Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

PubMed

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

RRM2 induces NF-{kappa}B-dependent MMP-9 activation and enhances cellular invasiveness

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

Duxbury, Mark S.; Whang, Edward E.

2007-03-02

Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-{kappa}B (NF-{kappa}B) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-{kappa}B-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-{kappa}B activity. NF-{kappa}B is a key mediator ofmore » the invasive phenotypic changes induced by RRM2 overexpression.« less

Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

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

Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

2005-01-20

Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation

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

Lee, Sang-Myeong; Kleiboeker, Steven B.

2005-11-10

Nuclear factor-kappaB (NF-{kappa}B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-{kappa}B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-{kappa}B activation was characterized by translocation of NF-{kappa}B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-{kappa}B-regulated gene expression. NF-{kappa}B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-{kappa}B activation. Degradationmore » of I{kappa}B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I{kappa}B{alpha} (I{kappa}B{alpha}DN) significantly suppressed NF-{kappa}B activation induced by PRRSV. However, I{kappa}B{alpha}DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-{kappa}B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-{kappa}B was activated by PRRSV infection. Moreover, NF-{kappa}B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-{kappa}B activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV.« less

Role of nutritional zinc in the prevention of osteoporosis.

PubMed

Yamaguchi, Masayoshi

2010-05-01

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and

Zinc in Infection and Inflammation.

PubMed

Gammoh, Nour Zahi; Rink, Lothar

2017-06-17

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

PubMed

Garrison, J B; Samuel, T; Reed, J C

2009-04-02

Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

Synergistic activation of NF-{kappa}B by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKK{beta}-I{kappa}B{alpha}, and p38 MAPK

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

Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida

2006-12-15

In review of the past studies on NF-{kappa}B regulation, most of them have focused on investigating how NF-{kappa}B is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-{kappa}B and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-{kappa}B-dependent inflammatory response via activation of multiple signaling pathways in vitromore » and in vivo. The classical IKK{beta}-I{kappa}B{alpha} and p38 MAPK pathways are involved in synergistic activation of NF-{kappa}B via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-{kappa}B via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-{kappa}B-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.« less

Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester.

PubMed

Majumdar, Sekhar; Lamothe, Betty; Aggarwal, Bharat B

2002-03-15

Thalidomide ([+]-alpha-phthalimidoglutarimide), a psychoactive drug that readily crosses the blood-brain barrier, has been shown to exhibit anti-inflammatory, antiangiogenic, and immunosuppressive properties through a mechanism that is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that thalidomide mediates its effects through suppression of NF-kappaB activation. We investigated the effects of thalidomide on NF-kappaB activation induced by various inflammatory agents in Jurkat cells. The treatment of these cells with thalidomide suppressed TNF-induced NF-kappaB activation, with optimum effect occurring at 50 microg/ml thalidomide. These effects were not restricted to T cells, as other hematopoietic and epithelial cell types were also inhibited. Thalidomide suppressed H(2)O(2)-induced NF-kappaB activation but had no effect on NF-kappaB activation induced by PMA, LPS, okadaic acid, or ceramide, suggesting selectivity in suppression of NF-kappaB. The suppression of TNF-induced NF-kappaB activation by thalidomide correlated with partial inhibition of TNF-induced degradation of an inhibitory subunit of NF-kappaB (IkappaBalpha), abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Thalidomide abolished the NF-kappaB-dependent reporter gene expression activated by overexpression of TNFR1, TNFR-associated factor-2, and NF-kappaB-inducing kinase, but not that activated by the p65 subunit of NF-kappaB. Overall, our results clearly demonstrate that thalidomide suppresses NF-kappaB activation specifically induced by TNF and H(2)O(2) and that this may contribute to its role in suppression of proliferation, inflammation, angiogenesis, and the immune system.

Cinnamaldehyde inhibits the tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in endothelial cells by suppressing NF-{kappa}B activation: Effects upon I{kappa}B and Nrf2

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

Liao, B.-C.; Hsieh, C.-W.; Liu, Y.-C.

The production of adhesion molecules and subsequent attachment of leukocytes to endothelial cells (ECs) are critical early events in atherogenesis. These adhesion molecules thus play an important role in the development of this disease. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of cinnamaldehyde, a Cinnamomum cassia Presl-specific diterpene. In our current study, we have examined the effects of both cinnamaldehyde and extracts of C. cassia on cytokine-induced monocyte/human endothelial cell interactions. We find that these compounds inhibit the adhesion of TNF{alpha}-induced monocytes to endothelial cells and suppress the expression of the cell adhesion molecules, VCAM-1 and ICAM-1, atmore » the transcriptional level. Moreover, in TNF{alpha}-treated ECs, the principal downstream signal of VCAM-1 and ICAM-1, NF-{kappa}B, was also found to be abolished in a time-dependent manner. Interestingly, cinnamaldehyde exerts its anti-inflammatory effects by blocking the degradation of the inhibitory protein I{kappa}B-{alpha}, but only in short term pretreatments, whereas it does so via the induction of Nrf2-related genes, including heme-oxygenase-1 (HO-1), over long term pretreatments. Treating ECs with zinc protoporphyrin, a HO-1 inhibitor, partially blocks the anti-inflammatory effects of cinnamaldehyde. Elevated HO-1 protein levels were associated with the inhibition of TNF{alpha}-induced ICAM-1 expression. In addition to HO-1, we also found that cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE-luciferase activity and upregulate thioredoxin reductase-1, another Nrf2-related gene. Moreover, cinnamaldehyde exposure rapidly reduces the cellular GSH levels in ECs over short term treatments but increases these levels after 9 h exposure. Hence, our present findings indicate that cinnamaldehyde suppresses TNF-induced singling pathways via two distinct mechanisms that are activated by different pretreatment

Zinc in Infection and Inflammation

PubMed Central

Gammoh, Nour Zahi; Rink, Lothar

2017-01-01

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli. PMID:28629136

Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

PubMed

Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

2010-06-01

Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

Count on kappa.

PubMed

Czodrowski, Paul

2014-11-01

In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classification tasks where ranking is not considered. The main advantage of kappa is its simplicity and the general applicability to multi-class problems which is the major difference to receiver operating characteristic area under the curve. In this manuscript, I will outline the usage of kappa for classification tasks, and I will evaluate the role and uses of kappa in specifically machine learning and cheminformatics.

Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2.

PubMed Central

Duckett, C S; Gedrich, R W; Gilfillan, M C; Thompson, C B

1997-01-01

CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we define the domains in CD30 which are required for NF-kappaB activation. Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappaB independently of one another were identified. The first domain (domain 1) mapped to a approximately 120-amino-acid sequence in the membrane-proximal region of the CD30 cytoplasmic tail, between residues 410 and 531. A second, more carboxy-terminal region (domain 2) was identified between residues 553 and 595. Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins. Coexpression of CD30 with TRAF1 or TRAF2 but not TRAF3 augmented NF-kappaB activation through domain 2 but not domain 1. NF-kappaB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB induction by domain 1 was not affected by alterations in TRAF protein levels. Together, these data support a model in which CD30 can induce NF-kappaB by both TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell. PMID:9032281

Pharmacological characterization of the cloned kappa opioid receptor as a kappa 1b subtype.

PubMed

Lai, J; Ma, S W; Zhu, R H; Rothman, R B; Lentes, K U; Porreca, F

1994-10-27

Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa 1 ligand [3H]U69,593 in mouse brain membranes, termed kappa 1a and kappa 1b, respectively. Whereas the kappa 1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha-neoendorphin, site kappa 1b has high affinity for bremazocine and alpha-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa 1 receptor subtypes and the recently cloned mouse kappa 1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, alpha-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa 1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa 1 site in mouse brain defined as kappa 1b.

Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

PubMed

Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

2017-08-01

Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Effects of Cot expression on the nuclear translocation of NF-kappaB in RBL-2H3 cells.

PubMed

Chikamatsu, Satomi; Furuno, Tadahide; Kinoshita, Yosuke; Inoh, Yoshikazu; Hirashima, Naohide; Teshima, Reiko; Nakanishi, Mamoru

2007-03-01

Cot is a serine/threonine protein kinase and is classified as a mitogen-activated protein (MAP) kinase kinase kinase. Overexpression of this protein has been shown to activate the extracellular signal-regulated kinase, the c-Jun N-terminal kinase, and the p38 MAP kinase pathways and to stimulate NF-AT and NF-kappaB-dependent transcription. Here we have shown that Cot kinase activity is intimately involved in the high affinity receptor for IgE (FcvarepsilonRI)-mediated nuclear translocation of NF-kappaB1 independent of NF-kappaB-inducing kinase (NIK) in rat basophilic leukemia (RBL-2H3) cells. A transfected green fluorescent protein-tagged NF-kappaB1 (GFP-NF-kappaB1) resided in the cytoplasm in RBL-2H3 cells and it remained in the cytoplasm even when Cot tagged with red fluorescent protein (Cot-RFP) was co-expressed. Western blotting analysis showed that IkappaB kinases (IKKs) were expressed in RBL-2H3 cells but NIK was not. GFP-NF-kappaB1 translocated from the cytoplasm to the nucleus after the aggregation of FcvarepsilonRI in Cot-transfected cells but not in kinase-deficient Cot-transfected cells. This finding gives a new insight into the role of Cot in the FcvarepsilonRI-mediated NF-kappaB activation in mast cells.

Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells.

PubMed

Van De Walle, Jacqueline; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2008-04-01

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappaB activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 microg/ml. Phosphorylation of inhibitor-kappaB (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF-kappaB and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-kappaB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.

The kappa statistic in rehabilitation research: an examination.

PubMed

Tooth, Leigh R; Ottenbacher, Kenneth J

2004-08-01

The number and sophistication of statistical procedures reported in medical rehabilitation research is increasing. Application of the principles and methods associated with evidence-based practice has contributed to the need for rehabilitation practitioners to understand quantitative methods in published articles. Outcomes measurement and determination of reliability are areas that have experienced rapid change during the past decade. In this study, distinctions between reliability and agreement are examined. Information is presented on analytical approaches for addressing reliability and agreement with the focus on the application of the kappa statistic. The following assumptions are discussed: (1) kappa should be used with data measured on a categorical scale, (2) the patients or objects categorized should be independent, and (3) the observers or raters must make their measurement decisions and judgments independently. Several issues related to using kappa in measurement studies are described, including use of weighted kappa, methods of reporting kappa, the effect of bias and prevalence on kappa, and sample size and power requirements for kappa. The kappa statistic is useful for assessing agreement among raters, and it is being used more frequently in rehabilitation research. Correct interpretation of the kappa statistic depends on meeting the required assumptions and accurate reporting.

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

PubMed

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

Bis(acesulfamato-kappaO4)diaquabis(3-methylpyridine-kappaN)nickel(II).

PubMed

Dege, Necmi; Içbudak, Hasan; Adiyaman, Elif

2007-01-01

In the crystal structure of the title compound [systematic name: diaquabis(6-methyl-2,2-dioxo-1,2,3-oxathiazin-4-olato-kappaO4)bis(3-methylpyridine-kappaN)nickel(II)], [Ni(C4H4NO4S)2(C6H7N)2(H2O)2], the Ni(II) centre resides on a centre of symmetry and has a distorted octahedral geometry. The basal plane is formed by two carbonyl O atoms of two monodentate trans-oriented acesulfamate ligands and two trans aqua ligands. The axial positions in the octahedron are occupied by two N atoms of two trans pyridine ligands. Molecules are stacked in columns running along the a axis. There are pi-pi stacking interactions between the molecules in each column, with a distance of 3.623 (2) A between the centroids of the pyridine rings. There are also O-H...O interactions between the columns.

Mechanisms generating kappa distributions in plasmas

NASA Astrophysics Data System (ADS)

Livadiotis, Georgios

2017-10-01

Kappa distributions have become increasingly widespread across plasma physics. Publication records reveal an exponential growth of papers relevant to kappa distributions. However, the vast majority of publications refer to statistical fits and applications of these distributions in plasmas. Up to date, there is no systematic analysis on the origin of kappa distributions, that is, the mechanisms that can generate kappa distributions in plasmas. The general scheme that characterizes these mechanisms is composed of two parts: (1) the generation of local correlations among particles, and (2) the thermalization, that is, the stabilization of the particle system into stationary states described by kappa distributions or combinations thereof. Several mechanisms are known in the literature, each characterized by a specific relationship between the plasma properties. These relationships serve as conditions that need to be fulfilled for the corresponding mechanisms to be applied in the plasma. Using these relationships, we identify three mechanisms that generate kappa distributions in the solar wind plasma: (i) Debye shielding, (ii) magnetic field binding, and (iii) thermal fluctuations, each one prevailing in different scales of the solar wind plasma and magnetic field properties. The work was supported in part by the project NNX17AB74G of NASA's HGI Program.

A quantitative study of NF-kappaB activation by H2O2: relevance in inflammation and synergy with TNF-alpha.

PubMed

de Oliveira-Marques, Virgínia; Cyrne, Luísa; Marinho, H Susana; Antunes, Fernando

2007-03-15

Although the germicide role of H(2)O(2) released during inflammation is well established, a hypothetical regulatory function, either promoting or inhibiting inflammation, is still controversial. In particular, after 15 years of highly contradictory results it remains uncertain whether H(2)O(2) by itself activates NF-kappaB or if it stimulates or inhibits the activation of NF-kappaB by proinflammatory mediators. We investigated the role of H(2)O(2) in NF-kappaB activation using, for the first time, a calibrated and controlled method of H(2)O(2) delivery--the steady-state titration--in which cells are exposed to constant, low, and known concentrations of H(2)O(2). This technique contrasts with previously applied techniques, which disrupt cellular redox homeostasis and/or introduce uncertainties in the actual H(2)O(2) concentration to which cells are exposed. In both MCF-7 and HeLa cells, H(2)O(2) at extracellular concentrations up to 25 microM did not induce significantly per se NF-kappaB translocation to the nucleus, but it stimulated the translocation induced by TNF-alpha. For higher H(2)O(2) doses this stimulatory role shifts to an inhibition, which may explain published contradictory results. The stimulatory role was confirmed by the observation that 12.5 microM H(2)O(2), a concentration found during inflammation, increased the expression of several proinflammatory NF-kappaB-dependent genes induced by TNF-alpha (e.g., IL-8, MCP-1, TLR2, and TNF-alpha). The same low H(2)O(2) concentration also induced the anti-inflammatory gene coding for heme oxygenase-1 (HO-1) and IL-6. We propose that H(2)O(2) has a fine-tuning regulatory role, comprising both a proinflammatory control loop that increases pathogen removal and an anti-inflammatory control loop, which avoids an exacerbated harmful inflammatory response.

[Concordance between the zinc sulphate flotation and centrifugal sedimentation methods for the diagnosis of intestinal parasites].

PubMed

Inês, Elizabete De Jesus; Pacheco, Flavia Thamiris Figueiredo; Pinto, Milena Carneiro; Mendes, Patrícia Silva de Almeida; Da Costa-Ribeiro, Hugo; Soares, Neci Matos; Teixeira, Márcia Cristina Aquino

2016-12-01

The diagnosis of intestinal parasitic infections depends on the parasite load, the specific gravity density of the parasite eggs, oocysts or cysts, and the density and viscosity of flotation or sedimentation medium where faeces are processed. To evaluate the concordance between zinc sulphate flotation and centrifugal sedimentation in the recovery of parasites in faecal samples of children. Faecal samples of 330 children from day care centers were evaluated by zinc sulphate flotation and centrifugal sedimentation techniques. The frequencies of detection of parasites by each method were determined and the agreement between the diagnostic techniques was evaluated using the kappa index, with 95% confidence intervals. The faecal flotation in zinc sulphate diagnosed significantly more cases of Trichuris trichiura infection when compared to centrifugal sedimentation (39/330; 11.8% vs. 13/330; 3.9%, p<0.001), with low diagnostic concordance between methods (kappa=0.264; 95% CI: 0.102-0.427). Moreover, all positive samples for Enterobius vermicularis eggs (n=5) and Strongyloides stercoralis larvae (n=3) were diagnosed only by zinc sulphate. No statistical differences were observed between methods for protozoa identification. The results showed that centrifugal flotation in zinc sulphate solution was significantly more likely to detect light helminths eggs such as those of T. trichiura and E. vermicularis in faeces than the centrifugal sedimentation process.

Characterizing Cometary Electrons with Kappa Distributions

NASA Technical Reports Server (NTRS)

Broiles, T. W.; Livadiotis, G.; Burch, J. L.; Chae, K.; Clark, G.; Cravens, T. E.; Davidson, R.; Eriksson, A.; Frahm, R. A.; Fuselier, S. A.;

Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.

PubMed

Lee, Kyung Mi; Kang, Nam Joo; Han, Jin Hee; Lee, Ki Won; Lee, Hyong Joo

2007-11-14

Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.

Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

PubMed

Foster, Meika; Samman, Samir

2010-11-15

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin.

PubMed

Chiang, Yi-Ming; Lo, Chiu-Ping; Chen, Yi-Ping; Wang, Sheng-Yang; Yang, Ning-Sun; Kuo, Yueh-Hsiung; Shyur, Lie-Fen

2005-10-01

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC(50) = 5.5 microg ml(-1)), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor kappaB (IkappaB) and the translocation of nuclear transcription factor-kappaB (NF-kappaB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-kappaB.DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and alpha,beta-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-kappaB.DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

NF-kappaB mediates FGF signal regulation of msx-1 expression.

PubMed

Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

2001-09-01

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

Obliquely Propagating Waves in Bi-Kappa Plasmas

NASA Astrophysics Data System (ADS)

Gaelzer, R.; Ziebell, L. F.; Meneses, A. R.

2016-12-01

The effects of kappa velocity distribution functions (VDFs) have been the subjectof intense research. Such functions have beenfound to provide a better fitting to the VDFs measured by spacecraftin the solar wind. An anisotropic VDF contains free energy that can excite wavesin the plasma. The induced turbulence also determines the observed shape of the VDF.The general treatment for waves excited by (bi-)Maxwellian plasmas is well-established.However, for kappa distributions (isotropic or anisotropic), the majority of the studieswere restricted to the limiting cases of purely parallel or perpendicular propagation.Contributions to the general case of obliquely-propagating waves have been scarcely reported.The absence of a general treatment prevents a complete analysis of the wave-particle interactionin kappa plasmas, since some instabilities can operate both in the parallel and oblique directions.A series of papers published by the authors begin to remedy this situation. In a first work [1],we have obtained the dielectric tensor and dispersion relations for quasi-perpendicular dispersive Alfvén waves resulting from a kappa VDF. This approach was later generalized by [2],where the formalism was extended to the general case of electrostatic/electromagnetic waves propagatingin an isotropic kappa plasma in any frequency range and for arbitrary angles.In the present work [3], we generalize even further the formalism by the derivation of thegeneral dielectric tensor of an anisotropic bi-kappa plasma. We present the state-of-the-art of theformalism and show how it enables a systematic study of waves and instabilities propagating inarbitrary directions and frequencies in a bi-kappa plasma.[1] R. Gaelzer, L. F. Ziebell, J. Geophys. Res. 119, 9334 (2014), doi: 10.1002/2014JA020667.[2] R. Gaelzer, L. F. Ziebell, Phys. Plasmas 23, 022110 (2016), doi: 10.1063/1.4941260.[3] R. Gaelzer et al., Phys. Plasmas 23, 062108 (2016), doi: 10.1063/1.4953430.

NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter.

PubMed

Borghaei, Ruth C; Rawlings, P Lyle; Javadi, Masoud; Woloshin, Joanna

2004-03-26

A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kappaB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kappaB in limiting the cytokine induced expression of MMP-3.

KAPPA -- Kernel Application Package

NASA Astrophysics Data System (ADS)

Currie, Malcolm J.; Berry, David. S.

KAPPA is an applications package comprising about 180 general-purpose commands for image processing, data visualisation, and manipulation of the standard Starlink data format---the NDF. It is intended to work in conjunction with Starlink's various specialised packages. In addition to the NDF, KAPPA can also process data in other formats by using the `on-the-fly' conversion scheme. Many commands can process data arrays of arbitrary dimension, and others work on both spectra and images. KAPPA operates from both the UNIX C-shell and the ICL command language. This document describes how to use KAPPA and its features. There is some description of techniques too, including a section on writing scripts. This document includes several tutorials and is illustrated with numerous examples. The bulk of this document comprises detailed descriptions of each command as well as classified and alphabetical summaries.

Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

PubMed

Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

2010-05-03

Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

Interrater reliability: the kappa statistic.

