-> 0 0 o 0 0...Ifc, «j 3 bXIBOn 0COU9 03 0 I . n O. O X Oil ) iHSUfO JJ 3 JJ ftJO B 0O0 9 0TJLiX0»~iU0

Dynamic phase transitions and dynamic phase diagrams of the Blume-Emery-Griffiths model in an oscillating field: the effective-field theory based on the Glauber-type stochastic dynamics

NASA Astrophysics Data System (ADS)

Ertaş, Mehmet; Keskin, Mustafa

2015-06-01

Using the effective-field theory based on the Glauber-type stochastic dynamics (DEFT), we investigate dynamic phase transitions and dynamic phase diagrams of the Blume-Emery-Griffiths model under an oscillating magnetic field. We presented the dynamic phase diagrams in (T/J, h0/J), (D/J, T/J) and (K/J, T/J) planes, where T, h0, D, K and z are the temperature, magnetic field amplitude, crystal-field interaction, biquadratic interaction and the coordination number. The dynamic phase diagrams exhibit several ordered phases, coexistence phase regions and special critical points, as well as re-entrant behavior depending on interaction parameters. We also compare and discuss the results with the results of the same system within the mean-field theory based on the Glauber-type stochastic dynamics and find that some of the dynamic first-order phase lines and special dynamic critical points disappeared in the DEFT calculation.

Characterization of a New HIV-1 CRF01_AE/ CRF07_BC recombinant virus in Tianjin, China.

PubMed

Zhou, Zhehua; Ma, Ping; Feng, Yi; Ou, Weidong; Qian, Jing; Gao, Liying; Zhang, Defa; Shao, Yiming; Wei, Min

2018-05-04

Human immunodeficiency virus (HIV) is notorious for its rapid evolving since its transmissions from money to human. Currently, HIV contains multiple subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs). Here, from an HIV-positive mother and her child in Tianjin, China, we identified a novel HIV-1 second-generation recombinant virus (TJ20170316 and TJ20170317) between CRF01_AE and CRF07_BC. Near full-length genomes were obtained from both samples, and they shared very close sequences, except some point mutations. Phylogenetic analyses of the near full-length genomes showed that they consist of CRF01_AE backbone and part CRF07_BC sequences. Recombinant Identification Program (RIP) and Simplot software identified four breakpoints in gag, pol, vif, tat genes in TJ20170316, totally different from other reported CRFs and URFs. The emergence of such URF in Tianjin, China, highlights the complexity of HIV-1 epidemic and more measures should be taken to prevent HIV transmissions.

Electron Bernstein Wave Emission Studies on the TJ-II Stellarator

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

Caughman, John B; Fernandez, A.; Cappa, A.

2009-01-01

Electron Bernstein Wave (EBW) heating is important for high-beta plasma experiments and will be used for heating over-dense plasmas on TJ-II. TJ-II is a medium sized Heliac operating at CIEMAT in Madrid, whose plasmas are created and heated by ECH via two 300 kW gyrotrons at second harmonic X-mode (53.2 GHz), with additional heating provided by two neutral beam injectors. Theoretical work has shown that the most suitable scheme for launching EBWs in TJ-II is O-X-B mode conversion, which has acceptable heating efficiency for central densities above 1.2 x 1019 m-3.[1] A system based on a 28 GHz-100ms diode gyrotronmore » will be used to deliver 300 kW through a corrugated waveguide. The microwave heating beam will be directed and focused by a steering mirror located inside the vacuum vessel. Prior to the heating experiments, measurement of the thermal EBW emission (EBE) from the plasma is being made to help determine the optimum launch angle for EBW mode conversion, and also to provide an indication of the electron temperature evolution in over-dense plasmas. A dual-polarized quad-ridged broadband horn is used to measure the EBW emission and polarization at 28 GHz. Initial measurements indicate that the emission in under-dense plasmas corresponds to oblique electron cyclotron emission (ECE) and then converts to EBE when the plasma becomes over-dense during neutral beam injection.« less

Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer

PubMed Central

Ichiki, Masao; Wataya, Hiroshi; Yamada, Kazuhiko; Tsuruta, Nobuko; Takeoka, Hiroaki; Okayama, Yusuke; Sasaki, Jun; Hoshino, Tomoaki

2017-01-01

Purpose Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash. Patients and methods First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and $ G3 skin toxicity (severe or medically significant but not immediately life-threatening). Results A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response. Conclusion The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash. PMID:29123409

Nanoscale current uniformity and injection efficiency of nanowire light emitting diodes

NASA Astrophysics Data System (ADS)

May, Brelon J.; Selcu, Camelia M.; Sarwar, A. T. M. G.; Myers, Roberto C.

2018-02-01

As an alternative to light emitting diodes (LEDs) based on thin films, nanowire based LEDs are the focus of recent development efforts in solid state lighting as they offer distinct photonic advantages and enable direct integration on a variety of different substrates. However, for practical nanowire LEDs to be realized, uniform electrical injection must be achieved through large numbers of nanowire LEDs. Here, we investigate the effect of the integration of a III-Nitride polarization engineered tunnel junction (TJ) in nanowire LEDs on Si on both the overall injection efficiency and nanoscale current uniformity. By using conductive atomic force microscopy (cAFM) and current-voltage (IV) analysis, we explore the link between the nanoscale nonuniformities and the ensemble devices which consist of many diodes wired in parallel. Nanometer resolved current maps reveal that the integration of a TJ on n-Si increases the amount of current a single nanowire can pass at a given applied bias by up to an order of magnitude, with the top 10% of wires passing more than ×3.5 the current of nanowires without a TJ. This manifests at the macroscopic level as a reduction in threshold voltage by more than 3 V and an increase in differential conductance as a direct consequence of the integration of the TJ. These results show the utility of cAFM to quantitatively probe the electrical inhomogeneities in as-grown nanowire ensembles without introducing uncertainty due to additional device processing steps, opening the door to more rapid development of nanowire ensemble based photonics.

Limit cycle oscillations at the L-I-H transition in TJ-II plasmas: triggering, temporal ordering and radial propagation

NASA Astrophysics Data System (ADS)

Estrada, T.; Ascasíbar, E.; Blanco, E.; Cappa, A.; Castejón, F.; Hidalgo, C.; van Milligen, B. Ph.; Sánchez, E.

2015-06-01

The spatiotemporal evolution of the interaction between turbulence and flows has been studied close to the L-H transition threshold conditions in the edge of TJ-II plasmas. As in other devices the temporal dynamics of the interaction displays limit cycle oscillations (LCO) with a characteristic predator-prey relationship between flows and turbulence. At TJ-II, the turbulence-flow front is found to propagate radially outwards at the onset of the LCO and in some particular cases, after a short time interval without oscillations, a reversal in the front propagation velocity is observed. Associated to this velocity reversal, a change in the temporal ordering of the LCO is measured. However, the change in the temporal ordering is not related to an intrinsic change in the nature of the LCO. In all cases the turbulence increase leads the process and produces an increase in the E × B flow shear. Dedicated experiments have been carried out to investigate the physical mechanisms triggering the onset of the LCO. At TJ-II the LCO are preferentially observed close to the transition threshold conditions at specific magnetic configurations having a low order rational surface located at the inner side of the E × B flow shear location. The behaviour of different frequency modes has been analysed and interpreted in terms of a geodesic acoustic mode generated by the non-linear mode coupling of Alfvén eigenmodes that evolves towards a low frequency flow, plus a MHD mode linked to the low order rational surface, as precursors of the LCO.

Temperature and doping dependence of the high-energy kink in cuprates.

PubMed

Zemljic, M M; Prelovsek, P; Tohyama, T

2008-01-25

It is shown that spectral functions within the extended t-J model, evaluated using the finite-temperature diagonalization of small clusters, exhibit the high-energy kink in single-particle dispersion consistent with recent angle-resolved photoemission results on hole-doped cuprates. The kink and waterfall-like features persist up to large doping and to temperatures beyond J; hence, the origin can be generally attributed to strong correlations and incoherent hole propagation at large binding energies. In contrast, our analysis predicts that electron-doped cuprates do not exhibit these phenomena in photoemission.

Comparison of the Direct Costs, Length of Recovery, and Incidence of Post Operative Anti-Emetic use After Anesthesia Induction with Propofol or a 1:1 Mixture of Thiopental and Propofol

DTIC Science & Technology

1999-10-01

other agent. The net result was enhanced GABA function. Further experiments need to be done to confirm this. Propofol and midazolam (a...REFERENCES Amrein, R., Hetzel, W., & Allen, S. R. (1995). Co-induction of anaesthesia: The rationale. European Journal of Anaesthesiology Supplement...alfentanil for a short gynecological procedure. Acta Anaesthesiology Scandinavia, 40(4), 416-420. 1:1 Mixture 47 Gan, T.J., Ginsberg, B., Grant, A.P

Structural Basis of a Key Factor Regulating the Affinity between the Zonula Occludens First PDZ Domain and Claudins.

PubMed

Nomme, Julian; Antanasijevic, Aleksandar; Caffrey, Michael; Van Itallie, Christina M; Anderson, James M; Fanning, Alan S; Lavie, Arnon

2015-07-03

The molecular seal between epithelial cells, called the tight junction (TJ), is built by several membrane proteins, with claudins playing the most prominent role. The scaffold proteins of the zonula occludens family are required for the correct localization of claudins and hence formation of the TJ. The intracellular C terminus of claudins binds to the N-terminal PDZ domain of zonula occludens proteins (PDZ1). Of the 23 identified human claudin proteins, nine possess a tyrosine at the -6 position. Here we show that the claudin affinity for PDZ1 is dependent on the presence or absence of this tyrosine and that the affinity is reduced if the tyrosine is modified by phosphorylation. The PDZ1 β2-β3 loop undergoes a significant conformational change to accommodate this tyrosine. Cell culture experiments support a regulatory role for this tyrosine. Plasticity has been recognized as a critical property of TJs that allow cell remodeling and migration. Our work provides a molecular framework for how TJ plasticity may be regulated. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Batch Covariance Relaxation (BCR) Adaptive Processing.

DTIC Science & Technology

1981-08-01

leads to the equivalent bandpass transfer function K Pk-8) Bpp (s) =17 - 22 where C2I is the radian IF frequency normalized by wc. Assuming, tacitly...transfer function in (2-3) is given by H +(f + fE) = H+ Bpp (I + 6 ) (2-13) provided that f and f, are understood to be normalized by fc = wc/2r. In...4..J - tj, 45I2 a I a N 1A CZ~ IJ~oa 1,1 2.0 X : Z 1-3 1 a * N -- e - -o 0 (A -1- 1U z 0 8 Or I W *IA O! IU fau a :at oc- -MZ a Iaaa a a m :wU I..- 1

Status of TJ-II project

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

Alejaldre, C.; Blaumoser, M.; Almoguera, L.

1995-04-01

The flexible Heliac TJ-II is a medium six device (R=1.5m, [a]=0.2 m, B(0)=1.0 T) in an advanced stage of construction at Centro de Investigaciones Energeticas Medio Ambientales y Tecnologicas (CIEMAT), Madrid. The problems encountered during manufacturing so far have been solved satisfactorily. Nevertheless the narrow tolerances, which result from the compact machine design, create real challenges for all the component manufacturers. In this paper we present the present status of the project with a particular emphasis on the construction situation of the main components. 1 ref., 2 figs., 1 tab.

Extremely correlated Fermi liquid theory of the t-J model in 2 dimensions: low energy properties

NASA Astrophysics Data System (ADS)

Shastry, B. Sriram; Mai, Peizhi

2018-01-01

Low energy properties of the metallic state of the two-dimensional t-J model are presented for second neighbor hopping with hole-doping (t\\prime ≤slant 0) and electron-doping (t\\prime > 0), with various superexchange energy J. We use a closed set of equations for the Greens functions obtained from the extremely correlated Fermi liquid theory. These equations reproduce the known low energies features of the large U Hubbard model in infinite dimensions. The density and temperature dependent quasiparticle weight, decay rate and the peak spectral heights over the Brillouin zone are calculated. We also calculate the resistivity, Hall conductivity, Hall number and cotangent Hall angle. The spectral features display high thermal sensitivity at modest T for density n≳ 0.8, implying a suppression of the effective Fermi-liquid temperature by two orders of magnitude relative to the bare bandwidth. The cotangent Hall angle exhibits a T 2 behavior at low T, followed by an interesting kink at higher T. The Hall number exhibits strong renormalization due to correlations. Flipping the sign of t\\prime changes the curvature of the resistivity versus T curves between convex and concave. Our results provide a natural route for understanding the observed difference in the temperature dependent resistivity of strongly correlated electron-doped and hole-doped matter.

Magnetostratigraphy of a Marine Triassic-Jurassic Boundary Section, Kennecott Point, Queen Charlotte Islands: Implications for the Temporal Correlation of a 'Big Five' Mass Extinction Event.

NASA Astrophysics Data System (ADS)

Hilburn, I. A.; Kirschvink, J. L.; Ward, P. D.; Haggart, J. W.; Raub, T. D.

2008-12-01

Several causes have been proposed for Triassic-Jurassic (T-J) boundary extinctions, including global ocean anoxia/euxinia, an impact event, and/or eruption of the massive Central Atlantic Magmatic Province (CAMP), but poor intercontinental correlation makes testing these difficult. Sections at Kennecott Point, Queen Charlotte Islands, British Columbia span the late Norian through Rhaetian (Triassic) and into the earliest Hettangian (Jurassic) and provide the best integrated magneto- and chemostratigraphic framework for placing necessary temporal constraints upon the T-J mass extinctions. At Kennecott Point, turnover of radiolaria and ammonoids define the T-J boundary marine extinction and are coincident with a 2 ‰ negative excursion in δ13Corg similar in magnitude to that observed at Ferguson Hill (Muller Canyon), Nevada (1, 2). With Conodont Alteration Index values in the 1-2 range, Kennecott Point provides the ideal setting for use of magnetostratigraphy to tie the marine isotope excursion into the chronostratigraphic framework of the Newark, Hartford, and Fundy Basins. In the summer of 2005, we collected a ~1m resolution magnetostratigraphic section from 105 m of deep marine, silt- and sandstone turbidites and interbedded mudstones, spanning the T-J boundary at Kennecott Point. Hybrid progressive demagnetization - including zero-field, low-temperature cycling; low-field AF cleaning; and thermal demagnetization in ~25°C steps to 445°C under flowing N2 gas (3) - first removed a Northerly, steeply inclined component interpreted to be a Tertiary overprint, revealing an underlying dual-polarity component of moderate inclination. Five major polarity zones extend through our section, with several short, one-sample reversals interspersed amongst them. Comparison of this pattern with other T-J boundary sections (4-6) argues for a Northern hemisphere origin of our site, albeit with large vertical-axis rotations. A long normal chron bounds the T-J boundary punctuated by two short but poorly-resolved reversed chrons and one brief zone of intermediate polarity. As such, our results could support the hypothesis (5, 7) that the surface onset of CAMP volcanism post-dates the T-J marine and terrestrial extinction events. Alternatively, these two reversed intervals in our column could correlate with two later "earliest Jurassic" reversed zones from the Hartford Basin (8), placing the marine extinction event contemporaneous with CAMP volcanism and after the palynofloral event found in the Newark and Hartford Basins. Correlation between the Tethyan / Oyuklu composite magnetostratigraphy (9) and others in North America and Britain remains a major problem for the Global Polarity Timescale. 1. P. D. Ward et al., Palaeo. Palaeo. Palaeo. 244, 281, 2007. 2. K. H. Williford et al., Palaeo. Palaeo. Palaeo. 244, 290, 2007. 3. J. L. Kirschvink et al., G3 9, 2008. 4. M. W. Hounslow et al., Palaeo. Palaeo. Palaeo. 213, 331, 2004. 5. D. V. Kent, P. E. Olsen, JGR-Sol. Earth 104, 12831, 1999. 6. D. V. Kent, P. E. Olsen, EPSL 179, 311, 2000. 7. J. H. Whiteside et al., Palaeo. Palaeo. Palaeo. 244, 345, 2007. 8. D. V. Kent, P. E. Olsen, JGR-Sol. Earth 113, 2008. 9. Y. Gallet et al., EPSL 255, 458, 2007.

Social Cognitive Theory Predictors of Exercise Behavior in Endometrial Cancer Survivors

PubMed Central

Basen-Engquist, Karen; Carmack, Cindy L.; Li, Yisheng; Brown, Jubilee; Jhingran, Anuja; Hughes, Daniel C.; Perkins, Heidi Y.; Scruggs, Stacie; Harrison, Carol; Baum, George; Bodurka, Diane C.; Waters, Andrew

2014-01-01

Objective This study evaluated whether social cognitive theory (SCT) variables, as measured by questionnaire and ecological momentary assessment (EMA), predicted exercise in endometrial cancer survivors. Methods One hundred post-treatment endometrial cancer survivors received a 6-month home-based exercise intervention. EMAs were conducted using hand-held computers for 10- to 12-day periods every 2 months. Participants rated morning self-efficacy and positive and negative outcome expectations using the computer, recorded exercise information in real time and at night, and wore accelerometers. At the midpoint of each assessment period participants completed SCT questionnaires. Using linear mixed-effects models, we tested whether morning SCT variables predicted minutes of exercise that day (Question 1) and whether exercise minutes at time point Tj could be predicted by questionnaire measures of SCT variables from time point Tj-1 (Question 2). Results Morning self-efficacy significantly predicted that day’s exercise minutes (p<.0001). Morning positive outcome expectations was also associated with exercise minutes (p=0.0003), but the relationship was attenuated when self-efficacy was included in the model (p=0.4032). Morning negative outcome expectations was not associated with exercise minutes. Of the questionnaire measures of SCT variables, only exercise self-efficacy predicted exercise at the next time point (p=0.003). Conclusions The consistency of the relationship between self-efficacy and exercise minutes over short (same day) and longer (Tj to Tj-1) time periods provides support for a causal relationship. The strength of the relationship between morning self-efficacy and exercise minutes suggest that real-time interventions that target daily variation in self-efficacy may benefit endometrial cancer survivors’ exercise adherence. PMID:23437853

Phase separation in the t-J model. [in theory of high-temperature superconductors

NASA Technical Reports Server (NTRS)

Emery, V. J.; Lin, H. Q.; Kivelson, S. A.

1990-01-01

A detailed understanding of the motion of 'holes' in an antiferromagnet is of fundamental importance for the theory of high-temperature superconductors. It is shown here that, for the t-J model, dilute holes in an antiferromagnet are unstable against phase separation into a hole-rich and a no-hole phase. When the spin-exchange interaction J exceeds a critical value Jc, the hole-rich phase has no electrons. It is proposed that, for J slightly less than Jc, the hole-rich phase is a low-density superfluid of electron pairs. Phase separation in related models is briefly discussed.

A school peer mediation program as a context for exploring therapeutic jurisprudence (TJ): Can a peer mediation program inform the law?

PubMed

McWilliam, Nicky

2010-01-01

This paper reports an exploratory study of a school peer mediation program implemented as an alternative way to manage bullying and other destructive conflict. The study explores the effects of the program on the well-being of members of the school community by examining perceptions of students, staff and a sample of parents and former students. Drawing on therapeutic jurisprudence (TJ) the study explores whether the component parts of the program, separately or together, promote intended or unintended therapeutic effects. The preliminary findings of the study emphasise the importance of peer mediation training and suggest that existing scholarship in the area of school conflict resolution and peer mediation, when viewed through a TJ lens, may provide valuable insights into how to optimally configure programs for development and adoption in schools and other community settings. The study highlights the lack of attention paid by the legal system to valuable scholarship in the area of school conflict resolution and peer mediation, which may have implications for the understanding and development of legal processes and the law in general. Copyright © 2010 Elsevier Ltd. All rights reserved.

A LIBS method for simultaneous monitoring of the impurities and the hydrogenic composition present in the wall of the TJ-II stellarator

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

López-Miranda, B., E-mail: belen.lopez@ciemat.es; Zurro, B.; Baciero, A.

The study of plasma-wall interactions and impurity transport in the plasma fusion devices is critical for the development of future fusion reactors. An experiment to perform laser induced breakdown spectroscopy, using minor modifications of our existing laser blow-off impurity injection system, has been set up thus making both experiments compatible. The radiation produced by the laser pulse focused at the TJ-II wall evaporates a surface layer of deposited impurities and the subsequent radiation produced by the laser-produced plasma is collected by two separate lens and fiber combinations into two spectrometers. The first spectrometer, with low spectral resolution, records a spectrummore » from 200 to 900 nm to give a survey of impurities present in the wall. The second one, with high resolution, is tuned to the wavelengths of the Hα and Dα lines in order to resolve them and quantify the hydrogen isotopic ratio present on the surface of the wall. The alignment, calibration, and spectral analysis method will be described in detail. First experimental results obtained with this setup will be shown and its relevance for the TJ-II experimental program discussed.« less

Nodal liquids in extended t-J models and dynamical supersymmetry

NASA Astrophysics Data System (ADS)

Mavromatos, Nick E.; Sarkar, Sarben

2000-08-01

In the context of extended t-J models, with intersite Coulomb interactions of the form -V∑ninj, with ni denoting the electron number operator at site i, nodal liquids are discussed. We use the spin-charge separation ansatz as applied to the nodes of a d-wave superconducting gap. Such a situation may be of relevance to the physics of high-temperature superconductivity. We point out the possibility of existence of certain points in the parameter space of the model characterized by dynamical supersymmetries between the spinon and holon degrees of freedom, which are quite different from the symmetries in conventional supersymmetric t-J models. Such symmetries pertain to the continuum effective-field theory of the nodal liquid, and one's hope is that the ancestor lattice model may differ from the continuum theory only by renormalization-group irrelevant operators in the infrared. We give plausible arguments that nodal liquids at such supersymmetric points are characterized by superconductivity of Kosterlitz-Thouless type. The fact that quantum fluctuations around such points can be studied in a controlled way, probably makes such systems of special importance for an eventual nonperturbative understanding of the complex phase diagram of the associated high-temperature superconducting materials.

Transcriptional profiles of Rel/NF-κB, inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) in the lipopolysaccharide (LPS) and two Vibrio sp.-exposed intertidal copepod, Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Jeong, Chang-Bum; Rhee, Jae-Sung; Lee, Jae-Seong

2014-02-01

The immune system and the role of immunity-related genes have rarely been studied in copepods, even though copepods have a primitive immune response system and also have a potential in pathogen transport higher trophic levels. In this study, we firstly cloned and characterized three core immune genes such as nuclear factor κB (NF-κB), inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) genes in the intertidal copepod Tigriopus japonicus. Several in silico analyses based on conserved domains, motifs, and phylogenetic relationships were supporting their annotations. To investigate the immune-related role of three genes, we exposed lipopolysaccharide (LPS) and two Vibrio sp. to T. japonicus. After exposure of different concentrations of LPS and two Vibrio sp., transcripts of TJ-IκB and TJ-LITAF genes were significantly elevated during the time course in a dose-dependent manner, while TJ-NF-κB transcripts were not significantly changed during exposure. These findings demonstrated that the copepod T. japonicus has a conserved immunity against infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spectral functions with the density matrix renormalization group: Krylov-space approach for correction vectors

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

None, None

Frequency-dependent correlations, such as the spectral function and the dynamical structure factor, help illustrate condensed matter experiments. Within the density matrix renormalization group (DMRG) framework, an accurate method for calculating spectral functions directly in frequency is the correction-vector method. The correction vector can be computed by solving a linear equation or by minimizing a functional. Our paper proposes an alternative to calculate the correction vector: to use the Krylov-space approach. This paper also studies the accuracy and performance of the Krylov-space approach, when applied to the Heisenberg, the t-J, and the Hubbard models. The cases we studied indicate that themore » Krylov-space approach can be more accurate and efficient than the conjugate gradient, and that the error of the former integrates best when a Krylov-space decomposition is also used for ground state DMRG.« less

Spectral functions with the density matrix renormalization group: Krylov-space approach for correction vectors

DOE PAGES

None, None

2016-11-21

Frequency-dependent correlations, such as the spectral function and the dynamical structure factor, help illustrate condensed matter experiments. Within the density matrix renormalization group (DMRG) framework, an accurate method for calculating spectral functions directly in frequency is the correction-vector method. The correction vector can be computed by solving a linear equation or by minimizing a functional. Our paper proposes an alternative to calculate the correction vector: to use the Krylov-space approach. This paper also studies the accuracy and performance of the Krylov-space approach, when applied to the Heisenberg, the t-J, and the Hubbard models. The cases we studied indicate that themore » Krylov-space approach can be more accurate and efficient than the conjugate gradient, and that the error of the former integrates best when a Krylov-space decomposition is also used for ground state DMRG.« less

Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

PubMed

Burgos, Jose L; Patterson, Thomas L; Graff-Zivin, Joshua S; Kahn, James G; Rangel, M Gudelia; Lozada, M Remedios; Staines, Hugo; Strathdee, Steffanie A

2016-01-01

We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component.

Role of catalytic iron and oxidative stress in nitrofen-induced congenital diaphragmatic hernia and its amelioration by Saireito (TJ-114).

PubMed

Hirako, Shima; Tsuda, Hiroyuki; Ito, Fumiya; Okazaki, Yasumasa; Hirayama, Tasuku; Nagasawa, Hideko; Nakano, Tomoko; Imai, Kenji; Kotani, Tomomi; Kikkawa, Fumitaka; Toyokuni, Shinya

2017-11-01

Congenital diaphragmatic hernia (CDH) is a life-threatening neonatal disease that leads to lung hypoplasia and pulmonary hypertension. We recently found that maternal prenatal administration of Saireito (TJ-114) ameliorates fetal CDH in a nitrofen-induced rat model. Here, we studied the role of iron and oxidative stress in neonates of this model and in lung fibroblasts IMR90-SV in association with nitrofen and Saireito. We observed increased immunostaining of 8-hydroxy-2'-deoxyguanosine in the lungs of neonates with CDH, which was ameliorated by maternal Saireito intake. Pulmonary transferrin receptor expression was significantly decreased in both CDH and CDH after Saireito in comparison to normal controls, indicating functional lung immaturity, whereas catalytic Fe(II) and pulmonary DMT1/ferroportin expression remained constant among the three groups. Saireito revealed a dose-dependent scavenging capacity with electron spin resonance spin trapping in vitro against hydroxyl radicals but not against superoxide. Finally, nitrofen revealed dose-dependent cytotoxicity to IMR90-SV cells, accompanied by an increase in oxidative stress, as seen by 5(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and catalytic Fe(II). Saireito ameliorated all of these in IMR90-SV cells. In conclusion, catalytic Fe(II)-dependent oxidative stress by nitrofen may be the pathogenic cause of CDH, and the antioxidative activity of Saireito is at least partially responsible for improving nitrofen-induced CDH.

Role of catalytic iron and oxidative stress in nitrofen-induced congenital diaphragmatic hernia and its amelioration by Saireito (TJ-114)

PubMed Central

Hirako, Shima; Tsuda, Hiroyuki; Ito, Fumiya; Okazaki, Yasumasa; Hirayama, Tasuku; Nagasawa, Hideko; Nakano, Tomoko; Imai, Kenji; Kotani, Tomomi; Kikkawa, Fumitaka; Toyokuni, Shinya

2017-01-01

Congenital diaphragmatic hernia (CDH) is a life-threatening neonatal disease that leads to lung hypoplasia and pulmonary hypertension. We recently found that maternal prenatal administration of Saireito (TJ-114) ameliorates fetal CDH in a nitrofen-induced rat model. Here, we studied the role of iron and oxidative stress in neonates of this model and in lung fibroblasts IMR90-SV in association with nitrofen and Saireito. We observed increased immunostaining of 8-hydroxy-2'-deoxyguanosine in the lungs of neonates with CDH, which was ameliorated by maternal Saireito intake. Pulmonary transferrin receptor expression was significantly decreased in both CDH and CDH after Saireito in comparison to normal controls, indicating functional lung immaturity, whereas catalytic Fe(II) and pulmonary DMT1/ferroportin expression remained constant among the three groups. Saireito revealed a dose-dependent scavenging capacity with electron spin resonance spin trapping in vitro against hydroxyl radicals but not against superoxide. Finally, nitrofen revealed dose-dependent cytotoxicity to IMR90-SV cells, accompanied by an increase in oxidative stress, as seen by 5(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and catalytic Fe(II). Saireito ameliorated all of these in IMR90-SV cells. In conclusion, catalytic Fe(II)-dependent oxidative stress by nitrofen may be the pathogenic cause of CDH, and the antioxidative activity of Saireito is at least partially responsible for improving nitrofen-induced CDH. PMID:29203958

Hole pairing and thermodynamic properties of the two dimensional frustrated t-J model

NASA Astrophysics Data System (ADS)

Roy, K.; Pal, P.; Nath, S.; Ghosh, N. K.