PubMed

McHugh, Mary L

2012-01-01

The kappa statistic is frequently used to test interrater reliability. The importance of rater reliability lies in the fact that it represents the extent to which the data collected in the study are correct representations of the variables measured. Measurement of the extent to which data collectors (raters) assign the same score to the same variable is called interrater reliability. While there have been a variety of methods to measure interrater reliability, traditionally it was measured as percent agreement, calculated as the number of agreement scores divided by the total number of scores. In 1960, Jacob Cohen critiqued use of percent agreement due to its inability to account for chance agreement. He introduced the Cohen's kappa, developed to account for the possibility that raters actually guess on at least some variables due to uncertainty. Like most correlation statistics, the kappa can range from -1 to +1. While the kappa is one of the most commonly used statistics to test interrater reliability, it has limitations. Judgments about what level of kappa should be acceptable for health research are questioned. Cohen's suggested interpretation may be too lenient for health related studies because it implies that a score as low as 0.41 might be acceptable. Kappa and percent agreement are compared, and levels for both kappa and percent agreement that should be demanded in healthcare studies are suggested.

[Study on solid phase extraction spectrophotometric determination of zinc with 2-(2-quinolylazo)-5-dimthylaminophenol].

PubMed

Zhou, Shi-ping; Duan, Chang-qun; Liu, Hong-cheng; Hu, Qiu-fen

2005-10-01

A highly sensitive, selective and rapid method for the determination of zinc based on the rapid reaction of zinc(II) with 2-(2-quinolylazo)-5-dimthylaminophenol (QADMAP) and the solid phase extraction of zinc ion with anion exchange resin cartridge was developed. In the presence of pH 8.5 buffer solution and Triton X-100 medium, QADMAP can react with zinc(II) to form a stable 2 :1 complex (QADMAP:Zn(II)). The molar absorptivity is 1.22 x 10(5)L x moL(-1) x cm(-1) at 590 nm. Beer's law is obeyed in the range of 0-1.0 microg x mL(-1). The zinc ions in the samples can be enriched and separated by solid phase extraction with anion exchange resincartridge. Testing results show that recovery for zinc(II) was from 95% to 104%, and RSD was below 3%. This method was applied to the determination of zinc in water and food with good results.

Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant.

PubMed

Itsumura, Naoya; Inamo, Yasuji; Okazaki, Fumiko; Teranishi, Fumie; Narita, Hiroshi; Kambe, Taiho; Kodama, Hiroko

2013-01-01

Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant.

Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant

PubMed Central

Itsumura, Naoya; Inamo, Yasuji; Okazaki, Fumiko; Teranishi, Fumie; Narita, Hiroshi; Kambe, Taiho; Kodama, Hiroko

2013-01-01

Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant. PMID:23741301

Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

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

Genetos, Damian C., E-mail: dgenetos@ucdavis.edu; Karin, Norman J.; Geist, Derik J.

2011-04-01

Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that themore » P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.« less

The Correlation between Angle Kappa and Ocular Biometry in Koreans

PubMed Central

Choi, Se Rang

2013-01-01

Purpose To investigate normative angle kappa data and to examine whether correlations exist between angle kappa and ocular biometric measurements (e.g., refractive error, axial length) and demographic features in Koreans. Methods Data from 436 eyes (213 males and 223 females) were analyzed in this study. The angle kappa was measured using Orbscan II. We used ocular biometric measurements, including refractive spherical equivalent, interpupillary distance and axial length, to investigate the correlations between angle kappa and ocular biometry. The IOL Master ver. 5.02 was used to obtain axial length. Results The mean patient age was 57.5 ± 12.0 years in males and 59.4 ± 12.4 years in females (p = 0.11). Angle kappa averaged 4.70 ± 2.70 degrees in men and 4.89 ± 2.14 degrees in women (p = 0.48). Axial length and spherical equivalent were correlated with angle kappa (r = -0.342 and r = 0.197, respectively). The correlation between axial length and spherical equivalent had a negative correlation (r = -0.540, p < 0.001). Conclusions Angle kappa increased with spherical equivalent and age. Thus, careful manipulation should be considered in older and hyperopic patients when planning refractive or strabismus surgery. PMID:24311927

NF-kappaB modulators from Valeriana officinalis.

PubMed

Jacobo-Herrera, Nadia J; Vartiainen, Nina; Bremner, Paul; Gibbons, Simon; Koistinaho, Jari; Heinrich, Michael

2006-10-01

Valeriana officinalis (Valerianaceae) has been of great interest for its therapeutic uses for treating mild nervous tension and temporary sleeping problems. In traditional European medicine it has been also reported as an antiinflammatory remedy. This study reports that the EtOAc extract of the underground parts of V. officinalis showed inhibitory activity against NF-kappaB at 100 microg/mL in the IL-6/Luc assay on HeLa cells and provided protection against excitotoxicity in primary brain cell cultures at micromolar concentrations. Bioassay-guided fractionation of the EtOAc extract led to the isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-kappaB activity to 4%, whereas valerenic acid (3) reduced NF-kappaB activity to 25%. Copyright 2006 John Wiley & Sons, Ltd.

Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

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

Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan

2005-07-01

Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayedmore » TNF-{alpha}-induced I{kappa}B{alpha} degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the I{kappa}B{alpha} stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.« less

Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes.

PubMed

Penkowa, M; Giralt, M; Thomsen, P S; Carrasco, J; Hidalgo, J

2001-04-01

The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured brains, zinc deficiency only affected significantly lectin (increasing) and glial fibrillary acidic protein (GFAP) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (decreasing) immunoreactivities (irs). In injured brains, a profound gliosis was observed in the area surrounding the lesion, along with severe damage to neurons as indicated by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis (measured by TUNEL) was dramatically increased. Zinc deficiency significantly altered brain response to TBI, potentiating the microgliosis and reducing the astrogliosis, while increasing the number of apoptotic cells. Metallothioneins (MTs) are important zinc- and copper-binding proteins in the CNS, which could influence significantly the brain response to TBI because of their putative roles in metal homeostasis and antioxidant defenses. MT-I+II expression was dramatically increased by TBI, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All these effects were attributable to zinc deficiency, since pair-fed rats did not differ from normally fed rats. In general, copper deficiency caused a similar pattern of responses

Inequalities between Kappa and Kappa-Like Statistics for "k x k" Tables

ERIC Educational Resources Information Center

Warrens, Matthijs J.

2010-01-01

The paper presents inequalities between four descriptive statistics that can be expressed in the form [P-E(P)]/[1-E(P)], where P is the observed proportion of agreement of a "kappa x kappa" table with identical categories, and E(P) is a function of the marginal probabilities. Scott's "pi" is an upper bound of Goodman and Kruskal's "lambda" and a…

The relationship between kappa and temperature in energetic ion spectra at Jupiter

NASA Technical Reports Server (NTRS)

Collier, Michael R.; Hamilton, D. C.

1995-01-01

A universal energy per charge kappa function fit is simultaneously applied to the spectra of Voyager 2 Low Energy Charged Particle (LECP) proton, helium, oxygen, sulfur, and carbon ions during 33 Jovian plasma sheet crossings from 26 to 160 R(sub J). The fits yield an approximately linear relationship between high energy spectral index, kappa, and core proton temperature of the form kappa (T(sub H)) approximately = eta dot T(sub H) + kappa(sub 0) with eta = 0.080 ke/V, kappa(sub 0) = 2.86, and T(sub H) measured in keV. Core proton temperatures range from 5 to 35 keV with spectral indices ranging from 3 to 6.

Hydrocracking with molten zinc chloride catalyst containing 2-12% ferrous chloride

DOEpatents

Zielke, Clyde W.; Bagshaw, Gary H.

1981-01-01

In a process for hydrocracking heavy aromatic polynuclear carbonaceous feedstocks to produce hydrocarbon fuels boiling below about 475.degree. C. by contacting the feedstocks with hydrogen in the presence of a molten zinc chloride catalyst and thereafter separating at least a major portion of the hydrocarbon fuels from the spent molten zinc chloride catalyst, an improvement comprising: adjusting the FeCl.sub.2 content of the molten zinc chloride to from about 2 to about 12 mol percent based on the mixture of ferrous chloride and molten zinc chloride.

The Zinc-Responsive Regulator Zur Controls a Zinc Uptake System and Some Ribosomal Proteins in Streptomyces coelicolor A3(2)▿

PubMed Central

Shin, Jung-Ho; Oh, So-Young; Kim, Soon-Jong; Roe, Jung-Hye

2007-01-01

In various bacteria, Zur, a zinc-specific regulator of the Fur family, regulates genes for zinc transport systems to maintain zinc homeostasis. It has also been suggested that Zur controls zinc mobilization by regulating some ribosomal proteins. The antibiotic-producing soil bacterium Streptomyces coelicolor contains four genes for Fur family regulators, and one (named zur) is located downstream of the znuACB operon encoding a putative zinc uptake transporter. We found that zinc specifically repressed the level of znuA transcripts and that this level was derepressed in a Δzur mutant. Purified Zur existing as homodimers bound to the znuA promoter region in the presence of zinc, confirming the role of Zur as a zinc-responsive repressor. We analyzed transcripts for paralogous forms of ribosomal proteins L31 (RpmE1 and RpmE2) and L33 (RpmG2 and RpmG3) for their dependence on Zur and found that RpmE2 and RpmG2 with no zinc-binding motif of conserved cysteines (C's) were negatively regulated by Zur. C-negative RpmG3 and C-positive RpmE1 were not regulated by Zur. Instead, they were regulated by the sigma factor σR as predicted from their promoter sequences. The rpmE1 and rpmG3 genes were partially induced by EDTA in a manner dependent on σR, suggesting that zinc depletion may stimulate the σR regulatory system. This finding reflects a link between thiol-oxidizing stress and zinc depletion. We determined the Zur-binding sites within znuA and rpmG2 promoter regions by footprinting analyses and identified a consensus inverted repeat sequence (TGaaAatgatTttCA, where uppercase letters represent the nucleotides common to all sites analyzed). This sequence closely matches that for mycobacterial Zur and allows the prediction of more genes in the Zur regulon. PMID:17416659

Homologous kappa-neurotoxins exhibit residue-specific interactions with the alpha 3 subunit of the nicotinic acetylcholine receptor: a comparison of the structural requirements for kappa-bungarotoxin and kappa-flavitoxin binding.

PubMed

McLane, K E; Weaver, W R; Lei, S; Chiappinelli, V A; Conti-Tronconi, B M

1993-07-13

kappa-Flavotoxin (kappa-FTX), a snake neurotoxin that is a selective antagonist of certain neuronal nicotinic acetylcholine receptors (AChRs), has recently been isolated and characterized [Grant, G. A., Frazier, M. W., & Chiappinelli, V. A. (1988) Biochemistry 27, 1532-1537]. Like the related snake toxin kappa-bungarotoxin (kappa-BTX), kappa-FTX binds with high affinity to alpha 3 subtypes of neuronal AChRs, even though there are distinct sequence differences between the two toxins. To further characterize the sequence regions of the neuronal AChR alpha 3 subunit involved in formation of the binding site for this family of kappa-neurotoxins, we investigated kappa-FTX binding to overlapping synthetic peptides screening the alpha 3 subunit sequence. A sequence region forming a "prototope" for kappa-FTX was identified within residues alpha 3 (51-70), confirming the suggestions of previous studies on the binding of kappa-BTX to the alpha 3 subunit [McLane, K. E., Tang, F., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 1537-1544] and alpha-bungarotoxin to the Torpedo AChR alpha subunit [Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230] that this sequence region is involved in formation of a cholinergic site. Single residue substituted analogues, where each residue of the sequence alpha 3 (51-70) was sequentially replaced by a glycine, were used to identify the amino acid side chains involved in the interaction of this prototope with kappa-FTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-{kappa}B

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

Bin Hafeez, Bilal; Ahmed, Salahuddin; Wang, Naizhen

2006-10-01

Development of chemotherapy resistance and evasion from apoptosis in osteosarcoma, a primary malignant bone tumor, is often correlated with constitutive nuclear factor-{kappa}B (NF-{kappa}B) activation. Here, we investigated the ability of a polyphenolic fraction of green tea (GTP) that has been shown to have antitumor effects on various malignant cell lines to inhibit growth and induce apoptosis in human osteosarcoma SAOS-2 cells. Treatment of SAOS-2 cells with GTP (20-60 {mu}g/ml) resulted in reduced cell proliferation and induction of apoptosis, which correlated with decreased nuclear DNA binding of NF-{kappa}B/p65 and lowering of NF-{kappa}B/p65 and p50 levels in the cytoplasm and nucleus. GTPmore » treatment of cells reduced I{kappa}B-{alpha} phosphorylation but had no effect on its protein expression. Furthermore, GTP treatment resulted in the inhibition of IKK-{alpha} and IKK-{beta}, the upstream kinases that phosphorylate I{kappa}B-{alpha}. The increase in apoptosis in SAOS-2 cells was accompanied with decrease in the protein expression of Bcl-2 and concomitant increase in the levels of Bax. GTP treatment of SAOS-2 cells also resulted in significant activation of caspases as was evident by increased levels of cleaved caspase-3 and caspase-8 in these cells. Treatment of SAOS-2 cells with a specific caspase-3 inhibitor Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) and general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) rescued SAOS-2 cells from GTP-induced apoptosis. Taken together, these results indicate that GTP is a candidate therapeutic for osteosarcoma that mediates its antiproliferative and apoptotic effects via activation of caspases and inhibition of NF-{kappa}B.« less

Novel synergistic mechanism for sst2 somatostatin and TNFalpha receptors to induce apoptosis: crosstalk between NF-kappaB and JNK pathways.

PubMed

Guillermet-Guibert, J; Saint-Laurent, N; Davenne, L; Rochaix, P; Cuvillier, O; Culler, M D; Pradayrol, L; Buscail, L; Susini, C; Bousquet, C

2007-02-01

Somatostatin is a multifunctional hormone that modulates cell proliferation, differentiation and apoptosis. Mechanisms for somatostatin-induced apoptosis are at present mostly unsolved. Therefore, we investigated whether somatostatin receptor subtype 2 (sst2) induces apoptosis in the nontransformed murine fibroblastic NIH3T3 cells. Somatostatin receptor subtype 2 expression induced an executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B (NF-kappaB) activity and subsequent inhibition of the mitogen-activated protein kinase JNK. Tumor necrosis factor alpha (TNFalpha) stimulated both NF-kappaB and c-Jun NH2-terminal kinase (JNK) activities, which had opposite action on cell survival. Importantly, sst2 sensitized NIH3T3 cells to TNFalpha-induced apoptosis by (1) upregulating TNFalpha receptor protein expression, and sensitizing to TNFalpha-induced caspase-8 activation; (2) enhancing TNFalpha-mediated activation of NF-kappaB, resulting in JNK inhibition and subsequent executioner caspase activation and cell death. We have here unraveled a novel signaling mechanism for a G protein-coupled receptor, which directly triggers apoptosis and crosstalks with a death receptor to enhance death ligand-induced apoptosis.

The disagreeable behaviour of the kappa statistic.

PubMed

Flight, Laura; Julious, Steven A

2015-01-01

It is often of interest to measure the agreement between a number of raters when an outcome is nominal or ordinal. The kappa statistic is used as a measure of agreement. The statistic is highly sensitive to the distribution of the marginal totals and can produce unreliable results. Other statistics such as the proportion of concordance, maximum attainable kappa and prevalence and bias adjusted kappa should be considered to indicate how well the kappa statistic represents agreement in the data. Each kappa should be considered and interpreted based on the context of the data being analysed. Copyright © 2014 John Wiley & Sons, Ltd.

Interrelationships among mediators of cellular zinc homeostasis in healthy and type 2 diabetes mellitus populations.

PubMed

Chu, Anna; Foster, Meika; Hancock, Dale; Petocz, Peter; Samman, Samir

2017-04-01

The involvement of zinc in multiple physiological systems requires tight control of cellular zinc concentration. This study aims to explore the relationships among selected mediators of cellular zinc homeostasis in an apparently healthy (AH) population and a cohort with type 2 diabetes mellitus (T2DM). Baseline data of three trials forming two cohorts, AH (n = 70) and T2DM (n = 42), were used for multivariate analyses to identify groupings within ten zinc transporter and metallothionein (MT) gene expressions, stratified by health status. Multiple regression models were used to explore relationships among zinc transporter/MT groupings and plasma zinc. Gene expression of zinc transporters and MTs, with the exception of ZnT6, were significantly lower in the T2DM cohort (p < 0.01). Cluster analysis showed that the groupings of zinc transporters and MTs were largely similar between the two cohorts, with the exception for ZnT1 and ZIP7. Zinc transporters and MTs were significant determinants of plasma zinc (r 2 = 0.48, p = 0.001) in the AH cohort, but not in the T2DM cohort. The current study suggests altered cellular zinc homeostasis in T2DM and supports the use of multiple zinc transporters and MTs groupings to further understand zinc homeostasis in health and T2DM. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB.

PubMed

Lee, Dong-Kee; Kang, Jae-Eun; Park, Hye-Jin; Kim, Myung-Hwa; Yim, Tae-Hee; Kim, Jung-Min; Heo, Min-Kyu; Kim, Kyu-Yeun; Kwon, Ho Jeong; Hur, Man-Wook

2005-07-29

The POZ domain is a highly conserved protein-protein interaction motif found in many regulatory proteins. Nuclear factor-kappaB (NF-kappaB) plays a key role in the expression of a variety of genes in response to infection, inflammation, and stressful conditions. We found that the POZ domain of FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) interacted with the Rel homology domain of the p65 subunit of NF-kappaB in both in vivo and in vitro protein-protein interaction assays. FBI-1 enhanced NF-kappaB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IkappaB alpha or IkappaB beta. In contrast, the POZ domain of FBI-1, which is a dominant-negative form of FBI-1, repressed NF-kappaB-mediated transcription, and the repression was cooperative with IkappaB alpha or IkappaB beta. In contrast, the POZ domain tagged with a nuclear localization sequence polypeptide of FBI-1 enhanced NF-kappaB-responsive gene transcription, suggesting that the molecular interaction between the POZ domain and the Rel homology domain of p65 and the nuclear localization by the nuclear localization sequence are important in the transcription enhancement mediated by FBI-1. Confocal microscopy showed that FBI-1 increased NF-kappaB movement into the nucleus and increased the stability of NF-kappaB in the nucleus, which enhanced NF-kappaB-mediated transcription of the E-selectin gene. FBI-1 also interacted with IkappaB alpha and IkappaB beta.

40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN P-97-553...

40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN P-97-553...

15-Deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2} induces renal epithelial cell death through NF-{kappa}B-dependent and MAPK-independent mechanism

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

Kang, Dae Sik; Kwon, Chae Hwa; Park, Ji Yeon

2006-11-01

The peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) ligand 15d-PGJ{sub 2} induces cell death in renal proximal tubular cells. However, the underlying molecular mechanism(s) remains unidentified. The present study was undertaken to examine the roles of reactive oxygen species (ROS), mitogen-activated protein kinase, and NF-{kappa}B in opossum kidney (OK) cell death induced by 15d-PGJ{sub 2}. Treatment of OK cells with 15d-PGJ{sub 2} resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. 15d-PGJ{sub 2} increased ROS production and the effect was inhibited by catalase and N-acetylcysteine. The 15d-PGJ{sub 2}-induced cell death was also prevented by these antioxidants, suggesting thatmore » the cell death was associated with ROS generation. The PPAR{gamma} antagonist GW9662 did not prevent the 15d-PGJ{sub 2}-induced cell death. 15d-PGJ{sub 2} caused a transient activation of extracellular signal-regulated kinase (ERK). However, inhibitors (PD98059 and U0126) of MEK, an ERK upstream kinase, did not alter the 15d-PGJ{sub 2}-induced cell death. Transfection with constitutively active MEK and dominant-negative MEK had no effect on the cell death. 15d-PGJ{sub 2} inhibited the NF-{kappa}B transcriptional activity, which was accompanied by an inhibition of nuclear translocation of the NF-{kappa}B subunit p65 and impairment in DNA binding. Inhibition of NF-{kappa}B with a NF-{kappa}B specific inhibitor pyrrolidinecarbodithioate and transfection with I{kappa}B{alpha} (S32A/36A) caused cell death. These results suggest that the 5d-PGJ{sub 2}-induced OK cell death was associated with ROS production and NF-{kappa}B inhibition, but not with MAPK activation.« less

Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

PubMed

Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

2015-02-01

Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

Involvement of nuclear factor {kappa}B in platelet CD40 signaling

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

Hachem, Ahmed; Yacoub, Daniel; Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1

Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Givenmore » that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against

Rosiglitazone attenuates NF-{kappa}B-dependent ICAM-1 and TNF-{alpha} production caused by homocysteine via inhibiting ERK{sub 1/2}/p38MAPK activation

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

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia

2007-08-17

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-{kappa}B) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-{kappa}B-mediated sICAM-1, TNF-{alpha} production and the possible involvement of ERK{sub 1/2}/p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-{alpha} in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-{kappa}B inhibitor; PD98059,more » MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B activity in HUVECs. The results show that Hcy activated both ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK{sub 1/2}/p38MAPK phosphorylation, suggesting that Hcy-induced ERK{sub 1/2}/p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-{kappa}B activation was mediated by activation of ERK{sub 1/2}/p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-{kappa}B-mediated sICAM-1 and TNF-{alpha} production induced by Hcy via inhibition of ERK{sub 1/2}/p38MAPK pa0011thw.« less

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

NASA Technical Reports Server (NTRS)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Translesion synthesis past equine estrogen-derived 2'-deoxyadenosine DNA adducts by human DNA polymerases eta and kappa.