2018-04-01

The frustrated t-J model is investigated by using the exact-diagonalization (ED) method on an 8-site cluster. The effect on next-nearest-neighbor (NNN) exchange interaction J' (frustration) on the hole pairing and the thermodynamic properties of the system is considered. Two holes initially remain unbound at smaller value of J'/t, but tend to bind at larger value. The maximum possibility of pair formation has been observed to be at NNN sites. Entropy calculation shows that the system goes to more disordered state with J'. The specific heat curves show a single peak structure. A decrease in effective exchange energy is observed due to the frustration.

The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer.

PubMed

Qi, Fanghua; Zhao, Lin; Zhou, Aiyan; Zhang, Bo; Li, Anyuan; Wang, Zhixue; Han, Junqing

2015-02-01

Recent studies indicate that Traditional Chinese medicine (TCM) can play an important role in the whole course of cancer treatment such as recovery stages of post-operative, radiotherapy or chemotherapy stages instead of only terminal stage of cancer. In this review, we have summarized current evidence for using TCM as adjuvant cancer treatment in different stages of cancer lesions. Some TCMs (e.g., TJ-41, Liu-jun-zi-tang, PHY906, Coumarin, and Aescine) are capable of improving the post-operative symptoms such as fatigue, pain, appetite, diarrhea, nausea, vomiting, and lymphedema. Some TCMs (e.g., Ginseng, Huang-Qi, BanZhiLian, TJ-48, Huachansu injection, Shenqi fuzheng injection, and Kanglaite injection) in combination with chemo- or radio-therapy are capable of enhancing the efficacy of and diminishing the side effects and complications caused by chemo- and radiotherapy. Taken together, they have great advantages in terms of suppressing tumor progression, relieving surgery complications, increasing the sensitivity of chemo- and radio- therapeutics, improving an organism's immune system function, and lessening the damage caused by surgery, chemo- or radio-therapeutics. They have significant effects on relieving breast cancer-related lymphedema, reducing cancer-related fatigue and pain, improving radiation pneumonitis and gastrointestinal side effects, protecting liver function, and even ameliorating bone marrow suppression. This review of those medicines should contribute to an understanding of Chinese herbal medicines as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer, by providing useful information for development of more effective anti-cancer drugs and making more patients "survival with cancer" for a long time.

hwhap_Ep40 Tough and Competent

NASA Image and Video Library

2018-04-13

Production Transcript for Ep40 Tough and Competent.mp3 Gary Jordan (Host): Houston, We Have A Podcast, welcome to the official podcast of the NASA Johnson Space Center, Episode 40, Tough and Competent. I'm Gary Jordan, and I'll be your host today. So on this podcast, we bring in the experts, NASA astronauts, NASA flight directors, sometimes folks who have done both, and that happens to be our guest today. Today we're talking with Colonel TJ Creamer. He's a Flight Director in mission control Houston, and he also happened to be an astronaut before that. He's the first and only person to do so. We had a great discussion about his story from his humble beginnings, all the way through his flight to the International Space Station. He talks about becoming a flight director, and the importance of what that means in mission control, especially leading a team of folks who, as Gene Kranz once said, are tough and competent. Applications to become a flight director just happen to be open right now, but not for much longer. If you're thinking that working in mission control will be cool and you would describe yourself as tough and competent, this episode is especially for you. If not, don't click away just yet, this was a really good conversation. You'll enjoy it. So, with no further delay, let's go lightspeed and jump right ahead to our talk with Colonel TJ Creamer. Enjoy! [ Music & Radio Transmissions ] TJ, thanks so much for coming on the podcast today! TJ Creamer: You are most welcome. Host: Awesome! I kind of wanted to start with your story, because it's an interesting one, so I know you were born in Arizona, but you consider yourself more of a Maryland boy? TJ Creamer: For the most part, I think that's geographically probably the best. I've -- in my lifetime, I've moved domiciles 23 times. Host: Wow. TJ Creamer: Dad was in the Army, I was in the Army, so add them up, you got bounced around quite a bit. Call me a citizen of the world, but I went to most of my schooling in the Maryland area. Host: So, citizen of the world, so outside the U.S. too? TJ Creamer: Oh, actually, yeah, I got a couple of years outside the U.S. Host: Really? Okay, what countries? TJ Creamer: I spent a grand total of six years in Germany. Host: Alright. TJ Creamer: And I've visited/slept in [inaudible] airport, touch and go, but have been, for some significant amount of time, in about 30 countries. Host: Amazing! Wow! Yeah, I can't say that [laughter], by any means. Alright, so growing up Maryland, what got you into space? What really influenced your path? TJ Creamer: So, it's kind of interesting in the sense that I didn't have a plan, let me just tell you what kind of kicked things off. When you get a handful of years old enough in the Army, the Army goes, hey, you know what, we know your primary specialty is an aviator. But we want you to pick a secondary speciality, and so I said great. I was a chemist, as the undergraduate degree program provided me with that background. So I said, research and development, and the Army said, great, what we'll do, and they did, they sent me a free subscription to RD&A magazine, Research, Development, and Acquisition. And the first issue I got, the inside back cover was an article entitled, Typical Profile of an Army Astronaut, and it wasn't until that age, mid-20's, that I went, oh! If they said brown eyes and brown hair, that would be me! [Gary chuckling] So I hadn't really had thought about it until that moment, to be quite honest with you. Host: Really? TJ Creamer: And after that, we started tracking a little bit about improving one's background and experiences to help with an application process. Host: So then what got you into the chemistry field then, before -- before you were even considering space? TJ Creamer: [Laughing] So I did really well in high school, except for chemistry. So I went into chemistry, because I obviously was doing something wrong, and actually that's how I became a chemistry major. Host: Really? Usually it's the opposite. Usually it's like, I'm really good at that, that's going to be my career. It's the opposite. Interesting. Okay, so then, so you read this and you said, okay, space -- space is an option for me. Is that when you started -- is that when you joined the ROTC in the Army? TJ Creamer: So, for college, I was a four year scholarship in ROTC, so I came in as an ROTC guy, as a freshman. Host: Okay. TJ Creamer: Got my commissioned at the end of the four years of -- of college and went into the Army. Ended up going to flight school, and went off to deployment into Germany for a couple of years there. So, the aviation world is a natural introduction to aeronautical stuff, which leads you into other types of flying, perhaps, but it was just a nice, little marriage of both interests, and -- and forward-thinking stuff. Host: So after you got your degree in chemistry, you realized that space was an option. Okay, to get there, maybe becoming an aviator is the way to go? TJ Creamer: Right, right. Host: That was the logic? TJ Creamer: Not -- actually, at that age, it was more like, this is what I would like to do. I would like to go fly, and that's kind of how that evolved. Host: [Laughing] I did -- I did Young Eagle's Scout, I think when I was 17, I was like right up against the 18 where they were like, okay, you're too old to fly, and Young Eagle's was you can just go to the airport and they had like a free fly day where you can just talk to a pilot and say, hey I want to go up, and that was my only flight experience. TJ Creamer: Why not? So, I do remember, when I was knee high to a grasshopper, Dad took us up, Dad was an aviator also, took us up for a family flight, and I was bitten by the flying the aviation bug at age 3. Basically. Host: That'll do it. TJ Creamer: And that kind of hung in there and off I went. Host: Alright! And then, so it seems like you moved up the ladder pretty quickly. You went to aviation school, and then become an Army -- Army aviator, and you were just kind of all over the Army after that, right? TJ Creamer: So, a lot of nice opportunities were presented. I -- I was able to take advantage of them. So you mentioned flight school for sure, I got to go to the Germany and picked up a second language in German. Came back to the states after the tour of duty in Germany, and, umm, through a couple of programs at schools, got offered a command in the 82nd Airborne Division. And on the way there, went to jump school, and later went to jumpmaster school, and so opportunities were able to come along, part of the natural career progression for the Army officer. Host: Was it just that , was it a -- it was an opportunity, and you said, okay, yeah, that's something I'm interested in? Did you get any push from...? TJ Creamer: No, no. No real -- no real push, to be honest with you. It was an opportunity [inaudible], it was the right op -- window of opportunity that it was open, and I kind of jumped through it. The truth of the matter is, when you -- when -- throughout my career, I really didn't have a plan for an end state to attain. I wasn't going for a specific rank or a specific job necessarily, I just kept trying to pick the hard thing. When option came up, I went the harder route, because I always felt if I chose the easier route, I'd always be going, oh, well, maybe I could have done it. So I tried the harder stuff, and that's -- that's how that kind of got me to some neat opportunities. Host: Yeah. What was -- what was the thing driving you to do -- was it just the, no, I really want to challenge myself? TJ Creamer: Yes! Largely. Very much so. Host: Incredible [laughing]. It's kind of the opposite of what -- a lot of the things I hear, I mean, honestly, like, I was interested in -- in film and -- and -- and production, and so I wanted to go to be a filmmaker, but I thought, well, there's really no backup, you either make it or break it as a filmmaker, so a nice, like, medium route for me was marketing. TJ Creamer: Oh, cool! Host: And that's -- and that's why I ended up choosing that one is, maybe a little bit opposite from your career path of choosing the harder route and say, you know what, it's hard, but I'm going to try it, and if I break, then I break, but this was -- I did the safe way. TJ Creamer: My -- my mom said if I ever fell in a river, she would tell the rescue forces to look upstream. Host: [Laughing] I like that, that's good. So then after -- after, you know, your -- you're a pilot, you're flying for the Army, you're -- you're joining all different kinds of challenging things, jumpmaster, right? So -- so then when did your master's come to play? TJ Creamer: I guess I was in my third year in -- at Fort Bragg. The Army called and said, hey, you did really well on the GREs, are you still interested in going back to graduate school? And I said, yes, I am! I'd like to go for internet -- networking security. And they said, well, we'd like you to go for physics. I said, okay, but I'd really like to go for networking security, that kind of stuff, and they said, well, we really need you in physics. And I said, well I'd really like to go back for networking security, that kind of stuff. And they said, we'll pay for physics. I said, okay. Host: [Laughing] So that's why! Okay. So was it -- what -- what was the -- what was the drive for the networking thing? TJ Creamer: Oh, just -- just an interest. Host: Interest? TJ Creamer: Yeah, exactly. The -- and so, the Army sent me back to graduate school for a physics degree and -- and I ended up going afterwards to West Point to be an assistant professor there to teach the cadets. Host: Oh, how was teaching? TJ Creamer: Oh, it was wonderful! Top notch cadre members to work side-by-side with, top notch future of America that we're teaching. It was a really excellent job. Host: Really? And you taught physics there? TJ Creamer: Yeah, sure did. Host: Okay. So, I know through these many different careers and -- and opportunities that you keep saying, for in the Army, I know one of them was space operations officer, right? What was that all about? TJ Creamer: So, you're asking a question that is really a time-based answer. When -- when I applied, the first time I applied, I didn't get invited for an interview, but the Army detachment here liked the application itself. It was strong enough to -- to reach some interesting folks who were taking a look at the next generation of astronauts. Host: Oh, so -- so you're talking about applying to be an astronaut? TJ Creamer: At the time, yes, so, what happened was I was teaching at West Pointe, a call came out for Army astronauts, which is the same thing -- at the same time NASA's putting out a call for astronauts. Host: Okay. TJ Creamer: So I asked if I could go apply, and they said, sure, go apply. So I applied. Once I got down here working as a support engineer, the military personnel system was wrestling with numbers, like we do all over the place. Do we have the right number of people here, do we have too many people, that kind of thing? And so we were looking to kind of classify the folks that are working down here at -- in Houston as support engineers, and even for that matter, how to classify the astronauts. And at that time, space operations officer didn't exist. The time I was here, we kind of evolved into it. We got the military personnel system to recognize a space operations officer as specialty, and that's how that came about, just about the time I was -- it was coming on board here. Host: So this -- so it was -- it was while you were at NASA? TJ Creamer: Yes. Exactly right. Host: Interesting. So you eventually -- so there's a couple steps here where you went from Army to NASA, so -- so what was the...? TJ Creamer: I got asked to come down to serve. TJ Creamer: Oh, you got asked, okay. And so I -- PCS, we moved the house down here, and so I ended up basically with a three year tour of duty before my 1998 astronaut selection. Host: Oh. TJ Creamer: And it was during that time frame that we were undergoing negotiations with the Army for a speciality that involves space operations officers and could we get classified as space operations officers here so we don't lose some of the -- the occupational time, while -- while you're serving here to support NASA. Host: So one of the things while you were at NASA was space shuttle vehicle integration test engineer, now you're working in engineering. You got physics, you got chemistry, you got Army, so where did engineering come to play? TJ Creamer: So, once I got down here, folks said, where would you like to work? And I said, I'd like to go work in as broad an environment as possible. Why? Well, as an aeroscout in the Army, I'm interfacing with a bunch of units left and right, up and down, all over the place, working with large units, liaising between them, or among them, and when I was here, I said, well, maybe I can do something akin to that. And so the vehicle integration test office is the place where folks were the hands and eyes and ears for the space shuttle crews, before they were going to launch, representing them at the engineering flow in KSC, getting the -- the crew cockpit, the crew environment, ready for the crews to -- to be coming on board. And so I got to work with a whole bunch of programmatic people at JSC, a whole bunch of engineering people at KSC, and we're doing the liaising thing again all over the place. Host: So it was that kind of team effort that you really kind of appreciated then? TJ Creamer: Absolutely. Host: So it seems like this -- this IT, it keeps coming up, you -- you really liked working in the IT room? TJ Creamer: So, while I was here at JSC, the early years, it was pretty clear that the IT arena needed some help, and so I kind of volunteered my -- the time that I had available to help that. It was, at the time when I arrived, the JSC CIO office was just standing up, prior to that time that it hadn't happened. And so I got into many discussions with John -- Jack Garman, and we started [inaudible] around, we started bouncing philosophical ideas, even technical, geeky stuff together, and because of that, ended up -- getting involved with the agency IT arena. So it just kind of sprung up. Host: So, is -- this is kind of jumping back a little bit. I'm trying to figure out where the origin of the IT interest came, because I know you had -- you had chemistry and -- and it was things that were challenging to you, was this something that maybe you were -- is easy to you, or something you were doing on the side? TJ Creamer: Mostly on the side. Host: Really? TJ Creamer: Easy for me, and also of interest, in 1984, the Apple Macintosh came out and I actually bought an Apple Mac way back when, and it became pretty clear that they helped me in my career, to be honest with you, I could produce briefings and presentations that were not matched by anybody else, and so... Host: Wow. TJ Creamer: ...because of the computer capabilities that I was able to take advantage of, I started getting more and more involved. Like, way back then, there was a big chasm between Macintosh and PC's, and I was able to help bridge that gap so that the two computer systems could talk to each other. Host: And that was part of that shuttle job, right? TJ Creamer: Oh, that was actually way before that. Host: Oh, that was before that. TJ Creamer: But that's where it started, and then I just kind of stuck with it because it was useful and fun. Host: So -- so how long were you doing this vehicle integration job until astronauts started... TJ Creamer: Three years. I arrived in '95, and -- and I got selected in '98. Host: Okay. TJ Creamer: So, for those three years, I was doing the vehicle integration stuff. Host: So how was the application process then? Did you -- how did that come up, and how -- you know, the call, all that kind of stuff? TJ Creamer: The call [chuckling]. The...call. Host: The call. TJ Creamer: So, periodically, NASA puts out a call for applications, and... Host: Yeah. TJ Creamer: And so, once again, I applied, and to be fair, being -- working here for 3 years has been a three year interview, sort of, kind of. It's not official like that, but -- but you get notice, you get -- can you play with and work well with others, are you a team member? That kind of thing, but the actual application process came out and I got asked to come interview, a week-long interview, just like any other interview. It makes up for the fact we're talking about a job that takes you to space. Host: So you weren't nervous then? TJ Creamer: No, not really. Not really. There is -- there is this, at least back then, I don't know what they're doing right at the moment, but back then there was a one hour interview in front of a big board, and it's a little bit anxiety producing, but if you just be yourself, that's a good start. Host: That's how, honestly, I think if you're more relaxed, that's actually how I ended up getting, at least a co-op, I mean, it's not as cool as a -- as an astronaut, but I was standing in line with a bunch of aerospace engineer, and I look down at my shirt, and it said, business administration, on my patch, because I was a sophmore and I couldn't declare a major yet. So it just said, business administration, like what am I doing here? Am I in the right line? I was like, you know what, what -- what's there to lose? What am I going to say? No. I mean, so I just -- I just approached it exactly like you were saying, nervous, like, what am I going to lose? I was just myself and it worked out. So, that has benefits, and it has a benefit for you, you get selected as an astronaut, and they... TJ Creamer: I was fortunate. I -- I feel blessed in that regard, I also feel most appreciative that given the chance to represent the country and doing something for the national interest. Host: Yeah. So, what were some of the first jobs you were doing? It seems like you -- you had quite a -- even after getting selected as an astronaut, you were kind of all over the place. TJ Creamer: So, yeah, I just can't -- I can't hold a job is what you're really saying [Gary laughing]. The -- the typical training and maturation of an astronaut. So you go through the basic systems, and, at the time, we were studying both shuttle and station systems. In preparation for a space mission. But aside from that, we're also supporting ongoing missions, and we do that in a number of ways, if you take a look today, that we have a number of -- of astronauts who are serving as capcom's, and talking to the crews on board. Back during my maturation years, there were a variety of things going on. For instance, the IT thing enters again into the fray. In January of 2000, I get a call to go over to Russia and work with Russians to -- to build a network from tip to toe on station. The Russians had a tiny, little network. At the time, the U.S. had a tiny, little network, and the -- the plan was to have a unified network up and down all of station, and so I got sent over there to help that happen. The IT background, the self-made IT background was very helpful in that regard. Other -- other ways, Expedition Three, Frank Culbertson was the commander, and I got asked to be his ground persona, his crew support astronaut, and during that time frame, also got to engage and talked with the crew then also, like the capcom's, so. Host: So a lot of -- a lot of teamwork going on here too. It seems like the interpersonal skills are pretty important in all of this. TJ Creamer: We're not individuals, by any means, we are definitely contributing to the team for the greater glory of the team because if we can't do that, then we tend to not be successful. So, it's important that we're able to help the -- the big picture. Host: Was it this drive to continue to challenge yourself? That made you want to tackle all of these -- all of these different jobs? TJ Creamer: A little bit. So in each area, you kind of go work and I contribute, and then you -- if you find the whole or find the item or the aspect that -- that really needs some bolstering, some help, and you can go off and make that better, than it's a contribution. Host: So you, crew support, you're -- you're working to connect Russian and -- and NASA as an IT system? TJ Creamer: Yeah, yeah. Host: You also worked on hardware, robotics, you were over in Huntsville, how are all of those coming up? TJ Creamer: So, it just turned out that there was an opportunity to go work in the robotics field, and so we were doing that in support of ongoing missions. So I did that for a number of, handful, two handfuls of months or whatever. The -- you mentioned the -- the Huntsville aspect of -- of my development, my background. So when I was on board, I was involved in not only systems maintenance, but also doing research activities, and so I was able to talk with the folks from Huntsville to help them out with items for research, in fact, I put together a couple of the racks that hadn't been put together yet so that they could do ground operation research, ground-based research using the facilities we have on board. So, now that I say that, once I got back, and we started doing the post-flight public relations tours and I got to know some of the folks in Huntsville. I noticed that there was one of those little areas that could possibly be helped. And that the area that I'm talking about is the two operations teams, Huntsville and Houston, I -- saw a way that we could possibly make it even better by -- by increasing the sharing across the Mississippi River, the liaisoning across the Mississippi River, in terms of making things better or more efficient for crews on board. So, for instance, historically, the first decade of station was building, with a little bit of payload operations. Well, when I got up there, we went up to six crew people, as opposed to three -- three person crews, and now the goal is to really maximize as much of the payload operations, the utilization of space station. We went from the era of construction of ISS to the era of using it, so hence the utilization, and I thought maybe if I'd go over to become a payload operations director, I can help blend the two communities, share a little bit of both sides of the river with -- with the other side, and getting each other more attuned to the items, the aspects, the flavors that -- that both operations, communities, were very sensitive to, or not aware of. So if I can get the two communities talking together, sharing across the river, we could probably help do utilization even better. Host: Huh. So from a high -- from a high view, for those who don't know the difference between maybe mission control here in Houston and the payload operations that are over in Huntsville, what are the responsibilities and relationships there? TJ Creamer: So, point blank, the flight director is in charge of the overall integration of what happens on space station. The primary charges, of course, are the safety of the crew first, safety of the vehicle, and then using those and assuring those, we're going to accomplish the mission objectives. In the payload operations world, their charge is to execute payload science, payload operations. And they coordinate with the Houston operation team for resources, for priorities, for actual execution during the day, and so with -- with their focus on payload operations and Houston's focus on largely the overall systemic support and the overall safety aspect of what's going on, it was good to get the marriage between the two operational communities. And then, today, as we go forward, even 2010 when I was onboard, as we go forward, the real reason why we're up there in space is to use space station. So, increasing the fluency of the payload operations community, there efficacy, so we're even more efficient onboard is a good thing. Host: So, that kind of blends in nicely with your -- your flight, your mission in 2010, you were a science officer, right? So it was -- it was through this -- was it through a little bit of that connection with understanding what Huntsville is doing, and... TJ Creamer: Yes. I mean, it was a nice -- it was a nice exposure. Host: Right. TJ Creamer: And post-flight, after your -- after all the bows are tied with your flight. So you got the public relations tour, all the after actions, all that kind of stuff, now you go back into a support role, supporting ongoing missions, and I saw an opportunity here to -- to go join our Huntsville friends and -- and do payload ops. Host: Okay, so what -- what were some of the -- going back to your mission, you know, you -- you launched in Soyuz, so how -- how was that? How was that whole experience? TJ Creamer: The Soyuz launch was [pause] -- was entertaining [laughter], was interesting, probably is the better word. Host: Okay. TJ Creamer: So imagine three guys who wear extra large shirts sitting in your bathtub. That's about as much room as we got, right? And then the second thing I say is the actual launch itself, it's liquid-fueled engines. It feels like an airliner taking off. It's just that we accelerate for eight, eight and a half minutes. And the airliner doesn't do that. But that sensation of being squished, smoothly squished into your seat, is what the -- the sensation is like. TJ Creamer: Okay, and then you spent a couple months on board, what were some of the top highlights from -- from what you were doing? So we arrived December 23rd in 2009, so first highlight is Christmas! [Gary laughing] But at the end of January was when the first of three shuttles came up to visit us. And the first of three shuttles brought Node 3 and the Cupola, the seven window window to the world, so that's pretty much a highlight there. Because you now get to -- it's -- imagine a sauna, but a small, slightly small-ish sauna, you can immerse yourself basically going to this window, and -- and view the world. And it's really breathtaking. [Pause] One way to describe how breathtaking it is is a couple crew members who had never looked out of the cupola before, I brought one-on-one, just by ourselves. The cupola window, all seven of them, have shutters on them, that we can control on the inside. So I would tell -- tell the crew member to close their eyes and I'd open up the seven windows, and then say, open up your eyes, and every single time I did this, they cried. It is mindblowing, breathtaking, heart stopping, beautiful. Host: What -- what is the most beautiful part about it? Is it the -- is it the perspective? TJ Creamer: The perspective, the vista, the colors. Host: The colors. [Laughing] TJ Creamer: It's just astounding. It is wonderfully beautiful. Host: What were some of the first thoughts racing through your head whenever you first looked out the window? TJ Creamer: More an aesthetic appreciation. The -- the classic line, there are no borders when you look through the window, but really it's the aesthetics. It -- it is just humblingly [pause] soul-searchingly beautiful. Then you go, wow, I'm actually up here. And you can also see, you know, the thin -- the thin, fingernail of air that keeps us alive around the earth's surface, and you go, yeah, this is kind of humbling. This thing is huge, and I'm just here. Host: Yeah, you're just a small part of it. TJ Creamer: But it's beautiful. Host: That's part of that overview effect, I guess. TJ Creamer: Absolutely, yes. Host: You're just looking down and you realize there's so much -- everything you know is -- is right below you, right? So, it's just humbling to think that you get that perspective. Very, very cool stuff. I think one of the -- one of the coolest highlights, at least for me reading your bio for the station was this IT background is coming -- it's following you even up in space, and you're improving the IT infrastructure of the station. TJ Creamer: So we got lucky. We got kind of lucky at the end of January. So, way back when, in 2000, I helped write the requirements for IT from station and one of the things we had put in there was internet access. So 10 years later, I happened to be onboard, and we had been striving for -- for about 8, 9 months, prior till I got -- to me getting there, trying to make the connections work. Trying to make all the boxes in the chain to allow a safe connection to the internet all happen at once. And it wasn't until one Saturday in January, 2 o'clock in the morning, I'm still fiddling, banging my head against the problem, and, poof, solved the problem. And I went looky there. So I look around, and there's nobody awake, I can't go up, look, we got it! So, I sent out the first tweet saying we've live [Gary laughing], because I didn't no what else to do. So, in the morning, to complete the story, in the morning, I tell the commander on board, and I go, hey, we were successful, I let the whole world know that we were successful, and he tells me that he was supposed to send out the first tweet, and I went, uh oh. So [laughter], and then, bless his heart, he immediately after that goes over and immediately sends his wife flowers, which I thought was kind of cool. Host: Aww, that's really cool. So you sent the first tweet from... TJ Creamer: Yeah, I did. Host: [Laughing] Well, that's awesome! First tweet from space, connect -- establishing the internet in -- in -- in space, that's -- that's quite an accomplishment. So you got back down to earth, and what were -- what were you starting to do after -- you said there was this postflight public affairs stuff, you know, what -- what were some of the things coming back? TJ Creamer: Um, the -- the national grind of the postflight mechanism was what drove my weeks, months, after that, plus the recovery, the typical, the postflight physical therapy recovery type stuff. But probably what's more important is that leads into what do you do next? And that's really -- all the astronauts get back into the mode of supporting ongoing operations or future operations. And, at some point, it was like, well, maybe I can go over to Huntsville and become a payload ops director, and to learn about their environment, to help the communications with Houston, to meld the two communities together, to be even better for space station, and that's what -- that's how that came about. Host: So was that your introduction to operations? Was -- was the Huntsville access? TJ Creamer: So, during Expedition Three, I was on console as a capcom. Host: Oh, okay, so you got capcom? TJ Creamer: Yep. Despite that, I would argue that since the time I was commissioned and when -- in flying, I've been doing real-time operations my entire life. So, that -- that's my take and that's my argument, in terms of specific space operations. The payload -- payload operations directorship was putting me on console, for sure. Host: So you must have enjoyed it then, because, yeah, because eventually you -- you're talking about what's next? Right? That's -- that element, and flight directing was apparently on the table, right, so? TJ Creamer: It was, but it was a surprise unto itself. Host: Really? TJ Creamer: So, I was traveling to Huntsville for three and a half years doing the pod thing, and it was in March of I guess 2015, I guess it was, where it was my last trip to Huntsville. So I came back and I was beginning to work with landing recovery for Orion, then that community, and I was at my desk when the email came out, nine days after my last trip to Huntsville, nine days after my last trip, the email come out and -- came out and said, hey, we're accepting applications for flight directorship, and that's when I looked skyward and I said, what do you really want me to do, Lord? [Laughter] Give me some sort of sign! So, and so I applied for the flight director. Host: Okay. So it was -- you took it as a sign that, okay, maybe this is my next step? TJ Creamer: Yeah, so, in that respect, yes, but more to the point, I think it's fair to say once you've been bitten by the real-time ops bug, and have been infected by the real-time ops, a virus, you don't get rid of it. It -- those folks who do real-time ops love real-time ops, and that's the truth for my entire military and NASA career, that that's the case. And so when this opportunity opened up like this, I went, shoot, man, that sounds like a natural calling. Host: [Laughing] So you kind of alluded to the fact that the flight director is sort of the top dog, right? The top dog in terms of in charge of the International Space Station, integrating with not just mission control center in Huntsville, but other mission control. TJ Creamer: So -- so we got five centers across the world. Host: Yeah. TJ Creamer: We got, you know, the Japanese with their center in Tsukuba, and the Europeans with their center just outside of Munich and [inaudible]. And the Russians, and, of course, [inaudible]. So it is very much an international partnership that's going on, and -- and international collaboration, in order to make space station successful. Right now, the only vehicle we are currently flying is Space Station, but we also are working with our other partners, SpaceX, Sierra Nevada, Boeing, for the vehicles that are coming up yet, and we have flight directors who are intimately involved in coordinating with them, getting our products and our processes and our operational philosophies and ops concepts down in order to both be successful in their operations, but also to help them execute. Host: So how'd you know that you were ready to take on that large responsibility? TJ Creamer: Um, to become a flight director you mean? Host: Yeah. TJ Creamer: Well, first, I think it's fair to say that with the life experience that I've had -- or say it the other way, yeah, I'm old. So, the -- with the life experience, but also the training that's gone through both the military aspects, as well as the NASA operations aspects, knowing also that the flight director early program, once selected, you go through the training required to hone skills that it's a matter of executing the training appropriately, and that's what we've done throughout the career, whether it's Army flying or astronaut flying or flight director. Host: So once you apply, you had a couple interviews, how -- how were those? What were some of the things they were asking you? TJ Creamer: So, I think it's very fair to say that the folks we are looking for for flight directors are folks who exhibit good leadership skills, have demonstrated the ability to have a good head on their shoulders, also the ability to see the battlefield, and I'm not talking about army battlefield, but in the metaphor, the battlefield -- with all the smoke on the battlefield, to be able to see clearly, the way to approach the problems, the environment, to be able to identify the risks that we need to be focusing on, to mitigate and to manage. So, we're looking for strong leadership skills, the ability to work with a multifaceted organization across the globe, we're not just talking simple MCC, we're talking multi organizations, many international partners, and you got to be able to see the big picture to be able to do this correctly. Host: So, you knew that you had the leadership skills, you knew that you had -- it seems like, I mean, from what you've said so far, you had so many different jobs, you were working with so many different teams, bringing people together, and that's -- I think a large part of flight directing is to make sure everyone's on board, and... TJ Creamer: You -- you said that well. Yeah. So, the pillars of safety crew and safety vehicle in order to accomplish the mission objectives are what we live by. We have to identify the risks, we have to manage the risks, and we have to get the community to buy in to understand what it is we're doing and how we're doing it to make sure that we're doing it correctly. You said, I knew I had leadership skills, I think it's fair to say, I believe I have the leadership skills. Everyday when I walk in the control room, I'm still learning things, it's not like I know everything, but the underlying principles of the leadership, the underlying principles of real-time execution in a high stress environment, they're there, and we're honing them everyday. Host: So then transitioning from applying to be a flight director to actually being selected as a flight director, now you're being trained as a flight director. How was -- how was the first couple months of training? TJ Creamer: So, a large portion of it is building the foundation so that everybody has the same awareness and exposure. So, for instance, in my class, we had somebody who was an OSO [phonetic], a guy working with the mechanical stuff and the tools. We had a spartan, a guy who really knew -- knows the power system. Mary came from the cronus [phonetic] world, in the command and data handling and the communications and video environment onboard. So we had different backgrounds of folks in our class. So let's -- let's build a foundation from which we can then spring forward. So we got a lot of academic training. So we get the opportunity to go to operational centers and see how they behave and how they operate, for instance, we talked to Goddard, we talked to White Sands, we went to Marshall Space Flight Center because they're doing payload ops, to broaden our exposure and to see how we were all interfacing together. Once you get that academic foundation, now you're starting to exercise the real-time aspects of it, and we start going into SIMs. And we are training in simulations, not for a nominal day, we're training for the Vince Lombardi moment, or Vince Lombardi told the -- the football teams, you know, practices are really hard because we wanted to make the game fun. So when you go on the -- on the gridiron for the game, you're -- you're ready for whatever's coming at you. In the similar sense, the SIMs that we're doing are to exercise our prioritizations, our risk mitigations, be able to draw on the team members all around the world, to be able to make conscious decisions, to keep the crew safe, to keep the vehicle safe, and to accomplish whatever that day's mission is. And when the -- the very evil, SIM, you know, SIM overlords, the SIM sups, the, we call them CTOs, but the guys who designed the training environment throw at us the malfunctions, the purpose is to exercise our good practices for risk mitigation, risk management, and including all the aspects that we need to be aware of for prioritization the appropriate recovery aspects. So when they throw the kitchen sink at us, often times, the kitchen sink is also broken, and we have to work how to -- how to repair, how to get to a functioning standpoint where we can keep the crew safe, and begin repairing the vehicle. Host: So how much of it is intimately knowing how to fix it versus intimately knowing who to talk to to get everyone together to fix it? TJ Creamer: So I will -- my -- my prophecy, my -- my view of the world is that there is no 100 percent answer. You gave me two options. I can't say it's 100 percent either case, in fact, it's a blend of both of those options. A little bit of experience knowing how the ISS system is built, and choices and likelihoods for path and decisions, but it's also relying upon the subject matter experts that we have in all the control centers around the world. The key thing is to be able to get the right person, to be able to offer up, at the right time with the right words so that the audience, the rest of the world, gets to hear that this is the solution path we should be going forward with. So a lot of the training that goes on in the SIMs is to get the subject matter experts who are -- who are in training to become subject matter experts, and part of that is the soft skills of being able to convey the thoughts that are in their heads. Host: They have to -- if there's a problem, they can't keep it to themselves, they got to let everyone know. TJ Creamer: And part of our job, as flight directors, is to flesh that out. Let's see if we can't get to the nuts and bolts of what you really are thinking and where the problems are so that we can get the right decisions on the table. Host: So it seems like a lot of the job is, at the very least, asking the right questions? TJ Creamer: Yes. The right question [Gary chuckling] -- questions are a very, very powerful tool, I agree with you. Host: So then what's the -- you sat in as a capcom, you sat in Huntsville, and now you're sitting as flight director. What are some of the main differences how you approach sitting in a room based on the job that your -- that you have? TJ Creamer: The best answer is, whenever you're working on a team, you have to understand the function that you're fulfilling on the team so that you can contribute for the greater betterment of the team. So, as a pod, for instance, I knew that I was contributing in the payload operations arena utilization activities, but also helping the flight director understand the prioritization, and how much crew time am I going to need to fix this problem now? So, if I'm asking for resources from the greater global team, I should be able to express that as a payload operations director. In a similar sense, as a flight director, now I'm asking people to speak to me in the inverse, speak to me in the terms of what they need, where the program's priorities fit in the overall decision matrix, and, of course, we are doing this negotiation, this exploration of options all under the umbrella of keeping everybody safe on board and keeping the vehicle safe. So, you asked me, how's it differ? I'm now looking for the inputs from the team, I'm trying to solicit the inputs, I'm trying to enable people to be able to give us the right nuggets of information so that we can execute. Host: So it's a little bit of them giving you the information, but then also making sure that you're empowering the team, to make sure that everyone's talking, but now you have, as a flight director, this higher thought that's, okay, number one, safety, both of the crew and then of the vehicle itself. No matter what decision is happening, those are the top two considerations that you always have in the back of your mind? TJ Creamer: Both when I was onboard, I knew the team was doing this. Now on the ground, with the people onboard, I know that they're relying upon us to keep them safe and keep the vehicle safe. Absolutely. They -- the key thing that we've left off from this discussion of gaining the information from folks, as well as enabling folks to give us the information is also to come back and go, now that we've got a lot of smoke on the battlefield, it's very confusing, the clarity we're going to achieve here is, we're going to go off in the northeast direction, as opposed to southerly direction. To add clarity to the -- the team, worldwide, the team's effort, we're in a situation now, the path through these woods is in often this direction, come follow me, we're going to go off and solve the problem in this direction. So, in much confusion, it is very important to be able to give clear goal attaining descriptions of what we're going to do next. Host: That's right, because each position is sort of responsible, like the thermal guy is going to say, well, you know, this is -- based on my perspective, this is where we need to go, the -- I don't know, the -- what's the ethos console? Yeah, life support, life support is going to say this, and then the inventory guy is going to say that, so, sure, you have to -- I -- that makes sense. So everyone's going to put in their input based on the perspective that they have. Okay, let's -- let's take a break, go into this direction, what are the next steps? TJ Creamer: And the better the flight controllers around the world are those who can -- can stand up a little bit taller and see the bigger picture. Flight director is going to need to be able to do that with great clarity to be able to bring everybody along with them. Host: Definitely leadership skills are among probably the top, and then also communication team building efforts, I can absolutely see it. So how did you -- how were you trained to -- to really know the potential of what you could accomplish in this role, were you shadowing other flight directors? It seems like you were traveling and getting a broad perspective of things too. TJ Creamer: I -- I think what you just said is a good summary. If I step back a little bit and go, how were we -- how were we trained in order to get to the flight director world, I have to simply say, the life experiences, the job responsibilities, that have led up to the actual application is what has been the majority of the leadership skill training. When you get into the flight director office, we're now honing those skills specifically for the -- the space operation execution, mission office. Host: Okay. So, yeah, it's more of the tactical approach, right, you already -- you already know, you've already shown that you have leadership skills, here's how you apply it to flight director? TJ Creamer: Exactly. And we're -- we're honing those throughout the SIMs, we're honing those through the precertification training phases for the flight directors, and now we're hoping and helping flight controllers as we are going forward in our simulations to also do that in their own disciplines for the greater team around the world. Host: So in -- in these SIMs, simulations, you -- they simulate a -- some sort of, not a normal day, but like you were saying, they simulate something going wrong, and you have to fix it. What was -- does a moment stick out in you of some failure going wrong, and you're like, maybe you had some hesitation or maybe you knew exactly what to do, maybe like a highlight in one of your SIMs? TJ Creamer: Off the top of my head, I -- we've done so many SIMs. We've gotten so many problems [Gary laughing], and the dynamics, at the time, was there another failure upstream that we're now adding a failure that's complicated [phonetic]? I can't give you the specific examples. Host: Okay. TJ Creamer: However, the question that you do ask, yes, often times, not all the time, but, often times, you go, wow, okay, I know how to deal with that malfunction. But what needs to be flushed out is that earlier in the SIM, you know, hours ago, something else was slightly off. For instance, a computer card is no longer communicating on the network, it's not being able -- you can't send commands for that computer guard. And, guess what? The command you need to send to fix that one malfunction has to go through that now no longer playing computer card. So -- so it adds a twist to it, and people have to be able to realize that the -- the easy solution path is not always the one that's available to you. So you have to make other approaches to solving the problem, or you begin to prioritize what it is you can deal without. Host: Okay. Do you often think back to the Apollo days? Whenever you're sitting in mission control, as a flight director, and -- and consider some of the lessons from some of the greatest, Chris Kraft, Gene Kranz, Glenn, like those guys, do you ever -- do you ever think back on...? TJ Creamer: So, we have the pleasure and the opportunity to talk with those folks. They come -- they come occasionally to -- to speak with us. We have socials that we include some of the -- the honor roll giants from our past to be able to speak with them, and -- and it's a large learning point for us. When our class gave the -- the flight director community a welcoming party, the new guy's giving the welcoming party, the older generation of flight directors did come and -- and join in on the celebration. And they were telling stories. And later, as the night wore on, everybody was sitting at the knees of -- of the giants, listening to their war stories. It -- make no mistake, it is a national important point in our history from which the rest of this space program has sprung, and we are executing the national will, the national intent for exploration, and it's because the -- the giants that existed conquered basically the unknown and set the template for us that we're now -- we're standing on the shoulders of the giants, don't get me wrong. So, part of the reflection that you're alluding to is not only in difference to them and learning from them, but also because we have the responsibility to carry on what they started. Host: So then maybe -- maybe it's from them, or maybe it's something that you, yourself, take to mission control with you everyday, if you're -- if you're sitting and your shift is now beginning and you sit down, what are some of the thoughts that run through your head, that say, okay, I'm ready to do this, I'm ready to start this shift. TJ Creamer: So there is this bit of an edge that you get. The edge that I'm talking about is to be able to be razor shape in the thinking process so that you don't make mistakes. We are in a business that isn't 100 percent safe. And we don't have the ability or the luxury to fail. But at the same time, we have to recognize that there are risks that we have to take in order to be successful, and so now, the onus, this responsibility that we have is to be able to identify those risks, manage them to a reasonable level so that we're not doing something willy, nilly, offhandish, sloppy, and to mitigate the risk to be able to keep the crew and the vehicle safe. So that edge that I'm talking about is everytime you step in that room, the ultimate consequence is possible. And it is incumbent upon us to recognize that responsibility and drive forward smartly. That's the edge I'm talking about. Host: So you approach everyday seriously, very seriously? Because the stakes are high. TJ Creamer: The stakes are very high. Host: You say we're standing on the shoulders of these giants that -- that sort of wrote the template, as you said, and we're, right now, we're, like you said, the vehicle that we're operating is the International Space Station, and -- and we've built the lessons from the Apollo days, going through shuttle, down to space station, you know, we've learned a lot, but there's this whole new era coming up, right, of -- of deep space exploration. What are some of the things you're looking forward to from -- from mission control in some of this exploration phase? TJ Creamer: So we can very easily get into the philosophical world which starts with, you know, a ship is always safest in its harbor, but it's not why we build ships. So, we do want to go farther, we want to go farther for a number of reasons. We want to go farther to extend life elsewhere, to make life better here, for people who are staying here, and to learn. As we go and -- and beat the problems, conquer the difficulties in order to extend life elsewhere, we have automatic benefits coming back to the folks on the earth. And that -- the whole spin off, the NASA spin off, series of -- of almanacs we put out yearly, expound upon this, but the -- the smoke detectors in the homes, the miniaturization for -- for watches and -- and smartphones, all are coming from space drivers. The heart pumps that we're dealing with as a result of what we've done in our space program. So, there are spin-offs all -- all over the place. So there's some natural benefits for conquering these problems we have to solve. There are spin-offs, people on earth benefit. Life improves here. The very same technology we're using on board right now for water recycling, we take that capability and go to third world countries to provide clean water, or we go to a disaster to -- to provide clean water. What we do on space station is helping us get a little bit farther away, and now we take the -- the species to another rock in the solar system. And why do I say it that way? Because right now we got all our eggs in one basket, and having eggs all in one basket is not a good thing, just ask the dinosaurs. And so I've gone off into my little philosophical diatribe there because of the question that you ask, although it also explains what we're looking forward to, to finding out new things, to be able to get farther away, to be able to do the missions that exist around the -- the -- our moon, to be able to extend farther to Mars and go, well, why did it lose its atmosphere? We've seen evidence of water in every place we've found water so far, we've found life. So, there's a lot to learn and that's what we're looking forward to. Host: Yeah, and, like you said, take it back down to earth too. You know, understanding the impacts out in the solar system, you can take these technologies right back down home, and put them into our watches. TJ Creamer: Exactly right. Host: [Chuckling] So I kind of wanted to blend in, that would have been a nice place to really wrap things up [laughter], with a philosophical thing, but I really wanted to talk about this application to become a flight director, you said, you -- there was a time where an application opened up and you applied, that's happening right now. TJ Creamer: It is. It is, indeed. And so, just for the podcast itself, in case people listen too late, the -- the application process closes on the 17th. Host: April 17th. TJ Creamer: April 17th, exactly right. And so we're hoping that folks are able to take advantage of the open window that currently exists right now. If folks have questions or queries, or want to learn more about what it's like to be a flight director, there is a book that's becoming available. Host: Oh, cool. TJ Creamer: And the title of the book is, The ISS: Operating on -- Operating and Outpost in the New Frontier, and the idea is that this is -- this book looks at the operations of the International Space Station from the perspective of Houston flight control team, and so because of that, if folks are interested and want to take a look at The ISS: Operating and Outpost in the New Frontier, it's available, or will be available, on nasa.gov/ebooks. Host: On the 16th. TJ Creamer: On the 16th. So, hurry up, read it, and apply! Host: [Laughing] If you're listening to this as soon as it comes out, then, yeah, you know, you'll have to wait a couple of days, but if you're, even day after, you can go and look it up, and we'll -- we'll share the link to that after the end of the episode. So for those who want to, who think they have, you know, who think they are tough and competent, who are -- who can follow in the footsteps of some of the giants, and -- and sit in mission control, what are some of the tips that you did to -- when you applied, but then also to understand that you are ready for this job? TJ Creamer: So, in broad strokes, we're looking for folks who can handle a fast-paced, high stress environment, where critical decisions can be made. We're also looking for folks who have demonstrated solid leadership capabilities, principles, practices, and have the ability to work across broad spectrum of folks, not just organizations, but different countries. The purpose of this job is to uphold the responsibility that we've -- we've sworn to of protecting the crew, whatever vehicle you're on, protecting the vehicle, whichever vehicle it is, in order to make these missions successful. So, as you go forward and apply, you want to be able to demonstrate, and it's not a bad thing to sell yourself in this regard, but to be able to demonstrate the leadership capabilities and how you're able to prioritize and how you're able to work with others, and how you're able to make critical decisions. Host: Okay, so what if -- so for those who are not in the flight operations world, what can you say that can make them feel like maybe -- maybe they're ready even though they haven't sat in mission control before? TJ Creamer: So, some of this is -- is a life experience question there, but it's also a facet of life, meaning if you close your eyes and you imagine areas to be working in that kind of fit those parameters, some things, you know, jump out at you immediately. There are -- are first responders, for instance, who are making critical life saving decisions in a heartbeat, no pun intended, but there's a high stress -- there's a high stress environment where critical decisions are being made. If you go to the -- the military arena, where there are some direct parallels in some of their specific operations that are also directly applicable, and I'm not trying to exclude any occupational area at all, but it doesn't have to be flight operations specifically, growing up and staying in the same pipeline that we've grown up for over the years, in fact, this year, we've done an internal NASA [inaudible] for flight director applications, and we've done an external one so that anybody in the U.S. who feels that they can meet their -- the descriptions we've talked about about the responsibilities and the capabilities can apply, and we're interested in bringing in the good people, good heads, good leadership capabilities, that can make critical decisions in critical time-crunched bits of time. Host: There you go. And we'll advertise some of those links again at the end here, but, TJ, thank you so much for coming on and sharing your story. This is -- it's quite a story that you have, but then also just sort of understanding the responsibility of being a flight director. Especially now, this is a good time for it [inaudible] application window. TJ Creamer: Absolutely. I agree with you. Host: Really appreciate your time, thank you! TJ Creamer: Thank you, sir! [ Music & Radio Transmissions ] Host: Hey, thanks for sticking around! So, as promised, I'm going to give you the magic link to apply to be a flight director. It's pretty simple. It's go.nasa.gov/flightdirector. You can go there and learn what it takes to be a flight director, and then actually apply. If you want to learn more about what it takes, they actually have a brand new blog post that just posted on nasa.tumblr.com. It's called, Five Myths About Becoming a Flight Director. Colonel Creamer also talked about this flight director's book. That will be posted on April 16th, www.nasa.gov/ebooks. It's called, The ISS: Operating and Outpost in the New Frontier. And you can learn about what it takes and -- to work in mission control, and then everything about it. If you want to learn more about what's going on at NASA, there are two other podcasts that you can listen to. One is called, Gravity Assist, hosted by Dr. Jim Green, that talks about planetary science, otherwise, you can listen to NASA in Silicon Valley, that's from our friends over at the Ames Research Center that talk about some of the research that goes on on the International Space Station. If you want more information about the space station specifically, nasa.gov/iss is a great place for that. Otherwise, you can join the conversation on social media, we're on Facebook, Twitter, and Instagram under as, The International Space Station, you can go to anyone of those accounts and use the hashtag AskNasa on your favorite platform to submit an idea, and we'll make sure to either answer it on a future episode or dedicate an entire episode to it, just make sure to mention it's for, Houston, We Have A Podcast. This episode was recorded on March 29th, 2018, thanks to Alex Perryman, Greg Wiseman, Pat Ryan, Brandy Dean, and the flight directors in our flight operations directorate for helping to put this episode together so quickly! Thanks again to Colonel TJ Creamer for coming on the show! We'll be back next week!

Performance of Surfactant Methyl Ester Sulphonate solution for Oil Well Stimulation in reservoir sandstone TJ Field

NASA Astrophysics Data System (ADS)

Eris, F. R.; Hambali, E.; Suryani, A.; Permadi, P.

2017-05-01

Asphaltene, paraffin, wax and sludge deposition, emulsion and water blocking are kinds ofprocess that results in a reduction of the fluid flow from the reservoir into formation which causes a decrease of oil wells productivity. Oil well Stimulation can be used as an alternative to solve oil well problems. Oil well stimulation technique requires applying of surfactant. Sodium Methyl Ester Sulphonate (SMES) of palm oil is an anionic surfactant derived from renewable natural resource that environmental friendly is one of potential surfactant types that can be used in oil well stimulation. This study was aimed at formulation SMES as well stimulation agent that can identify phase transitions to phase behavior in a brine-surfactant-oil system and altered the wettability of rock sandstone and limestone. Performance of SMES solution tested by thermal stability test, phase behavioral examination and rocks wettability test. The results showed that SMES solution (SMES 5% + xylene 5% in the diesel with addition of 1% NaCl at TJformation water and SMES 5% + xylene 5% in methyl ester with the addition of NaCl 1% in the TJ formation water) are surfactant that can maintain thermal stability, can mostly altered the wettability toward water-wet in sandstone reservoir, TJ Field.

A two-population sporadic meteoroid bulk density distribution and its implications for environment models

NASA Astrophysics Data System (ADS)

Moorhead, Althea V.; Blaauw, Rhiannon C.; Moser, Danielle E.; Campbell-Brown, Margaret D.; Brown, Peter G.; Cooke, William J.

2017-12-01

The bulk density of a meteoroid affects its dynamics in space, its ablation in the atmosphere, and the damage it does to spacecraft and lunar or planetary surfaces. Meteoroid bulk densities are also notoriously difficult to measure, and we are typically forced to assume a density or attempt to measure it via a proxy. In this paper, we construct a density distribution for sporadic meteoroids based on existing density measurements. We considered two possible proxies for density: the KB parameter introduced by Ceplecha and Tisserand parameter, TJ. Although KB is frequently cited as a proxy for meteoroid material properties, we find that it is poorly correlated with ablation-model-derived densities. We therefore follow the example of Kikwaya et al. in associating density with the Tisserand parameter. We fit two density distributions to meteoroids originating from Halley-type comets (TJ < 2) and those originating from all other parent bodies (TJ > 2); the resulting two-population density distribution is the most detailed sporadic meteoroid density distribution justified by the available data. Finally, we discuss the implications for meteoroid environment models and spacecraft risk assessments. We find that correcting for density increases the fraction of meteoroid-induced spacecraft damage produced by the helion/antihelion source.

Experimental studies and simulations of hydrogen pellet ablation in the stellarator TJ-II

NASA Astrophysics Data System (ADS)

Panadero, N.; McCarthy, K. J.; Koechl, F.; Baldzuhn, J.; Velasco, J. L.; Combs, S. K.; de la Cal, E.; García, R.; Hernández Sánchez, J.; Silvagni, D.; Turkin, Y.; TJ-II Team; W7-X Team

2018-02-01

Plasma core fuelling is a key issue for the development of steady-state scenarios in large magnetically-confined fusion devices, in particular for helical-type machines. At present, cryogenic pellet injection is the most promising technique for efficient fuelling. Here, pellet ablation and fuelling efficiency experiments, using a compact pellet injector, are carried out in electron cyclotron resonance and neutral beam injection heated plasmas of the stellarator TJ-II. Ablation profiles are reconstructed from light emissions collected by silicon photodiodes and a fast-frame camera system, under the assumptions that such emissions are loosely related to the ablation rate and that pellet radial acceleration is negligible. In addition, pellet particle deposition and fuelling efficiency are determined using density profiles provided by a Thomson scattering system. Furthermore, experimental results are compared with ablation and deposition profiles provided by the HPI2 pellet code, which is adapted here for the stellarators Wendelstein 7-X (W7-X) and TJ-II. Finally, the HPI2 code is used to simulate ablation and deposition profiles for pellets of different sizes and velocities injected into relevant W7-X plasma scenarios, while estimating the plasmoid drift and the fuelling efficiency of injections made from two W7-X ports.

F5-peptide induces aspermatogenesis by disrupting organization of actin- and microtubule-based cytoskeletons in the testis

PubMed Central

Gao, Ying; Mruk, Dolores D.; Lui, Wing-yee; Lee, Will M.; Cheng, C. Yan

2016-01-01

During the release of sperm at spermiation, a biologically active F5-peptide, which can disrupt the Sertoli cell tight junction (TJ) permeability barrier, is produced at the site of the degenerating apical ES (ectoplasmic specialization). This peptide coordinates the events of spermiation and blood-testis barrier (BTB) remodeling at stage VIII of the epithelial cycle, creating a local apical ES-BTB axis to coordinate cellular events across the epithelium. The mechanism(s) by which F5-peptide perturbs BTB restructuring, and its involvement in apical ES dynamics remain unknown. F5-peptide, besides perturbing BTB integrity, was shown to induce germ cell release from the epithelium following its efficient in vivo overexpression in the testis. Overexpression of F5-peptide caused disorganization of actin- and microtubule (MT)-based cytoskeletons, mediated by altering the spatiotemporal expression of actin binding/regulatory proteins in the seminiferous epithelium. F5-peptide perturbed the ability of actin microfilaments and/or MTs from converting between their bundled and unbundled/defragmented configuration, thereby perturbing adhesion between spermatids and Sertoli cells. Since apical ES and basal ES/BTB are interconnected through the underlying cytoskeletal networks, this thus provides an efficient and novel mechanism to coordinate different cellular events across the epithelium during spermatogenesis through changes in the organization of actin microfilaments and MTs. These findings also illustrate the potential of F5-peptide being a male contraceptive peptide for men. PMID:27611949

Better Advertising Practice.

ERIC Educational Resources Information Center

Schick, Dennis

1979-01-01

Offers suggestions for selling advertising space in student newspapers. Includes criteria for successful salespeople, a list of common time-wasters, and some principles for advertising salespeople. (TJ)

Junction restructuring and spermatogenesis: the biology, regulation, and implication in male contraceptive development.

PubMed

Yan, Helen H N; Mruk, Dolores D; Cheng, C Yan

2008-01-01

Spermatogenesis that occurs in the seminiferous epithelium of adult mammalian testes is associated with extensive junction restructuring at the Sertoli-Sertoli cell, Sertoli-germ cell, and Sertoli-basement membrane interface. While this morphological phenomenon is known and has been described in great details for decades, the biochemical and molecular changes as well as the mechanisms/signaling pathways that define changes at the cell-cell and cell-matrix interface remain largely unknown until recently. In this chapter, we summarize and discuss findings in the field regarding the coordinated efforts of the anchoring [e.g., adherens junction (AJ), such as basal ectoplasmic specialization (basal ES)] and tight junctions (TJs) that are present in the same microenvironment, such as at the blood-testis barrier (BTB), or at distinctly opposite ends of the Sertoli cell epithelium, such as between apical ectoplasmic specialization (apical ES) in the apical compartment, and the BTB adjacent to the basal compartment of the epithelium. These efforts, in turn, regulate and coordinate different cellular events that occur during the seminiferous epithelial cycle. For instance, the events of spermiation and of preleptotene spermatocyte migration across the BTB both take place concurrently at stage VIII of the epithelial cycle of spermatogenesis. Recent findings suggest that these events are coordinated by protein complexes found at the apical and basal ES and TJ, which are located at different ends of the Sertoli cell epithelium. Besides, we highlight important areas of research that can now be undertaken, and functional studies that can be designed to tackle different issues pertinent to junction restructuring during spermatogenesis.

"Too stubborn to ever be governed by enforced insanity": Some therapeutic jurisprudence dilemmas in the representation of criminal defendants in incompetency and insanity cases.

PubMed

Perlin, Michael L

2010-01-01

Little attention has been paid to the importance of the relationship between therapeutic jurisprudence (TJ) and the role of criminal defense lawyers in insanity and incompetency-to-stand-trial (IST) cases. That inattention is especially noteworthy in light of the dismal track record of counsel providing services to defendants who are part of this cohort of incompetency-status-raisers and insanity-defense-pleaders. On one hand, this lack of attention is a surprise as TJ scholars have, in recent years, turned their attention to virtually every other aspect of the legal system. On the other hand, it is not a surprise, given the omnipresence of sanism, an irrational prejudice of the same quality and character of other irrational prejudices that cause (and are reflected in) prevailing social attitudes of racism, sexism, homophobia, and ethnic bigotry, that infects both our jurisprudence and our lawyering practices. Sanism is largely invisible and largely socially acceptable, and is based predominantly upon stereotype, myth, superstition, and deindividualization. It is sustained and perpetuated by our use of alleged "ordinary common sense" (OCS) and heuristic reasoning in an unconscious response to events both in everyday life and in the legal process. This paper examines the literature that seeks to apply TJ principles to the criminal law process in general, drawing mostly on the work of Professor David Wexler. It considers why the lack of attention that I have referred to already is surprising (given TJ's mandate and the fact that many TJ issues are inevitably raised in any insanity or IST case). The paper then considers why this lack of attention is not surprising, given the omnipresence of sanism. It will consider some of the actual counseling issues that might arise in these contexts, and offer some suggestions to lawyers representing clients in cases in which mental status issues may be raised. The paper concludes that we must rigorously apply therapeutic jurisprudence principles to these issues, so as to strip away sanist behavior, pretextual reasoning and teleological decision making from the criminal competency and responsibility processes, so as to enable us to confront the pretextual use of social science data in an open and meaningful way. This gambit would also allow us to address-in a more successful way than has ever yet been done-the problems raised by the omnipresence of ineffective counsel in cases involving defendants with mental disabilities. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

PubMed Central

Burgos, Jose L.; Patterson, Thomas L.; Graff-Zivin, Joshua S.; Kahn, James G.; Rangel, M. Gudelia; Lozada, M. Remedios; Staines, Hugo; Strathdee, Steffanie A.