PubMed

Yasui, Manabu; Laxmi, Y R Santosh; Ananthoju, Sreenivasa R; Suzuki, Naomi; Kim, Sung Yeon; Shibutani, Shinya

2006-05-16

Hormone replacement therapy (HRT) increases the risk of developing breast, ovarian, and endometrial cancers. Equilin and equilenin are the major components of the widely prescribed drug used for HRT. 4-Hydroxyequilenin (4-OHEN), a major metabolite of equilin and equilenin, promotes 4-OHEN-modified dC, dA, and dG DNA adducts. These DNA adducts were detected in breast tumor and adjacent normal tissues of several patients receiving HRT. We have recently found that the 4-OHEN-dC DNA adduct is a highly miscoding lesion generating C --> T transitions and C --> G transversions. To explore the mutagenic potential of another major 4-OHEN-dA adduct, site-specifically modified oligodeoxynucleotides containing a single diastereoisomer of 4-OHEN-dA (Pk-1, Pk-2, and Pk-3) were prepared by a postsynthetic method and used as DNA templates for primer extension reactions catalyzed by human DNA polymerase (pol) eta and kappa that are highly expressed in the reproductive organs. Primer extension catalyzed by pol eta or pol kappa occurred rapidly on the unmodified template to form fully extended products. With the major 4-OHEN-dA-modified templates (Pk-2 and Pk-3), primer extension was retarded prior to the lesion and opposite the lesion; a fraction of the primers was extended past the lesion. Steady-state kinetic studies with pol eta and pol kappa indicated that dTMP, the correct base, was preferentially incorporated opposite the 4-OHEN-dA lesion. In addition, pol eta and pol kappa bypassed the lesion by incorporating dAMP and dCMP, respectively, opposite the lesion and extended past the lesion. The relative bypass frequency past the 4-OHEN-dA lesion with pol eta was at least 2 orders of magnitude higher than that observed with pol kappa. The bypass frequency past Pk-2 was more efficient than that past Pk-3. Thus, 4-OHEN-dA is a miscoding lesion generating A --> T transversions and A --> G transitions. The miscoding frequency and specificity of 4-OHEN-dA varied depending on the

2. Left side of Zinc Plant, from packless Cooling Tower ...

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

2. Left side of Zinc Plant, from packless Cooling Tower to midpoint of Cell Room, with majority of Upper Plant in view. View is to the east. - Sullivan Electrolytic Zinc Plant, Government Gulch, Kellogg, Shoshone County, ID

Kappa statistic to measure agreement beyond chance in free-response assessments.

PubMed

Carpentier, Marc; Combescure, Christophe; Merlini, Laura; Perneger, Thomas V

2017-04-19

The usual kappa statistic requires that all observations be enumerated. However, in free-response assessments, only positive (or abnormal) findings are notified, but negative (or normal) findings are not. This situation occurs frequently in imaging or other diagnostic studies. We propose here a kappa statistic that is suitable for free-response assessments. We derived the equivalent of Cohen's kappa statistic for two raters under the assumption that the number of possible findings for any given patient is very large, as well as a formula for sampling variance that is applicable to independent observations (for clustered observations, a bootstrap procedure is proposed). The proposed statistic was applied to a real-life dataset, and compared with the common practice of collapsing observations within a finite number of regions of interest. The free-response kappa is computed from the total numbers of discordant (b and c) and concordant positive (d) observations made in all patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging procedures in children that were evaluated by 2 independent raters, the free-response kappa statistic was 0.820. Aggregation of results within regions of interest resulted in overestimation of agreement beyond chance. The free-response kappa provides an estimate of agreement beyond chance in situations where only positive findings are reported by raters.

NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.

PubMed

Freudenthal, Ramiro; Boccia, Mariano M; Acosta, Gabriela B; Blake, Mariano G; Merlo, Emiliano; Baratti, Carlos M; Romano, Arturo

2005-05-01

Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

MicroRNA-22 and microRNA-140 suppress NF-{kappa}B activity by regulating the expression of NF-{kappa}B coactivators

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

Takata, Akemi; Otsuka, Motoyuki, E-mail: otsukamo-tky@umin.ac.jp; Kojima, Kentaro

2011-08-12

Highlights: {yields} miRNAs were screened for their ability to regulate NF-{kappa}B activity. {yields} miRNA-22 and miRNA-140-3p suppress NF-{kappa}B activity by regulating coactivators. {yields} miRNA-22 targets nuclear receptor coactivator 1 (NCOA1). {yields} miRNA-140-3p targets nuclear receptor-interacting protein 1 (NRIP1). -- Abstract: Nuclear factor {kappa}B (NF-{kappa}B) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-{kappa}B activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-{kappa}B activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-{kappa}B activity bymore » regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-{kappa}B coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-{kappa}B activity.« less

Curcumin inhibits interferon-{alpha} induced NF-{kappa}B and COX-2 in human A549 non-small cell lung cancer cells

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

Lee, Jeeyun; Im, Young-Hyuck; Jung, Hae Hyun

2005-08-26

The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-{alpha} treatment. The IFN-{alpha}-treated A549 cells showed increase in protein expression levels of NF-{kappa}B and COX-2. IFN-{alpha} induced NF-{kappa}B binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-{alpha}-induced COX-2 expression in A549 cells. Within 10 min, IFN-{alpha} rapidly induced the binding activity of a {gamma}-{sup 32}P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-{alpha}-induced activations of NF-{kappa}B and COX-2 were inhibited by the addition of curcumin in A549more » cells.« less

NF-KappaB2/p52 Activation and Androgen Receptor Signaling in Prostate Cancer

DTIC Science & Technology

2011-08-01

biosynthetic enzymes including AKR1C3, CYP17A1, HSD3B2, and SRD5A1 were found to be elevated in CaP cells expressing NF-kappaB2/p52. Luciferase assays...RESULTS: Expression levels of androgen biosynthetic enzymes including AKR1C3, CYP17A1, HSD3B2, and SRD5A1 were found to be elevated in CaP cells

Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

PubMed

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

2014-01-01

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight

Thyroid Hormone Upregulates Zinc-α2-glycoprotein Production in the Liver but Not in Adipose Tissue

PubMed Central

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M.

2014-01-01

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight

The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-{kappa}B) in endotoxic shock

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

Wang Zhi; Kang Jinsong; Li Yang

2006-08-01

To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-{kappa}B and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-{kappa}B was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg.kg{sup -1}). EMSA showed significantly increased NF-{kappa}B DNA-binding activitymore » in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-{kappa}B DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-{kappa}B DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-{kappa}B activation and nuclear translocation of NF-{kappa}B play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-{kappa}B activation.« less

Preliminary Estimation of Kappa Parameter in Croatia

NASA Astrophysics Data System (ADS)

Stanko, Davor; Markušić, Snježana; Ivančić, Ines; Mario, Gazdek; Gülerce, Zeynep

2017-12-01

Spectral parameter kappa κ is used to describe spectral amplitude decay “crash syndrome” at high frequencies. The purpose of this research is to estimate spectral parameter kappa for the first time in Croatia based on small and moderate earthquakes. Recordings of local earthquakes with magnitudes higher than 3, epicentre distances less than 150 km, and focal depths less than 30 km from seismological stations in Croatia are used. The value of kappa was estimated from the acceleration amplitude spectrum of shear waves from the slope of the high-frequency part where the spectrum starts to decay rapidly to a noise floor. Kappa models as a function of a site and distance were derived from a standard linear regression of kappa-distance dependence. Site kappa was determined from the extrapolation of the regression line to a zero distance. The preliminary results of site kappa across Croatia are promising. In this research, these results are compared with local site condition parameters for each station, e.g. shear wave velocity in the upper 30 m from geophysical measurements and with existing global shear wave velocity - site kappa values. Spatial distribution of individual kappa’s is compared with the azimuthal distribution of earthquake epicentres. These results are significant for a couple of reasons: to extend the knowledge of the attenuation of near-surface crust layers of the Dinarides and to provide additional information on the local earthquake parameters for updating seismic hazard maps of studied area. Site kappa can be used in the re-creation, and re-calibration of attenuation of peak horizontal and/or vertical acceleration in the Dinarides area since information on the local site conditions were not included in the previous studies.

A nonradial pulsation model for the rapidly rotating Delta Scuti star Kappa(2) Bootis

NASA Technical Reports Server (NTRS)

Kennelly, E. J.; Walker, G. A. H.; Hubeny, I.

1991-01-01

A sectorial nonradial pulsation model is used to construct theoretical line profiles which mimic the variations for Kappa(2) Boo. Synthetic spectra generated with the appropriate Teff and log g are used as input. It is found that the data can be reproduced by the combination of a high-degree l is approximately equal to 12 mode with P(osc) aproximately equal to 0.071 d, and a low-degree mode, l is approximately equal to 0-2 with P(osc) approximately equal to 0.071-0.079 d. The projected rotational velocity (v sin i - 115 +/-5 km/s) was determined by fitting synthetic line profiles to the observed spectra. The velocity amplitude of the high-degree oscillations is estimated to be about 3.5 km/s. It is found that the ratio of the horizontal and radial pulsation amplitudes is small (about 0.02) and consistent with p-mode oscillations. Comparisons are made with models invoking starspots, and it is impossible to fit the observations of Kappa(2) Boo by a starspot model without assuming unrealistic values of radius or equatorial velocity.

Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".

PubMed

Maret, Wolfgang

2017-10-31

In the last decade, we witnessed discoveries that established Zn 2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca 2+ and Mg 2+ , Zn 2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca 2+ , redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.

Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate.

PubMed

Ma, Guoyi; Tabanca, Nurhayat; Husnu Can Baser, K; Kirimer, Nese; Pasco, David S; Khan, Ikhlas A; Khan, Shabana I

2009-03-01

Breast cancer is one of the most prevalent woman cancers. Genomic instability, accumulative mutations, and subsequent changes in intracellular signaling cascades play key roles in the development of human breast cancers. Activation of nuclear factor-kappaB (NF-kappaB) has been implicated in oncogenesis of breast cancers and is known to be associated with resistance to anticancer agents and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in breast cancer therapy. The objective of this study is to investigate the in vitro effects of epoxypseudoisoeugenol-2-methyl butyrate (EPB), a phenylpropranoid isolated from Pimpinella corymbosa, on the activation of NF-kappaB, cell growth, cell cycle progression and apoptosis in MCF-7 (estrogen-dependent) and BT-549 (estrogen-independent) breast cancer cells. Transcriptional activity of NF-kappaB was measured by cell based reporter gene assay. Cell proliferation was determined by MTT assay. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assy. EPB inhibited the NF-kappaB-mediated transcription activity induced by tumor necrosis factor-alpha (TNF-alpha) and phorbol myristate acetate (PMA) in MCF-7 cells. EPB also inhibited constitutive NF-kappaB transcriptional activity in BT-549 cells. EPB inhibited the proliferation of both MCF-7 and BT-549 cells in a concentration- and time-dependent manner. EPB induced cell cycle arrest in G(1)/G(0) phase and apoptosis in both MCF-7 and BT 549 cells. These in vitro results indicated that EPB has a potential for use against both hormone-dependent and hormone-independent breast cancers and its effects seem to be mediated by inhibiting the NF-kappaB activity.

Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin

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

Kalra, Neetu; Bhui, Kulpreet; Roy, Preeti

2008-01-01

Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax andmore » subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-{kappa}B), we also investigated the effect of bromelain on Cox-2 and NF-{kappa}B expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-{kappa}B by blocking phosphorylation and subsequent degradation of I{kappa}B{alpha}. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-{kappa}B-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.« less

Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in Mouse macrophage cells by inhibition of transcription factor NF-kappaB.

PubMed

Choi, Soo-Youn; Hwang, Joon-Ho; Park, Soo-Young; Jin, Yeong-Jun; Ko, Hee-Chul; Moon, Sang-Wook; Kim, Se-Jae

2008-08-01

The goal of this study was to elucidate the antiinflammatory activities of Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Western blot analysis showed that fermented guava leaf extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the mechanism involved, the study examined the effect of fermented guava leaf extract on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf extract significantly inhibited LPS-induced NF-kappaB transcriptional activity. Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS-induced degradation of I-kappaBalpha. Taken together, the data indicate that fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for the antiinflammatory properties of fermented guava leaf extract.

Effects of zinc supplementation on Shiga toxin 2e-producing Escherichia coli in vitro.

PubMed

Uemura, Ryoko; Katsuge, Tomoko; Sasaki, Yosuke; Goto, Shinya; Sueyoshi, Masuo

2017-10-07

Swine edema disease is caused by Shiga toxin (Stx) 2e-producing Escherichia coli (STEC). Addition of highly concentrated zinc formulations to feed has been used to treat and prevent the disease, but the mechanism of the beneficial effect is unknown. The purpose of the present study was to investigate the effects of highly concentrated zinc formulations on bacterial growth, hemolysin production, and an Stx2e release by STEC in vitro. STEC strain MVH269 isolated from a piglet with edema disease was cultured with zinc oxide (ZnO) or with zinc carbonate (ZnCO 3 ), each at up to 3,000 ppm. There was no effect of zinc addition on bacterial growth. Nonetheless, the cytotoxic activity of Stx2e released into the supernatant was significantly attenuated in the zinc-supplemented media compared to that in the control, with the 50% cytotoxic dose values of 163.2 ± 12.7, 211.6 ± 33.1 and 659.9 ± 84.2 after 24 hr of growth in the presence of ZnO, ZnCO 3 , or no supplemental zinc, respectively. The hemolytic zones around colonies grown on sheep blood agar supplemented with zinc were significantly smaller than those of colonies grown on control agar. Similarly, hemoglobin absorbance after exposure to the supernatants of STEC cultures incubated in sheep blood broth supplemented with zinc was significantly lower than that resulting from exposure to the control supernatant. These in vitro findings indicated that zinc formulations directly impair the factors associated with the virulence of STEC, suggesting a mechanism by which zinc supplementation prevents swine edema disease.

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting under...

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting under...

Origins and properties of kappa distributions in space plasmas

NASA Astrophysics Data System (ADS)

Livadiotis, George

2016-07-01

Classical particle systems reside at thermal equilibrium with their velocity distribution function stabilized into a Maxwell distribution. On the contrary, collisionless and correlated particle systems, such as the space and astrophysical plasmas, are characterized by a non-Maxwellian behavior, typically described by the so-called kappa distributions. Empirical kappa distributions have become increasingly widespread across space and plasma physics. However, a breakthrough in the field came with the connection of kappa distributions to the solid statistical framework of Tsallis non-extensive statistical mechanics. Understanding the statistical origin of kappa distributions was the cornerstone of further theoretical developments and applications, some of which will be presented in this talk: (i) The physical meaning of thermal parameters, e.g., temperature and kappa index; (ii) the multi-particle description of kappa distributions; (iii) the phase-space kappa distribution of a Hamiltonian with non-zero potential; (iv) the Sackur-Tetrode entropy for kappa distributions, and (v) the new quantization constant, h _{*}˜10 ^{-22} Js.

Hyperaccumulation of zinc by zinc-depleted Candida utilis grown in chemostat culture.

PubMed

Lawford, H G; Pik, J R; Lawford, G R; Williams, T; Kligerman, A

1980-01-01

The steady-state levels of zinc in Candida utilis yeast grown in continuous culture under conditions of zinc limitations are <1nmol Zn2+/mg dry weight of cells. Unlike carbon-limited cells, zinc-depleted cells from a zinc-limited chemostat possess the capacity to accumulate and store zinc at levels far in excess of the steady-state level of 4 nmol/mg dry biomass observed in carbon-limited chemostat cultures. Zinc uptake is energy-dependent and apparently undirectional since accumulated 65Zn neither exists from preloaded cells nor exchanges with cold Zn2+. The transport system exhibits a high affinity for Zn2+ (Km =.36micrM) with a Vmaxof 2.2 nmol per minute per milligram dry weight of cells. Growth during the period of the uptake assay is responsible for the apparent plateau level of 35 nmol Zn2+/mg dry weight of cells achieved after 20-30 min in the presence of 65Zn at pH 4.5 and 30 degrees C. Inhibition of growth during the uptake assay by cycloheximide results in a biphasic linear pattern of zinc accumulation where the cellular zinc is about 60 nmol/mg dry weight after 1 h. The enhanced level of accumulated zinc is not inhibtory to growth. Zinc-depleted C. utilis contains elevated amounts of polyphosphate and this anionic evidence does not allow discrimination between possible regulation of zinc homestasis either by inhibitions of zinc efflux through control of the membrane carrier or by control of the synthesis of a cytoplasmic zinc-sequestering macromolecule.

Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells.

PubMed

Quesada, Isabel M; Bustos, Mario; Blay, Mayte; Pujadas, Gerard; Ardèvol, Anna; Salvadó, M Josepa; Bladé, Cinta; Arola, Lluís; Fernández-Larrea, Juan

2011-02-01

Catechins and their polymers procyanidins are health-promoting flavonoids found in edible vegetables and fruits. They act as antioxidants by scavenging reactive oxygen species and by chelating the redox-active metals iron and copper. They also behave as signaling molecules, modulating multiple cell signalling pathways and gene expression, including that of antioxidant enzymes. This study aimed at determining whether catechins and procyanidins interact with the redox-inactive metal zinc and at assessing their effect on cellular zinc homeostasis. We found that a grape-seed procyanidin extract (GSPE) and the green tea flavonoid (-)-epigallocatechin-3-gallate (EGCG) bind zinc cations in solution with higher affinity than the zinc-specific chelator Zinquin, and dose-dependently prevent zinc-induced toxicity in the human hepatocarcinoma cell line HepG2, evaluated by the lactate dehydrogenase test. GSPE and EGCG hinder intracellular accumulation of total zinc, measured by atomic flame absorption spectrometry, concomitantly increasing the level of cytoplasmic labile zinc detectable by Zinquin fluorescence. Concurrently, GSPE and EGCG inhibit the expression, evaluated at the mRNA level by quantitative reverse transcriptase-polymerase chain reaction, of zinc-binding metallothioneins and of plasma membrane zinc exporter ZnT1 (SLC30A1), while enhancing the expression of cellular zinc importers ZIP1 (SLC39A1) and ZIP4 (SLC39A4). GSPE and EGCG also produce all these effects when HepG2 cells are stimulated to import zinc by treatment with supplemental zinc or the proinflammatory cytokine interleukin-6. We suggest that extracellular complexation of zinc cations and the elevation of cytoplasmic labile zinc may be relevant mechanisms underlying the modulation of diverse cell signaling and metabolic pathways by catechins and procyanidins. Copyright © 2011 Elsevier Inc. All rights reserved.

Involvement of MAPKs, NF-{kappa}B and p300 co-activator in IL-1{beta}-induced cytosolic phospholipase A{sub 2} expression in canine tracheal smooth muscle cells

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

Luo, S.-F.; Lin, C.-C.; Chen, H.-C.

2008-11-01

Cytosolic phospholipase A{sub 2} (cPLA{sub 2}) plays a pivotal role in mediating agonist-induced arachidonic acid release for prostaglandin (PG) synthesis during stimulation with interleukin-1{beta} (IL-1{beta}). However, the mechanisms underlying IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis by canine tracheal smooth muscle cells (CTSMCs) have not been defined. IL-1{beta} induced cPLA{sub 2} protein and mRNA expression, PGE{sub 2} production, and phosphorylation of p42/p44 MAPK, p38 MAPK (ATF{sub 2}), and JNK (c-Jun) in a time- and concentration-dependent manner, determined by Western blotting, RT-PCR, and ELISA, which was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), ormore » transfection with dominant negative mutants of MEK1/2, p38, and JNK, respectively. Furthermore, IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis was inhibited by a selective NF-{kappa}B inhibitor (helenalin) or transfection with dominant negative mutants of NF-{kappa}B inducing kinase (NIK), I{kappa}B kinase (IKK)-{alpha}, and IKK-{beta}. Consistently, IL-1{beta} stimulated both I{kappa}B-{alpha} degradation and NF-{kappa}B translocation into nucleus in these cells. NF-{kappa}B translocation was blocked by helenalin, but not by U0126, SB202190, and SP600125. MAPKs together with NF-{kappa}B-activated p300 recruited to cPLA{sub 2} promoter thus facilitating the binding of NF-{kappa}B to cPLA{sub 2} promoter region and expression of cPLA{sub 2} mRNA. IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses. These results suggest that in CTSMCs, IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis was independently mediated through activation of MAPKs and NF-{kappa}B pathways and was connected to p300 recruitment and activation.« less

Elimination of endogenous aberrant kappa chain transcripts from sp2/0-derived hybridoma cells by specific ribozyme cleavage: utility in genetic therapy of HIV-1 infections.

PubMed Central

Duan, L; Pomerantz, R J

1994-01-01

The pooled degenerate-primer polymerase chain reaction (PCR) technology is now widely used in the amplification and cloning of murine hybridoma-specific immunoglobulin gene cDNAs. The design of primers is mainly based on the highly conserved 5' terminus of immunoglobulin gene variable regions and the constant region in the 3' terminus. Of note, most murine hybridoma cell lines are derived from the Sp2/0 cell line, which is demonstrated to express endogenous aberrant kappa chains (abV kappa). This high-level endogenous abV kappa mixes with specific kappa chains in the hybridomas and interferes with the efficiency of the reverse transcriptase (RT)-PCR cloning strategy. In this report, during the cloning of murine anti-human immunodeficiency virus type I (HIV-1) hybridoma immunoglobulin cDNAs, a specific primer-PCR screening system was developed, based on the abV kappa complementarity-defining region (CDR), to eliminate abV kappa-carrying plasmids. Furthermore, an abV kappa sequence-specific derived ribozyme was developed and packaged in a retroviral expression vector system. This abV kappa ribozyme can be transduced into different murine hybridomas, and expressed intracellularly to potently eliminate endogenous abV kappa RNA. Images PMID:7816635

ST2 suppresses IL-6 production via the inhibition of I{kappa}B degradation induced by the LPS signal in THP-1 cells

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

Takezako, Naoki; Hayakawa, Morisada; Hayakawa, Hiroko

2006-03-10

LPS induces the production of inflammatory cytokines via the stimulation of Toll-like receptors. In this study, we demonstrated that a soluble secreted form of the ST2 gene product (ST2), a member of the interleukin-1 receptor family, suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of nuclear factor-{kappa}B to the IL-6 promoter. Furthermore, the degradation of I{kappa}B in the cytoplasm after LPS stimulation was reduced by pretreatment with ST2. These results demonstrated thatmore » ST2 negatively regulates LPS-induced IL-6 production via the inhibition of I{kappa}B degradation in THP-1 cells.« less

Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways.

PubMed

Lai, Ching-Shu; Lee, Jong Hun; Ho, Chi-Tang; Liu, Cheng Bin; Wang, Ju-Ming; Wang, Ying-Jan; Pan, Min-Hsiung

2009-11-25

Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. In this study, we investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2. Treatment with rosmanol also reduced translocation of the nuclear factor-kappaB (NF-kappaB) subunits by prevention of the degradation and phosphorylation of inhibitor kappaB (IkappaB). Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB, signal transducer and activator of transcription-3 (STAT3), and the protein expression of C/EBPbeta and C/EBPdelta. We also found that rosmanol suppressed LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-kappaB and STAT3 through interfering with the activation of PI3K/Akt and MAPK signaling. Taken together, rosmanol might contribute to the potent anti-inflammatory effect of rosemary and may have potential to be developed into an effective anti-inflammatory agent.

Zinc Deficiency Impacts CO2 Assimilation and Disrupts Copper Homeostasis in Chlamydomonas reinhardtii*

PubMed Central

Malasarn, Davin; Kropat, Janette; Hsieh, Scott I.; Finazzi, Giovanni; Casero, David; Loo, Joseph A.; Pellegrini, Matteo; Wollman, Francis-André; Merchant, Sabeeha S.

2013-01-01

Zinc is an essential nutrient because of its role in catalysis and in protein stabilization, but excess zinc is deleterious. We distinguished four nutritional zinc states in the alga Chlamydomonas reinhardtii: toxic, replete, deficient, and limited. Growth is inhibited in zinc-limited and zinc-toxic cells relative to zinc-replete cells, whereas zinc deficiency is visually asymptomatic but distinguished by the accumulation of transcripts encoding ZIP family transporters. To identify targets of zinc deficiency and mechanisms of zinc acclimation, we used RNA-seq to probe zinc nutrition-responsive changes in gene expression. We identified genes encoding zinc-handling components, including ZIP family transporters and candidate chaperones. Additionally, we noted an impact on two other regulatory pathways, the carbon-concentrating mechanism (CCM) and the nutritional copper regulon. Targets of transcription factor Ccm1 and various CAH genes are up-regulated in zinc deficiency, probably due to reduced carbonic anhydrase activity, validated by quantitative proteomics and immunoblot analysis of Cah1, Cah3, and Cah4. Chlamydomonas is therefore not able to grow photoautotrophically in zinc-limiting conditions, but supplementation with 1% CO2 restores growth to wild-type rates, suggesting that the inability to maintain CCM is a major consequence of zinc limitation. The Crr1 regulon responds to copper limitation and is turned on in zinc deficiency, and Crr1 is required for growth in zinc-limiting conditions. Zinc-deficient cells are functionally copper-deficient, although they hyperaccumulate copper up to 50-fold over normal levels. We suggest that zinc-deficient cells sequester copper in a biounavailable form, perhaps to prevent mismetallation of critical zinc sites. PMID:23439652

Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins.

PubMed

Hanas, J S; Rodgers, J S; Bantle, J A; Cheng, Y G

1999-11-01

The association of lead with chromatin in cells suggests that deleterious metal effects may in part be mediated through alterations in gene function. To elucidate if and how lead may alter DNA binding of cysteine-rich zinc finger proteins, lead ions were analyzed for their ability to alter the DNA binding mechanism of the Cys(2)His(2) zinc finger protein transcription factor IIIA (TFIIIA). As assayed by DNase I protection, the interaction of TFIIIA with the 50-bp internal control region of the 5S ribosomal gene was partially inhibited by 5 microM lead ions and completely inhibited by 10 to 20 microM lead ions. Preincubation of free TFIIIA with lead resulted in DNA-binding inhibition, whereas preincubation of a TFIIIA/5S RNA complex with lead did not result in DNA-binding inhibition. Because 5S RNA binds TFIIIA zinc fingers, this result is consistent with an inhibition mechanism via lead binding to zinc fingers. The complete loss of DNase I protection on the 5S gene indicates the mechanism of inhibition minimally involves the N-terminal fingers of TFIIIA. Inhibition was not readily reversible and occurred in the presence of an excess of beta-mercaptoethanol. Inhibition kinetics were fast, progressing to completion in approximately 5 min. Millimolar concentrations of sulfhydryl-specific arsenic ions were not inhibitory for TFIIIA binding. Micromolar concentrations of lead inhibited DNA binding by Sp1, another Cys(2)His(2) finger protein, but not by the nonfinger protein AP2. Inhibition of Cys(2)His(2) zinc finger transcription factors by lead ions at concentrations near those known to have deleterious physiological effects points to new molecular mechanisms for lead toxicity in promoting disease.

Nonplanar ion acoustic waves with kappa-distributed electrons

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

Sahu, Biswajit

2011-06-15

Using the standard reductive perturbation technique, nonlinear cylindrical and spherical Kadomtsev-Petviashvili equations are derived for the propagation of ion acoustic solitary waves in an unmagnetized collisionless plasma with kappa distributed electrons and warm ions. The influence of kappa-distributed electrons and the effects caused by the transverse perturbation on cylindrical and spherical ion acoustic waves (IAWs) are investigated. It is observed that increase in the kappa distributed electrons (i.e., decreasing {kappa}) decreases the amplitude of the solitary electrostatic potential structures. The numerical results are presented to understand the formation of ion acoustic solitary waves with kappa-distributed electrons in nonplanar geometry. Themore » present investigation may have relevance in the study of propagation of IAWs in space and laboratory plasmas.« less

GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

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

Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie

2008-09-26

Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil andmore » lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.« less

Oxidation and Condensation of Zinc Fume From Zn-CO 2-CO-H 2O Streams Relevant to Steelmaking Off-Gas Systems

DOE PAGES

Bronson, Tyler Mark; Ma, Naiyang; Zhu, Liang Zhu; ...

2017-01-23

Here the objective of this research was to study the condensation of zinc vapor to metallic zinc and zinc oxide solid under varying environments to investigate the feasibility of in-process separation of zinc from steelmaking off-gas dusts. Water vapor content, temperature, degree of cooling, gas composition, and initial zinc partial pressure were varied to simulate the possible conditions that can occur within steelmaking off-gas systems, limited to Zn-CO 2-CO-H 2O gas compositions. The temperature of deposition and the effect of rapidly quenching the gas were specifically studied. A homogeneous nucleation model for applicable experiments was applied to the analysis of the experimental data. It was determined that under the experimental conditions, oxidation of zinc vapor by H 2O or CO 2 does not occur above 1108 K (835 °C) even for highly oxidizing streams (CO 2/CO = 40/7). Rate expressions that correlate CO 2 and H 2O oxidation rates to gas composition, partial pressure of water vapor, temperature, and zinc partial pressure were determined to be as follows: Ratemore » $$ \\left(\\frac{mol}{m^2s}\\right) $$ = 406 exp $$ \\left(\\frac{-50.2 kJ/mol}{RT}\\right) $$ (pZnpCO 2 $-$ PCO/K eqCO 2) $$\\frac{mol}{m^2 x s}$$ Rate $$ \\left(\\frac{mol}{m^2s}\\right) $$ = 32.9 exp $$ \\left(\\frac{-13.7 kJ/mol}{RT}\\right) $$ (pZnPH 2O $-$ PH 2/K eqH 2O) $$\\frac{mol}{m^2 x s}$$. It was proven that a rapid cooling rate (500 K/s) significantly increases the ratio of metallic zinc to zinc oxide as opposed to a slow cooling rate (250 K/s). SEM analysis found evidence of heterogeneous growth of ZnO as well as of homogeneous formation of metallic zinc. The homogeneous nucleation model fit well with experiments where only metallic zinc deposited. An expanded model with rates of oxidation by CO 2 and H 2O as shown was combined with the homogenous nucleation model and then compared with experimental data. The calculated results based on the model gave a reasonable fit to the

Oxidation and Condensation of Zinc Fume From Zn-CO 2-CO-H 2O Streams Relevant to Steelmaking Off-Gas Systems

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

Bronson, Tyler Mark; Ma, Naiyang; Zhu, Liang Zhu

Here the objective of this research was to study the condensation of zinc vapor to metallic zinc and zinc oxide solid under varying environments to investigate the feasibility of in-process separation of zinc from steelmaking off-gas dusts. Water vapor content, temperature, degree of cooling, gas composition, and initial zinc partial pressure were varied to simulate the possible conditions that can occur within steelmaking off-gas systems, limited to Zn-CO 2-CO-H 2O gas compositions. The temperature of deposition and the effect of rapidly quenching the gas were specifically studied. A homogeneous nucleation model for applicable experiments was applied to the analysis of the experimental data. It was determined that under the experimental conditions, oxidation of zinc vapor by H 2O or CO 2 does not occur above 1108 K (835 °C) even for highly oxidizing streams (CO 2/CO = 40/7). Rate expressions that correlate CO 2 and H 2O oxidation rates to gas composition, partial pressure of water vapor, temperature, and zinc partial pressure were determined to be as follows: Ratemore » $$ \\left(\\frac{mol}{m^2s}\\right) $$ = 406 exp $$ \\left(\\frac{-50.2 kJ/mol}{RT}\\right) $$ (pZnpCO 2 $-$ PCO/K eqCO 2) $$\\frac{mol}{m^2 x s}$$ Rate $$ \\left(\\frac{mol}{m^2s}\\right) $$ = 32.9 exp $$ \\left(\\frac{-13.7 kJ/mol}{RT}\\right) $$ (pZnPH 2O $-$ PH 2/K eqH 2O) $$\\frac{mol}{m^2 x s}$$. It was proven that a rapid cooling rate (500 K/s) significantly increases the ratio of metallic zinc to zinc oxide as opposed to a slow cooling rate (250 K/s). SEM analysis found evidence of heterogeneous growth of ZnO as well as of homogeneous formation of metallic zinc. The homogeneous nucleation model fit well with experiments where only metallic zinc deposited. An expanded model with rates of oxidation by CO 2 and H 2O as shown was combined with the homogenous nucleation model and then compared with experimental data. The calculated results based on the model gave a reasonable fit to the

Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

PubMed

Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

2015-12-01

A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

Dietary phytate, zinc and hidden zinc deficiency.

PubMed

Sandstead, Harold H; Freeland-Graves, Jeanne H

2014-10-01

Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

Translesion synthesis past equine estrogen-derived 2'-deoxycytidine DNA adducts by human DNA polymerases eta and kappa.

PubMed

Suzuki, Naomi; Yasui, Manabu; Santosh Laxmi, Y R; Ohmori, Haruo; Hanaoka, Fumio; Shibutani, Shinya

2004-09-07

Estrogen replacement therapy (ERT), composed of equilenin, is associated with increased risk of breast, ovarian, and endometrial cancers. Several diastereoisomers of unique dC and dA DNA adducts were derived from 4-hydroxyequilenin (4-OHEN), a metabolite of equilenin, and have been detected in women receiving ERT. To explore the miscoding property of 4-OHEN-dC adduct, site-specifically modified oligodeoxynucleotides (Pk-1, Pk-2, Pk-3, and Pk-4) containing a single diastereoisomer of 4-OHEN-dC were prepared by a postsynthetic method. Among them, major 4-OHEN-dC-modified oligodeoxynucleotides (Pk-3 and Pk-4) were used to prepare the templates for primer extension reactions catalyzed by DNA polymerase (pol) alpha, pol eta, and pol kappa. Primer extension was retarded one base prior to the lesion and opposite the lesion; stronger blockage was observed with pol alpha, while with human pol eta or pol kappa, a fraction of the primers was extended past the lesion. Steady-state kinetic studies showed that both pol kappa and pol eta inserted dCMP and dAMP opposite the 4-OHEN-dC and extended past the lesion. Never or less-frequently, dGMP, the correct base, was inserted opposite the lesion. The relative bypass frequency past the 4-OHEN-dC lesion with pol eta was at least 3 orders of magnitude higher than that for pol kappa, as observed for primer extension reactions. The bypass frequency past the dA.4-OHEN-dC adduct in Pk-4 was 2 orders of magnitude more efficient than that past the adduct in Pk-3. Thus, 4-OHEN-dC is a highly miscoding lesion capable of generating C --> T transitions and C --> G transversions. The miscoding frequency and specificity of 4-OHEN-dC were strikingly influenced by the adduct stereochemistry and DNA polymerase used.

Nuclear factor kappa B: a potential target for anti-HIV chemotherapy.

PubMed

Pande, V; Ramos, M J

2003-08-01

The Nuclear Factor Kappa B (NF-kappaB) is a lymphoid-specific transcription factor, which is sequestered in the cytoplasm by the protein IkappaB. NF-kappaB plays a major role in the regulation of HIV-1 gene expression. Upon activation, NF-kappaB is released from IkappaB, moves to the nucleus, and binds to its sites on the HIV long terminal repeat to start transcription of integrated HIV genome. The present review focuses on the NF-kappaB as a potential target for the development of chemotherapy against HIV-1. Beginning from the viral-binding to reverse transcription, integration, and gene expression, to the virion maturation, the life cycle of HIV presents drug-targets at all the stages. As a result, many drugs have been developed and have entered clinical trials. Some of the most important of these are reverse transcriptase and protease inhibitors, which have been used mostly in clinical studies in the form of combined therapy. But, this combined therapy has presented the problem of resistance, due to mutations in the virus. However, targeting NF-kappaB for the suppression of virus does not present the problem of resistance, as NF-kappaB is a normal part of the human T-4 cell, and is not subject to mutations, as is the virus. An overview of the NF-kappaB system and its role in HIV-1 is presented, followed by a critical review of its current and potential synthetic inhibitors. The drugs studied against NF-kappaB fall mainly into three categories: (1) Antioxidants, against oxidative stress conditions, which aid in NF-kappaB activation, (2) IkappaB phosphorylation and degradation inhibitors (the phosphorylation and degradation of IkappaB is necessary to make NF-kappaB free and move to the nucleus), and (3) NF-kappaB DNA binding inhibitors. The antioxidants include N-Acetyl-L-cysteine (NAC), alpha-Lipoic acid, glutathione monoester, pyrrolidine dithiocarbamate, and tepoxalin, of which NAC is the best studied. The IkappaB phosphorylation and degradation inhibitors

Polyphenol-rich beverages enhance zinc uptake and metallothionein expression in Caco-2 cells.

PubMed

Sreenivasulu, Kilari; Raghu, Pullakhandam; Nair, K Madhavan

2010-05-01

The effect of red wine (RW), red grape juice (RGJ), green tea (GT), and representative polyphenols on Caco-2 cell (65)Zn uptake was explored. RW, RGJ, and GT enhanced the uptake of zinc from rice matrix. Fractionation of RW revealed that enhancing activity of zinc uptake was exclusively resided in the polyphenol fraction. Among the polyphenols tested, only tannic acid and quercitin stimulated the uptake of zinc while others did not influence the uptake. In tune with these results, only tannic acid and quercitin competed with zinquin (a zinc selective fluorophore) for zinc in vitro. Although all the polyphenols tested appear to enhance the expression of metallothionein (MT), the induction was higher with tannic acid, quercitin, and RW extract. Furthermore, phytic acid abrogated the tannic acid-induced MT expression. These results suggest that polyphenol-rich beverages, tannic acid, and quercitin bind and stimulate the zinc uptake and MT expression in Caco-2 cells.

LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase

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

Schroecksnadel, Sebastian; Jenny, Marcel; Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck

2010-09-03

Research highlights: {yields} LPS induces NF-{kappa}B, neopterin formation and tryptophan degradation in THP-1 cells. {yields} Close dose- and time-dependent correlations exist between these biochemical events. {yields} Data provides some evidence for a parallel induction of them upon TLR stimulation. {yields} Results can be of considerable relevance also in vivo. -- Abstract: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-{gamma} (IFN-{gamma}). In parallel, IFN-{gamma} induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-{kappa}B (NF-{kappa}B) is induced bymore » ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-{kappa}B expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-{kappa}B activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-{kappa}B inducible reporter system. In cells stimulated with LPS, a significant induction of NF-{kappa}B was observed, and this was paralleled by an increase of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-{kappa}B activation, neopterin release and trp degradation (all p < 0.001). We conclude that there is a parallel induction of NF-{kappa}B, neopterin

Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

PubMed

Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

2015-06-01

The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Some Paradoxical Results for the Quadratically Weighted Kappa

ERIC Educational Resources Information Center

Warrens, Matthijs J.

2012-01-01

The quadratically weighted kappa is the most commonly used weighted kappa statistic for summarizing interrater agreement on an ordinal scale. The paper presents several properties of the quadratically weighted kappa that are paradoxical. For agreement tables with an odd number of categories "n" it is shown that if one of the raters uses the same…

40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN P...

40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN P...

Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.

PubMed

Hemilä, Harri

2017-05-01

To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect. Meta-analysis. Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method. Seven randomised trials with 575 participants with naturally acquired common colds. Duration of the common cold. The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32). Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further.

Zinc

USDA-ARS?s Scientific Manuscript database

Zinc was recognized as an essential trace metal for humans during the studies of Iranian adolescent dwarfs in the early 1960s. Zinc metal existing as Zn2+ is a strong electron acceptor in biological systems without risks of oxidant damage to cells. Zn2+ functions in the structure of proteins and is ...

Dietary zinc deficiency reduced growth performance, intestinal immune and physical barrier functions related to NF-κB, TOR, Nrf2, JNK and MLCK signaling pathway of young grass carp (Ctenopharyngodon idella).

PubMed

Song, Zheng-Xing; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Zhou, Xiao-Qiu; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Feng, Lin

2017-07-01

Our study investigated the effects of dietary zinc (Zn) deficiency on growth performance, intestinal immune and physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 630 grass carp (244.14 ± 0.40 g) were fed graded levels of zinc lactate (10.71, 30.21, 49.84, 72.31, 92.56, 110.78 mg Zn/kg diet) and one zinc sulfate group (56.9 mg Zn/kg diet) for 60 days. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila for 14 days. These results indicated that compared with optimal dietary Zn level, dietary Zn deficiency (10.71 mg/kg diet) decreased the production of antibacterial compounds, up-regulated pro-inflammatory cytokines related to nuclear factor kappa B (NF-κB) and down-regulated anti-inflammatory cytokines related to target of rapamycin (TOR) in three intestinal segments of young grass carp (P < 0.05), suggesting that dietary Zn deficiency could impair intestinal immune barrier of fish; decreased the activities and mRNA levels of antioxidant enzymes related to NF-E2-related factor 2 (Nrf2), up-regulated the mRNA levels of caspase-3, -7, -8, -9 related to p38 mitogen activated protein (p38 MAPK) and c-Jun N-terminal protein kinase (JNK), down-regulated the mRNA levels of tight junction complexes (TJs) related to myosin light chain kinase (MLCK) in three intestinal segments of young grass carp (P < 0.05), demonstrating that dietary Zn deficiency could injury intestinal physical barrier of fish. Besides, the Zn requirements (zinc lactate as Zn source) based on percent weight gain (PWG), against enteritis morbidity, acid phosphatase (ACP) activity in the proximal intestine (PI) and malondialdehyde (MDA) content in the PI of young grass carp was estimated to be 61.2, 61.4, 69.2 and 69.5 mg/kg diet, respectively. Finally, based on specific growth rate (SGR), feed efficiency (FE) and against enteritis morbidity of young grass carp, the efficacy of zinc lactate relative to zinc sulfate were 132.59%, 135

Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

PubMed

Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

2016-04-25

Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process.

Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-{kappa}B pathway, and MMP-9 expression

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

Kang, Myoung Hee; Oh, Sang Cheul; Lee, Hyun Joo

2011-07-15

Bone morphogenetic proteins (BMPs) have been implicated in tumorigenesis and metastatic progression in various types of cancer cells, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of phosphoinositide 3-kinase (PI3K)/AKT, extracellular signal-regulated protein kinase (ERK), nuclear factor (NF)-{kappa}B, and matrix metalloproteinase (MMP) expression in BMP-2-mediated metastatic function in gastric cancer. We found that stimulation of BMP-2 in gastric cancer cells enhanced the phosphorylation of AKT and ERK. Accompanying activation of AKT and ERK kinase, BMP-2 also enhanced phosphorylation/degradation of I{kappa}B{alpha} and the nuclear translocation/activation of NF-{kappa}B.more » Interestingly, blockade of PI3K/AKT and ERK signaling using LY294002 and PD98059, respectively, significantly inhibited BMP-2-induced motility and invasiveness in association with the activation of NF-{kappa}B. Furthermore, BMP-2-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with PI3K/AKT, ERK, or NF-{kappa}B inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of BMP-2 and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the BMP-2 signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the PI3K/AKT or MAPK pathway followed by the induction of NF-{kappa}B and MMP-9 activity, indicating that BMP-2 has the potential to be a therapeutic molecular target to decrease metastasis.« less

Spectrophotometric studies and applications for the determination of Ni2+ in zinc-nickel alloy electrolyte

NASA Astrophysics Data System (ADS)

Qiao, Xiaoping; Li, Helin; Zhao, Wenzhen; Li, Dejun

The absorption properties of zinc-nickel alloy electrolyte were studied by visible spectrophotometer. The results show that the relationship between the absorbance of the zinc-nickel alloy electrolyte and Ni2+ concentration in the electrolyte obeys Beer's law at 660 nm. In addition, other components except Ni2+ in the zinc-nickel alloy electrolyte such as zinc chloride, ammonium chloride, potassium chloride and boric acid have no obvious effect on the absorbance of zinc-nickel alloy electrolyte. Based on these properties, a new method is developed to determine Ni2+ concentration in zinc-nickel alloy electrolyte. Comparing with other methods, this method is simple, direct and accurate. Moreover, the whole testing process does not consume any reagent and dilution, and after testing, the electrolyte samples can be reused without any pollution to the environment.

Rising atmospheric CO2 lowers food zinc, iron, and protein concentrations

USDA-ARS?s Scientific Manuscript database

Dietary deficiencies of zinc and iron are a major global public health problem. Most people who experience these deficiencies depend on agricultural crops for zinc and iron. In this context, the influence of rising concentrations of atmospheric CO2 on the availability of these nutrients from crops i...

Regulation of the nuclear factor (NF)-kappaB pathway by ISGylation.

PubMed

Minakawa, Miki; Sone, Takayuki; Takeuchi, Tomoharu; Yokosawa, Hideyoshi

2008-12-01

Post-translational modification with ISG15 (interferon-stimulated gene 15 kDa) (ISGylation) is mediated by a sequential reaction similar to ubiquitination, and various target proteins for ISGylation have been identified. We previously reported that ISGylation of the E2 ubiquitin-conjugating enzyme Ubc13 suppresses its E2 activity. Ubc13 forms a heterodimer with Uev1A, a ubiquitin-conjugating enzyme variant, and the Ubc13-Uev1A complex catalyzes the assembly of a Lys63-linked polyubiquitin chain, which plays a non-proteolytic role in the nuclear factor (NF)-kappaB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor beta-activated kinase (TAK)-1-dependent NF-kappaB activation. We found that expression of the ISGylation system suppresses NF-kappaB activation via TRAF6 and TAK1 and that the level of polyubiquitinated TRAF6 is reduced by expression of the ISGylation system. Taken together, the results suggest that the NF-kappaB pathway is negatively regulated by ISGylation.

Generation of Kappa Distributions in Solar Wind at 1 au

NASA Astrophysics Data System (ADS)

Livadiotis, G.; Desai, M. I.; Wilson, L. B., III

2018-02-01

We examine the generation of kappa distributions in the solar wind plasma near 1 au. Several mechanisms are mentioned in the literature, each characterized by a specific relationship between the solar wind plasma features, the interplanetary magnetic field (IMF), and the kappa index—the parameter that governs the kappa distributions. This relationship serves as a signature condition that helps the identification of the mechanism in the plasma. In general, a mechanism that generates kappa distributions involves a single or a series of stochastic or physical processes that induces local correlations among particles. We identify three fundamental solar wind plasma conditions that can generate kappa distributions, noted as (i) Debye shielding, (ii) frozen IMF, and (iii) temperature fluctuations, each one prevailing in different scales of solar wind plasma and magnetic field properties. Moreover, our findings show that the kappa distributions, and thus, their generating mechanisms, vary significantly with solar wind features: (i) the kappa index has different dependence on the solar wind speed for slow and fast modes, i.e., slow wind is characterized by a quasi-constant kappa index, κ ≈ 4.3 ± 0.7, while fast wind exhibits kappa indices that increase with bulk speed; (ii) the dispersion of magnetosonic waves is more effective for lower kappa indices (i.e., further from thermal equilibrium); and (iii) the kappa and polytropic indices are positively correlated, as it was anticipated by the theory.

Zinc Information

MedlinePlus

... for Eye Conditions Clinical Digest: Hepatitis C and Dietary Supplements Related Resources From Other Agencies Age-Related Eye Disease Study 2 (AREDS2) ( NEI ) Can Zinc Be Harmful? ( ODS ) Zinc ( ODS ) Follow NCCIH: Read our disclaimer ...

Studies on the bioavailability of zinc in humans: intestinal interaction of tin and zinc.

PubMed

Solomons, N W; Marchini, J S; Duarte-Favaro, R M; Vannuchi, H; Dutra de Oliveira, J E

1983-04-01

Mineral/mineral interactions at the intestinal level are important in animal nutrition and toxicology, but only limited understanding of their extent or importance in humans has been developed. An inhibitory interaction of dietary tin on zinc retention has been recently described from human metabolic studies. We have explored the tin/zinc interaction using the change-in-plasma-zinc-concentration method with a standard dosage of 12.5 mg of zinc as zinc sulfate in 100 ml of Coca-Cola. Sn/Zn ratios of 2:1, 4:1, and 8:1, constituted by addition of 25, 50, and 100 mg of tin as stannous chloride, had no significant overall effect on zinc uptake. The 100-mg dose of tin produced noxious gastrointestinal symptoms. Addition of iron as ferrous sulfate to form ratios of Sn/Fe/Zn of 1:1:1 and 2:2:1 with the standard zinc solution and the appropriate doses of tin produced a reduction of zinc absorption not dissimilar from that seen previously with zinc and iron alone, and addition of picolinic acid did not influence the uptake of zinc from the solution with the 2:2:1 Sn/Fe/Zn ratio.

Zinc and Autophagy

PubMed Central

Liuzzi, Juan P.; Guo, Liang; Yoo, Changwon; Stewart, Tiffanie S

2014-01-01

Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated.Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria.Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake. PMID:25012760

African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

PubMed

Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

2002-04-01

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

Method for rapidly determining a pulp kappa number using spectrophotometry

DOEpatents

Chai, Xin-Sheng; Zhu, Jun Yong

2002-01-01

A system and method for rapidly determining the pulp kappa number through direct measurement of the potassium permanganate concentration in a pulp-permanganate solution using spectrophotometry. Specifically, the present invention uses strong acidification to carry out the pulp-permanganate oxidation reaction in the pulp-permanganate solution to prevent the precipitation of manganese dioxide (MnO.sub.2). Consequently, spectral interference from the precipitated MnO.sub.2 is eliminated and the oxidation reaction becomes dominant. The spectral intensity of the oxidation reaction is then analyzed to determine the pulp kappa number.

Resampling probability values for weighted kappa with multiple raters.

PubMed

Mielke, Paul W; Berry, Kenneth J; Johnston, Janis E

2008-04-01

A new procedure to compute weighted kappa with multiple raters is described. A resampling procedure to compute approximate probability values for weighted kappa with multiple raters is presented. Applications of weighted kappa are illustrated with an example analysis of classifications by three independent raters.

Kappa-Electrons Downstream of the Solar Wind Termination Shock

NASA Astrophysics Data System (ADS)

Fahr, H. J.

2017-12-01

A theoretical description of the solar wind electron distribution function downstream of the termination shock under the influence of the shock-induced injection of overshooting KeV-energetic electrons will be presented. A kinetic phasespace transport equation in the bulk frame of the heliosheath plasma flow is developed for the solar wind electrons, taking into account shock-induced electron injection, convective changes, magnetic cooling processes and whistler wave-induced energy diffusion. Assuming that the local electron distribution under the prevailing Non-LTE conditions can be represented by a local kappa function with a local kappa parameter that varies with the streamline coordinates, we determine the parameters of the resulting, initial kappa distribution for the downstream electrons. From this initial function spectral electron fluxes can be derived and can be compared with those measured by the VOYAGER-1 spacecraft in the range between 40 to 70 KeV. It can then be shown that with kappa values around kappa = 6 one can in fact fit these data very satisfactorily. In addition it is shown that for isentropic electron flows kappa-distributed electrons have to undergo simultaneous changes of both parameters, i.e. kappa and theta, of the electron kappa function. It is also shown then that under the influence of energy sinks and sources the electron flux becomes non-isentropic with electron entropies changing along the streamline.

Keep your fingers off my DNA: protein-protein interactions mediated by C2H2 zinc finger domains.

PubMed

Brayer, Kathryn J; Segal, David J

2008-01-01

Cys2-His2 (C2H2) zinc finger domains (ZFs) were originally identified as DNA-binding domains, and uncharacterized domains are typically assumed to function in DNA binding. However, a growing body of evidence suggests an important and widespread role for these domains in protein binding. There are even examples of zinc fingers that support both DNA and protein interactions, which can be found in well-known DNA-binding proteins such as Sp1, Zif268, and Ying Yang 1 (YY1). C2H2 protein-protein interactions (PPIs) are proving to be more abundant than previously appreciated, more plastic than their DNA-binding counterparts, and more variable and complex in their interactions surfaces. Here we review the current knowledge of over 100 C2H2 zinc finger-mediated PPIs, focusing on what is known about the binding surface, contributions of individual fingers to the interaction, and function. An accurate understanding of zinc finger biology will likely require greater insights into the potential protein interaction capabilities of C2H2 ZFs.

Structural and Functional Studies of the Protamine 2-Zinc Complex from Syrian Gold Hamster (Mesocricetus Auratus) Spermatids and Sperm

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

Dolan, Cheryl E.

The research described in this dissertation consists of four major areas: (1) sequence analysis of protamine 2 from Muroid rodents to identify potential zinc-binding domain(s) of protamine 2; (2) structural studies of the protamine 2-zinc complex from Syrian Gold hamster sperm and spermatids to elucidate the role of zinc during spermiogenesis; (3) structural studies of an unique protamine 2-zinc complex from chinchilla sperm; and (4) Nuclear Magnetic Resonance (NMR) studies of soluble complexes of hairpin oligonucleotides with synthetic arginine-rich peptides or protamine 1 isolated from bull sperm. First, zinc was quantitated in spermatids and sperm by Proton-Induced X-ray Emission (PIXE)more » to determine whether zinc is present in the early stages of spermiogenesis. The PIXE results revealed the zinc content varies proportionately with the amount of protamine 2 in both spermatid and sperm nuclei. An exception was chinchilla sperm containing twice the amount of protamine 2 than zinc. Further analyses by PIXE and X-ray Absorption Spectroscopy (XAS) of zinc bound to protamines isolated from hamster sperm confirmed the majority of the zinc is bound to protamine and identified the zinc ligands of protamine 2 in hamster spermatids and sperm in vivo. These studies established that zinc is bound to the protamine 2 precursor in hamster spermatids and the coordination of zinc by protamine 2 changes during spermiogenesis. Finally, the sequence analysis combined with the XAS results suggest that the zinc-binding domain in protamine 2 resides in the amino-terminus. Similar analyses of chinchilla sperm by XAS were performed to clarify the unusual PIXE results and revealed that chinchilla has an atypical protamine 2-zinc structure. Two protamine 2 molecules coordinate one zinc atom, forming homodimers that facilitate the binding of protamine 2 to DNA and provide an organizational scheme that would accommodate the observed species-specific protamine stoichiometry in

Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: Inefficacy of genetic or pharmacological disruption of COX-2

PubMed Central

Fong, Louise Y.Y.; Jiang, Yubao; Riley, Maurisa; Liu, Xianglan; Smalley, Karl J.; Guttridge, Denis C.; Farber, John L.

2009-01-01

Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced for-estomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive bio-markers COX-2, nuclear factor (NF)-κ B p65 and leukotriene A4 hydrolase (LTA4H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-2−/− forestomachs displayed strong LTA4H immunostaining, indicating activation of an alter-native pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. PMID:17985342

Nonequilibrium approach regarding metals from a linearised kappa distribution

NASA Astrophysics Data System (ADS)

Domenech-Garret, J. L.

2017-10-01

The widely used kappa distribution functions develop high-energy tails through an adjustable kappa parameter. The aim of this work is to show that such a parameter can itself be regarded as a function, which entangles information about the sources of disequilibrium. We first derive and analyse an expanded Fermi-Dirac kappa distribution. Later, we use this expanded form to obtain an explicit analytical expression for the kappa parameter of a heated metal on which an external electric field is applied. We show that such a kappa index causes departures from equilibrium depending on the physical magnitudes. Finally, we study the role of temperature and electric field on such a parameter, which characterises the electron population of a metal out of equilibrium.

Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.

PubMed

Rodríguez-Calvo, Ricardo; Serrano, Lucía; Coll, Teresa; Moullan, Norman; Sánchez, Rosa M; Merlos, Manuel; Palomer, Xavier; Laguna, Juan C; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2008-08-01

Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes. First, we examined whether the PPARbeta/delta agonist GW501516 prevents lipopolysaccharide (LPS)-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the signal transducer and activator of transcription 3 (STAT3)-Suppressor of cytokine signaling 3 (SOCS3) pathway. This effect was associated with the capacity of GW501516 to impede LPS-induced NF-kappaB activation. Second, in in vivo studies, white adipose tissue from Zucker diabetic fatty (ZDF) rats, compared with that of lean rats, showed reduced PPARbeta/delta expression and PPAR DNA-binding activity, which was accompanied by enhanced IL-6 expression and NF-kappaB DNA-binding activity. Furthermore, IL-6 expression and NF-kappaB DNA-binding activity was higher in white adipose tissue from PPARbeta/delta-null mice than in wild-type mice. Because mitogen-activated protein kinase-extracellular signal-related kinase (ERK)1/2 (MEK1/2) is involved in LPS-induced NF-kappaB activation in adipocytes, we explored whether PPARbeta/delta prevented NF-kappaB activation by inhibiting this pathway. Interestingly, GW501516 prevented ERK1/2 phosphorylation by LPS. Furthermore, white adipose tissue from animal showing constitutively increased NF-kappaB activity, such as ZDF rats and PPARbeta/delta-null mice, also showed enhanced phospho-ERK1/2 levels. These findings indicate that activation of PPARbeta/delta inhibits enhanced cytokine production in adipocytes by preventing NF-kappaB activation via ERK1/2, an effect that may help prevent insulin resistance.

Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes.

PubMed

Stevenson, M A; Zhao, M J; Asea, A; Coleman, C N; Calderwood, S K

1999-11-15

Sodium salicylate (NaSal) and other nonsteroidal anti-inflammatory drugs (NSAIDs) coordinately inhibit the activity of NF-kappa B, activate heat shock transcription factor 1 and suppress cytokine gene expression in activated monocytes and macrophages. Because our preliminary studies indicated that these effects could be mimicked by inhibitors of signal transduction, we have studied the effects of NSAIDs on signaling molecules potentially downstream of LPS receptors in activated macrophages. Our findings indicate that ribosomal S6 kinase 2 (RSK2), a 90-kDa ribosomal S6 kinase with a critical role as an effector of the RAS-mitogen-activated protein kinase pathway and a regulator of immediate early gene transcription is a target for inhibition by the NSAIDs. NSAIDs inhibited the activity of purified RSK2 kinase in vitro and of RSK2 in mammalian cells and suppressed the phosphorylation of RSK2 substrates cAMP response element binding protein (CREB) and I-kappa B alpha in vivo. Additionally, NaSal inhibited the phosphorylation by RSK2 of CREB and I-kappa B alpha on residues crucial for their transcriptional activity in vivo and thus repressed CREB and NF-kappa B-dependent transcription. These experiments suggest that RSK2 is a target for NSAIDs in the inhibition of monocyte-specific gene expression and indicate the importance of RSK2 and related kinases in cell regulation, indicating a new area for anti-inflammatory drug discovery.

Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography

PubMed Central

Yeo, Joon Hyung; Moon, Nam Ju

2017-01-01

Purpose To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Methods Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. Results The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. Conclusions We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. PMID:28471103

Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography.

PubMed

Yeo, Joon Hyung; Moon, Nam Ju; Lee, Jeong Kyu

2017-06-01

To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. © 2017 The Korean Ophthalmological Society

Contribution of Zinc Solubilizing Bacteria in Growth Promotion and Zinc Content of Wheat.

PubMed

Kamran, Sana; Shahid, Izzah; Baig, Deeba N; Rizwan, Muhammad; Malik, Kauser A; Mehnaz, Samina

2017-01-01

Zinc is an imperative micronutrient required for optimum plant growth. Zinc solubilizing bacteria are potential alternatives for zinc supplementation and convert applied inorganic zinc to available forms. This study was conducted to screen zinc solubilizing rhizobacteria isolated from wheat and sugarcane, and to analyze their effect on wheat growth and development. Fourteen exo-polysaccharides producing bacterial isolates of wheat were identified and characterized biochemically as well as on the basis of 16S rRNA gene sequences. Along these, 10 identified sugarcane isolates were also screened for zinc solubilizing ability on five different insoluble zinc sources. Out of 24, five strains, i.e., EPS 1 ( Pseudomonas fragi) , EPS 6 ( Pantoea dispersa) , EPS 13 ( Pantoea agglomerans) , PBS 2 ( E. cloacae) and LHRW1 ( Rhizobium sp.) were selected (based on their zinc solubilizing and PGP activities) for pot scale plant experiments. ZnCO 3 was used as zinc source and wheat seedlings were inoculated with these five strains, individually, to assess their effect on plant growth and development. The effect on plants was analyzed based on growth parameters and quantifying zinc content of shoot, root and grains using atomic absorption spectroscopy. Plant experiment was performed in two sets. For first set of plant experiments (harvested after 1 month), maximum shoot and root dry weights and shoot lengths were noted for the plants inoculated with Rhizobium sp. (LHRW1) while E. cloacae (PBS 2) increased both shoot and root lengths. Highest zinc content was found in shoots of E. cloacae (PBS 2) and in roots of P. agglomerans (EPS 13) followed by zinc supplemented control. For second set of plant experiment, when plants were harvested after three months, Pantoea dispersa (EPS 6), P. agglomerans (EPS 13) and E. cloacae (PBS 2) significantly increased shoot dry weights. However, significant increase in root dry weights and maximum zinc content was recorded for Pseudomonas fragi (EPS

Novel selective kappa-opioid ligands.

PubMed

Peeters, O M; Jamroz, D; Blaton, N M; De Ranter, C J

1999-03-15

The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

Eluted zinc ions stimulate osteoblast differentiation and mineralization in human dental pulp stem cells for bone tissue engineering.