2016-01-01

Background We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008–2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. Methods A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). Findings For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310–$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310–$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104–$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. Interpretation In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component. PMID:26890001

Worm Algorithm simulations of the hole dynamics in the t-J model

NASA Astrophysics Data System (ADS)

Prokof'ev, Nikolai; Ruebenacker, Oliver

2001-03-01

In the limit of small J << t, relevant for HTSC materials and Mott-Hubbard systems, computer simulations have to be performed for large systems and at low temperatures. Despite convincing evidence against spin-charge separation obtained by various methods for J > 0.4t there is an ongoing argument that at smaller J spin-charge separation is still possible. Worm algorithm Monte Carlo simulations of the hole Green function for 0.1 < J/t < 0.4 were performed on lattices with up to 32x32 sites, and at temperature J/T = 40 (for the largest size). Spectral analysis reveals a single, delta-function sharp quasiparticle peak at the lowest edge of the spectrum and two distinct peaks above it at all studied J. We rule out the possibility of spin-charge separation in this parameter range, and present, apparently, the hole spectral function in the thermodynamic limit.

Implementation of a multichannel soft x-ray diagnostic for electron temperature measurements in TJ-II high-density plasmas

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

Baiao, D.; Varandas, C.; Medina, F.

2012-10-15

Based on the multi-foil technique, a multichannel soft x-ray diagnostic for electron temperature measurements has been recently implemented in the TJ-II stellarator. The diagnostic system is composed by four photodiodes arrays with beryllium filters of different thickness. An in-vacuum amplifier board is coupled to each array, aiming at preventing induced noise currents. The Thomson scattering and the vacuum ultraviolet survey diagnostics are used for assessing plasma profiles and composition, being the analysis carried out with the radiation code IONEQ. The electron temperature is determined through the different signal-pair ratios with temporal and spatial resolution. The design and preliminary results frommore » the diagnostic are presented.« less

3D effects on transport and plasma control in the TJ-II stellarator

NASA Astrophysics Data System (ADS)

Castejón, F.; Alegre, D.; Alonso, A.; Alonso, J.; Ascasíbar, E.; Baciero, A.; de Bustos, A.; Baiao, D.; Barcala, J. M.; Blanco, E.; Borchardt, M.; Botija, J.; Cabrera, S.; de la Cal, E.; Calvo, I.; Cappa, A.; Carrasco, R.; Castro, R.; De Castro, A.; Catalán, G.; Chmyga, A. A.; Chamorro, M.; Dinklage, A.; Eliseev, L.; Estrada, T.; Fernández-Marina, F.; Fontdecaba, J. M.; García, L.; García-Cortés, I.; García-Gómez, R.; García-Regaña, J. M.; Guasp, J.; Hatzky, R.; Hernanz, J.; Hernández, J.; Herranz, J.; Hidalgo, C.; Hollmann, E.; Jiménez-Denche, A.; Kirpitchev, I.; Kleiber, R.; Komarov, A. D.; Kozachoek, A. S.; Krupnik, L.; Lapayese, F.; Liniers, M.; Liu, B.; López-Bruna, D.; López-Fraguas, A.; López-Miranda, B.; López-Razola, J.; Losada, U.; de la Luna, E.; Martín de Aguilera, A.; Martín-Díaz, F.; Martínez, M.; Martín-Gómez, G.; Martín-Hernández, F.; Martín-Rojo, A. B.; Martínez-Fernández, J.; McCarthy, K. J.; Medina, F.; Medrano, M.; Melón, L.; Melnikov, A. V.; Méndez, P.; Merino, R.; Miguel, F. J.; van Milligen, B.; Molinero, A.; Momo, B.; Monreal, P.; Moreno, R.; Navarro, M.; Narushima, Y.; Nedzelskiy, I. S.; Ochando, M. A.; Olivares, J.; Oyarzábal, E.; de Pablos, J. L.; Pacios, L.; Panadero, N.; Pastor, I.; Pedrosa, M. A.; de la Peña, A.; Pereira, A.; Petrov, A.; Petrov, S.; Portas, A. B.; Poveda, E.; Rattá, G. A.; Rincón, E.; Ríos, L.; Rodríguez, C.; Rojo, B.; Ros, A.; Sánchez, J.; Sánchez, M.; Sánchez, E.; Sánchez-Sarabia, E.; Sarksian, K.; Satake, S.; Sebastián, J. A.; Silva, C.; Solano, E. R.; Soleto, A.; Sun, B. J.; Tabarés, F. L.; Tafalla, D.; Tallents, S.; Tolkachev, A.; Vega, J.; Velasco, G.; Velasco, J. L.; Wolfers, G.; Yokoyama, M.; Zurro, B.

2017-10-01

The effects of 3D geometry are explored in TJ-II from two relevant points of view: neoclassical transport and modification of stability and dispersion relation of waves. Particle fuelling and impurity transport are studied considering the 3D transport properties, paying attention to both neoclassical transport and other possible mechanisms. The effects of the 3D magnetic topology on stability, confinement and Alfvén Eigenmodes properties are also explored, showing the possibility of controlling Alfvén modes by modifying the configuration; the onset of modes similar to geodesic acoustic modes are driven by fast electrons or fast ions; and the weak effect of magnetic well on confinement. Finally, we show innovative power exhaust scenarios using liquid metals.

Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein.

PubMed

Facciuto, Florencia; Bugnon Valdano, Marina; Marziali, Federico; Massimi, Paola; Banks, Lawrence; Cavatorta, Ana Laura; Gardiol, Daniela

2014-05-01

High-risk human papillomavirus (HPV) infection is the principal risk factor for the development of cervical cancer. The HPV E6 oncoprotein has the ability to target and interfere with several PSD-95/DLG/ZO-1 (PDZ) domain-containing proteins that are involved in the control of cell polarity. This function can be significant for E6 oncogenic activity because a deficiency in cell polarisation is a marker of tumour progression. The establishment and control of polarity in epithelial cells depend on the correct asymmetrical distribution of proteins and lipids at the cell borders and on specialised cell junctions. In this report, we have investigated the effects of HPV E6 protein on the polarity machinery, with a focus on the PDZ partitioning defective 3 (Par3) protein, which is a key component of tight junctions (TJ) and the polarity network. We demonstrate that E6 is able to bind and induce the mislocalisation of Par3 protein in a PDZ-dependent manner without significant reduction in Par3 protein levels. In addition, the high-risk HPV-18 E6 protein promotes a delay in TJ formation when analysed by calcium switch assays. Taken together, the data presented in this study contribute to our understanding of the molecular mechanism by which HPVs induce the loss of cell polarity, with potential implications for the development and progression of HPV-associated tumours. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway.

PubMed

Lin, Zhijie; Zhang, Yong-Guo; Xia, Yinglin; Xu, Xiulong; Jiao, Xinan; Sun, Jun

2016-12-23

Salmonella pathogenesis studies to date have focused on Salmonella typhimurium, and the pathogenesis of a second major serotype, Salmonella enteritidis, is poorly understood. Salmonella spp. possess effector proteins that display biochemical activities and modulate host functions. Here, we generated a deletion mutant of the effector AvrA, S.E-AvrA - , and a plasmid-mediated complementary strain, S.E-AvrA - /pAvrA + (S.E-AvrA + ), in S. Enteritidis. Using in vitro and in vivo infection models, we showed that AvrA stabilizes epithelial tight junction (TJ) proteins, such as ZO-1, in human intestinal epithelial cells. Transepithelial electrical resistance was significantly higher in cells infected with S.E-AvrA + than in cells infected with S.E-AvrA - Inhibition of the JNK pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA inhibited JNK activity in cells infected with wild type or S.E-AvrA + strains. Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of the JNK pathway. Furthermore, the S.E-AvrA - strain led to enhanced bacterial invasion, both in vitro and in vivo Taken together, our data reveal a novel role for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and attenuates bacterial invasion. The manipulation of JNK activity and TJs in microbial-epithelial interactions may be a novel therapeutic approach for the treatment of infectious diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway*

PubMed Central

Lin, Zhijie; Zhang, Yong-Guo; Xia, Yinglin; Xu, Xiulong; Jiao, Xinan

2016-01-01

Salmonella pathogenesis studies to date have focused on Salmonella typhimurium, and the pathogenesis of a second major serotype, Salmonella enteritidis, is poorly understood. Salmonella spp. possess effector proteins that display biochemical activities and modulate host functions. Here, we generated a deletion mutant of the effector AvrA, S.E-AvrA−, and a plasmid-mediated complementary strain, S.E-AvrA−/pAvrA+ (S.E-AvrA+), in S. Enteritidis. Using in vitro and in vivo infection models, we showed that AvrA stabilizes epithelial tight junction (TJ) proteins, such as ZO-1, in human intestinal epithelial cells. Transepithelial electrical resistance was significantly higher in cells infected with S.E-AvrA+ than in cells infected with S.E-AvrA−. Inhibition of the JNK pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA inhibited JNK activity in cells infected with wild type or S.E-AvrA+ strains. Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of the JNK pathway. Furthermore, the S.E-AvrA− strain led to enhanced bacterial invasion, both in vitro and in vivo. Taken together, our data reveal a novel role for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and attenuates bacterial invasion. The manipulation of JNK activity and TJs in microbial-epithelial interactions may be a novel therapeutic approach for the treatment of infectious diseases. PMID:27875307

Calcium supplements

MedlinePlus

... d-important-every-age . Updated May 2015. Accessed March 14, 2017. The National Osteoporosis Foundation (NOF). Clinician's guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014. Weber TJ. Osteoporosis. ...

How to Become a Pro.

ERIC Educational Resources Information Center

Wilson, Joan M.

1980-01-01

Describes the experiences of a freelance photographer: how she got started, some differences between freelancing and working for a newspaper, and the difficulties involved in being a freelance photographer. (TJ)

Smashed fingers

MedlinePlus

... Crushed digits Images Smashed fingers References Brunton LM, Graham TJ, Atkinson RE. Hand injuries. In: Miller MD, ... Review Date 4/18/2017 Updated by: C. Benjamin Ma, MD, Professor, Chief, Sports Medicine and Shoulder ...

Developing Leadership Traits.

ERIC Educational Resources Information Center

Hall, Susan King

1980-01-01

Defines six leadership traits that are necessary to and fostered by editing a college newspaper: delegating authority, developing subordinates, motivating others, being approachable, commanding respect, and bringing out optimum performances in others. (TJ)

TMJ disorders

MedlinePlus

... conditions can cause TMJ symptoms, from arthritis to whiplash injuries. Experts who are specially trained in facial ... Garza I, Schwedt TJ, Robertson CE, Smith JH. Headache and other craniofacial pain. In: Daroff RB, Jankovic ...

Therapeutic jurisprudence and outpatient commitment law: Kendra's Law and case study.

PubMed

Perlin, Michael L

2003-01-01

This article considers the implications of assisted outpatient commitment laws (OPC), with specific focus on New York's "Kendra's Law" through the lens of therapeutic jurisprudence (TJ). In this article, the author offers perspectives on the relationship between involuntary civil commitment, outpatient commitment, and the concept of the "least restrictive alternative"; considers pertinent empirical research, and looks at OPC's controversial relationship to forced drugging. Here, the civil libertarian critique is briefly considered, as well as the MacArthur Research Network research. Finally, the author looks closely at Kendra's Law, providing a brief overview of the law itself, and identifying some "pressure points" and pivotal issues, and considers the TJ implications of Kendra's Law, to determine how it "fits" into the public's "take" on all of mental disability law.

Poisoning

MedlinePlus

... The Harriet Lane Handbook . 21st ed. Philadelphia, PA: Elsevier; 2018:chap 2. Kostic MA. Poisoning. In: Kliegman ... Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 63. Meehan TJ. Approach to the ...

Effect of retinoic acid on the tight junctions of the retinal pigment epithelium-choroid complex of guinea pigs with lens-induced myopia in vivo

PubMed Central

WANG, SHA; LIU, SHUANGZHEN; MAO, JUNFENG; WEN, DAN

2014-01-01

Zonula occludens-1 (ZO-1) and occludin are important tight junction (TJ)-associated proteins, which are expressed in the retinal pigment epithelium (RPE)-choroid complex. Retinoic acid (RA) is a regulator of eye growth and may play an important role in forming functional TJs. The aim of this study was to detect the changes that occur in the expression of ZO-1 and occludin in the RPE-choroid complex of guinea pigs with lens-induced myopia (LIM), and to investigate the effect of RA on TJ-associated proteins in vivo. We developed an animal model of myopia by placing a −6.00 D negative lens on the right eyes of 3-week-old guinea pigs. The refractive error and axial length of the eye were measured on days 0, 3, 7 and 14. High-performance liquid chromatography (HPLC) was performed to detect the changes in endogenous RA in the RPE-choroid complex. The expression of ZO-1 and occludin was observed by immunofluorescence and assayed by western blot analysis. Additionally, 2 μl LE540 (2.5 μg/μl), an antagonist of RA receptors (RARs), was injected into the vitreous chamber of the eyes of guinea pigs with LIM and 2 μl phosphate-buffered saline (PBS) (2.5 μg/μl) were injected as a negative control. We observed no obvious change in RA, ZO-1 and occludin expression in the normal control group within 14 days. In the LIM and LIM plus PBS groups, the level of RA and the expression of ZO-1 and occludin in the RPE-choroid complex significantly increased within 14 days along with the development of myopia. However, the level of RA was inhibited and the expression of TJ-associated proteins decreased in the eyes of guinea pigs with LIM following the injection of LE540. Thus, we consider that the expression of ZO-1 and occludin is increased in the RPE-choroid complex during the development of myopia. This change in expression may be regulated by RA, a factor known to be involved in the regulation of eye growth. PMID:24535401

The Z2/A Dependence in Heavy-Ion Fusion for the Reactions of Chlorine on Thulium, Lutetium, Tantalum and Tungsten.

DTIC Science & Technology

1980-06-01

N NLL 0 0 C~CP (qw ) P /.op -40- individual excitation functions for each evaporation channel. For this study the lower...c’ + a" (alpha particles) =8a + a" (protons) £ £’ + P " (neutrons) C ’’, = 1 or 0 1ŕ,81","," = I or 0 V + V’ - I INDIVIDUAL (a, p or n ) VELOCITY...velocity profile of +10%, 0, -10% of v0 was taken. All angular distributions * - -- - - - - 76- M0 U3 LuL I M (0w DN~ N + 1 tJ < N I $ P ll7 -77-

Sensitivity Functions and Their Uses in Inverse Problems

DTIC Science & Technology

2007-07-21

Σ0 is used in formu- lating the standard errors for our estimates θ̂n; these are given by SEk = √ (Σ0)kk, k = 1, 2, ..., p. (5) Because θ0 in (4) is...standard formula SEk = √ σ̂2(χT χ)−1kk , k = 1, 2, ..., p, (7) with χ(θ) an n× p sensitivity matrix for our model given by χjk(θ) = ∂f(tj, θ) ∂θk . (8) 5 For...Note that since θ = (K, r, x0), the standard error for K is indicated as the first entry in each of the ordered sets in each table, i.e., SEK = SEθ1

In vitro micro-physiological immune-competent model of the human skin.

PubMed

Ramadan, Qasem; Ting, Fiona Chia Wan

2016-05-21

Skin allergy, in particular, allergic contact dermatitis and irritant contact dermatitis, are common occupational and environmental health problems affecting the quality of life of a significant proportion of the world population. Since all new ingredients to be incorporated into a product are potential skin allergens, it is essential that these ingredients be first tested for their allergenic potential. However, despite the considerable effort using animal models to understand the underlying mechanism of skin sensitization, to date, the molecular and cellular responses due to skin contact with sensitizers are still not fully understood. To replace animal testing and to improve the prediction of skin sensitization, significant attention has been directed to the use of reconstructed organotypic in vitro models of human skin. Here we describe a miniaturized immune competent in vitro model of human skin based on 3D co-culture of immortalized human keratinocytes (HaCaT) as a model of the epidermis barrier and human leukemic monocyte lymphoma cell line (U937) as a model of human dendritic cells. The biological model was fitted in a microfluidic-based cell culture system that provides a dynamic cellular environment that mimics the in vivo environment of skin. The dynamic perfusion of culture media significantly improved the tight junction formation as evidenced by measuring higher values of TEER compared to static culture. This setting also maintained the high viability of cells over extended periods of time up to 17 days. The perfusion-based culture also allows growth of the cells at the air-liquid interface by exposing the apical side of the cells to air while providing the cell nutrients through a basolateral fluidic compartment. The microsystem has been evaluated to investigate the effect of the chemical and physical (UV irradiation) stimulation on the skin barrier (i.e. the TJ integrity). Three-tiered culture differential stimulation allowed the investigation of the role of the keratinocyte layer as a protection barrier to chemical/biological hazards.

Breast cancer resistance protein (Bcrp) and the testis—an unexpected turn of events

PubMed Central

Qian, Xiaojing; Cheng, Yan-Ho; Mruk, Dolores D; Cheng, C Yan

2013-01-01

Breast cancer resistance protein (Bcrp) is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens (e.g., genistein, daidzein, coumestrol), xenoestrogens and steroids (e.g., dehydroepiandrosterone sulfate). Bcrp is an integral membrane protein in cancer and normal cells within multiple organs (e.g., brain, placenta, intestine and testis) that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood–brain barrier located on endothelial cells near tight junctions (TJs). However, Bcrp is absent at the Sertoli cell blood–testis barrier (BTB); instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation (ES) in stage VI–early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F (filamentous)-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII–VIII tubules. These findings will be carefully evaluated in this brief review. PMID:23665760

Noise alters guinea pig's blood-labyrinth barrier ultrastructure and permeability along with a decrease of cochlear Claudin-5 and Occludin.

PubMed

Wu, Yong-Xiang; Zhu, Guo-Xia; Liu, Xin-Qin; Sun, Fei; Zhou, Ke; Wang, Shuang; Wang, Chun-Mei; Jia, Jin-Wen; Song, Jian-Tao; Lu, Lian-Jun

2014-12-24

Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultrastructure of cochlea and permeability of BLB but also the expression of TJP within the guinea pig cochlea. Male albino guinea pigs were exposed to white noise for 4 h or 2 consecutive days (115 dB sound pressure level, 6 hours per day) and the hearing impairments and light microscopic change of BLB were evaluated with auditory brainstem responses (ABR) and the cochlear sensory epithelia surface preparation, respectively. The cochlear ultrastructure and BLB permeability after NE 2d were revealed with transmission electron microscope (TEM) and lanthanum nitrate-tracing techniques, respectively. The potential alterations of TJPs Claudin-5 and Occludin were quantified with immunohistochemistry and western blot. NE induced significant hearing impairment and NE 2d contributed to significant outer hair cell (OHC) loss that is most severe in the first row of outer hair cells. Furthermore, the loosen TJ and an obvious leakage of lanthanum nitrate particles beneath the basal lamina were revealed with TEM. Moreover, a dose-dependent decrease of Claudin-5 and Occludin was observed in the cochlea after NE. All these findings suggest that both decrease of Claudin-5 and Occludin and increased BLB permeability are involved in the pathologic process of noise-induced hearing impairment; however, the causal relationship and underlying mechanisms should be further investigated.

Deodorant poisoning

MedlinePlus

... Poisoning and Drug Overdose . 4th ed. Philadelphia, PA: Elsevier Saunders; 2007:chap 100. Farmer B, Seger DL. ... Textbook of Critical Care . 7th ed. Philadelphia, PA: Elsevier; 2017:chap 153. Meehan TJ. Approach to the ...

Vomiting blood

MedlinePlus

... in the vomit References Goralnick E, Meguerdichian DA. Gastrointestinal bleeding. In: Marx JA, Hockberger RS, Walls RM, et ... Saunders; 2016:chap 135. Savides TJ, Jensen DM. Gastrointestinal bleeding. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

Habitat traits and food availability determine the response of marine invertebrates to ocean acidification.

PubMed

Pansch, Christian; Schaub, Iris; Havenhand, Jonathan; Wahl, Martin

2014-03-01

Energy availability and local adaptation are major components in mediating the effects of ocean acidification (OA) on marine species. In a long-term study, we investigated the effects of food availability and elevated pCO2 (ca. 400, 1000 and 3000 μatm) on growth of newly settled Amphibalanus (Balanus) improvisus to reproduction, and on their offspring. We also compared two different populations, which were presumed to differ in their sensitivity to pCO2 due to differing habitat conditions: Kiel Fjord, Germany (Western Baltic Sea) with naturally strong pCO2 fluctuations, and the Tjärnö Archipelago, Sweden (Skagerrak) with far lower fluctuations. Over 20 weeks, survival, growth, reproduction and shell strength of Kiel barnacles were all unaffected by elevated pCO2 , regardless of food availability. Moulting frequency and shell corrosion increased with increasing pCO2 in adults. Larval development and juvenile growth of the F1 generation were tolerant to increased pCO2 , irrespective of parental treatment. In contrast, elevated pCO2 had a strong negative impact on survival of Tjärnö barnacles. Specimens from this population were able to withstand moderate levels of elevated pCO2 over 5 weeks when food was plentiful but showed reduced growth under food limitation. Severe levels of elevated pCO2 negatively impacted growth of Tjärnö barnacles in both food treatments. We demonstrate a conspicuously higher tolerance to elevated pCO2 in Kiel barnacles than in Tjärnö barnacles. This tolerance was carried over from adults to their offspring. Our findings indicate that populations from fluctuating pCO2 environments are more tolerant to elevated pCO2 than populations from more stable pCO2 habitats. We furthermore provide evidence that energy availability can mediate the ability of barnacles to withstand moderate CO2 stress. Considering the high tolerance of Kiel specimens and the possibility to adapt over many generations, near future OA alone does not seem to present a major threat for A. improvisus. © 2013 John Wiley & Sons Ltd.

A Corporate Communication Major for Clarke College.

ERIC Educational Resources Information Center

Turney, Michael L.

1980-01-01

Describes a program in which students are specifically trained in corporate communication. Lists courses required for completion of the program and tells about students' involvement in operating a communication agency simulation. (TJ)

Full Page Departmental Advertising.

ERIC Educational Resources Information Center

Van Zante, Ben

1978-01-01

States that many school newspapers are condensing all advertising into one or two pages. Indicates that advertisers find this to be acceptable, students continue to read the ads, and the content pages look better. (TJ)

The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

PubMed Central

Errede, Mariella; Girolamo, Francesco; Rizzi, Marco; Bertossi, Mirella; Roncali, Luisa; Virgintino, Daniela

2014-01-01

This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration, and before cortex lamination, with BBB-endothelial cell markers, namely tight junction (TJ) proteins (occludin and claudin-5) and influx and efflux transporters (Glut-1 and P-glycoprotein), the latter supporting evidence for functional effectiveness of the fetal BBB. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analyzed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43) were utilized as markers of radial glia cells, CD105 (endoglin) as a marker of angiogenically activated endothelial cells (ECs), and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial (RG) fibers in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical, vessel-specific RG fiber swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of RG varicosities reveals colocalization of CXCL12 with Cx43, which is possibly implicated in vessel-specific chemokine signaling. PMID:25360079

Creamer stows urine samples in MELFI

NASA Image and Video Library

2010-05-02

ISS023-E-030773 (2 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, services the Minus Eighty Laboratory Freezer for ISS (MELFI-1) in the Kibo laboratory of the International Space Station.

Creamer stows urine samples in MELFI

NASA Image and Video Library

2010-05-02

ISS023-E-030771 (2 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, services the Minus Eighty Laboratory Freezer for ISS (MELFI-1) in the Kibo laboratory of the International Space Station.

Creamer stows urine samples in MELFI

NASA Image and Video Library

2010-05-02

ISS023-E-030780 (2 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, services the Minus Eighty Laboratory Freezer for ISS (MELFI-1) in the Kibo laboratory of the International Space Station.

Creamer stows urine samples in MELFI

NASA Image and Video Library

2010-05-02

ISS023-E-030772 (2 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, services the Minus Eighty Laboratory Freezer for ISS (MELFI-1) in the Kibo laboratory of the International Space Station.

Pneumonia - children - community acquired

MedlinePlus

... of Pediatric Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 22. Kelly MS, Sandora TJ. ... Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2016:chap 400. Kronman MP, Shah SS. Pneumonia and ...

Cedar leaf oil poisoning

MedlinePlus

... eds. Auerbach's Wilderness Medicine . 7th ed. Philadelphia, PA: Elsevier; 2017:chap 45. Graeme KA. Toxic plant ingestions. ... eds. Auerbach's Wilderness Medicine . 7th ed. Philadelphia, PA: Elsevier; 2017:chap 65. Meehan TJ. Approach to the ...

Herbert Hoover and William Shakespeare: Two Writers on Ethics.

ERIC Educational Resources Information Center

Somers, Margaret L.

1979-01-01

Outlines the ways in which Herbert Hoover and William Shakespeare wrote about professional ethics (for engineers and kings, respectively) using the writing techniques of concreteness, audience awareness, and development by induction. (TJ)

Kernel reconstruction methods for Doppler broadening - Temperature interpolation by linear combination of reference cross sections at optimally chosen temperatures

NASA Astrophysics Data System (ADS)

Ducru, Pablo; Josey, Colin; Dibert, Karia; Sobes, Vladimir; Forget, Benoit; Smith, Kord

2017-04-01

This article establishes a new family of methods to perform temperature interpolation of nuclear interactions cross sections, reaction rates, or cross sections times the energy. One of these quantities at temperature T is approximated as a linear combination of quantities at reference temperatures (Tj). The problem is formalized in a cross section independent fashion by considering the kernels of the different operators that convert cross section related quantities from a temperature T0 to a higher temperature T - namely the Doppler broadening operation. Doppler broadening interpolation of nuclear cross sections is thus here performed by reconstructing the kernel of the operation at a given temperature T by means of linear combination of kernels at reference temperatures (Tj). The choice of the L2 metric yields optimal linear interpolation coefficients in the form of the solutions of a linear algebraic system inversion. The optimization of the choice of reference temperatures (Tj) is then undertaken so as to best reconstruct, in the L∞ sense, the kernels over a given temperature range [Tmin ,Tmax ]. The performance of these kernel reconstruction methods is then assessed in light of previous temperature interpolation methods by testing them upon isotope 238U. Temperature-optimized free Doppler kernel reconstruction significantly outperforms all previous interpolation-based methods, achieving 0.1% relative error on temperature interpolation of 238U total cross section over the temperature range [ 300 K , 3000 K ] with only 9 reference temperatures.

Are additive effects of dietary surfactants on intestinal tight junction integrity an overlooked human health risk? - A mixture study on Caco-2 monolayers.

PubMed

Glynn, Anders; Igra, Annachiara Malin; Sand, Salomon; Ilbäck, Nils Gunnar; Hellenäs, Karl Erik; Rosén, Johan; Aspenström-Fagerlund, Bitte

2017-08-01

Surfactants may cause dysfunction of intestinal tight junctions (TJs), which is a common feature of intestinal autoimmune diseases. Effects of dietary surfactants on TJ integrity, measured as trans-epithelial resistance (TEER), were studied in Caco-2 cell monolayers. Cytotoxicity was assessed as apical LDH leakage. Monolayers were apically exposed for 60 min to the dietary surfactants solanine and chaconine (SC, potato glycoalkaloids, 0-0.25 mM), perfluorooctane sulfonic acid (PFOS, industrial contaminant, 0-0.8 mM), and sucrose monolaurate (SML, food emulsifier E 473, 0-2.0 mM) separately and as a mixture. Dose-response modelling of TEER EC 50 showed that SC were 2.7- and 12-fold more potent than PFOS and SML, respectively. The mixture was composed of 1 molar unit SC, 2.7 units PFOS and 12 units SML ("SC TEER equivalent" proportions 1:1:1). Mixture exposure (0-0.05 mM SC equivalents) dose-response modelling suggested additive action on TJ integrity. Increasing SC and SML concentrations caused increased LDH leakage, but PFOS decreased LDH leakage at intermediate exposure concentrations. In the mixture PFOS appeared to protect from extensive SC- and SML-induced LDH leakage. Complex mixtures of surfactants in food may act additively on intestinal TJ integrity, which should be considered in risk assessment of emulsifier authorisation for use in food production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Of Bacon and Bananas.

ERIC Educational Resources Information Center

Saffioti, Carol Lee

1977-01-01

Exercises in sketching a scene of words, focusing, describing elemental structure (using comparison, contrast, analogy, and antithesis), and sketching and writing about still-life arrangements can heighten students' awareness of sense impressions and lead to improved writing skills. (TJ)

Conducting Intelligent Business Dialogue.

ERIC Educational Resources Information Center

Hulbert, Jack E.

1980-01-01

Indicates that speaking skills (especially dialogue) are not adequately taught in management education. Describes effective dialogue as: defining the problem, gathering facts, interpreting the evidence, considering alternatives, and reaching decisions. Discusses various aspects of agreement and disagreement. (TJ)

Creamer works with IVGEN Experiment Payload in Columbus MSG

NASA Image and Video Library

2010-05-03

ISS023-E-033108 (6 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, is pictured near the Microgravity Science Glovebox (MSG) located in the Columbus laboratory of the International Space Station.