PubMed

Yusa, Kazuyuki; Yamamoto, Osamu; Iino, Mitsuyoshi; Takano, Hiroshi; Fukuda, Masayuki; Qiao, Zhiwei; Sugiyama, Toshihiro

2016-11-01

Zinc is an essential element for proliferation, differentiation and survival in various cell types. In a previous study, we found that zinc ions released from zinc-modified titanium surfaces (eluted zinc ions; EZ) stimulate cell viability, osteoblast marker gene expression and calcium deposition in human bone marrow-derived mesenchymal cells (hBMCs). The aim of the present study was to investigate the effects of EZ on osteoblast differentiation among dental pulp stem cells (DPSCs) in vitro. In this study, we evaluated the effects of EZ on osteogenesis in DPSCs. Osteoblast and osteoclast marker gene expression was evaluated by real-time PCR. We also evaluated alkaline phosphatase (ALP) staining and calcium deposition. We found that EZ stimulated osteoblast marker gene (type I collagen, alkaline phosphatase (ALP), osteocalcin (OCN) and Runx2) expression, vascular endothelial growth factor A (VEGF-A), and TGF-beta signaling pathway-related gene expression after 7days of incubation. Osteoclastogenesis occurs in a receptor for activated nuclear-factor kappa B ligand (RANKL)/osteoprotegerin (OPG)-independent manner. Real-time PCR analysis revealed that EZ did not affect RANKL or OPG mRNA expression. It was also revealed that EZ induced alkaline phosphatase (ALP) staining and calcium deposition in DPSCs. Collectively, these results demonstrate the potential for clinical application to prospective treatment of bone diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Depletion of the cellular levels of Bag-1 proteins attenuates phorbol ester-induced downregulation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B

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

Maier, Jana V., E-mail: Jana.maier@kit.edu; Volz, Yvonne; Berger, Caroline

2010-10-22

Research highlights: {yields}Bag-1 depletion only marginally affects the action of the glucocorticoid receptor but strongly regulates the activity of NF-{kappa}B. {yields}Bag-1 depletion attenuates phosphorylation and degradation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B p65 and p50. {yields}Bag-1 interacts with I{kappa}B{alpha} and partially restores I{kappa}B{alpha} and NF-{kappa}B activation in Bag-1 depleted cells. -- Abstract: Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulatemore » the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-{kappa}B. Furthermore phosphorylation and degradation of the inhibitor protein I{kappa}B{alpha} and nuclear accumulation of p65 and p50 NF-{kappa}B proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored I{kappa}B{alpha} and NF-{kappa}B activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.« less

NF-{kappa}B regulates Lef1 gene expression in chondrocytes

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

Yun, Kangsun; Choi, Yoo Duk; Nam, Jong Hee

The relation of Wnt/{beta}-catenin signaling to osteoarthritis progression has been revealed with little information on the underlying molecular mechanism. In this study we found overexpression of Lef1 in cartilage tissue of osteoarthritic patients and elucidated molecular mechanism of NF-{kappa}B-mediated Lef1 gene regulation in chondrocytes. Treatment of IL-1{beta} augmented Lef1 upregulation and nuclear translocation of NF-{kappa}B in chondrocytes. Under IL-1{beta} signaling, treatment of NF-{kappa}B nuclear translocation inhibitor SN-50 reduced Lef1 expression. A conserved NF-{kappa}B-binding site between mouse and human was selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1 transcription initiation site. NF-{kappa}B binding to the sitemore » was confirmed by chromatin immunoprecipitation assay. Lef1 expression was synergistically upregulated by interactions of NF-{kappa}B with Lef1/{beta}-catenin in chondrocytes. Our results suggest a pivotal role of NF-{kappa}B in Lef1 expression in arthritic chondrocytes or cartilage degeneration.« less

IKK{epsilon} modulates RSV-induced NF-{kappa}B-dependent gene transcription

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

Bao Xiaoyong; Indukuri, Hemalatha; Liu Tianshuang

2010-12-20

Respiratory syncytial virus (RSV), a negative-strand RNA virus, is the most common cause of epidemic respiratory disease in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B). In this study we have investigated the role of the non canonical I{kappa}B kinase (IKK){epsilon} in modulating RSV-induced NF-{kappa}B activation. Our results show that inhibition of IKK{epsilon} activation results in significant impairment of viral-induced NF-{kappa}B-dependent gene expression, through a reduction in NF-{kappa}B transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absencemore » of IKK{epsilon} results in a significant decrease of RSV-induced NF-{kappa}B phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-{kappa}B-dependent gene expression, known to regulate NF-{kappa}B transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKK{epsilon} regulates viral-induced cellular signaling.« less

Synthesis and Crystal Structure of Dibromido{2-[(4-tert-butylmethylphenyl) iminomethyl]pyridine-κ2 N, N'}Zinc

NASA Astrophysics Data System (ADS)

Khalaj, M.; Ghazanfarpour-Darjani, M.; Seftejani, F. B.; Lalegani, A.

2017-12-01

The title compound [Zn( dip)Br2] was synthesized using the Schiff base bidentate ligand (E)-4- tert-butyl- N-(pyridine-2-ylmethylene)benzeneamine ( dip) and zinc(II) bromide salts. It has been characterized by elemental analysis, X-ray diffraction, and optical spectroscopy. The X-ray diffraction analysis demonstrates that in this structure, the zinc(II) ion is located on an inversion center and exhibits a ZnN2Br2 tetrahedral geometry. In this structure the dip ligand is coordinated with zinc(II) ion in a cyclic-bidentate fashion forming a five-membered metallocyclic ring. The compound crystallizes in the monoclinic sp. gr. P21/ m with a = 9.2700(13) Å, b = 7.6128(11) Å, c = 12.3880(17) Å, and β = 97.021(3)°.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

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

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage

Synthesis of zinc sulfide nanoparticles during zinc oxidization by H2S and H2S/H2O supercritical fluids

NASA Astrophysics Data System (ADS)

Vostrikov, A. A.; Fedyaeva, O. N.; Sokol, M. Ya.; Shatrova, A. V.

2014-12-01

Formation of zinc sulfide nanoparticles was detected during interaction of bulk samples with hydrogen sulfide at supercritical parameters. Synthesis proceeds with liberation of H2 by the reaction nZn + nH2S = (ZnS) n + nH2. It has been found by the X-ray diffraction method, scanning electron microscopy, and mass spectrometry that the addition of water stimulates coupled reactions of nanoparticle synthesis nZn + nH2O = (ZnO) n + nH2 and (ZnO) n + nH2S = (ZnS) n + nH2O and brings about an increase in the synthesis rate and morphological changes of (ZnS) n nanoparticles.

Zinc-Nucleated D 2 and H 2 Crystal Formation from Their Liquids

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

Bernat, T. P.; Petta, N.; Kozioziemski, B.

Calorimetric measurements at University of Rochester Laboratory for Laser Energetics of D 2 crystallization from the melt indicate that zinc can act as a heterogeneous nucleation seed with suppressed supercooling. We further studied in this paper this effect for a variety of zinc substrates using the optical-access cryogenic sample cell at Lawrence Livermore National Laboratory. Small supercoolings are observed, some as low as 5 mK, but results depend on the zinc history and sample preparation. In general, thin samples prepared by physical vapor deposition were not effective in nucleating crystal formation. Larger (several-millimeter) granules showed greater supercooling suppression, depending onmore » surface modification and granule size. Surfaces of these granules are morphologically varied and not uniform. Scanning electron microscope images were not able to correlate any particular surface feature with enhanced nucleation. Finally, application of classical nucleation theory to the observed variation of supercooling level with granule size is consistent with nucleation features with sizes <100 nm and with wetting angles of a few degrees.« less

Zinc-Nucleated D 2 and H 2 Crystal Formation from Their Liquids

DOE PAGES

Bernat, T. P.; Petta, N.; Kozioziemski, B.; ...

2016-09-01

Calorimetric measurements at University of Rochester Laboratory for Laser Energetics of D 2 crystallization from the melt indicate that zinc can act as a heterogeneous nucleation seed with suppressed supercooling. We further studied in this paper this effect for a variety of zinc substrates using the optical-access cryogenic sample cell at Lawrence Livermore National Laboratory. Small supercoolings are observed, some as low as 5 mK, but results depend on the zinc history and sample preparation. In general, thin samples prepared by physical vapor deposition were not effective in nucleating crystal formation. Larger (several-millimeter) granules showed greater supercooling suppression, depending onmore » surface modification and granule size. Surfaces of these granules are morphologically varied and not uniform. Scanning electron microscope images were not able to correlate any particular surface feature with enhanced nucleation. Finally, application of classical nucleation theory to the observed variation of supercooling level with granule size is consistent with nucleation features with sizes <100 nm and with wetting angles of a few degrees.« less

Cationization of kappa- and iota-carrageenan--Characterization and properties of amphoteric polysaccharides.

PubMed

Barahona, Tamara; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L; Fissore, Eliana L; Gerschenson, Lia N; Matulewicz, María C

2015-08-01

Commercial kappa- and iota carrageenans were cationized with 3-chloro-2-hydroxypropyltrimethylammonium chloride in aqueous sodium hydroxide solution. For kappa-carrageenan three derivatives with different degrees of substitution were obtained. Native and amphoteric kappa-carrageenans were characterized by NMR and infrared spectroscopy, scanning electron and atomic force microscopy; methanolysis products were studied by electrospray ionization mass spectrometry. Young moduli and the strain at break of films, differential scanning calorimetry, rheological and flocculation behavior were also evaluated; the native and the amphoteric derivatives showed different and interesting properties. Cationization of iota-carrageenan was more difficult, indicating as it was previously observed for agarose, that substitution starts preferentially on the 2-position of 3,6-anhydrogalactose residues; in iota-carrageenan this latter unit is sulfated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kappa angles in different positions in patients with myopia during LASIK

PubMed Central

Qi, Hui; Jiang, Jing-Jing; Jiang, Yan-Ming; Wang, Li-Qiang; Huang, Yi-Fei

2016-01-01

AIM To investigate the difference in kappa angle between sitting and supine positions during laser-assisted in situ keratomileusis (LASIK). METHODS A retrospective study was performed on 395 eyes from 215 patients with myopia that received LASIK. Low, moderate, and high myopia groups were assigned according to diopters. The horizontal and vertical components of kappa angle in sitting position were measured before the operation, and in supine position during the operation. The data from the two positions were compared and the relationship between kappa angle and diopters were analyzed. RESULTS Two hundred and twenty-three eyes (56.5%) in sitting position and 343 eyes (86.8%) in supine position had positive kappa angles. There were no significant differences in horizontal and vertical components of kappa angle in the sitting position or horizontal components of kappa angle in the supine position between the three groups (P>0.05). A significant difference in the vertical components of kappa angle in the supine position was seen in the three groups (P<0.01). Differences in both horizontal and vertical components of kappa angles were significant between the sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angles (P<0.05) were found and vertical components of kappa angle in sitting and supine positions were negatively correlated with the degree of myopia (sitting position: r=-0.109; supine position: r=-0.172; P<0.05). CONCLUSION There is a correlation in horizontal and vertical components of kappa angle in sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angle in sitting and supine positions till the end of the results. This result still needs further observation. Clinicians should take into account different postures when excimer laser surgery needs to be performed. PMID:27162734

40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc...

40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc...

Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

PubMed

Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

2016-09-01

The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B.

PubMed

Bourke, E; Moynagh, P N

1999-08-15

Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein I kappa B, which inhibits the transcription factor NF-kappa B. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce I kappa B or inhibit activation of NF-kappa B by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kappa B by demonstrating that an oligonucleotide, containing the wild-type NF-kappa B-binding motif, inhibited formation of the NF-kappa B-DNA complexes whereas a mutated form of the NF-kappa B-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kappa B complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kappa B correlated with its inability to induce I kappa B and the ability of IL-1 to cause degradation of I kappa B, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kappa B.

5-Arylvinyl-2,2′-bipyridyls: Bright “push–pull” dyes as components in fluorescent indicators for zinc ions

PubMed Central

Zhu, Lei; Younes, Ali H.; Yuan, Zhao; Clark, Ronald J.

2015-01-01

This article reviews the zinc(II)-dependent photophysical properties of arylvinylbipyridines (AVBs), a class of fluoroionophores in which 2,2′-bipyridyl and an aryl moiety are electronically conjugated. Zinc(II) binding of an AVB may lead to an emission bathochromic shift of the fluoroionophore without diminishing its fluorescence quantum yield. This observation can be explained using the excited state model of electron donor–π bridge–electron acceptor “push–pull” fluorophores, in which the bipy moiety acts as an electron acceptor, and zinc(II)-coordination strengthens its electron affinity. The spectral sensitivity of bipy-containing fluoroionophores, such as AVBs, to zinc(II) can be exploited to prepare fluorescent indicators for this ion. In several cases, AVB moieties are incorporated in fluorescent heteroditopic ligands, so that the variation of zinc(II) concentration over a relatively large range can be correlated to fluorescence changes in either intensity or color. AVB fluoroionophores are also used to introduce an intramolecular Förster resonance energy transfer (FRET) strategy for creating zinc(II) indicators with high photostability and a narrow emission band, two desired characteristics of dyes used in fluorescence microscopy. PMID:26190906

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats.

PubMed

Kuldeep, Anjana; Nair, Neena; Bedwal, Ranveer Singh

2017-06-01

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30-40 days of age, pre-pubertal period) of 40-50 g body weight were divided into the following: the ZC (zinc control) group-fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group-fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group-received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

NF-{kappa}B inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

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

Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

2008-07-15

Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-{kappa}B) in this process. Exposure of rats to 80 mg/m{sup 3} tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-{kappa}Bmore » activity, noted by suppression of inhibitor of {kappa}B (I{kappa}B) kinase (IKK), accumulation of I{kappa}B{alpha}, decrease of NF-{kappa}B DNA binding activity, and downregulation of NF-{kappa}B-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-{kappa}B pathway in tobacco smoke-induced apoptosis.« less

Ion-cyclotron instability in plasmas described by product-bi-kappa distributions

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

Santos, M. S. dos; Ziebell, L. F., E-mail: luiz.ziebell@ufrgs.br; Gaelzer, R., E-mail: rudi.gaelzer@ufrgs.br

The dispersion relation for parallel propagating waves in the ion-cyclotron branch is investigated numerically by considering that the velocity distribution of the ion population is a function of type product-bi-kappa. We investigate the effects of the non-thermal features and of the anisotropy associated with this type of distribution on the ion-cyclotron instability, as well as the influence of different forms of the electron distribution, by considering Maxwellian distributions, bi-kappa distributions, and product-bi-kappa distributions. The cases of ions described by either Maxwellian or bi-kappa distributions are also considered, for comparison. The results of the numerical analysis show that the increase inmore » the non-thermal character associated with the anisotropic kappa distributions for ions contributes to enhance the instability as compared to that obtained in the Maxwellian case, in magnitude and in wave number range, with more significant enhancement for the case of ion product-bi-kappa distributions than for the case of ion bi-kappa distributions. It is also shown that the ion-cyclotron instability is decreased if the electrons are described by product-bi-kappa distributions, while electrons described by bi-kappa distributions lead to growth rates which are very similar to those obtained considering a Maxwellian distribution for the electron population.« less

ICI 204448: a kappa-opioid agonist with limited access to the CNS.

PubMed Central

Shaw, J. S.; Carroll, J. A.; Alcock, P.; Main, B. G.

1989-01-01

1. A number of compounds were evaluated in an attempt to identify a kappa-opioid receptor agonist with limited access to the central nervous system. 2. Quaternary derivatives of the kappa-opioid agonists tifluadom, U-50488H and ethylketocyclazocine were essentially devoid of opioid activity in a range of isolated tissue preparations. 3. A novel compound - ICI 204448 - is described which produced a potent and naloxone-reversible inhibition of electrically-evoked contraction of the guinea-pig ileum, mouse vas deferens and rabbit vas deferens preparations. ICI 204448 was shown to displace the binding of the kappa-opioid ligand [3H]-bremazocine from guinea-pig cerebellum membranes. 4. Ex vivo binding studies in mice showed ICI 204448 to be well absorbed following subcutaneous administration. The brain levels achieved by ICI 20448 were substantially lower than those produced by kappa-agonists such as U-50488H and tifluadom. 5. A good correlation was found for a range of opioids between lipophilicity and degree of CNS penetration. PMID:2568146

Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets.

PubMed

Schwiebert, Erik M; Liang, Lihua; Cheng, Nai-Lin; Williams, Clintoria Richards; Olteanu, Dragos; Welty, Elisabeth A; Zsembery, Akos

2005-12-01

In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential.

Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA.

PubMed Central

Naranjo, David

2002-01-01

kappa-Conotoxin-PVIIA (kappa-PVIIA) is a 27-residue basic (+4) peptide from the venom of the predator snail Conus purpurascens. A single kappa-PVIIA molecule interrupts ion conduction by binding to the external mouth of Shaker K channels. The blockade of Shaker by kappa-PVIIA was studied at the single channel level in membrane patches from Xenopus oocytes. The amplitudes of blocked and closed events were undistinguishable, suggesting that the toxin interrupts ion conduction completely. Between -20 and 40 mV kappa-PVIIA increased the latency to the first opening by one order of magnitude in a concentration-independent fashion. Because kappa-PVIIA has higher affinity for the closed channels at high enough concentration to block >90% of the resting channels, the dissociation rate could be estimated from the analysis of the first latency. At 0 mV, the dissociation rate was 20 s(-1) and had an effective valence of 0.64. The apparent closing rate increased linearly with [kappa-PVIIA] indicating an association rate of 56 microM(-1) s(-1). The toxin did not modify the fraction of null traces. This result suggests that the structural rearrangements in the external mouth contributing to the slow inactivation preserve the main geometrical features of the toxin-receptor interaction. PMID:12023223

c-rel activates but v-rel suppresses transcription from kappa B sites.

PubMed Central

Inoue, J; Kerr, L D; Ransone, L J; Bengal, E; Hunter, T; Verma, I M

1991-01-01

We show that the product of the protooncogene c-rel is a constituent of an NF-kappa B-like complex that binds to the kappa B site originally identified in the enhancer of immunoglobulin kappa light chain gene. c-rel protein synthesized in bacteria binds to the kappa B site in a sequence-specific manner. The rel-kappa B complex can be disrupted by incubation with anti-rel antibodies. The rel protein can form oligomers. The c-rel protein can activate transcription from promoters containing kappa B sites; v-rel, on the other hand, suppresses the transcription of genes linked to kappa B sites. Thus, v-rel may interfere with the normal transcriptional machinery of the cell by acting as a dominant negative mutant. Images PMID:2023921

2,6-diacetylpyridine bis(thiosemicarbazones) zinc complexes: synthesis, structure, and biological activity.

PubMed

Rodriguez-Argüelles, M C; Belicchi Ferrari, M; Gasparri Fava, G; Pelizzi, C; Tarasconi, P; Albertini, R; Dall'Aglio, P P; Lunghi, P; Pinelli, S

1995-05-15

The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds--[Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal--bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds.

Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

PubMed

Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

2005-04-01

Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P < 0.001), Smad4 (P = 0.002), and kangai 1 (P < 0.001) expression. An in vitro study showed that NF-kappaB activity in gastric cancer cells is controlled by and controls Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation.

PubMed Central

Brown, Sharron A N; Richards, Christine M; Hanscom, Heather N; Feng, Sheau-Line Y; Winkles, Jeffrey A

2003-01-01

Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein. The human Fn14 protein was recently identified as a cell-surface receptor for the tumour necrosis factor (TNF) superfamily member named TWEAK (TNF-like weak inducer of apoptosis). In the present paper, we report that the human TWEAK extracellular domain can also bind the murine Fn14 protein. Furthermore, site-specific mutagenesis and directed yeast two-hybrid interaction assays revealed that the TNFR-associated factor (TRAF) 1, 2, 3 and 5 adaptor molecules bind the murine Fn14 cytoplasmic tail at an overlapping, but non-identical, amino acid sequence motif. We also found that TWEAK treatment of quiescent NIH 3T3 cells stimulates inhibitory kappaBalpha phosphorylation and transcriptional activation of a nuclear factor-kappaB (NF-kappaB) enhancer/luciferase reporter construct. Fn14 overexpression in transiently transfected NIH 3T3 cells also promotes NF-kappaB activation, and this cellular response requires an intact TRAF binding site. These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway. PMID:12529173

Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

PubMed

Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

2018-01-15

Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Angiotensin II potentiates zinc-induced cortical neuronal death by acting on angiotensin II type 2 receptor.

PubMed

Park, Mi-Ha; Kim, Ha Na; Lim, Joon Seo; Ahn, Jae-Sung; Koh, Jae-Young

2013-12-01

The angiotensin system has several non-vascular functions in the central nervous system. For instance, inhibition of the brain angiotensin system results in a reduction in neuronal death following acute brain injury such as ischemia and intracerebral hemorrhage, even under conditions of constant blood pressure. Since endogenous zinc has been implicated as a key mediator of ischemic neuronal death, we investigated the possibility that the angiotensin system affects the outcome of zinc-triggered neuronal death in cortical cell cultures. Exposure of cortical cultures containing neurons and astrocytes to 300 μM zinc for 15 min induced submaximal death in both types of cells. Interestingly, addition of angiotensin II significantly enhanced the zinc-triggered neuronal death, while leaving astrocytic cell death relatively unchanged. Both type 1 and 2 angiotensin II receptors (AT1R and AT2R, respectively) were expressed in neurons as well as astrocytes. Zinc neurotoxicity was substantially attenuated by PD123319, a specific inhibitor of AT2R, and augmented by CGP42112, a selective activator of AT2R, indicating a critical role for this receptor subtype in the augmentation of neuronal cell death.Because zinc toxicity occurs largely through oxidative stress, the levels of superoxides in zinc-treated neurons were assessed by DCF fluorescence microscopy. Combined treatment with zinc and angiotensin II substantially increased the levels of superoxides in neurons compared to those induced by zinc alone. This increase in oxidative stress by angiotensin II was completely blocked by the addition of PD123319. Finally, since zinc-induced oxidative stress may be caused by induction and/or activation of NADPH oxidase, the activation status of Rac and the level of the NADPH oxidase subunit p67phox were measured. Angiotensin II markedly increased Rac activity and the levels of p67phox in zinc-treated neurons and astrocytes in a PD123319-dependent manner. The present study shows that the

TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.