Creamer works with IVGEN Experiment Payload in Columbus MSG

NASA Image and Video Library

2010-05-03

ISS023-E-033107 (6 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, is pictured near the Microgravity Science Glovebox (MSG) located in the Columbus laboratory of the International Space Station.

What You Can Learn from the 1979 Pacemakers.

ERIC Educational Resources Information Center

Brasler, Wayne

1980-01-01

Indicates that prizewinning school publications differ from good publications in having three qualities: wide-ranging content reflecting organized, creative approaches to coverage; intelligence and sensitivity in content; and thoughtful design. Includes illustrations from prizewinners. (TJ)

How to Put Together Community Coverage.

ERIC Educational Resources Information Center

Wilson, Marjorie

1980-01-01

Suggests that school newspapers pursue out-of-school news in areas such as school-related concerns, government, community agencies and services, entertainment, service agencies and programs, sports, first-person accounts, national problems, and problem investigation. (TJ)

Writing Rock Music Reviews.

ERIC Educational Resources Information Center

Brown, Donal

1980-01-01

Suggests ways student reviewers of rock music groups can write better reviews. Among the suggestions made are that reviewers occasionally discuss the audience or what makes a particular group unique, support general comment with detail, and avoid ecstatic adjectives. (TJ)

Liven up Your Student Dramatics with Commedia dell' Arte.

ERIC Educational Resources Information Center

Potter, Jonathan

1980-01-01

Suggests using the ancient Commedia dell' Arte technique of establishing characters and a plot and then allowing the actors to create their own play. Indicates that this improves student performances even in more traditional plays. (TJ)

Ostomy

MedlinePlus

... Chapter 31. Intestinal Stomas. Chapter in Beck, D.E., Roberts, P.L., Saclarides, T.J., Senagore, A.J., Stamos, M.J., Wexner, S.D., Eds. ASCRS Textbook of Colon and Rectal Surgery, 2nd Edition. Springer, New York, NY: 2011. National Digestive Disease Information ...

Resonant slepton production yields CMS e e j j and e p Tj j excesses

NASA Astrophysics Data System (ADS)

Allanach, Ben; Biswas, Sanjoy; Mondal, Subhadeep; Mitra, Manimala

2015-01-01

Recent CMS searches for dileptoquark production report local excesses of 2.4 σ in an e e j j channel and 2.6 σ in an e p Tj j channel. Here, we simultaneously explain both excesses with resonant slepton production in R -parity violating supersymmetry. We consider resonant slepton production, which decays to a lepton and a chargino/neutralino, followed by three-body decays of the neutralino/chargino via an R -parity violating coupling. There are regions of parameter space which are also compatible at the 95% confidence level with a 2.8 σ e e j j excess in a recent CMS WR search, while being compatible with other direct search constraints. Phase II of the GERDA neutrinoless double beta decay (0 ν β β ) experiment will probe a sizable portion of the good-fit region.

Ginzburg-Landau Theory for Flux Phase and Superconductivity in t-J Model

NASA Astrophysics Data System (ADS)

Kuboki, Kazuhiro

2018-02-01

Ginzburg-Landau (GL) equations and GL free energy for flux phase and superconductivity are derived microscopically from the t-J model on a square lattice. Order parameter (OP) for the flux phase has direct coupling to a magnetic field, in contrast to the superconducting OP which has minimal coupling to a vector potential. Therefore, when the flux phase OP has unidirectional spatial variation, staggered currents would flow in a perpendicular direction. The derived GL theory can be used for various problems in high-Tc cuprate superconductors, e.g., states near a surface or impurities, and the effect of an external magnetic field. Since the GL theory derived microscopically directly reflects the electronic structure of the system, e.g., the shape of the Fermi surface that changes with doping, it can provide more useful information than that from phenomenological GL theories.

An experimental system for spectral line ratio measurements in the TJ-II stellarator.

PubMed

Zurro, B; Baciero, A; Fontdecaba, J M; Peláez, R; Jiménez-Rey, D

2008-10-01

The chord-integrated emissions of spectral lines have been monitored in the TJ-II stellarator by using a spectral system with time and space scanning capabilities and relative calibration over the entire UV-visible spectral range. This system has been used to study the line ratio of lines of different ionization stages of carbon (C(5+) 5290 A and C(4+) 2271 A) for plasma diagnostic purposes. The local emissivity of these ions has been reconstructed, for quasistationary profiles, by means of the inversion Fisher method described previously. The experimental line ratio is being empirically studied and in parallel a simple spectroscopic model has been developed to account for that ratio. We are investigating whether the role played by charge exchange processes with neutrals and the existence of non-Maxwellian electrons, intrinsic to Electron Cyclotron Resonance Heating (ECRH) heating, leave any distinguishable mark on this diagnostic method.

Spectral Properties of Composite Excitations in the t-J Model

NASA Astrophysics Data System (ADS)

Otaki, Takashi; Yahagi, Yuta; Matsueda, Hiroaki

2017-08-01

In quantum many-body systems, the equation of motion for a simple fermionic operator does not close, and higher-order processes induce composite operators dressed with several types of nonlocal quantum fluctuation. We systematically examine the spectral properties of these composite excitations in the t-J model in one spatial dimension by both numerical and theoretical approaches. Of particular interest, with the help of the Bethe ansatz for the large-U Hubbard model, is the classification of which composite excitations are due to the string excitation, which is usually hidden in the single-particle spectrum, as well as the spinon and holon branches. We examine how the mixing between the spinon and string excitations is prohibited in terms of the composite operator method. Owing to the dimensionality independent nature of the present approach, we discuss the implications of the mixing in close connection with the pseudogap in high-Tc cuprates.

Exact expression of the t-J model in terms of local spin and fermionic holon operators

NASA Astrophysics Data System (ADS)

Wang, Y. R.; Rice, M. J.

1994-02-01

An exact expression for the Hamiltonian H of the t-J model in terms of local spin (Si) and fermionic holon (ei) operators is derived which requires no constraint between these operators. The result for the Hamiltonian H is H=-t tsumijeie°j(1/2+2Si.Sj)+(J/2)t smij(1-e°iei)(Si.Sj-1/4)(1-e°je The number of electrons at site i is given by ni=1-e°iei, and the true spin operator S~i, is related to the local spin operator by S~i=(1-e°iei)Si. The expression correctly produces the Nagaoka theorem in the limit J-->0, and preserves the time-reversal symmetry of the original model. For a bipartite lattice, H describes a competition between ferromagnetism, favored by the hopping term, and antiferromagnetism, favored by the Heisenberg term.

Investigation of a Multifrequency Reconfigurable Phased Array Antenna

DTIC Science & Technology

1991-05-01

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Hurricane Maria, 2017 Hydrographic Response for Puerto Rico and U.S. Virgin Islands by the NOAA Ship Thomas Jefferson

NASA Astrophysics Data System (ADS)

Gump, D.; Klemm, A.; van Westendorp, C.; Wood, D. A.; Doroba, J.

2017-12-01

After many coastal natural disasters, ports and harbors must be surveyed for navigation dangers, cleared, and opened as quickly as possible to facilitate recovery and reconstruction. The appropriate survey asset to use varies by location and condition. Routinely, hydrographic response to a natural disaster is conducted by survey teams with trailer-hitched vessels deployed quickly by land. This was the case for Hurricanes Harvey, Irma and Nate which struck mainland U.S. In the U.S. territories of Puerto Rico and the Virgin Islands post-Hurricane Maria, however, the devastation to the regional infrastructure resulted in a dearth of adequate accommodations, fuel, security and passable roads required to support a land-based response. On September 24th, 2017, NOAA Ship Thomas Jefferson (TJ), a 208-foot-long hydrographic survey vessel with a 38-person complement and two 28-foot-long survey launches, began an uninterrupted 20-day cruise to survey major ports around the islands. The ship's crew acquired high-resolution multibeam echo sounder (MBES) and concurrent object-detection side scan sonar (SSS) in and around 18 individual port facilities in 13 areas. The TJ is the appropriate platform for sustained remote response due to a self-contained infrastructure that supports deployment and recovery of survey launches, as well as 24/7 data processing facilities. The TJ crew produced digital terrain models and SSS mosaics, in addition to developing new reports on specific hazards overnight. These products quickly informed responders, stakeholders and responsible authorities about the efficacy of waterways.

MLCK-mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI-IBS mice.

PubMed

Long, Y; Du, L; Kim, J J; Chen, B; Zhu, Y; Zhang, Y; Yao, S; He, H; Zheng, X; Huang, Z; Dai, N

2018-04-11

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model. Trichinella spiralis-infected PI-IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens-1) and MLCK-associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension. Eight weeks after inoculation with T. spiralis, PI-IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens-1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI-IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1-dominant immune profile in PI-IBS mice. MLCK is a pivotal step in inducing increased intestinal permeability promoting low-grade intestinal immune activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS. © 2018 John Wiley & Sons Ltd.

Stress the Local Angle...Keep the Yearbook Currently Eventful.

ERIC Educational Resources Information Center

Stano, Randy

1980-01-01

Suggests that while current events should be recorded in school yearbooks, the local angle should be stressed. Provides illustrations of how this might be done with such topics as gasoline prices, inflation, foreign events, and political campaigns. (TJ)

Genetics Home Reference: Bosma arhinia microphthalmia syndrome

MedlinePlus

... Xue S, Yigit G, Filali H, Chen K, Rosin N, Yoshiura KI, Oufadem M, Beck TJ, McGowan R, ... AD, Nürnberg P, Meschede D, Mühlbauer W, Okamoto N, Varghese V, Irving R, Sigaudy S, Williams D, Ahmed ...

Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea.

PubMed

Takasuna, K; Hagiwara, T; Watanabe, K; Onose, S; Yoshida, S; Kumazawa, E; Nagai, E; Kamataki, T

2006-10-01

An antitumor camptothecin derivative CPT-11 has proven a broad spectrum of solid tumor malignancy, but its severe diarrhea has often limited its more widespread use. We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect. In the present study, we assessed the efficacy of several potential treatments in our rat model to clarify which is the most promising treatment for CPT-11-induced delayed diarrhea. Oral dosing (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000 mg/kg improved the decrease in body weight and the delayed diarrhea symptoms induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice daily from days -1 to 4). In a separate experiment using rats bearing breast cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P-glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP-glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without modifying CPT-11's antitumor activity. The result clearly demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset diarrhea, suggesting the treatments decreasing the exposure of the intestines to the luminal SN-38 are valuable for improvement of CPT-11-induced intestinal toxicity. In contrast, the treatments affecting the biliary excretion of CPT-11 and its metabolites might have undesirable results.

Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

PubMed

Roda, E; Nion, S; Bernocchi, G; Coccini, T

2014-10-02

Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.

2012-01-01

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172

77 FR 57133 - T.J. Mcnichol, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... medication as prescribed, and that there is ``no such thing in this clinic * * * of running out of medication. Id. at 14-16. Respondent further explained that ``one of the reasons why we don't run out here'' is...

A Coordinated Business System.

ERIC Educational Resources Information Center

Emmett, Marion B.

1980-01-01

Describes a student publications department business system in which students take responsibility for selling advertisements for the newspaper and yearbook, make sure that layouts are satisfactory to customers, keep all records of accounting and billing procedures, and maintain budget supervision of student publications activities. (TJ)

Potential barrier classification by short-time measurement

NASA Astrophysics Data System (ADS)

Granot, Er'El; Marchewka, Avi

2006-03-01

We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function.

Mouse Mast Cell Protease 4 and 5 Mediate Epidermal Injury Through Disruption of Tight Junctions

PubMed Central

Bankova, Lora G.; Lezcano, Cecilia; Pejler, Gunnar; Stevens, Richard L.; Murphy, George F.; Austen, K. Frank; Gurish, Michael F.

2014-01-01

We previously established a mast cell (MC)-dependent thermal injury model in mice with ulceration and scar formation that depended on non-redundant functions of mouse MC protease 4 (mMCP4) and mMCP5. We hypothesized that MC activation is an early event and now find by histology that exocytosis of granule contents occurred by 2 min after thermal injury in wild type (WT) C57BL/6 mice and in the mMCP4- or mMCP5-deficient mice. The degranulation was equivalent for MCs in the dermis and hypodermis of all three strains, but only the WT mice showed an appreciable increase in epidermal thickness. There was no loss of total MCs, partially degranulated plus intact, over the 4 h of observation. By electron microscopy, MCs in all strains showed early zonal degranulation at 30 s with marked progression in magnitude by 120 s and no mitochondrial injury or cellular necrosis. Concomitantly there was an increase in intercellular spaces indicative of tight junction (TJ) disruption in WT mice but not in the mMCP4- or mMCP5-deficient strains. The desmosomes were intact in all strains. Immunodetection of the TJ protein claudin 4 in WT and mMCP5-deficient mice indicated a significant reduction after scald injury while mMCP4−/− mice showed no significant changes. Taken together, these findings reveal that a second degree burn injury can initiate an immediate novel zonal degranulation of MCs throughout all skin layers and a disruption of the epidermal TJs dependent on the non-redundant presence of mMCP4 and mMCP5. PMID:24523504

Nitrogen isotope record of a perturbed paleoecosystem in the aftermath of the end-Triassic crisis, Doniford section, SW England

NASA Astrophysics Data System (ADS)

Paris, Guillaume; Beaumont, ValéRie; Bartolini, Annachiara; CléMence, Marie-Emilie; Gardin, Silvia; Page, Kevin

2010-08-01

The Triassic-Jurassic transition (TJ) is characterized by successive perturbations of the carbon cycle during a time of biotic disruption as recorded by the carbon isotopic composition of organic matter (δ13Corg). The nitrogen isotopic composition of sedimentary organic matter (δ15Norg) constitutes a key parameter to explore the functioning of the ecosystem during carbon cycle perturbations and biological crises, because it provide information on seawater redox conditions and/or nutrient cycling. Here we report the first continuous δ15Norg record across the TJ transition at the Doniford Bay section (Bristol Channel Basin, UK), combined with δ13Corg, kerogen typology and carbon (δ13Cmin) and oxygen (δ18Omin) isotopic composition of bulk carbonates. The end Triassic is characterized by a major negative excursion both in δ13Corg and δ13Cmin, very low TOC (Total Organic Carbon, wt%) and high δ15Norg values, associated with a sea level lowstand. A second δ13Corg negative excursion occurs during the lower Hettangian. This interval is characterized by phases of carbonate production increase alternated with phases of exceptional accumulations of type I organic matter (up to 12%) associated with lower δ15Norg and δ13Corg. This alternation likely reflects a succession of nutrient input increase to the basin leading to enhanced productivity and eutrophication, which promoted a primary production driven by organic-walled prokaryotic organisms. The following OM export increase generates anaerobic conditions within the basin. These events occur between periods of relatively good seawater column ventilation and nutrient recycling boosting the carbonate producer recovery. Ecosystems remain perturbed in the Bristol Channel Basin during the aftermath of the end-Triassic crisis.

The evidence for ocean acidification across the Triassic-Jurassic boundary

NASA Astrophysics Data System (ADS)

Martindale, R. C.; Greene, S. E.; Ritterbush, K. A.; Bottjer, D. J.; Corsetti, F. A.; Berelson, W.

2012-12-01

The end-Triassic extinction is one of the "Big Five" mass extinctions of the Phanerozoic and until recently no consensus regarding the cause of this extinction has been established. Over the last decade, a robust temporal correlation between the eruption of the Central Atlantic Magmatic Province (CAMP) and the end-Triassic extinction has been established. This correlation has led to the speculation that the release of CO2 and volatiles from the CAMP flood basalts induced a carbon cycle perturbation that acidified the Triassic oceans. It has also been suggested that an acidification event could have been the key mechanism that caused the end-Triassic marine ecosystem collapse. By combining observations and data from multiple fields such as volcanology, paleoceanography, chemostratigraphy, paleontology, and sedimentology, one can assess whether or not there was an ocean acidification event and to what degree it contributed to the extinction. The eruption of the CAMP flood basalts began at the very end of the Triassic period, albeit before the official Triassic-Jurassic (T-J) boundary, (defined as the first Jurassic ammonite). CAMP is one of the largest continental flood basalts of the Phanerozoic (2-4 million cubic km) and was emplaced extremely rapidly (<1.6-2 Myr) in three to five pulses (possibly hundreds to tens of thousands of years). The massive injection of CAMP CO2 and other volcanic volatiles over such a short period of time would have caused a major change in ocean carbonate chemistry and, if short enough in duration, could have caused significant declines in oceanic carbonate saturation state (an ocean acidification event), possibly even undersaturating parts of the surface ocean with respect to aragonite and calcite. Although the change in saturation state of the ocean is extremely difficult to detect or quantify in the rock record, there is a distinct paucity of primary carbonate sediments in the T-J boundary interval, consistent with an ocean acidification event. Of the seventeen T-J boundary sections only three or four record potentially continuous carbonate deposition across the extinction interval, even so these carbonates are often marls and so may not be truly continuous. Finally, the end-Triassic extinction was particularly selective against pH-sensitive organisms (more so than perhaps any other extinction event). Not only was this extinction event one of the most severe extinctions of the 'Modern Fauna' in the geologic record, it also decimated reef ecosystems built by corals and hypercalcified sponges. End-Triassic extinction rates amongst acid-intolerant organisms and ecosystems are elevated and differ significantly from background extinction so that ocean acidification is a reasonable explanation for the interpreted extinction selectivity during this time interval. Given the volcanic, geochemical, sedimentological, and paleontological changes or events across the T-J interval it is likely that the end-Triassic extinction was heavily influenced by a CAMP-induced ocean acidification event. The dramatic taxonomic and ecosystem turnover at the T-J event implies that short-term acidification events may have long-term effects on ecosystems, a repercussion that has not previously been correlated with acidification events and has implications for future changes in ocean chemistry.

Using Persuasion to Plan a Moon Walk.

ERIC Educational Resources Information Center

Harris, Muriel

1977-01-01

Describes an exercise in learning about persuasion using a NASA exercise in group decision-making centered on a theoretical crash landing on the moon. Students experience the power of the authoritative voice, the persuasive power of facts, the bandwagon approach, and group manipulation. (TJ)

QCD on the BlueGene/L Supercomputer

NASA Astrophysics Data System (ADS)

Bhanot, G.; Chen, D.; Gara, A.; Sexton, J.; Vranas, P.

2005-03-01

In June 2004 QCD was simulated for the first time at sustained speed exceeding 1 TeraFlops in the BlueGene/L supercomputer at the IBM T.J. Watson Research Lab. The implementation and performance of QCD in the BlueGene/L is presented.

Some Advertising Sales Tips.

ERIC Educational Resources Information Center

Schick, C. Dennis

1980-01-01

Enumerates information that advertising sales people for school newspapers should have before they call on potential customers. Includes ideas on what to know about a number of items, including the publication, readers and nonreaders, advertising, sales opportunities, prospects, prospects' problems, shopping factors, and stores' images. (TJ)

Estimating Neutral Atmosphere Drivers using a Physical Model

DTIC Science & Technology

2009-03-30

Araujo-Pradere, M. Fedrizzi, 2007, Memory effects in the ionosphere storm response. EGU General Assembly , Vienna, Austria Codrescu, M., T.J. Fuller...Strickland, D, 2007: Application of thermospheric general circulation models for space weather operations. J. Adv. Space Res., edited by Schmidtke

Genetics Home Reference: anauxetic dysplasia

MedlinePlus

... one gene that provides instructions for making a protein component of the RNase MRP enzyme complex can also cause anauxetic ... A, Donskoi M, Kenna TJ, Thomas GP, Clark GR, Duncan EL, Brown MA. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as ...

USSR Literature on Air Pollution and Related Occupational ...

EPA Pesticide Factsheets

... On the basis of test results obtained with a model, a screen as described just above ... lf,F1TJ1~~ I / ~~1L .~ ~~ , I /',1 / I / / 2 7 3 6 5 12 II GI .D " -+' . II ...

U.S. EPA, Pesticide Product Label, CHLORINATING TABLETS, 02/18/1989

EPA Pesticide Factsheets

2011-04-21

... "sidu.1 un ~. uinhined • t ill Iiln ACCEPTED puu • Unf~n !! .. - r: ~''!I,!;!~ I!',~~i::"ide. Furl~;"i: _, . -:J!i ',,i " •• ii,h. Act. 01 Uu .. ~.; f~r tj.~ ;'tJ· .. &l.cide ...

Incident Energy Dependence of p t Correlations at RHIC

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

Adams, J.; Aggarwal, M. M.; Ahammed, Z.

2005-10-01

We present results for two-particle transverse momentum correlations, Δp t,iΔ t,j, as a function of event centrality for Au+Au collisions at √( sNN) = 20, 62, 130, and 200 GeV at the Relativistic Heavy Ion Collider. We observe correlations decreasing with centrality that are similar at all four incident energies. The correlations multiplied by the multiplicity density increase with incident energy and the centrality dependence may show evidence of processes such as thermalization, jet production, or the saturation of transverse flow. The square root of the correlations divided by the event-wise average transverse momentum per event shows little or nomore » beam energy dependence and generally agrees with previous measurements at the Super Proton Synchrotron.« less

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.

PubMed

Alimperti, Stella; Mirabella, Teodelinda; Bajaj, Varnica; Polacheck, William; Pirone, Dana M; Duffield, Jeremy; Eyckmans, Jeroen; Assoian, Richard K; Chen, Christopher S

2017-08-15

The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo. Interestingly, we observed a rapid physical withdrawal of mural cells from the endothelium that was accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA activity in the mural cells themselves upon inflammation. Using a system to chemically induce activity in exogenously expressed Rac1 or RhoA within minutes of stimulation, we demonstrated RhoA activation induced loss of mural cell coverage on the endothelium and reduced endothelial barrier function, and this effect was abrogated when Rac1 was simultaneously activated. We further showed that N -cadherin expression in mural cells plays a key role in barrier function, as CRISPR-mediated knockout of N -cadherin in the mural cells led to loss of barrier function, and overexpression of N -cadherin in CHO cells promoted barrier function. In summary, this bicellular model demonstrates the continuous and rapid modulation of adhesive interactions between endothelial and mural cells and its impact on vascular barrier function and highlights an in vitro platform to study the biology of perivascular-endothelial interactions.

The diagnosed mobile limiters of the TJ-II stellarator for plasma boundary studies

NASA Astrophysics Data System (ADS)

de la Cal, E.; Tabarés, F. L.; Tafalla, D.; Cortés, I. García.; Hidalgo, C.; López-Fraguas, A.

TJ-II is a medium size (major radius R=1.5 m, average plasma radius a <0.25 m, on axis magnetic field B=1 T) helical axis stellarator. The main characteristic is its magnetic configuration flexibility, due to the separate control of the different magnetic field coils. The two diagnosed mobile limiters are installed to reduce thermal loads on the thin protection plates of the contacting plasma-chamber regions and to study the plasma edge. First diagnostics are a set of thermocouples, Langmuir probes, H α-detectors and a CCD video camera with different filters (atomic lines of HeI, H α and near IR) looking at the limiter. A method of passive spectroscopy is proposed to map the electron temperature and density over the whole limiter surface by analysing the emission of helium recycling neutrals. It is expected from previous results of other stellarators, that the boundary magnetic topology will have a strong influence on the plasma-wall interaction. The mobile limiters can control the last closed magnetic surface and diagnose the plasma boundary. A qualitative different plasma edge scenario is foreseen between the limiter and the natural island divertor configuration (rational rotational transform inside the limiter radius). Plasma-wall interaction in TJ-II shows very specific features and the optimisation of the plasma edge topology can influence strongly the core plasma parameters. In particular, impurity screening will be a challenge due to the large power density which will be available in future (up to 2 MW NBI for 0.5 s). A safe operation for future high β-plasmas is also required and the mobile limiters should help to remove a fraction of the conductive/convective power.

Transport Study of Egg-Derived Antihypertensive Peptides (LKP and IQW) Using Caco-2 and HT29 Coculture Monolayers.

PubMed

Xu, Qingbiao; Fan, Hongbing; Yu, Wenlin; Hong, Hui; Wu, Jianping

2017-08-30

The objective of this study was to investigate the mechanisms of the transport of antihypertensive tripeptides LKP (Leu-Lys-Pro) and IQW (Ile-Gln-Trp) derived from egg white using a coculture system of Caco-2 and HT29 cell monolayers. The results revealed that LKP and IQW have no cytotoxicity to the cell viability after 2 h incubation, could be transported intact across coculture monolayers (apparent permeability coefficient: (18.11 ± 1.57) × 10 -8 and (13.21 ± 1.12) × 10 -8 cm/s, respectively), and were resistant to peptidase secreted by enterocytes. In addition, the transports were significantly inhibited by dipeptide Gly-Pro (P < 0.05), a competitive substance of peptide transporter 1 (PepT1). The transports from apical to basolateral side were significantly higher than that of the reverse direction (P < 0.05). These results suggest that PepT1 is involved in LKP and IQW transports. The transports were also significantly decreased by theaflavin-3'-O-gallate (P < 0.05), an enhancer of tight junction (TJ) and increased by cytochalasin D (P < 0.05), a disruptor of TJ but not influenced by wortamanin, a transcytosis inhibitor, suggesting that passive paracellular route via TJs is also involved in LKP and IQW transports but not transcytosis. In addition, siRNA was also used to knockdown the expression of PepT1 and significantly inhibited the transport (P < 0.05), confirming that PepT1 is involved in transport process. Therefore, both passive paracellular route via TJ and active route via PepT1 coexist in the transport of antihypertensive LKP and IQW across Caco-2/HT29 coculture monolayers.

Investigation of the role of electron cyclotron resonance heating and magnetic configuration on the suprathermal ion population in the stellarator TJ-II using a luminescent probe

NASA Astrophysics Data System (ADS)

Martínez, M.; Zurro, B.; Baciero, A.; Jiménez-Rey, D.; Tribaldos, V.

2018-02-01

Numerous observation exist of a population of high energetic ions with energies well above the corresponding thermal values in plasmas generated by electron cyclotron resonance (ECR) heating in TJ-II stellarator and in other magnetically confined plasmas devices. In this work we study the impact of ECR heating different conditions (positions and powers) on fast ions escaping from plasmas in the TJ-II stellarator. For this study, an ion luminescent probe operated in counting mode is used to measure the energy distribution of suprathermal ions, in the range from 1 to 30 keV. It is observed that some suprathermal ions characteristics (such as temperature, particle and energy fluxes) are related directly with the gyrotron power and focus position of the heating beam in the plasma. Moreover, it is found that suprathermal ion characteristics vary during a magnetic configuration scan (performed along a single discharge). By investigating the suprathermal ions escaping from plasmas generated using two gyrotrons, one with fixed power and the other modulated (on/off) at low frequency (10 Hz), the de-confinement time of the suprathermal ions can be measured, which is of the order of a few milliseconds (<4 ms). A model that uses a zero-dimensional power balance is used to understand the de-confinement times in terms of the interaction of suprathermal ions and plasma components. This model also can be used to interpret experimental results of energy loss due to suprathermal ions. Finally, observations of increases (peaks) in the population of escaping suprathermal ions, which are well localized at discrete energies, is documented, these peaks being observed in the energy distributions along a discharge.

Transition temperature from band to hopping direct current conduction in crystalline semiconductors with hydrogen-like impurities: Heat versus Coulomb attraction

NASA Astrophysics Data System (ADS)

Poklonski, N. A.; Vyrko, S. A.; Poklonskaya, O. N.; Zabrodskii, A. G.

2011-12-01

For nondegenerate bulk semiconductors, we have used the virial theorem to derive an expression for the temperature Tj of the transition from the regime of "free" motion of electrons in the c-band (or holes in the υ-band) to their hopping motion between donors (or acceptors). Distribution of impurities over the crystal was assumed to be of the Poisson type, while distribution of their energy levels was assumed to be of the Gaussian type. Our conception of the virial theorem implementation is that the transition from the band-like conduction to hopping conduction occurs when the average kinetic energy of an electron in the c-band (hole in the υ-band) is equal to the half of the absolute value of the average energy of the Coulomb interaction of an electron (hole) with the nearest neighbor ionized donor (acceptor). Calculations of Tj according to our model agree with experimental data for crystals of Ge, Si, diamond, etc. up to the concentrations of a hydrogen-like impurity, at which the phase insulator-metal transition (Mott transition) occurs. Under the temperature Th ≈ Tj /3, when the nearest neighbor hopping conduction via impurity atoms dominates, we obtained expressions for the electrostatic field screening length Λh in the Debye-Hückel approximation, taking into account a nonzero width of the impurity energy band. It is shown that the measurements of quasistatic capacitance of the semiconductor in a metal-insulator-semiconductor structure in the regime of the flat bands at the temperature Th allow to determine the concentration of doping impurity or its compensation ratio by knowing Λh.