PubMed

Lim, Diana M; Narasimhan, Sneha; Michaylira, Carmen Z; Wang, Mei-Lun

2009-12-01

Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. In the present study, we investigated the inflammatory response and signaling pathways activated by TLR stimulation of human esophageal cells in vitro. Using quantitative RT-PCR, we profiled the expression pattern of human TLRs 1-10 in primary esophageal keratinocytes (EPC2), immortalized nontransformed esophageal keratinocytes (EPC2-hTERT), and normal human esophageal mucosal biopsies and found that TLRs 1, 2, 3, and 5 were expressed both in vivo and in vitro. Using the cytokine IL-8 as a physiological read out of the inflammatory response, we found that TLR3 is the most functional of the expressed TLRs in both primary and immortalized esophageal epithelial cell lines in response to its synthetic ligand polyinosinic polycytidylic acid [poly(I:C)]. Through reporter gene studies, we show that poly(I:C)-induced NF-kappaB activation is critical for the transactivation of the IL-8 promoter in vitro and that nuclear translocation of NF-kappaB occurs at an early time point following poly(I:C) stimulation of esophageal epithelial cells. Importantly, we also show that poly(I:C) stimulation induces the NF-kappaB-dependent esophageal epithelial expression of TLR2, leading to enhanced epithelial responsiveness of EPC2-hTERT cells to TLR2 ligand stimulation, suggesting an important regulatory role for TLR3-mediated NF-kappaB signaling in the innate immune response of esophageal epithelial cells. Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-kappaB signaling may play an important regulatory role in esophageal epithelial homeostasis.

Anti-inflammatory function of Withangulatin A by targeted inhibiting COX-2 expression via MAPK and NF-kappaB pathways.

PubMed

Sun, Lijuan; Liu, Jianwen; Cui, Daling; Li, Jiyu; Yu, Youjun; Ma, Lei; Hu, Lihong

2010-02-15

Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent. (c) 2009 Wiley-Liss, Inc.

99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON ...

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

99. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, LOOKING NORTH. NOTE ONE STYLE OF DENVER AGITATOR IN LOWER RIGHT CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

Prediction of Serum Zinc Levels in Mexican Children at 2 Years of Age Using a Food Frequency Questionnaire and Different Zinc Bioavailability Criteria

PubMed Central

Cantoral, Alejandra; Téllez-Rojo, Martha; Shamah-Levy, Teresa; Schnaas, Lourdes; Hernández-Ávila, Mauricio; Peterson, Karen; Ettinger, Adrienne

2017-01-01

Background The 2006 Mexican National Health and Nutrition Survey documented a prevalence of zinc deficiency of almost 30% in children aged one to two years old. Objective We sought to validate a Food Frequency Questionnaire (FFQ) for quantifying dietary bioavailable zinc intake in two-year old Mexican children accounting for phytic acid intake and using serum zinc as a reference. Methods This cross-sectional study was nested within a longitudinal birth cohort of 333 young children in Mexico City. Non-fasting serum zinc concentration was measured and dietary zinc intake was calculated on the basis of a semi-quantitative FFQ administered to their mothers. The relationship between dietary zinc intake and serum zinc was assessed using linear regression, adjusting for phytic acid intake, and analyzed according to two distinct international criteria to estimate bioavailable zinc. Models were stratified by zinc deficiency status. Results Dietary zinc, adjusted for phytic acid intake, explained the greatest proportion of the variance of serum zinc. For each mg of dietary zinc intake, serum zinc increased on average by 0.95 μg/dL (0.15 μmol/L) (p=0.06). When stratified by zinc status, this increase was 0.74 μg/dL (p=0.12) for each milligram of zinc consumed among children with adequate serum zinc (N=276) whereas among those children with zinc deficiency (N=57), serum zinc increased by only 0.11 μg/dL (p=0.82). Conclusion A semi-quantitative FFQ can be used for predicting serum zinc in relation to dietary intake in young children, particularly among those who are zinc-replete, and when phytic acid/phytate intake is considered. Future studies should be conducted accounting for both zinc status and dietary zinc inhibitors to further elucidate and validate these findings. PMID:26121697

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory.

PubMed

Sindreu, Carlos; Palmiter, Richard D; Storm, Daniel R

2011-02-22

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

PubMed

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-06-27

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

PubMed Central

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-01-01

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use. PMID:28487501

Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

USDA-ARS?s Scientific Manuscript database

To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

Zinc phthalocyanine nanowires based flexible sensor for room temperature Cl2 detection

NASA Astrophysics Data System (ADS)

Devi, Pooja; Saini, Rajan; Singh, Rajinder; Mahajan, A.; Bedi, R. K.; Aswal, D. K.; Debnath, A. K.

2018-04-01

We have fabricated highly sensitive and Cl2 selective flexible sensor by depositing solution processed zinc phthalocyanine nanowires onto the flexible PET substrate and studied its Cl2 sensing characteristics in Cl2 concentration range 5-1500 ppb. The flexible sensor has a minimum detection limit as low as 5 ppb of Cl2 and response as high as 550% within 10 seconds. Interestingly, the sensor exhibited enhanced and faster response kinetics under bending conditions. The gas sensing mechanism of sensor has been discussed on the basis of XPS and Raman spectroscopic studies which revealed that zinc ions were the preferred sites for Cl2 interactions.

Zinc pharmacokinetic parameters in the determination of body zinc status in children.

PubMed

Vale, S H L; Leite, L D; Alves, C X; Dantas, M M G; Costa, J B S; Marchini, J S; França, M C; Brandão-Neto, J

2014-02-01

Serum or tissue zinc concentrations are often used to assess body zinc status. However, all of these methods are relatively inaccurate. Thus, we investigated three different kinetic methods for the determination of zinc clearance to establish which of these could detect small changes in the body zinc status of children. Forty apparently healthy children were studied. Renal handling of zinc was investigated during intravenous zinc administration (0.06537 mg Zn/kg of body weight), both before and after oral zinc supplementation (5 mg Zn/day for 3 months). Three kinetic methods were used to determine zinc clearance: CZn-Formula A and CZn-Formula B were both used to calculate systemic clearance; the first is a general formula and the second is used for the specific analysis of a single-compartment model; CZn-Formula C is widely used in medical practices to analyze kinetic routine. Basal serum zinc values, which were within the reference range for healthy children, increased significantly after oral zinc supplementation. The three formulas used gave different results for zinc clearance both before and after oral zinc supplementation. CZn-Formula B showed a positive correlation with basal serum zinc concentration after oral supplementation (R2=0.1172, P=0.0306). In addition, CZn-Formula B (P=0.0002) was more effective than CZn-Formula A (P=0.6028) and CZn-Formula C (P=0.0732) in detecting small variations in body zinc status. All three of the formulas used are suitable for studying zinc kinetics; however, CZn-Formula B is particularly effective at detecting small changes in body zinc status in healthy children.

Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.

PubMed

Voisard, R; Huber, N; Baur, R; Susa, M; Ickrath, O; Both, A; Koenig, W; Hombach, V

2001-01-01

Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50. The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

PubMed Central

Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

1999-01-01

Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. α2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because α2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35–60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2–IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented α2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and α2-macroglobulin (r = 0.75, P< 0.01, r = 0.78, P< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in α2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. © 1999 Cancer Research Campaign PMID:9888464

The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

PubMed Central

Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

2009-01-01

The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

Electrochemical behavior of zinc particles with silica based coatings as anode material for zinc air batteries with improved discharge capacity

NASA Astrophysics Data System (ADS)

Schmid, M.; Willert-Porada, M.

2017-05-01

Silica coatings on zinc particles as anode material for alkaline zinc air batteries are expected to reduce early formation of irreversible ZnO passivation layers during discharge by controlling zinc dissolution and precipitation of supersaturated zincates, Zn(OH)42-. Zinc particles were coated with SiO2 (thickness: 15 nm) by chemical solution deposition and with Zn2SiO4 (thickness: 20 nm) by chemical vapor deposition. These coatings formed a Si(OH)4 gel in aqueous KOH and retarded hydrogen evolution by 40%. By treatment in aqueous KOH and drying afterwards, the silica coatings were changed into ZnO-K2O·SiO2 layers. In this work, the electrochemical performance of such coated zinc particles is investigated by different electrochemical methods in order to gain a deeper understanding of the mechanisms of the coatings, which reduce zinc passivation. In particular, zinc utilization and changes in internal resistance are investigated. Moreover, methods for determination of diffusion coefficients, charge carrier numbers and activation energies for electrochemical oxidation are determined. SiO2-coated zinc particles show improved discharge capacity (CVD-coated zinc: 69% zinc utilization, CSD-coated zinc: 62% zinc utilization) as compared to as-received zinc (57% zinc utilization) at C/20 rate, by reducing supersaturation of zincates. Additionally, KOH-modified SiO2-coated zinc particles enhance rechargeability after 100% depth-of-discharge.

Direct covalent modification as a strategy to inhibit nuclear factor-kappa B.

PubMed

Pande, Vineet; Sousa, Sérgio F; Ramos, Maria João

2009-01-01

Nuclear Factor-KkappaB (NF-kappaB) is a transcription factor whose inappropriate activation may result in the development of a number of diseases including cancer, inflammation, neurodegeneration and AIDS. Recent studies on NF-kappaB mediated pathologies, made therapeutic interventions leading to its inhibition an emerging theme in pharmaceutical research. NF-kappaB resides in the cytoplasm and is activated by several time-dependent factors, leading to proteasome-dependent degradation of its inhibitory protein (IkappaB), resulting in free NF-kappaB (p50 and p65 subunits, involved in disease states), which binds to target DNA sites, further resulting in enhanced transcription of several disease associated proteins. The complex pathway of NF-kappaB, finally leading to its DNA binding, has attracted several approaches interfering with this pathway. One such approach is that of a direct covalent modification of NF-kappaB. In this article, we present a critical review on the pharmacological agents that have been studied as inhibitors of NF-kappaB by covalently modifying redox-regulated cysteine residues in its subunits, ultimately resulting in the inhibition of kappaB DNA recognition and binding. Beginning with a general overview of NF-kappaB pathway and several possibilities of chemical interventions, the significance of redox-regulation in NF-kappaB activation and DNA binding is presented. Further, protein S-thiolation, S-nitrosylation and irreversible covalent modification are described as regular biochemical events in the cell, having provided a guideline for the development of NF-kappaB inhibitors discussed further. Although just a handful of inhibitors, with most of them being alkylating agents have been studied in the present context, this approach presents potential for the development of a new class of NF-kappaB-inhibitors.

Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-{kappa}B in HepG2 cells

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

Feng Gong, E-mail: gong-feng@northwestern.edu; Anong Biotech Institute, Tianjin; Li Ying

Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apoptosis. Fas receptor (Fas) and Fas ligand (FasL) system is a critical signaling network triggering apoptosis. In current study, we investigated whether nodularin can induce Fas and FasL expression in HepG2 cell, a well used in vitro model for the study of human hepatocytes. Our data showed nodularinmore » induced Fas and FasL expression, at both mRNA and protein level, in a time- and dose-dependent manner. We also found nodularin induced apoptosis at the concentration and incubation time that Fas and FasL were significantly induced. Neutralizing antibody to FasL reduced nodularin-induced apoptosis. Further studies demonstrated that nodularin promoted nuclear translocation and activation of p65 subunit of NF-{kappa}B. By applying siRNA targeting p65, which knocked down p65 in HepG2 cells, we successfully impaired the activation of NF-{kappa}B by nodularin. In these p65 knockdown cells, we observed that Fas and FasL expression and apoptosis induced by nodularin were significantly reduced. These findings suggest the induction of Fas and FasL expression and thus cell apoptosis in HepG2 cells by nodularin is mediated through NF-{kappa}B pathway.« less

Kappa and Hirschberg ratio measured with an automated video gaze tracker.

PubMed

Schaeffel, Frank

2002-05-01

To develop a fast automated procedure to measure kappa and the Hirschberg ratio for immediate use in a video gaze tracker. Using the hardware platform of the PowerRefractor and a 200 mm lens, the pupil was imaged with a resolution of 57 pixels/mm, at a camera distance of 90 cm. Both the positions of the first Purkinje image and the edges of the pupil were located at 25 Hz sampling rate with subpixel resolution using video image processing software developed under Borland C++. Subjects fixated on a red spot on the left side of the monitor. If their fixation was stable (standard deviation <0.2 degrees in 25 subsequent measurements evaluated in 1 s), the fixation spot appeared automatically on the right side, and the procedure was repeated. Data on the angular position of the optical axis for both targets were stored and provided kappa and the Hirschberg ratio with a standard deviation of about 0.2 degrees or better. This enabled the system to track fixation with a resolution of about 0.2 degrees. (1) Kappa was +3.91+/-2.73 degrees (right eyes), -3.93+/-2.68 degrees (left eyes, mean +/- SD from 24 young adults). Kappa was highly correlated in both eyes (r = 0.8996), but there were significant asymmetries between both eyes in three subjects (delta up to 3 degrees). (2) The Hirschberg ratios were 12.93+/-1.23 degrees/mm = 22.56 delta/mm (right eyes) and 12.82+/-1.49 degrees/mm = 22.38 delta/mm (left eyes). They were also highly correlated in both eyes (r = 0.931). (3) Neither kappa nor the Hirschberg ratios were correlated to refractive errors (range +0.50 to -7.75 D, mean -1.73+/-2.29 D [spherical equivalents]). (1) The video gaze tracker measured fixation with an angular resolution high enough to display the eye position during reading of individual words on the computer screen. (2) The applicable Hirschberg ratio changed with the power of the spectacles of the subjects by about 3% per diopter. (3) In some subjects, there were significant differences in the geometry

C2H2 type of zinc finger transcription factors in foxtail millet define response to abiotic stresses.

PubMed

Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Mishra, Awdhesh Kumar; Khandelwal, Rohit; Khan, Yusuf; Roy, Riti; Prasad, Manoj

2014-09-01

C2H2 type of zinc finger transcription factors (TFs) play crucial roles in plant stress response and hormone signal transduction. Hence considering its importance, genome-wide investigation and characterization of C2H2 zinc finger proteins were performed in Arabidopsis, rice and poplar but no such study was conducted in foxtail millet which is a C4 Panicoid model crop well known for its abiotic stress tolerance. The present study identified 124 C2H2-type zinc finger TFs in foxtail millet (SiC2H2) and physically mapped them onto the genome. The gene duplication analysis revealed that SiC2H2s primarily expanded in the genome through tandem duplication. The phylogenetic tree classified these TFs into five groups (I-V). Further, miRNAs targeting SiC2H2 transcripts in foxtail millet were identified. Heat map demonstrated differential and tissue-specific expression patterns of these SiC2H2 genes. Comparative physical mapping between foxtail millet SiC2H2 genes and its orthologs of sorghum, maize and rice revealed the evolutionary relationships of C2H2 type of zinc finger TFs. The duplication and divergence data provided novel insight into the evolutionary aspects of these TFs in foxtail millet and related grass species. Expression profiling of candidate SiC2H2 genes in response to salinity, dehydration and cold stress showed differential expression pattern of these genes at different time points of stresses.

Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-{kappa}B Activity

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

Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.

2009-10-01

Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-{kappa}B (NF-{kappa}B)more » activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-{kappa}B activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-{kappa}B activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of {kappa}B alpha, inhibition of inhibitor of {kappa}B kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-{kappa}B-regulated gene products (Bcl-2, Bcl-x{sub L}, inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-{kappa}B activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.« less

A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc.

PubMed

Wastney, Meryl E; McDonald, Christine M; King, Janet C

2018-05-01

Zinc deficiency limits infant growth and increases susceptibility to infections, which further compromises growth. Zinc supplementation improves the growth of zinc-deficient stunted infants, but the amount, frequency, and duration of zinc supplementation required to restore growth in an individual child is unknown. A dynamic model of zinc metabolism that predicts changes in weight and length of zinc-deficient, stunted infants with dietary zinc would be useful to define effective zinc supplementation regimens. The aims of this study were to develop a dynamic model for zinc metabolism in stunted, zinc-deficient infants and to use that model to predict the growth response when those infants are given zinc supplements. A model of zinc metabolism was developed using data on zinc kinetics, tissue zinc, and growth requirements for healthy 9-mo-old infants. The kinetic model was converted to a dynamic model by replacing the rate constants for zinc absorption and excretion with functions for these processes that change with zinc intake. Predictions of the dynamic model, parameterized for zinc-deficient, stunted infants, were compared with the results of 5 published zinc intervention trials. The model was then used to predict the results for zinc supplementation regimes that varied in the amount, frequency, and duration of zinc dosing. Model predictions agreed with published changes in plasma zinc after zinc supplementation. Predictions of weight and length agreed with 2 studies, but overpredicted values from a third study in which other nutrient deficiencies may have been growth limiting; the model predicted that zinc absorption was impaired in that study. The model suggests that frequent, smaller doses (5-10 mg Zn/d) are more effective for increasing growth in stunted, zinc-deficient 9-mo-old infants than are larger, less-frequent doses. The dose amount affects the duration of dosing necessary to restore and maintain plasma zinc concentration and growth.

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory

PubMed Central

Sindreu, Carlos; Palmiter, Richard D.; Storm, Daniel R.

2011-01-01

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory. PMID:21245308

Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

PubMed Central

Chu, Anna; Foster, Meika; Samman, Samir

2016-01-01

Zinc is an essential trace element with proposed therapeutic effects in Type 2 diabetes mellitus (DM), however, the associations between zinc status and the prospective risks of cardiovascular diseases (CVD) and Type 2 DM have not been evaluated. The current systematic review aims to determine the relationships between zinc intake or plasma/serum zinc levels and prospective incidence of CVD and Type 2 DM. Fourteen papers describing prospective cohort studies were included, reporting either CVD (n = 91,708) and/or Type 2 DM (n = 334,387) outcomes. Primary analyses from four out of five studies reported no association between zinc intake and CVD events, when adjusted for multiple variables. Higher serum zinc level was associated with lower risk of CVD in three out of five studies; pronounced effects were observed in vulnerable populations, specifically those with Type 2 DM and patients referred to coronary angiography. The limited evidence available suggests no association between zinc status and Type 2 DM risk. Further investigations into the mechanisms of zinc’s action on the pathogenesis of chronic diseases and additional evidence from observational studies are required to establish a recommendation for dietary zinc in relation to the prevention of CVD and Type 2 DM. PMID:27827959

Zinc at glutamatergic synapses.

PubMed

Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

2009-01-12

It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation

PubMed Central

2013-01-01

Background Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster. Results A set of plasma membrane-resident zinc transporters was identified to be responsible for absorbing zinc from the lumen into the enterocyte and the subsequent exit of zinc to the circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Exit of zinc to the circulation is mediated through another two functionally overlapping zinc exporters, dZnT1, and its homolog CG5130 (dZnT77C). Somewhat surprisingly, it appears that the array of intracellular ZnT proteins, including the Golgi-resident dZnT7, is not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that regulation of dietary zinc absorption, in contrast to that of iron, is unresponsive to bodily needs or zinc status outside the gut. The zinc transporters that are involved in dietary zinc absorption, including the importers dZip1 and dZip2, and the exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte. Conclusions Our study using the model organism Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulatory control, a process that is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies, and also enable an appreciation of this important process from an evolutionary perspective. PMID:24063361

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

PubMed

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats.

PubMed

Rawls, Scott M; Ding, Zhe; Gray, Alex M; Cowan, Alan

2005-05-01

ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures. Copyright (c) 2005 S. Karger AG, Basel.

Zinc electrode and rechargeable zinc-air battery

DOEpatents

Ross, Jr., Philip N.

1989-01-01

An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.