Inter-machine validation study of neoclassical transport modelling in medium- to high-density stellarator-heliotron plasmas

NASA Astrophysics Data System (ADS)

Dinklage, A.; Yokoyama, M.; Tanaka, K.; Velasco, J. L.; López-Bruna, D.; Beidler, C. D.; Satake, S.; Ascasíbar, E.; Arévalo, J.; Baldzuhn, J.; Feng, Y.; Gates, D.; Geiger, J.; Ida, K.; Isaev, M.; Jakubowski, M.; López-Fraguas, A.; Maaßberg, H.; Miyazawa, J.; Morisaki, T.; Murakami, S.; Pablant, N.; Kobayashi, S.; Seki, R.; Suzuki, C.; Suzuki, Y.; Turkin, Yu.; Wakasa, A.; Wolf, R.; Yamada, H.; Yoshinuma, M.; LHD Exp. Group; TJ-II Team; W7-AS Team

2013-06-01

A comparative study of energy transport for medium- to high-density discharges in the stellarator-heliotrons TJ-II, W7-AS and LHD is carried out. The specific discharge parameters are chosen to apply a recently concluded benchmarking study of neoclassical (NC) transport coefficients (Beidler et al 2011 Nucl. Fusion 51 076001) to perform this validation study. In contrast to previous experiments at low densities for which electron transport was predominant (Yokoyama et al 2007 Nucl. Fusion 47 1213), the current discharges also exhibit significant ion energy transport. As it affects the energy transport in 3D devices, the ambipolar radial electric field is addressed as well. For the discharges described, ion-root conditions, i.e. a small negative radial electric field were found. The energy transport in the peripheral region cannot be explained by NC theory. Within a ‘core region’(r/a < 1/2 ˜ 2/3), the predicted NC energy fluxes comply with experimental findings for W7-AS. For TJ-II, compliance in the core region is found for the particle transport and the electron energy transport. For the specific LHD discharges, the core energy transport complied with NC theory except for the electron energy transport in the inward-shifted magnetic configuration. The NC radial electric field tends to agree with experimental results for all devices but is measured to be more negative in the core of both LHD and TJ-II. As a general observation, the energy confinement time approaches the gyro-Bohm-type confinement scaling ISS04 (Yamada et al 2005 Nucl. Fusion 45 1684). This work is carried out within the International Stellarator-Heliotron Profile Database (www.ipp.mpg.de/ISS and http://ishpdb.nifs.ac.jp/index.html).

The Electron Bernstein Waves Heating Project In The TJ-II Stellarator

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

Fernandez, A.; Cappa, A.; Castejon, F.

2007-09-28

TJ-II is a middle sized flexible Heliac operating in Madrid, whose plasmas are created and heated by ECRH via two 300 kW gyrotrons at second harmonic X-mode (53.2 GHz). Neutral beam injection is used for second phase heating. Since the cut off density for the 2nd harmonic X-mode (n{sub c} = 1.7x10 {sup 19} m{sup -3}) is reached during NBI, EBWs are considered both for providing additional heating after NBI switch on and to perform kinetic studies in high-density plasmas. Previous work has shown that the most suitable scheme for launching EBWs in TJ-II is O-X-B mode conversion, which hasmore » acceptable heating efficiency for central densities above 1.2x10{sup 19} m{sup -3}, with an operating frequency of 28 GHz. In this work, the most relevant theoretical calculations are presented, including the relativistic effects both in ray trajectory and absorption, as well as the results of the optimization of the beam parameters that provide the maximum O-X conversion efficiency at the critical layer. A system based on a 28 GHz-100 ms diode gyrotron will be used to deliver 300 kW through a corrugated waveguide. The microwave beam is directed and focused by a steerable mirror located inside the vacuum vessel. A diagnostic for measuring the EBW emission has been designed and tested on the bench. It uses a section of corrugated waveguide and a glass lens to focus the emission from the plasma into the aperture of a dual polarized quad-ridged horn. It will allow us to determine the EBW mode conversion efficiency, and also provides an indication of the electron temperature evolution in overdense plasmas.« less

Small synthetic peptides homologous to segments of the first external loop of occludin impair tight junction resealing.

PubMed

Lacaz-Vieira, F; Jaeger, M M; Farshori, P; Kachar, B

1999-04-01

This study shows that resealing of opened tight junctions (TJs) is impaired by interaction with oligopeptides homologous to the external domain of chick occludin. The experiments were carried out with confluent A6 cell monolayers grown on collagen supports under stable transepithelial electrical resistance (TER). The monolayers were bathed on the apical side with a 75 mm KCl solution and on the basolateral side by NaCl-Ringer's solution. TJ opening was induced by basolateral Ca2+ removal and was characterized by a marked drop of TER. The reintroduction of Ca2+ triggered junction resealing as indicated by an elevation of TER to control values. Custom-made peptides SNYYGSGLSY (corresponding to the residues 100 to 109) and SNYYGSGLS (residues 100 to 108), homologous to segments of the first external loop of chick occludin molecule, impaired junction resealing when the peptides were included in the apical bathing fluid (concentrations in the range of 0.5 to 1.5 mg/ml). Peptide removal from the apical solution usually triggered a slow recovery of TER, indicating a slow recovery of the TJ seal. Changes in localization of ZO-1, a cytoplasmic protein that underlies the membrane at the TJs, were evaluated immunocytochemically following Ca2+ removal and reintroduction. The presence or absence of the oligopeptides showed no influence on the pattern of change of ZO-1 localization. These observations support the hypothesis that the TJ seal results from the interaction of specific homologous segments of occludin on the surface of adjacent cells. Additionally, our results show that small peptides homologous to segments of the occludin first external loop can be used as specific reagents to manipulate the permeability of tight junctions.

Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats.

PubMed

Molina-Jijón, Eduardo; Rodríguez-Muñoz, Rafael; González-Ramírez, Ricardo; Namorado-Tónix, Carmen; Pedraza-Chaverri, José; Reyes, Jose L

2017-01-01

Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed. In diabetic rats, the serum ALD levels were increased, and SPL-treatment did not have effect on these levels or in hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats. Glomerular damage, evaluated by nephrin and Wilm's tumor 1 (WT1) protein expressions, and proximal tubular damage, evaluated by kidney injury molecule 1 (Kim-1) and heat shock protein 72 kDa (Hsp72) expressions, were ameliorated by SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and occludin in proximal tubules by decreasing oxidative stress, evaluated by superoxide anion (O2●-) production, and oxidative stress markers. In distal tubules, SPL ameliorated increase in mRNA, protein expression, and phosphorylation in threonine residues of claudin-4 and -8, through a serum and glucocorticoid-induced kinase 1 (SGK1), and with-no-lysine kinase 4 (WNK4) signaling pathway. In conclusion, this is the first study that demonstrates that ALD modulates the expression of renal TJ proteins in diabetes, and that the blockade of its actions with SPL, may be a promising therapeutic strategy to prevent alterations of TJ proteins in diabetic nephropathy.

Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport

PubMed Central

Wulfmeyer, Vera Christine; Drewell, Hoora; Mutig, Kerim; Hou, Jianghui; Breiderhoff, Tilman; Müller, Dominik; Fromm, Michael; Bleich, Markus; Günzel, Dorothee

2017-01-01

The thick ascending limb (TAL) of Henle’s loop drives paracellular Na+, Ca2+, and Mg2+ reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing (trans) plasma membranes. The claudins Cldn10b, -16, and -19 facilitate cation reabsorption in the TAL, and their absence leads to a severe disturbance of renal ion homeostasis. We combined electrophysiological measurements on microperfused mouse TAL segments with subsequent analysis of claudin expression by immunostaining and confocal microscopy. Claudin interaction properties were examined using heterologous expression in the TJ-free cell line HEK 293, live-cell imaging, and Förster/FRET. To reveal determinants of interaction properties, a set of TAL claudin protein chimeras was created and analyzed. Our main findings are that (i) TAL TJs show a mosaic expression pattern of either cldn10b or cldn3/cldn16/cldn19 in a complex; (ii) TJs dominated by cldn10b prefer Na+ over Mg2+, whereas TJs dominated by cldn16 favor Mg2+ over Na+; (iii) cldn10b does not interact with other TAL claudins, whereas cldn3 and cldn16 can interact with cldn19 to form joint strands; and (iv) further claudin segments in addition to ECS2 are crucial for trans interaction. We suggest the existence of at least two spatially distinct types of paracellular channels in TAL: a cldn10b-based channel for monovalent cations such as Na+ and a spatially distinct site for reabsorption of divalent cations such as Ca2+ and Mg2+. PMID:28028216

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

PubMed

Inoue, Takuya; Takagi, Hironori; Owada, Yuki; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Yokouchi, Hiroshi; Kanazawa, Kenya; Ohbuchi, Katsuya; Fukushima, Takahisa; Munakata, Mitsuru; Suzuki, Hiroyuki

2017-10-18

Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S

2012-12-13

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

A Numerical Comparison of Barrier and Modified Barrier Methods for Large-Scale Bound-Constrained Optimization

NASA Technical Reports Server (NTRS)

Nash, Stephen G.; Polyak, R.; Sofer, Ariela

1994-01-01

When a classical barrier method is applied to the solution of a nonlinear programming problem with inequality constraints, the Hessian matrix of the barrier function becomes increasingly ill-conditioned as the solution is approached. As a result, it may be desirable to consider alternative numerical algorithms. We compare the performance of two methods motivated by barrier functions. The first is a stabilized form of the classical barrier method, where a numerically stable approximation to the Newton direction is used when the barrier parameter is small. The second is a modified barrier method where a barrier function is applied to a shifted form of the problem, and the resulting barrier terms are scaled by estimates of the optimal Lagrange multipliers. The condition number of the Hessian matrix of the resulting modified barrier function remains bounded as the solution to the constrained optimization problem is approached. Both of these techniques can be used in the context of a truncated-Newton method, and hence can be applied to large problems, as well as on parallel computers. In this paper, both techniques are applied to problems with bound constraints and we compare their practical behavior.

Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

PubMed Central

Erickson, Michelle A.

2018-01-01

Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contributes to physiologic processes, adaptive responses, and disease states. In this review, we discuss the highly specialized features of brain barriers that regulate neuroimmune communication in health and disease. In section I, we discuss the concept of immune privilege, provide working definitions of brain barriers, and outline the historical work that contributed to the understanding of CNS barrier functions. In section II, we discuss the unique anatomic, cellular, and molecular characteristics of the vascular blood–brain barrier (BBB), blood–cerebrospinal fluid barrier, and tanycytic barriers that confer their functions as neuroimmune interfaces. In section III, we consider BBB-mediated neuroimmune functions and interactions categorized as five neuroimmune axes: disruption, responses to immune stimuli, uptake and transport of immunoactive substances, immune cell trafficking, and secretions of immunoactive substances. In section IV, we discuss neuroimmune functions of CNS barriers in physiologic and disease states, as well as pharmacological interventions for CNS diseases. Throughout this review, we highlight many recent advances that have contributed to the modern understanding of CNS barriers and their interface functions. PMID:29496890

[Recent studies on corneal epithelial barrier function].

PubMed

Liu, F F; Li, W; Liu, Z G; Chen, W S

2016-08-01

Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635).

Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study.

PubMed

Hammami, I; Nahdi, A; Atig, F; El May, A; El May, M V

2016-12-01

Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed. © 2016 Blackwell Verlag GmbH.

Forty Years Tomorrow: A Teacher Looks Back.

ERIC Educational Resources Information Center

Stern, Adele

1980-01-01

Reviews experiences during the author's 40 years as a teacher. Indicates changes that have occurred over the years but notes one constant: special teachers who are proud of what they do know how important they are and accept their mission with stamina and enthusiasm. (TJ)

Molecular Machine-Based Active Plasmonics

DTIC Science & Technology

2011-07-21

C. S. Lin, M. Lu, T. Gao, T.J. Huang), J. Appl. Phys. 2010, 108, 043514. 33. Ordered Au nanodisk and nanohole arrays: fabrication and applications...Stoddart), J. Am. Chem. Soc. 2011, 133, 4538–4547. 41. Frequency-addressed tunable transmission in optically thin metallic nanohole arrays with

Characterizing Munitions Constituents from Artillery and Small Arms Ranges

DTIC Science & Technology

2011-05-01

SCALE LEGEND D QUATERNARY ALLUVIUM D ~b~.’rr~EfoER~~o D ~~~CF~ri’~!R8~ EOCENE D ~lci’~~~~~b~~~<f~N~UARO and ~PREDOMINANT FOREST t::J WETlANDS

Creamer gives Skvortsov a Haircut in Node 2

NASA Image and Video Library

2010-05-09

ISS023-E-036484 (9 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, trims Russian cosmonaut Alexander Skvortsov's hair in the Harmony node of the International Space Station. Creamer used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Creamer gives Skvortsov a Haircut in Node 2

NASA Image and Video Library

2010-05-09

ISS023-E-036485 (9 May 2010) --- NASA astronaut T.J. Creamer, Expedition 23 flight engineer, trims Russian cosmonaut Alexander Skvortsov's hair in the Harmony node of the International Space Station. Creamer used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Open Up Your Newspaper with Advertising.

ERIC Educational Resources Information Center

Spielberger, Ronald E.

1980-01-01

Suggests ways the business office of a student newspaper can ease the conflicts between news and advertising space, including: raising advertising rates, selling ads only in uniform sizes, charging extra for premium space, selling special features, and selling space around a monthly calendar of special events. (TJ)

INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.

EPA Science Inventory

INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.
A.S. Bale*; P.J. Bushnell; C.A. Meacham; T.J. Shafer
Neurotoxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC, USA
Toluene (TOL...

U.S. EPA, Pesticide Product Label, , 01/30/1985

EPA Pesticide Factsheets

2011-04-14

... est.:u:an'S S ..... re y,U:'> I.. :tj" ,""l!oiI:, Zees J.(:.. 111 :.1".;; eL; •• \\'t:·-rt :'") :1. ~'J.Jt\\::--k·~~" . I;-.~·r-,r.·'-lktht'r .\\,';j ".i;\\:., r! ••.• d. ... ...

Improving Performance Efficiency in the Warfighter

DTIC Science & Technology

2007-12-01

knockout teaches us about GnRH activity: hypogonadal mice and neuronal grafts. Hormones and Behavior 31:212-220. 20. Wu, T.J., M.J. Gibson, A.J...Silverman (1996) FOS expression in grafted gonadotropin- releasing hormone neurons in the hypogonadal mouse: mating and steroid induction. Journal of

Nitrogen isotope and trace metal analyses from the Mingolsheim core (Germany): Evidence for redox variations across the Triassic-Jurassic boundary

NASA Astrophysics Data System (ADS)

Quan, Tracy M.; van de Schootbrugge, Bas; Field, M. Paul; Rosenthal, Yair; Falkowski, Paul G.

2008-06-01

The Triassic-Jurassic (T-J) boundary was one of the largest but least understood mass extinction events in the Phanerozoic. We measured bulk organic nitrogen and carbon isotopes and trace metal concentrations from a core near Mingolsheim (Germany) to infer paleoenvironmental conditions associated with this event. Poorly fossiliferous claystones across the boundary have relatively low δ15N values and low concentrations of redox-sensitive elements, characteristic of an oxic environment with significant terrestrial input. The Early Jurassic features enrichment in δ15N coincident with high redox-sensitive element concentrations, indicating an increase in water column denitrification and decreased oxygen concentrations. These redox state variations are concordant with shifts in abundance and species composition in terrestrial and marine microflora. We propose that the mass extinction at the T-J boundary was caused by a series of events resulting in a long period of stratification, deep-water hypoxia, and denitrification in this region of the Tethys Ocean basin.

On the axisymmetric stability of heated supersonic round jets

PubMed Central

2016-01-01

We perform an inviscid, spatial stability analysis of supersonic, heated round jets with the mean properties assumed uniform on either side of the jet shear layer, modelled here via a cylindrical vortex sheet. Apart from the hydrodynamic Kelvin–Helmholtz (K–H) wave, the spatial growth rates of the acoustically coupled supersonic and subsonic instability waves are computed for axisymmetric conditions (m=0) to analyse their role on the jet stability, under increased heating and compressibility. With the ambient stationary, supersonic instability waves may exist for any jet Mach number Mj≥2, whereas the subsonic instability waves, in addition, require the core-to-ambient flow temperature ratio Tj/To>1. We show, for moderately heated jets at Tj/To>2, the acoustically coupled instability modes, once cut on, to govern the overall jet stability with the K–H wave having disappeared into the cluster of acoustic modes. Sufficiently high heating makes the subsonic modes dominate the jet near-field dynamics, whereas the supersonic instability modes form the primary Mach radiation at far field. PMID:27274691

Audiovisual communication and therapeutic jurisprudence: Cognitive and social psychological dimensions.

PubMed

Feigenson, Neal

2010-01-01

The effects of audiovisual communications on the emotional and psychological well-being of participants in the legal system have not been previously examined. Using as a framework for analysis what Slobogin (1996) calls internal balancing (of therapeutic versus antitherapeutic effects) and external balancing (of therapeutic jurisprudence [TJ] effects versus effects on other legal values), this brief paper discusses three examples that suggest the complexity of evaluating courtroom audiovisuals in TJ terms. In each instance, audiovisual displays that are admissible based on their arguable probative or explanatory value - day-in-the-life movies, victim impact videos, and computer simulations of litigated events - might well reduce stress and thus improve the psychological well-being of personal injury plaintiffs, survivors, and jurors, respectively. In each situation, however, other emotional and cognitive effects may prove antitherapeutic for the target or other participants, and/or may undermine other important values including outcome accuracy, fairness, and even the conception of the legal decision maker as a moral actor. Copyright © 2010 Elsevier Ltd. All rights reserved.

Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants.

PubMed

Simal-Gándara, J; Sarria-Vidal, M; Koorevaar, A; Rijk, R

2000-08-01

The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.

A Lagrange multiplier and Hopfield-type barrier function method for the traveling salesman problem.

PubMed

Dang, Chuangyin; Xu, Lei

2002-02-01

A Lagrange multiplier and Hopfield-type barrier function method is proposed for approximating a solution of the traveling salesman problem. The method is derived from applications of Lagrange multipliers and a Hopfield-type barrier function and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the method searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that lower and upper bounds on variables are always satisfied automatically if the step length is a number between zero and one. At each iteration, the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the method converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the method seems more effective and efficient than the softassign algorithm.

A globally convergent Lagrange and barrier function iterative algorithm for the traveling salesman problem.

PubMed

Dang, C; Xu, L

2001-03-01

In this paper a globally convergent Lagrange and barrier function iterative algorithm is proposed for approximating a solution of the traveling salesman problem. The algorithm employs an entropy-type barrier function to deal with nonnegativity constraints and Lagrange multipliers to handle linear equality constraints, and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the algorithm searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that the nonnegativity constraints are always satisfied automatically if the step length is a number between zero and one. At each iteration the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the algorithm converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the algorithm seems more effective and efficient than the softassign algorithm.

Standards for the Protection of Skin Barrier Function.

PubMed

Giménez-Arnau, Ana

2016-01-01

The skin is a vital organ, and through our skin we are in close contact with the entire environment. If we lose our skin we lose our life. The barrier function of the skin is mainly driven by the sophisticated epidermis in close relationship with the dermis. The epidermal epithelium is a mechanically, chemically, biologically and immunologically active barrier submitted to continuous turnover. The barrier function of the skin needs to be protected and restored. Its own physiology allows its recovery, but many times this is not sufficient. This chapter is focused on the standards to restore, treat and prevent barrier function disruption. These standards were developed from a scientific, academic and clinical point of view. There is a lack of standardized administrative recommendations. Still, there is a walk to do that will help to reduce the social and economic burden of diseases characterized by an abnormal skin barrier function. © 2016 S. Karger AG, Basel.

Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases

PubMed Central

Surapisitchat, James

2014-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction. PMID:21695641

Regulation of endothelial barrier function by cyclic nucleotides: the role of phosphodiesterases.

PubMed

Surapisitchat, James; Beavo, Joseph A

2011-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction.

U.S. EPA, Pesticide Product Label, , 01/12/1973

EPA Pesticide Factsheets

2011-04-21

, #J ;j .i. I'; : I :l :. j :qJ $-J =':ITI'it j', ,~~ L;'tf1 T'J ;-~'tt"n : r~rf)\\ "l P"h,' ''' n 11:1" t'I'~ .,.y~ . ~ r; ~',, _ •.... f "",) . 1:' 'It(F.~~ ;~R f:!i ~~-'- ...

Light Scattering by Marine Particles: Modeling with Non-spherical Shapes

DTIC Science & Technology

2011-09-30

coccoliths detached from Emiliania huxleyi, Limnology and Oceanography, 46, 1438−1454, 2001. Gordon, H.R., T.J. Smyth, W.M. Balch, and G.C. Boynton...Light scattering by coccoliths detached from Emiliania huxleyi, Applied Optics, (2009). PUBLICATIONS H.R. Gordon, Light scattering by randomly

Arctigenin from Fructus Arctii (Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

PubMed Central

Shin, Hee Soon; Jung, Sun Young; Back, Su Yeon; Do, Jeong-Ryong; Shon, Dong-Hwa

2015-01-01

Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function. PMID:26550018

The impact of aging on epithelial barriers.

PubMed

Parrish, Alan R

2017-10-02

The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space. With the increased focus on age-dependent alterations in organ structure and function, there is an emerging interest in the impact of age on epithelial barriers. This review will focus on the impact of aging on the epithelial barrier of several organs, including the skin, lung, gastrointestinal tract and the kidney, at a structural and functional level.

Homoclinic orbits and critical points of barrier functions

NASA Astrophysics Data System (ADS)

Cannarsa, Piermarco; Cheng, Wei

2015-06-01

We interpret the close link between the critical points of Mather's barrier functions and minimal homoclinic orbits with respect to the Aubry sets on {{T}}n . We also prove a critical point theorem for barrier functions and the existence of such homoclinic orbits on {{T}}2 as an application.

Dietary fibre-based SCFA mixtures promote both protection and repair of intestinal epithelial barrier function in a Caco-2 cell model.

PubMed

Chen, Tingting; Kim, Choon Young; Kaur, Amandeep; Lamothe, Lisa; Shaikh, Maliha; Keshavarzian, Ali; Hamaker, Bruce R

2017-03-22

Impaired gut barrier function plays an important role in the development of many diseases such as obesity, inflammatory bowel disease, and in HIV infection. Dietary fibres have been shown to improve intestinal barrier function through their fermentation products, short chain fatty acids (SCFAs), and the effects of individual SCFAs have been studied. Here, different SCFA mixtures representing possible compositions from fibre fermentation products were studied for protective and reparative effects on intestinal barrier function. The effect of fermentation products from four dietary fibres, i.e. resistant starch, fructooligosaccharides, and sorghum and corn arabinoxylan (varying in their branched structure) on barrier function was positively correlated with their SCFA concentration. Pure SCFA mixtures of various concentrations and compositions were tested using a Caco-2 cell model. SCFAs at a moderate concentration (40-80 mM) improved barrier function without causing damage to the monolayer. In a 40 mM SCFA mixture, the butyrate proportion at 20% and 50% showed both a protective and a reparative effect on the monolayer to disrupting agents (LPS/TNF-α) applied simultaneously or prior to the SCFA mixtures. Relating this result to dietary fibre selection, slow fermenting fibres that deliver appropriate concentrations of SCFAs to the epithelium with a high proportion of butyrate may improve barrier function.

Kids and Cults: Who Joins, and Why.

ERIC Educational Resources Information Center

Swope, George W.

1980-01-01

States that the social conditions that produce cults are favorable today and that those young people who are attracted to cult membership are idealistic, innocent, inquisitive, independent, identity-seeking, insecure, and vulnerable. Suggests that educators can help students be aware of the seriousness of the problems cults can cause. (TJ)

Justice-Sensitive Education: The Implications of Transitional Justice Mechanisms for Teaching and Learning

ERIC Educational Resources Information Center

Davies, Lynn

2017-01-01

This article introduces the notion of "justice-sensitive education"--derived from the ideals and practices of transitional justice (TJ) in countries emerging from conflict. It describes three mechanisms for this: structural reforms (relating to inequity and division); curriculum change (the treatment of history, human rights and…

The Use of Tympanometry to Detect Aerotitis Media in Hypobaric Chamber Operations

DTIC Science & Technology

1990-03-01

1972; 81:1654-78. for transient pathologic conditions of the middle ear 3. Brookler KH. Etiologic factors in non-supperotive otitis media . such as upper...Bluestone CD, Fria TJ,. Stool SE, Quinter CB, Sabo post-flight residual pathological conditions. These DL. Identification of otitis media with

U.S. EPA, Pesticide Product Label, , 07/13/1983

EPA Pesticide Factsheets

2011-04-21

... 1'1;. '. , Net \\ ight __ _ MIT ICI f!?G'~n~le-;':r~fo~?n~/~on~~~~a~e~le ·ELq\\VJ~~r t~ ttl{' F!·,~pr:tl In~f'('tj("idE'. Il'tmgicidi. i~.'l H(~!t'nti('id(· Act ...

U.S. EPA, Pesticide Product Label, , 09/28/1983

EPA Pesticide Factsheets

2011-04-14

... lind HI"knti,·.,~ l~'\\ &1 Dtpf'mcd. I.,r t1, l'" ,tj .... ,ii{ ... Ul#-'~~U I), CtI.,If ... ~1 c' .... Q. '"fJ 0.''"'1.-(.01,1 .ntcI •• rod#' II(..JI ettec1lwe ';au",,1 SIa;."flo)(oec .. ...

MODULATION OF HYPOXIC PULMONARY VASOCONSTRICTION BY ERYTHROCYTIC NITRIC OXIDE

EPA Science Inventory

Abstract
American Heart Association 2001

Modulation of Hypoxic Pulmonary Vasoconstriction by Erythrocytic NO
McMahon TJ1, Gow AJ1, Huang YCT4, Stamler JS1,2,3
Departments of Medicine1 and Biochemistry2, and Howard Hughes Medical Institute3,
Duke University Med...

Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

EPA Science Inventory

EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

Human Systems Integration and Automation Issues in Small Unmanned Aerial Vehicles

DTIC Science & Technology

2004-10-01

display (HMD) bounce. Motion sickness occurs in these situations due to a combination of actual motion plus “ cybersickness ” (McCauley and Sharkey...Research Laboratory. McCauley, M.E. and Sharkey, T.J. (Summer 1992). Cybersickness : Perception of Self-Motion in Virtual Environments. Presence

Workplace Education Initiative: Year Two Observations.

ERIC Educational Resources Information Center

Sperazi, Laura; Astrein, Bruce

Site visits to 17 workplace education projects funded in the second year of the Massachusetts Workplace Education Initiative are reported for year 1 and year 2 projects. The year one projects are as follows: EASCO Handtool Company (Springfield), T.J. Maxx Distribution Center (Worcester), laundry workers (Boston/Lynn), AT&T (Lawrence), and…

TV News Analysis Project Motivates Broadcast Class.

ERIC Educational Resources Information Center

Smith, James R.

1980-01-01

Describes the use of content analysis by a journalism class in studying television news. Indicates that the method is flexible, generates familiarity with quantitative approaches to the analysis of broadcast journalism, can result in increased awareness of the complexity of the broadcast news medium, and increases student motivation. (TJ)

Theory of superconductivity and spin excitations in cuprates

NASA Astrophysics Data System (ADS)

Plakida, Nikolay M.

2018-06-01

A microscopic theory of high-temperature superconductivity in strongly correlated systems as cuprates is presented. The two-subband extended Hubbard model is considered where the intersite Coulomb repulsion and electron-phonon interaction are taken into account. The low-energy spin excitations are considered within the t-J model.

Metal Matrix Superconductor Composites for SMES-Driven, Ultra High Power BEP Applications: Part 2

NASA Astrophysics Data System (ADS)

Gross, Dan A.; Myrabo, Leik N.

2006-05-01

A 2.5 TJ superconducting magnetic energy storage (SMES) design presentation is continued from the preceding paper (Part 1) with electromagnetic and associated stress analysis. The application of interest is a rechargeable power-beaming infrastructure for manned microwave Lightcraft operations. It is demonstrated that while operational performance is within manageable parameter bounds, quench (loss of superconducting state) imposes enormous electrical stresses. Therefore, alternative multiple toroid modular configurations are identified, alleviating simultaneously all excessive stress conditions, operational and quench, in the structural, thermal and electromagnetic sense — at some reduction in specific energy, but presenting programmatic advantages for a lengthy technology development, demonstration and operation schedule. To this end several natural units, based on material properties and operating parameters are developed, in order to identify functional relationships and optimization paths more effectively.

Symmetry analysis of a model for the exercise of a barrier option

NASA Astrophysics Data System (ADS)

O'Hara, J. G.; Sophocleous, C.; Leach, P. G. L.

2013-09-01

A barrier option takes into account the possibility of an unacceptable change in the price of the underlying stock. Such a change could carry considerable financial loss. We examine one model based upon the Black-Scholes-Merton Equation and determine the functional forms of the barrier function and rebate function which are consistent with a solution of the underlying evolution partial differential equation using the Lie Theory of Extended Groups. The solution is consistent with the possibility of no rebate and the barrier function is very similar to one adopted on an heuristic basis.

Schottky barrier amorphous silicon solar cell with thin doped region adjacent metal Schottky barrier

DOEpatents

Carlson, David E.; Wronski, Christopher R.

1979-01-01

A Schottky barrier amorphous silicon solar cell incorporating a thin highly doped p-type region of hydrogenated amorphous silicon disposed between a Schottky barrier high work function metal and the intrinsic region of hydrogenated amorphous silicon wherein said high work function metal and said thin highly doped p-type region forms a surface barrier junction with the intrinsic amorphous silicon layer. The thickness and concentration of p-type dopants in said p-type region are selected so that said p-type region is fully ionized by the Schottky barrier high work function metal. The thin highly doped p-type region has been found to increase the open circuit voltage and current of the photovoltaic device.

Flexible barrier film, method of forming same, and organic electronic device including same

DOEpatents

Blizzard, John; Tonge, James Steven; Weidner, William Kenneth

2013-03-26

A flexible barrier film has a thickness of from greater than zero to less than 5,000 nanometers and a water vapor transmission rate of no more than 1.times.10.sup.-2 g/m.sup.2/day at 22.degree. C. and 47% relative humidity. The flexible barrier film is formed from a composition, which comprises a multi-functional acrylate. The composition further comprises the reaction product of an alkoxy-functional organometallic compound and an alkoxy-functional organosilicon compound. A method of forming the flexible barrier film includes the steps of disposing the composition on a substrate and curing the composition to form the flexible barrier film. The flexible barrier film may be utilized in organic electronic devices.

War experiences, general functioning and barriers to care among former child soldiers in Northern Uganda: the WAYS study.

PubMed

Amone-P'Olak, Kennedy; Jones, Peter; Meiser-Stedman, Richard; Abbott, Rosemary; Ayella-Ataro, Paul Stephen; Amone, Jackson; Ovuga, Emilio

2014-12-01

Exposure to war is associated with considerable risks for long-term mental health problems (MHP) and poor functioning. Yet little is known about functioning and mental health service (MHS) use among former child soldiers (FCS). We assessed whether different categories of war experiences predict functioning and perceived need for, sources of and barriers to MHS among FCS. Data were drawn from an on-going War-affected Youths (WAYS) cohort study of FCS in Uganda. Participants completed questionnaires about war experiences, functioning and perceived need for, sources of and barriers to MHS. Regression analyses and parametric tests were used to assess between-group differences. Deaths, material losses, threat to loved ones and sexual abuse significantly predicted poor functioning. FCS who received MHS function better than those who did not. Females reported more emotional and behavioural problems and needed MHS more than males. FCS who function poorly indicated more barriers to MHS than those who function well. Stigma, fear of family break-up and lack of health workers were identified as barriers to MHS. Various war experiences affect functioning differently. A significant need for MHS exists amidst barriers to MHS. Nevertheless, FCS are interested in receiving MHS and believe it would benefit them. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of polysaccharide from mycelia of Ganoderma lucidum on intestinal barrier functions of rats.

PubMed

Jin, Mingliang; Zhu, Yimin; Shao, Dongyan; Zhao, Ke; Xu, Chunlan; Li, Qi; Yang, Hui; Huang, Qingsheng; Shi, Junling

2017-01-01

The intestinal mucosal barriers play essential roles not only in the digestion and absorption of nutrients, but also the innate defense against most intestinal pathogens. In the present study, polysaccharide from the mycelia of Ganoderma lucidum was given via oral administration to rats (100mg/kg body weight, 21days) to investigate its effects on intestinal barrier functions, including the mechanical barrier, immunological barrier and biological barrier function. It was found that the polysaccharide administration could significantly up-regulate the expression of occludin, nuclear factor-κB p65 (NF-κB p65) and secretory immunoglobulin A (SIgA) in ileum, markedly improve the levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and IL-4, and decrease the level of diamine oxidase (DAO) in serum. Meanwhile, rats from the polysaccharide group showed significant higher microbiota richness in cecum as reflected by the Chao 1 index compared with the control group. Moreover, the polysaccharide decreased the Firmicutes-to-Bacteroidetes ratio. Our results indicated that the polysaccharide from the mycelia of G. lucidum might be used as functional agent to regulate the intestinal barrier functions. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal Barrier Function in Gastrointestinal Disorders.

PubMed

Farré, Ricard; Vicario, María

2017-01-01

There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.

[Advance in studies on food allergy mechanism based on gut barrier].

PubMed

Wang, Juan-hong; Li, Huan-zhou; Li, Meng; Pan, Su-hua

2015-04-01

Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.

An oncological view on the blood-testis barrier.

PubMed

Bart, Joost; Groen, Harry J M; van der Graaf, Winette T A; Hollema, Harry; Hendrikse, N Harry; Vaalburg, Willem; Sleijfer, Dirk T; de Vries, Elisabeth G E

2002-06-01

The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular wall, connected together with narrow tight junctions, and a myoid-cell layer around the seminiferous tubule. Second, an efflux-pump barrier that contains P-glycoprotein in the luminal capillary endothelium and on the myoid-cell layer; and multidrug-resistance associated protein 1 located basolaterally on Sertoli cells. Third, an immunological barrier, consisting of Fas ligand on Sertoli cells. Inhibition of P-glycoprotein function offers the opportunity to increase the delivery of cytotoxic drugs to the testis. In the future, visualisation of function in the blood-testis barrier may also be helpful to identify groups of patients in whom testis conservation is safe or to select drugs that are less harmful to fertility.

43 CFR 3186.1-2 - Model Exhibit “B”.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Pen 50% Max Pen 1% Frost Oil Co. 100%. Sec. 28: All Sam Small 50% Sam Small 1% 4 Sec. 27: All 1,280.00... T.J. Cook: 100% W.W. Smith 100% Sam Spade 1% W.W. Smith 100%. 10 Sec. 34: All 640.00 6-30-82 A.A...

43 CFR 3186.1-2 - Model Exhibit “B”.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Pen 50% Max Pen 1% Frost Oil Co. 100%. Sec. 28: All Sam Small 50% Sam Small 1% 4 Sec. 27: All 1,280.00... T.J. Cook: 100% W.W. Smith 100% Sam Spade 1% W.W. Smith 100%. 10 Sec. 34: All 640.00 6-30-82 A.A...

43 CFR 3186.1-2 - Model Exhibit “B”.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Pen 50% Max Pen 1% Frost Oil Co. 100%. Sec. 28: All Sam Small 50% Sam Small 1% 4 Sec. 27: All 1,280.00... T.J. Cook: 100% W.W. Smith 100% Sam Spade 1% W.W. Smith 100%. 10 Sec. 34: All 640.00 6-30-82 A.A...

43 CFR 3186.1-2 - Model Exhibit “B”.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Pen 50% Max Pen 1% Frost Oil Co. 100%. Sec. 28: All Sam Small 50% Sam Small 1% 4 Sec. 27: All 1,280.00... T.J. Cook: 100% W.W. Smith 100% Sam Spade 1% W.W. Smith 100%. 10 Sec. 34: All 640.00 6-30-82 A.A...

Performance Study of Two-Stage-To-Orbit Reusable Launch Vehicle Propulsion Alternatives

DTIC Science & Technology

2004-03-01

100476 101198 102053 102548 103152 Wprop2 (lbf) 652552 663896 670744 677276 683392 688966 694527 699642 Wpay (lbf) 24961 25092 25193 25223 25265...Wpay (lbf) 24961 25092 25193 25223 25265 25501 25378 25413 Total Inert Weight (lbf) 182497 171036 164045 157484 151325 145515 140076 134927 TJ-Rkt2

Selective AAK1 and GAK Inhibitors for Combating Dengue and Other Emerging Viral Infections

DTIC Science & Technology

2017-10-01

Hemorrhagic Fever Viruses, Santa Fe, New Mexico , December 2016. 7. PARTICIPANTS & OTHER COLLABORATING ORGANIZATIONS Individuals who have worked on the... varicella -zoster virus glycoprotein I, a protein localized in the trans-Golgi network. EMBO J. 1996;15(22):6096–6110. 18. Bhattacharyya S, Hope TJ

Topic Models in Information Retrieval

DTIC Science & Technology

2007-08-01

Information Processing Systems, Cambridge, MA, MIT Press, 2004. Brown, P.F., Della Pietra, V.J., deSouza, P.V., Lai, J.C. and Mercer, R.L., Class-based...2003. http://www.wkap.nl/prod/b/1-4020-1216-0. Croft, W.B., Lucia , T.J., Cringean, J., and Willett, P., Retrieving Documents By Plausible Inference

Optimizing the use of Limb Tourniquets in Tactical Combat Casualty Care: TCCC Guidelines Change 14-02

DTIC Science & Technology

2014-02-01

Sebesta JA, Blackbourne LH, Herbert GS, Kauvar DS, Baer DG, Walters TJ, Mullenix PS, Holcomb JB, 31 st Combat Support Hospital Research Group...K, Dixon P, Cowart J, Spencer J, Rasmussen TE. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and

Derated Application of Parts for ESD (Electronic Systems Division) System Development. Revision

DTIC Science & Technology

1985-03-01

SSVAC Coearaen ~ree , neem ! adIrcuit ’design)~ Stress derating., __ o~~~~~:.mponent anplicatieonl ~blc ,ub~ This documnent establishes part...Channel & Breakdown Voltage 60% 70% 70% o N Channel) Max Tj (C) 95 105 125 48 MAXDM ALLOWABLE ABSOLUTE VALUE * OIL PERCENT OF RATED VALUE PART TYPE

A Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin

DTIC Science & Technology

2006-08-10

Doyle, L.R. Beuchat, T.J. Montville (Eds.), Food Microbiology : Fundamentals and Fron- tiers, Second ed., ASM Press, Washington, D.C., 2001, pp. 351...D.E. Lorant, A.E. Bryant, G.A. Zimmerman, T.M. McIn- tyre, D.L. Stevens, S.M. Prescott , Alpha toxin from Clostridium per- fringens induces

U.S. EPA, Pesticide Product Label, EN SURE EMULSIFIABLE CONCENTRATE INSECTICIDE, 04/18/1975

EPA Pesticide Factsheets

2011-04-14

... tr('atH! t'(':'j , :"nllr1 ;,.>4 hOllr') of <1J)pl, C;.Jtl'J[' "h"'JlcJ :.I:,jI ,.roll·' I .f: (ict'l:ng Thl') I,rvkr:' ", tOt,,- to ft.', dnd '1.rldllit: B,rch if:('ei;ng

U.S. EPA, Pesticide Product Label, , 10/17/1985

EPA Pesticide Factsheets

2011-04-14

... I(lu(h,rl'l t',11 10 (,I HHIJ.l! 'III,", t,·, ,,f [," . 'l" ,. vnrnillflq /,f q'vf' "tf1.,ltlllllj tJ, fI"\\~I!I\\ Ir,

Sir Gawain Was Just Out of Middle School....

ERIC Educational Resources Information Center

Probst, Robert E.

2002-01-01

Notes that what all middle school students need is another kid like them but with words. Presents some examples of adolescents going through the rites of passage--someone like T.J. in Chris Crutcher's "Whale Talk," or Sara Louise Bradshaw in Katherine Paterson's "Jacob Have I Loved," or Brian in Gary Paulson's…

Analysis, Simulation, and Fabrication of Current Mode Controlled DC-DC Power Converters

DTIC Science & Technology

1999-12-01

susceptibility), vou/ vin . 3 . The output impedance including the load. 22 The crossover frequency, coc, appears in all poles and is defined as: oo... VIN - 3 0 VIN - 3 V Delay to Outputs (TJ=25*C, (Note 2) 200 500 200 500 ns ( Current Limit Adjust Section Current Limit Offset

Talking with TJ: Conflict Resolution Series. Program Kit [Multimedia].

ERIC Educational Resources Information Center

Hallmark Corporate Foundation, Omaha, NE.

Noting that just as violent behavior is learned, so is nonviolent behavior, this instruction program is designed to help children in grades 2-4 learn to resolve conflicts without resorting to violence. Through the program, children develop important skills of managing anger and choosing alternatives to violence, respecting different points of view…

High Peak Power Ka-Band Gyrotron Oscillator Experiments with Slotted and Unslotted Cavities.

DTIC Science & Technology

1987-11-10

cylindrical graphite cathode by explosive plasma formation. (In order to optimize the compression ratio for these experiments, a graphite cathode was employed...48106 Attn: S.B. Segall I copy Lawrence Livermore National Laboratory P.O. Box 808 Livermore, California 94550 Attn: Dr. D. Prosnitz 1 copy Dr. T.J

Megavolt, Multi-Kiloamp Ka-Band Gyrotron Oscillator Experiment

DTIC Science & Technology

1989-03-15

pulseline accelerator with 20 K2 output impedance and 55 nsec voltage pulse was used to generate a multi-kiloamp annular electron beam by explosive plasma...Lawrence Livermore National Laboratory P.O. Box 808 Livermore, California 94550 Attn: Dr. D. Prosnitz 1 copy Dr. T.J. Orzechowski 1 copy Dr. J. Chase 1

Optoelectronic Materials Center

DTIC Science & Technology

1991-06-11

surface - emitting GaAs/AIGaAs vertical - cavity laser (TJ- VCSEL ) incorporating wavelength-resonant...multi-quantum well, vertical cavity surface - emitted laser . This structure consists entirely of undoped epilayers, thus simplifying the problems of... cavity surface - emitting lasers ( VCSELs ) for doubling and for parallel optical data processing. Progress - GaAIAs/GaAs and InGaAs/GaAs RPG- VCSEL

Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.

PubMed

Lau, W F; Tabernero, L; Sack, J S; Iwanowicz, E J

1995-08-01

A novel series of retro-binding tripeptide thrombin active-site inhibitors was recently developed (Iwanowicz, E. I. et al. J. Med. Chem. 1994, 37, 2111(1)). It was hypothesized that the binding mode for these inhibitors is similar to that of the first three N-terminal residues of hirudin. This binding hypothesis was subsequently verified when the crystal structure of a member of this series, BMS-183,507 (N-[N-[N-[4-(Aminoiminomethyl)amino[-1-oxobutyl]-L- phenylalanyl]-L-allo-threonyl]-L-phenylalanine, methyl ester), was determined (Taberno, L.J. Mol. Biol. 1995, 246, 14). The methodology for developing the binding models of these inhibitors, the structure-activity relationships (SAR) and modeling studies that led to the elucidation of the proposed binding mode is described. The crystal structure of BMS-183,507/human alpha-thrombin is compared with the crystal structure of hirudin/human alpha-thrombin (Rydel, T.J. et al. Science 1990, 249,227; Rydel, T.J. et al. J. Mol Biol. 1991, 221, 583; Grutter, M.G. et al. EMBO J. 1990, 9, 2361) and with the computational binding model of BMS-183,507.

All metalorganic chemical vapor phase epitaxy of p/n-GaN tunnel junction for blue light emitting diode applications

NASA Astrophysics Data System (ADS)

Neugebauer, S.; Hoffmann, M. P.; Witte, H.; Bläsing, J.; Dadgar, A.; Strittmatter, A.; Niermann, T.; Narodovitch, M.; Lehmann, M.

2017-03-01

We report on III-Nitride blue light emitting diodes (LEDs) comprising a GaN-based tunnel junction (TJ) all realized by metalorganic vapor phase epitaxy in a single growth process. The TJ grown atop the LED structures consists of a Mg-doped GaN layer and subsequently grown highly Ge-doped GaN. Long thermal annealing of 60 min at 800 °C is important to reduce the series resistance of the LEDs due to blockage of acceptor-passivating hydrogen diffusion through the n-type doped top layer. Secondary ion mass spectroscopy measurements reveal Mg-incorporation into the topmost GaN:Ge layer, implying a non-abrupt p-n tunnel junction and increased depletion width. Still, significantly improved lateral current spreading as compared to conventional semi-transparent Ni/Au p-contact metallization and consequently a more homogeneous electroluminescence distribution across 1 × 1 mm2 LED structures is achieved. Direct estimation of the depletion width is obtained from electron holography experiments, which allows for a discussion of the possible tunneling mechanism.

Theoretical calculation of performance enhancement in lattice-matched SiGeSn/GeSn p-channel tunneling field-effect transistor with type-II staggered tunneling junction

NASA Astrophysics Data System (ADS)

Wang, Hongjuan; Han, Genquan; Wang, Yibo; Peng, Yue; Liu, Yan; Zhang, Chunfu; Zhang, Jincheng; Hu, Shengdong; Hao, Yue

2016-04-01

In this work, a lattice-matched SiGeSn/GeSn heterostructure p-channel tunneling field-effect transistor (hetero-PTFET) with a type-II staggered tunneling junction (TJ) is investigated theoretically. Lattice matching and type-II band alignment at the Γ-point is obtained at the SiGeSn/GeSn interface by tuning Sn and Si compositions. A steeper subthreshold swing (SS) and a higher on state current (I ON) are demonstrated in SiGeSn/GeSn hetero-PTFET than in GeSn homo-PTFET. Si0.31Ge0.49Sn0.20/Ge0.88Sn0.12 hetero-PTFET achieves a 2.3-fold higher I ON than Ge0.88Sn0.12 homo-PTFET at V DD of 0.3 V. Hetero-PTFET achieves a more abrupt hole profile and a higher carrier density near TJ than the homo-PTFET, which contributes to the significantly enhanced band-to-band tunneling (BTBT) rate and tunneling current in hetero-PTFET.

Hybrid tunnel junction contacts to III-nitride light-emitting diodes

NASA Astrophysics Data System (ADS)

Young, Erin C.; Yonkee, Benjamin P.; Wu, Feng; Oh, Sang Ho; DenBaars, Steven P.; Nakamura, Shuji; Speck, James S.

2016-02-01

In this work, we demonstrate highly doped GaN p-n tunnel junction (TJ) contacts on III-nitride heterostructures where the active region of the device and the top p-GaN layers were grown by metal organic chemical vapor deposition and highly doped n-GaN was grown by NH3 molecular beam epitaxy to form the TJ. The regrowth interface in these hybrid devices was found to have a high concentration of oxygen, which likely enhanced tunneling through the diode. For optimized regrowth, the best tunnel junction device had a total differential resistivity of 1.5 × 10-4 Ω cm2, including contact resistance. As a demonstration, a blue-light-emitting diode on a (20\\bar{2}\\bar{1}) GaN substrate with a hybrid tunnel junction and an n-GaN current spreading layer was fabricated and compared with a reference sample with a transparent conducting oxide (TCO) layer. The tunnel junction LED showed a lower forward operating voltage and a higher efficiency at a low current density than the TCO LED.

Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications.

PubMed

Sullivan, Timothy J; Dairaghi, Daniel J; Krasinski, Antoni; Miao, Zhenhua; Wang, Yu; Zhao, Bin N; Baumgart, Trageen; Berahovich, Rob; Ertl, Linda S; Pennell, Andrew; Seitz, Lisa; Miao, Shichang; Ungashe, Solomon; Wei, Zheng; Johnson, Dan; Boring, Landin; Tsou, Chia-Lin; Charo, Israel F; Bekker, Pirow; Schall, Thomas J; Jaen, Juan C

2012-06-05

The following manuscript was published as a Fast Forward article on February 29, 2012: Sullivan TJ, Dairaghi DJ, Krasinski A, Miao Z, Wang Y, Zhao BN, Baumgart T, Berahovich R, Ertl LS, Pennell A, Seitz L, Miao S, Ungashe S, Wei Z, Johnson D, Boring L, Tsou C-L, Charo IF, Bekker P, Schall TJ, and Jaen JC, Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications. J Pharmacol Exp Ther jpet.111.190918; doi:10.1124/jpet.111.190918 It was later found that the chemical identity of a compound cited in the article, CCX140-B, was not sufficiently disclosed. The authors are unable, at this time, to provide the chemical identity of CCX140-B in accordance with the editorial policies of The Journal of Pharmacology and Experimental Therapeutics. As a result, the authors have voluntarily withdrawn this manuscript from publication. We apologize for any inconvenience this may cause JPET's readers.

Starting a new conversation: Engaging Veterans with spinal cord injury in discussions of what function means to them, the barriers/facilitators they encounter, and the adaptations they use to optimize function.

PubMed

Hill, Jennifer N; Balbale, Salva; Lones, Keshonna; LaVela, Sherri L

2017-01-01

Assessments of function in persons with spinal cord injury (SCI) often utilize pre-defined constructs and measures without consideration of patient context, including how patients define function and what matters to them. We utilized photovoice to understand how individuals define function, facilitators and barriers to function, and adaptations to support functioning. Veterans with SCI were provided with cameras and guidelines to take photographs of things that: (1) help with functioning, (2) are barriers to function, and (3) represent adaptations used to support functioning. Interviews to discuss photographs followed and were audio-recorded, transcribed, and analyzed using grounded-thematic coding. Nvivo 8 was used to store and organize data. Participants (n = 9) were male (89%), Caucasian (67%), had paraplegia (75%), averaged 64 years of age, and were injured, on average, for 22 years. Function was described in several ways: the concept of 'normalcy,' aspects of daily living, and ability to be independent. Facilitators included: helpful tools, physical therapy/therapists, transportation, and caregivers. Barriers included: wheelchair-related issues and interior/exterior barriers both in the community and in the hospital. Examples of adaptations included: traditional examples like ramps, and also creative examples like the use of rubber bands on a can to help with grip. Patient-perspectives elicited in-depth information that expanded the common definition of function by highlighting the concept of "normality," facilitators and barriers to function, and adaptations to optimize function. These insights emphasize function within a patient-context, emphasizing a holistic definition of function that can be used to develop personalized, patient-driven care plans. Published by Elsevier Inc.

Topical Apigenin Improves Epidermal Permeability Barrier Homeostasis in Normal Murine Skin by Divergent Mechanisms

PubMed Central

Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L.; Park, Kyungho; Crumrine, Debra; Lin, Tzu-kai; Santiago, Juan Luis; Mauro, Theodora M.; Elias, Peter M.; Man, Mao-Qiang

2013-01-01

The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, Chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice-daily for 9 days. At the end of treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homeostasis after tape stripping, though basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were up-regulated by apigenin. Finally, both CAMP and mBD3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels, and impaired antimicrobial defenses, such as atopic dermatitis. PMID:23489424

"Symptoms of something all around us": Mental health, Inuit culture, and criminal justice in Arctic communities in Nunavut, Canada.

PubMed

Ferrazzi, Priscilla; Krupa, Terry

2016-09-01

Rehabilitation-oriented criminal court mental health initiatives to reduce the number of people with mental illness caught in the criminal justice system exist in many North American cities and elsewhere but not in the mainly Inuit Canadian Arctic territory of Nunavut. This study explores whether the therapeutic aims of these resource-intensive, mainly urban initiatives can be achieved in criminal courts in Nunavut's resource constrained, culturally distinct and geographically remote communities. A qualitative multiple-case study in the communities of Iqaluit, Arviat and Qikiqtarjuaq involved 55 semi-structured interviews and three focus groups with participants representing four sectors essential to these initiatives: justice, health, community organizations and community members. These interviews explored whether the therapeutic jurisprudence (TJ) principles that guide criminal court mental health initiatives and the component objectives of these principles could be used to improve the criminal court response to people with mental illness in Nunavut. Interviews revealed 13 themes reflecting perceptions of Inuit culture's influence on the identification of people with mental illness, treatment, and collaboration between the court and others. These themes include cultural differences in defining mental illness, differences in traditional and contemporary treatment models, and the importance of mutual cultural respect. The findings suggest Inuit culture, including its recent history of cultural disruption and change, affects the vulnerability of Nunavut communities to the potential moral and legal pitfalls associated with TJ and criminal court mental health initiatives. These pitfalls include the dominance of biomedical approaches when identifying a target population, the medicalization of behaviour and culture, the risk of "paternalism" in therapeutic interventions, and shortcomings in interdisciplinary collaboration that limit considerations of Inuit culture. The pitfalls are not fatal to efforts to bring the rehabilitative benefits of these initiatives to Nunavut, but they require careful vigilance when employing TJ principles in an Indigenous circumpolar context. Copyright © 2016. Published by Elsevier Ltd.

Recherche d'une politique de gestion des stocks d'eau de barrages-réservoirs en vue de soutenir les étiages. 2. Utilisation d'un modèle alterné annuel apports-déficits pour la recherche des conditions de gestion

NASA Astrophysics Data System (ADS)

Bocquillon, C.; Masson, J. M.

1983-01-01

In the upper catchment of the River Loire, France, the construction of five reservoir dams has been planned to sustain the low flows in the Loire valley. The management of these reservoirs, to be built successively, must be approached from partial or complete points of view in order to establish the daily draft decisions at every stage of the project. A hydrological criteria concerning the low flows at a station in the valley (namely the "objective point") is used to judge the results. It is possible to determine the optimal carry-over storage for this criterion with the use of a long series of simulated inflows to reservoirs and annual deficits, when the future conditions are presumed to be known. The statistical analysis of the results helps in the formulation of the objectives for long-term Q1 assuring the carry-over storage for a predetermined risk of failure. This objective for long-term Q1 will not hold good if the low flow is severe. Thus some deterministic and statistical hypotheses have been used to formulate an objective for the mean term of flow Q2 ( tj) which is calculated each day tj and adjusted to the hydrological conditions of the year. The target draft Cb at the objective point is the minimum of the pair [( Q1, Q2 ( tj)]. Water is discharged each day to meet this target flow, while maintaining all the constraints of the flows downstream to the reservoirs. It takes into account the time needed for transfer of water and permits a good prediction of either the flow propagation in the upper watershed or the evolution of the inflows from downstream catchments. A modular model is used to calculate the daily flow. The results obtained from simulation were satisfactory.

Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

PubMed

Smith, I M; Baker, A; Arneborg, N; Jespersen, L

2015-11-01

The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.

Schottky-type grain boundaries in CCTO ceramics

NASA Astrophysics Data System (ADS)

Felix, A. A.; Orlandi, M. O.; Varela, J. A.

2011-10-01

In this work we studied electrical barriers existing at CaCu 3Ti 4O 12 (CCTO) ceramics using dc electrical measurements. CCTO pellets were produced by solid state reaction method and X-ray diffractograms showed which single phase polycrystalline samples were obtained. The samples were electrically characterized by dc and ac measurements as a function of temperature, and semiconductor theory was applied to analyze the barrier at grain boundaries. The ac results showed the sample's permittivity is almost constant ( 104) as function of temperature at low frequencies and it changes from 100 to 104 as the temperature increases at high frequencies. Using dc measurements as a function of temperature, the behavior of barriers was studied in detail. Comparison between Schottky and Poole-Frenkel models was performed, and results prove that CCTO barriers are more influenced by temperature than by electric field (Schottky barriers). Besides, the behavior of barrier width as function of temperature was also studied and experimental results confirm the theoretical assumptions.

Barriers to activity and participation for stroke survivors in rural China.

PubMed

Zhang, Lifang; Yan, Tiebin; You, Liming; Li, Kun

2015-07-01

To investigate environmental barriers reported by stroke survivors in the rural areas of China and to determine the impact of environmental barriers on activity and participation relative to demographic characteristics and body functioning. Cross-sectional survey. Structured interviews in the participants' homes. Community-dwelling stroke survivors in the rural areas of China (N=639). Not applicable. Activity and participation (Chinese version of the World Health Organization Disability Assessment Schedule 2.0), environmental barriers (Craig Hospital Inventory of Environmental Factors), neurological function (Canadian Neurological Scale), cognitive function (Abbreviated Mental Test), and depression (6-item Hamilton Rating Scale for Depression). Physical/structural barriers are the major impediment to activity and participation for these participants (odds ratio, 1.86 and 1.99 for activity and participation, respectively; P<.01). Services/assistance barriers primarily impede participation rather than activity (odds ratio, 1.58 in participation; P<.05). Physical/structural and services/assistance barriers were considered the dominant barriers to activity and participation for stroke survivors in the rural areas of China. Attitudinal/support and policy barriers did not emerge as serious concerns. To generate an enabling environment, physical/structural and services/assistance barriers are the environmental barriers to be decreased and eliminated first. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Probiotics promote endocytic allergen degradation in gut epithelial cells

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

Song, Chun-Hua; Liu, Zhi-Qiang; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON

Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barriermore » function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.« less

Functions of an engineered barrier system for a nuclear waste repository in basalt

NASA Astrophysics Data System (ADS)

Coons, W. E.; Moore, E. L.; Smith, M. J.; Kaser, J. D.

1980-01-01

The functions of components selected for an engineered barrier system for a nuclear waste repository in basalt are defined providing a focal point for barrier material research and development by delineating the purpose and operative lifetime of each component of the engineered system. A five component system (comprised of waste form, canister, buffer, overpack, and tailored backfill) is discussed. Redundancy is provided by subsystems of physical and chemical barriers which act in concert with the geology to provide a formidable barrier to transport of hazardous materials to the biosphere. The barrier system is clarified by examples pertinent to storage in basalt, and a technical approach to barrier design and material selection is proposed.

HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: Potential role of the thiol antioxidant N-acetylcysteine amide

PubMed Central

Banerjee, Atrayee; Zhang, Xinsheng; Manda, Kalyan Reddy; Banks, William A; Ercal, Nuran

2010-01-01

An increased risk of HIV-1 associated dementia (HAD) has been observed in patients abusing methamphetamine (METH). Since both HIV viral proteins (gp120, Tat) and METH induce oxidative stress, drug abusing patients are at a greater risk of oxidative stress-induced damage. The objective of this study was to determine if N-acetylcysteine amide (NACA) protects the blood brain barrier (BBB) from oxidative stress-induced damage in animals exposed to gp120, Tat and METH. To study this, CD-1 mice pre-treated with NACA/saline, received injections of gp120, Tat, gp120 + Tat or saline for 5 days, followed by three injections of METH/saline on the fifth day, and sacrificed 24 h after the final injection. Various oxidative stress parameters were measured, and animals treated with gp120+Tat+Meth were found to be the most challenged group, as indicated by their GSH and MDA levels. Treatment with NACA significantly rescued the animals from oxidative stress. Further, NACA-treated animals had significantly higher expression of TJ proteins and BBB permeability as compared to the group treated with gp120+Tat+METH alone, indicating that NACA can protect the BBB from oxidative stress-induced damage in gp120, Tat and METH exposed animals, and thus could be a viable therapeutic option for patients with HAD. PMID:20188164

Actin nucleator Spire 1 is a regulator of ectoplasmic specialization in the testis.

PubMed

Wen, Qing; Li, Nan; Xiao, Xiang; Lui, Wing-Yee; Chu, Darren S; Wong, Chris K C; Lian, Qingquan; Ge, Renshan; Lee, Will M; Silvestrini, Bruno; Cheng, C Yan

2018-02-12

Germ cell differentiation during the epithelial cycle of spermatogenesis is accompanied by extensive remodeling at the Sertoli cell-cell and Sertoli cell-spermatid interface to accommodate the transport of preleptotene spermatocytes and developing spermatids across the blood-testis barrier (BTB) and the adluminal compartment of the seminiferous epithelium, respectively. The unique cell junction in the testis is the actin-rich ectoplasmic specialization (ES) designated basal ES at the Sertoli cell-cell interface, and the apical ES at the Sertoli-spermatid interface. Since ES dynamics (i.e., disassembly, reassembly and stabilization) are supported by actin microfilaments, which rapidly converts between their bundled and unbundled/branched configuration to confer plasticity to the ES, it is logical to speculate that actin nucleation proteins play a crucial role to ES dynamics. Herein, we reported findings that Spire 1, an actin nucleator known to polymerize actins into long stretches of linear microfilaments in cells, is an important regulator of ES dynamics. Its knockdown by RNAi in Sertoli cells cultured in vitro was found to impede the Sertoli cell tight junction (TJ)-permeability barrier through changes in the organization of F-actin across Sertoli cell cytosol. Unexpectedly, Spire 1 knockdown also perturbed microtubule (MT) organization in Sertoli cells cultured in vitro. Biochemical studies using cultured Sertoli cells and specific F-actin vs. MT polymerization assays supported the notion that a transient loss of Spire 1 by RNAi disrupted Sertoli cell actin and MT polymerization and bundling activities. These findings in vitro were reproduced in studies in vivo by RNAi using Spire 1-specific siRNA duplexes to transfect testes with Polyplus in vivo-jetPEI as a transfection medium with high transfection efficiency. Spire 1 knockdown in the testis led to gross disruption of F-actin and MT organization across the seminiferous epithelium, thereby impeding the transport of spermatids and phagosomes across the epithelium and perturbing spermatogenesis. In summary, Spire 1 is an ES regulator to support germ cell development during spermatogenesis.

Systematic low-energy effective field theory for magnons and holes in an antiferromagnet on the honeycomb lattice

NASA Astrophysics Data System (ADS)

Kämpfer, F.; Bessire, B.; Wirz, M.; Hofmann, C. P.; Jiang, F.-J.; Wiese, U.-J.

2012-02-01

Based on a symmetry analysis of the microscopic Hubbard and t-J models, a systematic low-energy effective field theory is constructed for hole-doped antiferromagnets on the honeycomb lattice. In the antiferromagnetic phase, doped holes are massive due to the spontaneous breakdown of the SU(2)s symmetry, just as nucleons in Quantum Chromodynamics (QCD) pick up their mass from spontaneous chiral symmetry breaking. In the broken phase, the effective action contains a single-derivative term, similar to the Shraiman-Siggia term in the square lattice case. Interestingly, an accidental continuous spatial rotation symmetry arises at leading order. As an application of the effective field theory, we consider one-magnon exchange between two holes and the formation of two-hole bound states. As an unambiguous prediction of the effective theory, the wave function for the ground state of two holes bound by magnon exchange exhibits f-wave symmetry.

Multidimensionally constrained relativistic mean-field study of triple-humped barriers in actinides

NASA Astrophysics Data System (ADS)

Zhao, Jie; Lu, Bing-Nan; Vretenar, Dario; Zhao, En-Guang; Zhou, Shan-Gui

2015-01-01

Background: Potential energy surfaces (PES's) of actinide nuclei are characterized by a two-humped barrier structure. At large deformations beyond the second barrier, the occurrence of a third barrier was predicted by macroscopic-microscopic model calculations in the 1970s, but contradictory results were later reported by a number of studies that used different methods. Purpose: Triple-humped barriers in actinide nuclei are investigated in the framework of covariant density functional theory (CDFT). Methods: Calculations are performed using the multidimensionally constrained relativistic mean field (MDC-RMF) model, with the nonlinear point-coupling functional PC-PK1 and the density-dependent meson exchange functional DD-ME2 in the particle-hole channel. Pairing correlations are treated in the BCS approximation with a separable pairing force of finite range. Results: Two-dimensional PES's of 226,228,230,232Th and 232,235,236,238U are mapped and the third minima on these surfaces are located. Then one-dimensional potential energy curves along the fission path are analyzed in detail and the energies of the second barrier, the third minimum, and the third barrier are determined. The functional DD-ME2 predicts the occurrence of a third barrier in all Th nuclei and 238U . The third minima in 230 ,232Th are very shallow, whereas those in 226 ,228Th and 238U are quite prominent. With the functional PC-PK1 a third barrier is found only in 226 ,228 ,230Th . Single-nucleon levels around the Fermi surface are analyzed in 226Th, and it is found that the formation of the third minimum is mainly due to the Z =90 proton energy gap at β20≈1.5 and β30≈0.7 . Conclusions: The possible occurrence of a third barrier on the PES's of actinide nuclei depends on the effective interaction used in multidimensional CDFT calculations. More pronounced minima are predicted by the DD-ME2 functional, as compared to the functional PC-PK1. The depth of the third well in Th isotopes decreases with increasing neutron number. The origin of the third minimum is due to the proton Z =90 shell gap at relevant deformations.

The Drosophila blood-brain barrier: development and function of a glial endothelium.

PubMed

Limmer, Stefanie; Weiler, Astrid; Volkenhoff, Anne; Babatz, Felix; Klämbt, Christian

2014-01-01

The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

Inventory of Military Real Property

DTIC Science & Technology

1966-12-21

priate manner. The covers used for binding will be of a stiff hard - back material of sufficient strength to permit stowing on edge within file cabinets...SYRMBH0L S FO OM UNI TS O F MEV.A SOUBA 5241/01. UINT SF MEASSURE SYMBOL SlTJ OF IERS//IS AC acresl .. O A. aaiyKilonolt-saperrn, rapacity (KVA) B/D

USING THE SEDIMENT QUALITY TRIAD (SQT) APPROACH TO ASSESS SEDIMENTARY CONTAMINATION IN THE ANACOSTIA RIVER, WASHINGTON

EPA Science Inventory

Using the Sediment Quality Triad (SQT) Approach to Assess Sedimentary Contamination in the Anacostia River, Washington, D.C. Velinsky, DJ*1, Ashley, JTF1,2, Pinkney, F.3, McGee, BL3 and Norberg-King, TJ.4 1Academy of Natural Sciences-PCER, Philadelphia, PA. 2Philadelphia Universi...

Dosage Effects of a Preventive Social-Emotional Learning Intervention on Achievement Loss Associated with Middle School Transition

ERIC Educational Resources Information Center

Rosenblatt, Jennifer L.; Elias, Maurice J.

2008-01-01

A number of studies have documented a normative decline in academic achievement across the transition from elementary school to middle or junior high school. The current study examined the effectiveness of varying levels of a social-emotional learning intervention, "Talking with TJ," in limiting achievement loss across transition. Data were…

Multi-Stage Maximum Likelihood Target Estimator

DTIC Science & Technology

2006-03-31

Compute the range at ti with respect to 19 the sensor associated with the ith 20 measurement (Ri): 23 1 R, = VRx ’+ Ryl’ (3 2 2.) Compute the range...the ith measurement 12 ii. Compute the range at tj with respect tothe 13 sensor associated with the ith measurement (R4) 14 = VRx + Ry (323) 15 iii

Debriefing Process for the Maintenance Sections of the Israeli Air Force Fighter Squadrons

DTIC Science & Technology

1988-12-01

researchers ( Ivancevich and McMahon, 1982) have found the "self" as a higher efficienc source of feedback. It is suggested to employ the self-debriefing...subordinate Relationships and Performance," Personal Psychology, 14, pp. 357-374. Ivancevich , M.J. and McMahon, T.J. (1982), "The Effects of Goal Setting

U.S. EPA, Pesticide Product Label, BONIDE MOLETOX II POISON BAIT, 05/21/1981

EPA Pesticide Factsheets

2011-04-13

... ',1 t,) (,I PI,j ;'II tJ :!- fl1 •. - C\\ (j L~I fl) rii ::j :<:: 1ft: -11""1 •. "U 2:(") n ""\\rd .. ;0 0' Lsd (:':'j L/ '" » g c: ~-l -o 2 :;0 /fY'lI ):;:. n :c'Jr: ~ ~ C"":ll 5~ ~~ ~ ~ d ...

Selecting Electricity Generation Sources in Remote Locations

DTIC Science & Technology

2007-03-01

A.N., & Chubb, T.J. (2005). Optimization of a PV with Diesel- Battery System for Remote Villages. International Solar Energy Journal , 6, 107- 118...List of Figures Page Figure 1. Electrification Rates by Region, 1970-2003 ( International , 2002) .................. 25 Figure 2. World Bank...xii List of Tables Page Table 1. Countries in 2000 with Low Electrification Rates ( International , 2002) .......... 13

Analysis of effluent filtrate in the hydro-entanglement process for producing cotton nonwovens: a progress report

USDA-ARS?s Scientific Manuscript database

A number of hydro-entangled cotton nonwoven fabrics were produced on commercial equipment, using UltraCleanTM Cotton (T.J. Beall Company). Polypropylene “sock” filters were used in the production trials to clean the effluent water for recycling it in the hydro-entanglement process. After each trial ...

Feasibility Study of 5.56 MM Folded Ammunition/Weapon System

DTIC Science & Technology

1976-09-01

blt 50 nd reeh pn te ct 57 wll nabe hll xhausting operaetively developed pressure gas there- longitudintl5motion ei the holti5505thrwill htii it ful...187 ) N g7 tjN U (1%! I ,c 0,----- o /009 cz U I C5 Zoo-. ’ -.P1 SY .. .............................. oATM ................... SU ,J .C T

Optimized Breech Location in the Harry Diamond Laboratories 4-Inch Gas Gun

DTIC Science & Technology

1982-04-01

GAMA-iy*SQRrA BAR*(1-FRAC L~(GAMA-1))) IF INIT_G(BRL%)<=START TJ - THEN PRINT #BRL% USTNG FORM4$,INIT G(BRL%).VEL ELSE FLAG( BRU ) = 1 - 130 NEXT...CA 93041 COMMANDER DAVID W. TAYLOR NAVAL SHIP RESEARCH S DEVELOPMENT CENTER ATTN ELIZABETH DEMPSEY, CODE 534 ATTN PAUL GRANVILLE, CODE 581

Activation of Alternative Wnt Signaling Pathways in Human Mammary Gland and Breast Cancer Cells

DTIC Science & Technology

2006-06-01

Parlow AF, Luhmann UF, Berger W, and Richards JS. Mice null for Frizzled4 (Fzd4–/–) are infertile and exhibit impaired corpora lutea formation and...proliferation, and matrix metalloproteinases pro- duction and regulated angiogenesis. J Immunol 170: 3369—3376, 2003. 39. Lobov IB, Rao S, Carroll TJ, Vallance

Small Unit Operations

DTIC Science & Technology

1998-06-29

regardless of size; therefore very small systems may have JA ~ 0.5, whereas bigger systems may have to be buried , making /^ < 1. It would be desirable to...OATn PaQ {^xfRcTjPRF /D\\ 4 SNR= MrTO U) =32dB’ «"> It is worth noting here the capabilities of the SAR in transmitting and in receiving messages

Counterintuitive and Alternative Moves Choice in the Water Jug Task

ERIC Educational Resources Information Center

Carder, Hassina P.; Handley, Simon J.; Perfect, Timothy J.

2008-01-01

MOVE problems, like the Tower of London (TOL) or the Water Jug (WJ) task, are planning tasks that appear structurally similar and are assumed to involve similar cognitive processes. Carder et al. [Carder, H.P., Handley, S.J., & Perfect, T.J. ( 2004). Deconstructing the Tower of London: Alternative moves and conflict resolution as predictors of…

High Peak Power Ka-Band Gyrotron Oscillator Experiment.

DTIC Science & Technology

1987-09-21

edge of a 3.44-cm- diam. cylindrical carbon cathode by means of explosive plasma formation. The diode is immersed in the field of the main solenoidal... Prosnitz Dr. T.J. Orzechowski C ’ ’ Dr. J. Thase 56 ’V Los Alamos Scientific Laboratory P.O. Box 1663, AT5-827 Los Alamos, New Mexico 87545 Attn

Accounting for Genocide: Transitional Justice, Mass (Re)Education and the Pedagogy of Truth in Present-Day Rwanda

ERIC Educational Resources Information Center

Bentrovato, Denise

2017-01-01

Vigorous debate has recently arisen on the particular contribution of education to transitional justice (TJ). This article, focusing on the case of post-genocide Rwanda, raises the question of the possibilities, limitations and desirability of approaches which seek to impose, through education, top-down forms of reconciliation. The article employs…

AN IP3 RECEPTOR-SENSITIVE CALCIUM STORE MEDIATES DISTURBANCES IN INTRACELLULAR CALCIUM UPON EXPOSURE TO AROCLOR 1254 AND ORTHO-SUBSTITUTED PCBS.

EPA Science Inventory

An IP3 Receptor-Sensitive Ca2+ Store Mediates Disturbances In Intracellular Ca2+ Upon Exposure To Aroclor 1254 And Ortho-Substituted PCBs JR Inglefield, WR Mundy, and TJ Shafer. Neurotoxicol. Div., NHEERL, US EPA, RTP, NC. Sponsor: L Birnbaum

Polychlorinated biphenyls (...

A novel, topical, nonsteroidal, TRPV1 antagonist, PAC-14028 cream improves skin barrier function and exerts anti-inflammatory action through modulating epidermal differentiation markers and suppressing Th2 cytokines in atopic dermatitis.

PubMed

Lee, Ji-Hae; Choi, Chang Soon; Bae, Il-Hong; Choi, Jin Kyu; Park, Young-Ho; Park, Miyoung

2018-04-30

Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown. Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD. AD-like dermatitis was induced in hairless mice by repeated oxazolone (Ox) challenges to hairless mice. The functional studies concerning skin barrier function, anti-inflammatory action, and molecular mechanism by TRPV1 antagonism were conducted by histopathological assays, ELISA, qPCR, western blotting, and skin blood flow measurement. Topically administered TRPV1 antagonist, PAC-14028 (Asivatrep: C 21 H 22 F 5 N 3 O 3 S), improved AD-like dermatitis and skin barrier functions, and restored the expression of epidermal differentiation markers. In addition, the PAC-14028 cream significantly inhibited cutaneous inflammation by decreasing the expression of serum IgE, and the epidermal expression of IL-4, and IL-13 in Ox-AD mice. These results may provide a novel insight into the molecular mechanism of PAC-14028 cream involved in anti-inflammatory effects and skin barrier functions by suppressing the multiple signaling pathways including IL-4/-13-mediated activation of JAK/STAT, TRPV1, and neuropeptides. PAC-14028 cream can be a potential therapeutic tool for the treatment of chronic inflammation and disrupted barrier function in patients with AD. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Effects of Fe particle irradiation on human endothelial barrier structure and function

NASA Astrophysics Data System (ADS)

Sharma, Preety; Guida, Peter; Grabham, Peter

2014-07-01

Space travel involves exposure to biologically effective heavy ion radiation and there is consequently a concern for possible degenerative disorders in humans. A significant target for radiation effects is the microvascular system, which is crucial to healthy functioning of the tissues. Its pathology is linked to disrupted endothelial barrier function and is not only a primary event in a range of degenerative diseases but also an important influencing factor in many others. Thus, an assessment of the effects of heavy ion radiation on endothelial barrier function would be useful for estimating the risks of space travel. This study was aimed at understanding the effects of high LET Fe particles (1 GeV/n) and is the first investigation of the effects of charged particles on the function of the human endothelial barrier. We used a set of established and novel endpoints to assess barrier function after exposure. These include, trans-endothelial electrical resistance (TEER), morphological effects, localization of adhesion and cell junction proteins (in 2D monolayers and in 3D tissue models), and permeability of molecules through the endothelial barrier. A dose of 0.50 Gy was sufficient to cause a progressive reduction in TEER measurements that were significant 48 hours after exposure. Concurrently, there were morphological changes and a 14% loss of cells from monolayers. Gaps also appeared in the normally continuous cell-border localization of the tight junction protein - ZO-1 but not the Platelet endothelial cell adhesion molecule (PECAM-1) in both monolayers and in 3D vessel models. Disruption of barrier function was confirmed by increased permeability to 3 kDa and 10 kDa dextran molecules. A dose of 0.25 Gy caused no detectible change in cell number, morphology, or TEER, but did cause barrier disruption since there were gaps in the cell border localization of ZO-1 and an increased permeability to 3 kDa dextran. These results indicate that Fe particles potently have impact on human endothelial barrier function and represent a risk for degenerative diseases in the space environment.

Apoplastic Diffusion Barriers in Arabidopsis

PubMed Central

Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J.; Kunst, Ljerka

2013-01-01

During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented. PMID:24465172

Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors

PubMed Central

2012-01-01

Background Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. Results In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, 3H-mannitol fluxes, short-circuit current (Cl− secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl− secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca2+]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. Conclusions Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS. PMID:22553939

Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors.

PubMed

Cuppoletti, John; Blikslager, Anthony T; Chakrabarti, Jayati; Nighot, Prashant K; Malinowska, Danuta H

2012-05-03

Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, (3)H-mannitol fluxes, short-circuit current (Cl(-) secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl(-) secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca(2+)]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS.

Executive Functioning, Barriers to Adherence, and Nonadherence in Adolescent and Young Adult Transplant Recipients.

PubMed

Gutiérrez-Colina, Ana M; Eaton, Cyd K; Lee, Jennifer L; Reed-Knight, Bonney; Loiselle, Kristin; Mee, Laura L; LaMotte, Julia; Liverman, Rochelle; Blount, Ronald L

2016-08-01

OBJECTIVE : To evaluate levels of executive functioning in a sample of adolescent and young adult (AYA) transplant recipients, and to examine executive functioning in association with barriers to adherence and medication nonadherence.  METHOD : In all, 41 caregivers and 39 AYAs were administered self- and proxy-report measures.  RESULTS : AYA transplant recipients have significant impairments in executive functioning abilities. Greater dysfunction in specific domains of executive functioning was significantly associated with more barriers to adherence and greater medication nonadherence.  CONCLUSION : AYA transplant recipients are at increased risk for executive dysfunction. The assessment of executive functioning abilities may guide intervention efforts designed to decrease barriers to adherence and promote developmentally appropriate levels of treatment responsibility. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.

PubMed

Liu, Xinchun; Zhou, Xiaoshu; Yuan, Wei

2014-10-15

In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8. Copyright © 2014 Elsevier Inc. All rights reserved.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 compared to a pH 5.8 w/o emulsion in aged skin.

PubMed

Angelova-Fischer, I; Fischer, T W; Abels, C; Zillikens, D

2018-03-25

Increased skin surface pH is an important host-related factor for deteriorated barrier function in the aged. We investigated whether restoration of the skin pH through topical application of a water-in-oil (w/o) emulsion with pH 4 improved the barrier homeostasis in aged skin and compared the effects to an identical galenic formulation with pH 5.8. The effects of the test formulations on the barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of the barrier function in aged skin. The long-term effects of the pH 4 and pH 5.8 emulsions were analyzed by investigation of the barrier integrity/cohesion, the skin surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. The application of the pH 4 emulsion accelerated the barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH4-treated and acetone control field were significant. Furthermore, the long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin surface roughness and scaliness. At the same time points, the pH 5.8 formulation exerted only minor effects on the barrier function parameters. Exogenous acidification through topical application of a w/o emulsion with pH 4 leads to improvement of the barrier function and maintenance of the barrier homeostasis in aged skin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Barrier-protective function of intestinal epithelial Toll-like receptor 2.

PubMed

Cario, E

2008-11-01

The intestinal epithelial cell (IEC) barrier plays an important role in maintaining mucosal immune homeostasis. Dysregulated IEC barrier function appears to trigger and perpetuate inflammation in inflammatory bowel diseases (IBD). Novel risk variants in the Toll-like receptor 2 (TLR2) gene have previously been associated with a more severe disease phenotype in a subgroup of IBD patients. Recent studies have provided important insights of the commensal and host defense mechanisms to maintain functional barrier integrity of the intestinal epithelium through TLR2. Deficient TLR2 signaling may imbalance commensal-dependent intestinal epithelial barrier defense, facilitating mucosal injury and leading to increased susceptibility of colitis. Treatment with a synthetic TLR2 ligand significantly suppresses mucosal inflammation by efficiently protecting tight junction-associated integrity of the intestinal epithelium in vivo. These beneficial effects may be supplemented by TLR2-induced anti-inflammatory immune responses (such as interleukin-10 production) in lamina propria mononuclear cells. Thus, cell-specific TLR2 targeting may offer a novel therapeutic approach to human IBD therapy by protecting IEC barrier function.

Altered Expression of ZO-1 and ZO-2 in Sertoli Cells and Loss of Blood-Testis Barrier Integrity in Testicular Carcinoma In Situ1

PubMed Central

Fink, Cornelia; Weigel, Roswitha; Hembes, Tanja; Lauke-Wettwer, Heidrun; Kliesch, Sabine; Bergmann, Martin; Brehm, Ralph H

2006-01-01

Abstract Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular germ cell tumors. In normal seminiferous epithelium, specialized tight junctions between Sertoli cells constitute the major component of the blood-testis barrier. Sertoli cells associated with CIS exhibit impaired maturation status, but their functional significance remains unknown. The aim was to determine whether the blood-testis barrier is morphologically and/or functionally altered. We investigated the expression and distribution pattern of the tight junction proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules, ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region, but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we assessed the functional integrity of the blood-testis barrier by lanthanum tracer study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier function. PMID:17217619

Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

PubMed Central

Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

2013-01-01

The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

Fusion cross sections for reactions involving medium and heavy nucleus-nucleus systems

NASA Astrophysics Data System (ADS)

Atta, Debasis; Basu, D. N.

2014-12-01

Existing data on near-barrier fusion excitation functions of medium and heavy nucleus-nucleus systems have been analyzed by using a simple diffused-barrier formula derived assuming the Gaussian shape of the barrier-height distributions. The fusion cross section is obtained by folding the Gaussian barrier distribution with the classical expression for the fusion cross section for a fixed barrier. The energy dependence of the fusion cross section, thus obtained, provides good description to the existing data on near-barrier fusion and capture excitation functions for medium and heavy nucleus-nucleus systems. The theoretical values for the parameters of the barrier distribution are estimated which can be used for fusion or capture cross-section predictions that are especially important for planning experiments for synthesizing new superheavy elements.

Overall accessibility to traveling by rail for the elderly with and without functional limitations: the whole-trip perspective.

PubMed

Sundling, Catherine; Berglund, Birgitta; Nilsson, Mats E; Emardson, Ragne; Pendrill, Leslie R

2014-12-01

Elderly persons' perceived accessibility to railway traveling depends on their functional limitations/diseases, their functional abilities and their travel behaviors in interaction with the barriers encountered during whole trips. A survey was conducted on a random sample of 1000 city residents (65-85 years old; 57% response rate). The travels were perceived least accessible by respondents with severely reduced functional ability and by those with more than one functional limitation/disease (e.g., restricted mobility and chronic pain). Those who traveled "often", perceived the accessibility to be better than those who traveled less frequently. For travelers with high functional ability, the main barriers to more frequent traveling were travel costs and low punctuality. For those with low functional ability, one's own health was reported to be the main barrier. Our results clarify the links among existing functional limitations/functional abilities, the barriers encountered, the travel behavior, and the overall accessibility to traveling. By operationalizing the whole-trip concept as a chain of events, we deliver practical knowledge on vulnerable groups for decision-making to improve the transport environment for all.

Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion.

PubMed

Song, Ji Youn; Kang, Hyun A; Kim, Mi-Yeon; Park, Young Min; Kim, Hyung Ok

2004-03-01

Superficial chemical peeling and microdermabrasion have become increasingly popular methods for producing facial rejuvenation. However, there are few studies reporting the skin barrier function changes after these procedures. To evaluate objectively the degree of damage visually and the time needed for the skin barrier function to recover after glycolic acid peeling and aluminum oxide crystal microdermabrasion using noninvasive bioengineering methods. Superficial chemical peeling using 30%, 50%, and 70% glycolic acid and aluminum oxide crystal microdermabrasion were used on the volar forearm of 13 healthy women. The skin response was measured by a visual observation and using an evaporimeter, corneometer, and colorimeter before and after peeling at set time intervals. Both glycolic acid peeling and aluminum oxide crystal microdermabrasion induced significant damage to the skin barrier function immediately after the procedure, and the degree of damage was less severe after the aluminum oxide crystal microdermabrasion compared with glycolic acid peeling. The damaged skin barrier function had recovered within 24 hours after both procedures. The degree of erythema induction was less severe after the aluminum oxide crystal microdermabrasion compared with the glycolic acid peeling procedure. The degree of erythema induced after the glycolic acid peeling procedure was not proportional to the peeling solution concentration used. The erythema subsided within 1 day after the aluminum oxide crystal microdermabrasion procedure and within 4 days after the glycolic acid peeling procedure. These results suggest that the skin barrier function is damaged after the glycolic acid peeling and aluminum oxide crystal microdermabrasion procedure but recovers within 1 to 4 days. Therefore, repeating the superficial peeling procedure at 2-week intervals will allow sufficient time for the damaged skin to recover its barrier function.

Total Quality Management (TQM): Group Dynamics Workshop

DTIC Science & Technology

1990-05-15

interactions with other OSD decision-making bodies. " Remove barriers /facilitate implementation. " Direct action on unresolved process problems referred...TQM leadership. - Total Quality Management FUNCTIONS: * Translate goals to tangible internal initiatives. " Remove barriers . " Establish and...Quality Management FUNCTIONS: • Identify and remove barriers . " Develop practical process improvements. " Install solutions and measurement systems for

Preventing PTSD: A Randomized Controlled Trial of Brief Anxiety Reducation Treatment for Acute Trauma (ARTAT). Addendum

DTIC Science & Technology

2013-08-01

stress disorder. Journal of Psychiatric Research 45(6): 735-41. Galatzer-Levy, I.R., Madan , A., Neylan, T.C, Henn-Haase, C., Marmar, C. R. (2011...Journal of Traumatic Stress 24(5): 557-565. Komarovskaya, I., Maguen, S., McCaslin,S.E., Metzler, T.J., Madan , A., Brown, A.D., Galatzer-Levy, I.R

Fiscal Year 2013 Comprehensive Oversight Plan for Southwest Asia

DTIC Science & Technology

2012-09-26

Republic JO Jordan TJ Tajikistan KZ Kazakhstan TM Turkmenistan KW Kuwait AE United Arab Emirates KG Kyrgyzstan UZ Uzbekistan LB Lebanon YE Yemen...effective, responsive, democratic, transparent, accountable, and gender sensitive municipal governance in select municipalities in Afghanistan? (Project...CAII-Creative Associates International, Inc., Ambassador’s Small Grants Program to Support Gender Equality in Afghanistan – ASGP Objective: 306-A-00

Superfund Record Of Decision United Creosoting TX Second ...

EPA Pesticide Factsheets

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