The radiant ephemerides of kappa-Cygnids from the IMO video database

NASA Astrophysics Data System (ADS)

Triglav-Cekada, Mihaela

2006-08-01

The analysis of single-station IMO video network data of the July and August period with 36 576 meteors in search of kappa-Cygnid, alpha-Lyrid and zeta-Draconid meteor showers was made using the program Radiant. These showers will be named kappa-Cygnid meteor complex radiants. The detailed analysis of the whole August period from 1993-2004 included the behavior of radiants in different magnitude ranges and different years from 2000 on. Detailed radiant calculations for different velocities for 5g and 10g solar longitude intervals were also done. In 10g solar longitude intervals also the calculations for different magnitude ranges were conducted. The activity of the kappa-Cygnid radiant and the alpha-Lyrid radiant was proven, unlike the zeta-Draconid radiant, where no activity could be confirmed. For the whole August period also the behavior of radiants in separate years 2000-2004, when day-to-day meteor coverage is available, was made. From that it can be hinted on alternating bigger activity of the kappa-Cygnid and alpha-Lyrid radiants. In the years 2000 and 2001 the alpha-Lyrid radiant is more active, when on the contrary in 2002, 2003 and 2004 the kappa-Cygnid radiant is more active. The year 2003 is interesting from another aspect, as three radiants can be seen. If the third radiant is the zeta-Draconid radiant, a few years more video observations will have to be gathered and the radiant calculations repeated. For the day of the kappa-Cygnid meteor complex maximum, on August 18, the mean radiant positions were deduced: the more active kappa-Cygnid radiant lies at alpha=280 deg and delta=+58 deg with an area of the maximum probability of 10 deg x 15 deg, and the less active alpha-Lyrid radiant is placed at alpha=292 deg and delta=+52 deg with a radius of maximum probability of 2 deg. The radiant drift was not possible to obtain as in the 5 deg and 10 deg solar longitude interval calculations the positions of both radiants apparently oscillate. As no change can

Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in lipopolysaccharide-stimulated RAW 264.7 macrophages

PubMed Central

Adewoyin, Malik; Mohsin, Sumaiyah Megat Nabil; Arulselvan, Palanisamy; Hussein, Mohd Zobir; Fakurazi, Sharida

2015-01-01

Background Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA. Methods In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined. Results Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only. Conclusion The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control. PMID:25995619

Zinc and Chlamydia trachomatis

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

Sugarman, B.; Epps, L.R.

1985-07-01

Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 x 10/sup -4/ M) in the inoculation media compared with standard Chlamydia cultivation media (8 x 10/sup -6/ M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remainedmore » constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10/sup -4/ M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptibility to Chamydia trachomatis infections.« less

Loss of ErbB2-PI3K/Akt signaling prevents zinc pyrithione-induced cardioprotection during ischemia/reperfusion.

PubMed

Thokala, Sandhya; Inapurapu, Santhipriya; Bodiga, Vijaya Lakshmi; Vemuri, Praveen Kumar; Bodiga, Sreedhar

2017-04-01

The purpose of this study was to determine if zinc homeostasis is affected during ischemia/reperfusion, if so, whether zinc pyrithione limits myocardial cell death and improves hemodynamics when administered as an adjunct to reperfusion and if ErbB receptor tyrosine kinases that are important for the long-term structural integrity of the heart are indispensable for reperfusion salvage. Isolated perfused rat hearts were subjected to 35min of global ischemia and reperfused for 120min to determine the relative intracellular zinc levels by TSQ staining. The hearts were reperfused in the presence of incremental concentrations of zinc pyrithione for the first 10min during reperfusion. Silencing or blockade of ErbB2 using a monoclonal antibody, ErbB2 kinase inhibition and PI3kinase inhibition was used to study their critical role in zinc pyrithione-induced cardioprotection. We found that there was a profound decrease in intracellular zinc after ischemia/reperfusion resulting in increased apoptosis, caspase-3 activation, and infarct size. A dose-dependent reduction of infarct size with zinc pyrithione in the range of 5-20μmol/l (optimal protection was seen at 10μmol/l with infarct size of 16±2% vs. I/R vehicle, 33±2%, p<0.01). Increased TUNEL staining and caspase-3 activity observed after ischemia/reperfusion were attenuated by zinc pyrithione administration during the reperfusion. Moreover, this protection was sensitive to silencing and blockade of ErbB2, inhibition of ErbB2 kinase activity or PI3-kinase activity. Western blot analysis revealed that zinc pyrithione resulted in decreased caspase-3 activation, rapid stabilization of ErbB2/ErbB1 heterodimers, and increased activation of PI3K/Akt signaling cascade. Zinc pyrithione attenuates lethal perfusion-induced injury in a manner that is reliant on ErbB2/PI3K/Akt activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Ferritin: a zinc detoxicant and a zinc ion donor.

PubMed Central

Price, D; Joshi, J G

1982-01-01

Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

Pre-folding IkappaBalpha alters control of NF-kappaB signaling.

PubMed

Truhlar, Stephanie M E; Mathes, Erika; Cervantes, Carla F; Ghosh, Gourisankar; Komives, Elizabeth A

2008-06-27

Transcription complex components frequently show coupled folding and binding but the functional significance of this mode of molecular recognition is unclear. IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB via its ankyrin repeat (AR) domain. The beta-hairpins in ARs 5-6 in IkappaBalpha are weakly-folded in the free protein, and their folding is coupled to NF-kappaB binding. Here, we show that introduction of two stabilizing mutations in IkappaBalpha AR 6 causes ARs 5-6 to fold cooperatively to a conformation similar to that in NF-kappaB-bound IkappaBalpha. Free IkappaBalpha is degraded by a proteasome-dependent but ubiquitin-independent mechanism, and this process is slower for the pre-folded mutants both in vitro and in cells. Interestingly, the pre-folded mutants bind NF-kappaB more weakly, as shown by both surface plasmon resonance and isothermal titration calorimetry in vitro and immunoprecipitation experiments from cells. One consequence of the weaker binding is that resting cells containing these mutants show incomplete inhibition of NF-kappaB activation; they have significant amounts of nuclear NF-kappaB. Additionally, the weaker binding combined with the slower rate of degradation of the free protein results in reduced levels of nuclear NF-kappaB upon stimulation. These data demonstrate clearly that the coupled folding and binding of IkappaBalpha is critical for its precise control of NF-kappaB transcriptional activity.

Relationship between carbachol hyperstimulation-induced pancreatic intracellular trypsinogen and NF-kappa B activation in rats in vitro.

PubMed

Jiang, Chunfang; Zheng, Hai; Liu, Sunan; Fang, Kaifeng

2008-02-01

The relationship between intracellular trypsinogen activation and NF-kappa B activation in rat pancreatic acinar cells induced by M3 cholinergic receptor agonist (carbachol) hyperstimulation was studied. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc) and NF-kappa B inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The activity of NF-kappa B was monitored by using electrophoretic mobility shift assay. The results showed that after pretreatment with 2 mmol/L pefabloc, the activities of trypsin and NF-kappa B in pancreatic acinar cells treated with high concentrations of carbachol (10(-3) mol/L) in vitro was significantly decreased as compared with control group (P<0.01). The addition of 10(-2) mol/L PDTC resulted in a significant decrease of NF-kappa B activities in pancreatic acinar cells after treated with high concentrations of carbachol (10(-3) mol/L) in vitro, but the intracellular trypsinogen activity was not obviously inhibited (P>0.05). It was concluded that intracellular trypsinogen activation is likely involved in the regulation of high concentrations of carbachol-induced NF-kappa B activation in pancreatic acinar cells in vitro. NF-kappa B activation is likely not necessary for high concentrations of carbachol-induced trypsinogen activation in pancreatic acinar cells in vitro.

Stabilized nickel-zinc battery

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

Himy, A.; Wagner, O.C.

An alkaline nickel-zinc cell which has (1) a nickel-nickel hydroxide cathode; (2) a zinc-zinc oxide anode containing (A) a corrosion inhibitor such as PBO, SNO2, Tl2O3, in(OH)3 or mixtures thereof; (B) a slight corrosion accelerator such as cdo, bi2o3, ga2o3, or mixtures thereof; and (C) a zinc active material; (3) a mass-transport separator; (4) an alkaline electrolyte; and (5) means for charging the cell with an interrupted current having a frequency of from more than zero to 16 hertz with a rest period of not less than 60 milliseconds. Another desirable feature is the use of a pressure-cutoff switch tomore » terminate charging when the internal pressure of the cell reaches a selected value in the range of from 5 to 8 psig.« less

Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.

PubMed

Kontos, Stylianos; Kominea, Athina; Melachrinou, Maria; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

2010-09-01

To investigate the expression of nuclear factor-kappaB (NF-kappaB) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappaB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappaB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappaB was shown. No correlation between NF-kappaB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data. Our immunohistochemical study suggests the possible inverse regulation of NF-kappaB and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappaB, might represent a possible new treatment strategy for bladder urothelial tumors.

Synthesis, structural characterization and DNA interaction of zinc complex from 2,6-diacetylpyridine dihydrazone and {4-[(2E)-2-(hydroxyimino)acetyl]phenoxy} acetic acid.

PubMed

Gup, Ramazan; Gökçe, Cansu; Dilek, Nefise

2015-03-01

A new water soluble zinc complex has been prepared and structurally characterized. The Zn(II) complex was synthesized by the reaction of 2,6-diacetylpyridine dihydrazone (dph) with {4-[(2E)-2-(hydroxyimino)acetyl]phenoxy} acetic acid (H₂L) in the presence of zinc(II) acetate. Single crystal X-ray diffraction study revealed that the zinc ion is situated in distorted trigonal-bipyramidal environment where the equatorial position is occupied by the nitrogen atom of pyridine ring and the oxygen atoms of acetate groups of two oxime ligands (H₂L) whereas the axial positions of the zinc complex are occupied by the imine nitrogen atoms of dph ligand. Characterization of the complex with FTIR, (1)H and (13)C NMR, UV-vis and elemental analysis also confirmed the proposed structure. Interaction of the Zn(II) complex with calf-thymus DNA (CT-DNA) was investigated through UV-vis spectroscopy and viscosity measurements. The results suggest that the complex preferably bind to DNA through the groove binding mode. The zinc complex cleaves plasmid pBR 322 DNA in the presence and absence of an oxidative agent (H₂O₂), possibly through a hydrolytic pathway which is also supported by DNA cleave experiments in the presence of different radical scavengers. The nuclease activity of the zinc complex significantly depends on concentration of the complex and incubation time both in the presence and absence of H₂O₂. DNA cleave activity is inhibited in the presence of methyl green indicating that the zinc complex seems to bind the major groove of DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

The Role of the Noncanonical NF-KappaB Pathway in Colon Cancer

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-13-1-0321 TITLE: The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer PRINCIPAL INVESTIGATOR: Yatrik Shah...2013 - 29 May 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0321 The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer 5b...inflammatory bowel disease samples that the non-canonical NF -κB2 signaling cascade is highly activated in intestinal epithelial cells compared to normal

NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

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

Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi

2010-01-15

Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effectmore » of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.« less

Kappa statistic for clustered matched-pair data.

PubMed

Yang, Zhao; Zhou, Ming

2014-07-10

Kappa statistic is widely used to assess the agreement between two procedures in the independent matched-pair data. For matched-pair data collected in clusters, on the basis of the delta method and sampling techniques, we propose a nonparametric variance estimator for the kappa statistic without within-cluster correlation structure or distributional assumptions. The results of an extensive Monte Carlo simulation study demonstrate that the proposed kappa statistic provides consistent estimation and the proposed variance estimator behaves reasonably well for at least a moderately large number of clusters (e.g., K ≥50). Compared with the variance estimator ignoring dependence within a cluster, the proposed variance estimator performs better in maintaining the nominal coverage probability when the intra-cluster correlation is fair (ρ ≥0.3), with more pronounced improvement when ρ is further increased. To illustrate the practical application of the proposed estimator, we analyze two real data examples of clustered matched-pair data. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role of zinc-metallothionein in zinc-induced genoprotection.

PubMed

Jourdan, Eric; Emonet-Piccardi, Nathalie; Didier, Christine; Beani, Jean-Claude; Favier, Alain; Richard, Marie-Jeanne

2002-09-15

Zinc is an essential oligoelement for cell growth and cell survival and has been demonstrated to protect cells from oxidative stress induced by UVA or from genotoxic stress due to UVB. In a recent work we demonstrated that the antioxidant role of zinc could be related to its ability to induce metallothioneins (MTs). In this study we identified the mechanism of zinc protection against solar-simulated light (SSL) injury. Cultured human keratinocytes (HaCaT) were used to examine MTs expression and localization in response to solar-simulated radiation. We found translocation to the nucleus, with overexpression of MTs in irradiated cells, a novel observation. The genoprotective effect of zinc was dependent on time and protein synthesis. DNA damage was significantly decreased after 48 h of ZnCl(2) (100 microM) treatment and is inhibited by actinomycin D. ZnCl(2) treatment (100 microM) led to an intense induction, redistribution, and accumulation of MT in the nucleus of irradiated cells. MT expression correlated with the time period of ZnCl(2) treatment. CdCl(2), a potent MT inducer, did not show any genoprotection, although the MTs were expressed in the nucleus. Overall our findings demonstrate that MTs could be a good candidate for explaining the genoprotection mediated by zinc on irradiated cells.

Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

DOEpatents

Adler, T.C.; McLarnon, F.R.; Cairns, E.J.

1994-04-12

An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K[sub 2]CO[sub 3] salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics. 8 figures.

Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

DOEpatents

Adler, Thomas C.; McLarnon, Frank R.; Cairns, Elton J.

1994-01-01

An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K.sub.2 CO.sub.3 salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics.

Curcumin Regulates Low-Linear Energy Transfer {gamma}-Radiation-Induced NF{kappa}B-Dependent Telomerase Activity in Human Neuroblastoma Cells

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

Aravindan, Natarajan, E-mail: naravind@ouhsc.ed; Veeraraghavan, Jamunarani; Madhusoodhanan, Rakhesh

2011-03-15

Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NF{kappa}B regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NF{kappa}B-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells. Methods and Materials: SK-N-MC or SH-SY5Y cells exposed to IR and treated with curcumin (10-100 nM) with or without IR were harvested after 1 h through 24 h. NF{kappa}B-dependent regulation was investigated either by luciferase reporter assays using pNF{kappa}B-, pGL3-354-, pGL3-347-, or pUSE-I{kappa}B{alpha}-Luc, p50/p65, or RelA siRNA-transfectedmore » cells. NF{kappa}B activity was analyzed using an electrophoretic mobility shift assay and hTERT expression using the quantitative polymerase chain reaction. TA was determined using the telomerase repeat amplification protocol assay and cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide and clonogenic assay. Results: Curcumin profoundly inhibited IR-induced NF{kappa}B. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering telomerase reverse transcriptase (TERT) promoter activation. Moreover, NF{kappa}B becomes functionally activated after IR and mediates TA upregulation by binding to the {kappa}B-binding region in the promoter region of the TERT gene. Consistently, elimination of the NF{kappa}B-recognition site on the telomerase promoter or inhibition of NF{kappa}B by the I{kappa}B{alpha} mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, curcumin inhibited hTERT mRNA and TA in NF{kappa}B overexpressed cells. Furthermore, curcumin

Short-Term Subclinical Zinc Deficiency in Weaned Piglets Affects Cardiac Redox Metabolism and Zinc Concentration.

PubMed

Brugger, Daniel; Windisch, Wilhelm M

2017-04-01

Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism. Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets. Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients. Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively ( P < 0.0001). Further reduction in dietary zinc promoted a linear decrease of glutathione and α-tocopherol (30 and 0.6 nmol/mg dietary Zn, respectively; P < 0.05) and a linear increase of gene expression [0.02, 0.01, 0.003, and 0.02 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05)]. Tissue zinc declined linearly with reduction in dietary zinc (0.21 mg tissue Zn/mg dietary Zn; P = 0.004) from 88.0 to 42.7 mg/kg ( P < 0.0001), below which it linearly increased inversely to further reduction in dietary zinc (0.57 mg tissue Zn/mg dietary Zn; P = 0.006). H 2 O 2 -detoxification activity and metallothionein 1A gene expression decreased linearly with reduction in dietary zinc from 88.0 to 28.1 mg/kg [0.02 mU and 0.008 Log 10 (2 -ΔΔCt )/mg dietary Zn, respectively; P < 0.05]. Fas cell-surface death receptor, etoposide-induced 2.4 and cyclin-dependent kinase inhibitor 1A gene expression correlated

Longitudinal changes in zinc transport kinetics, metallothionein, and zinc transporter expression in a blood-brain barrier model in response to a moderately excessive zinc environment$

PubMed Central

Gauthier, Nicole A.; Karki, Shakun; Olley, Bryony J.; Thomas, W. Kelly

2008-01-01

A blood-brain barrier (BBB) model composed of porcine brain capillary endothelial cells (BCEC) was exposed to a moderately excessive zinc environment (50 µmol Zn/L) in cell culture and longitudinal measurements were made of zinc transport kinetics, ZnT-1 (SLC30A1) expression, and changes in the protein concentration of metallothionein (MT), ZnT-1, ZnT-2 (SLC30A2), and Zip1 (SLC39A1). Zinc release by cells of the BBB model was significantly increased after 12–24 h of exposure, but decreased back to control levels after 48–96 h, as indicated by transport across the BBB from both the ablumenal (brain) and lumenal (blood) directions. Expression of ZnT-1, the zinc export protein, increased 169% within 12 h, but was no longer different from controls after 24 h. Likewise, ZnT-1 protein content increased transiently after 12 h of exposure but returned to control levels by 24 h. Capacity for zinc uptake and retention increased from both the lumenal and ablumenal directions within 12–24 h of exposure and remained elevated. MT and ZnT-2 were elevated within 12 h and remained elevated throughout the study. Zip1 was unchanged by the treatment. The BBB’s response to a moderately high zinc environment was dynamic and involved multiple mechanisms. The initial response was to increase the cell’s capacity to sequester zinc with additional MT and increase zinc export with the ZnT-1 protein. But, the longer term strategy involved increasing ZnT-2 transporters, presumably to sequester zinc into intracellular vesicles as a mechanism to protect the brain and maintain brain zinc homeostasis. PMID:18061429

Zinc Absorption by Young Adults from Supplemental Zinc Citrate Is Comparable with That from Zinc Gluconate and Higher than from Zinc Oxide123

PubMed Central

Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnić, Marica; Hurrell, Richard F.

2014-01-01

The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with 67Zn and 70Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6–71.0) and was not different from that from zinc gluconate with 60.9% (50.6–71.7). Absorption from zinc oxide at 49.9% (40.9–57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627. PMID:24259556

Effects of Zinc Gluconate and 2 Other Divalent Cationic Compounds on Olfactory Function in Mice

PubMed Central

Duncan-Lewis, Christopher A; Lukman, Roy L; Banks, Robert K

2011-01-01

Intranasal application of zinc gluconate has commonly been used to treat the common cold. The safety of this treatment, however, has come into question recently. In addition to a United States recall of a homeopathic product that contains zinc gluconate, abundant literature reports cytotoxic effects of zinc on the olfactory epithelium. Additional research suggests that divalent cations (such as zinc) can block ion channels that facilitate the transduction of odors into electrical signals on the olfactory epithelium. The purpose of the current study was 2-fold: to confirm whether zinc gluconate causes anosmia and to reveal whether any other divalent cationic compounds produce a similar effect. Groups of mice underwent a buried food-pellet test to gauge olfactory function and then were nasally irrigated with 1 of 3 divalent cationic compounds. When tested after treatment, mice irrigated with zinc gluconate and copper gluconate experienced a marked increase in food-finding time, indicating that they had lost their ability to smell a hidden food source. Control mice irrigated with saline had a significantly lower increase in times. These results confirm that zinc gluconate can cause anosmia and reveal that multiple divalent cations can negatively affect olfaction. PMID:22330252

Association of reduced zinc status with poor glycemic control in individuals with type 2 diabetes mellitus.

PubMed

Bandeira, Verônica da Silva; Pires, Liliane Viana; Hashimoto, Leila Leiko; Alencar, Luciane Luca de; Almondes, Kaluce Gonçalves Sousa; Lottenberg, Simão Augusto; Cozzolino, Silvia Maria Franciscato

2017-12-01

This study evaluated the relationship between the zinc-related nutritional status and glycemic and insulinemic markers in individuals with type 2 diabetes mellitus (T2DM). A total of 82 individuals with T2DM aged between 29 and 59 years were evaluated. The concentration of zinc in the plasma, erythrocytes, and urine was determined by the flame atomic absorption spectrometry method. Dietary intake was assessed using a 3-day 24-h recall. In addition, concentrations of serum glucose, glycated hemoglobin percentage, total cholesterol and fractions, triglycerides, and serum insulin were determined. The insulin resistance index (HOMA-IR) and β-cell function (HOMA- β) were calculated. The markers of zinc status (plasma: 83.3±11.9μg/dL, erythrocytes: 30.1±4.6μg/g Hb, urine: 899.1±622.4μg Zn/24h, and dietary: 9.9±0.8mg/day) were classified in tertiles and compared to insulinemic and glycemic markers. The results showed that lower zinc concentrations in plasma and erythrocytes, as well as its high urinary excretion, were associated with higher percentages of glycated hemoglobin, reflecting a worse glycemic control in individuals with T2DM (p<0.05). Furthermore, there was a significant inverse correlation between plasma zinc levels and glycated hemoglobin percentage (r=-0.325, p=0.003), and a positive correlation between urinary zinc excretion and glycemia (r=0.269, p=0.016), glycated hemoglobin percentage (r=0.318, p=0.004) and HOMA-IR (r=0.289, p=0.009). According to our study results, conclude that T2DM individuals with reduced zinc status exhibited poor glycemic control. Copyright © 2017 Elsevier GmbH. All rights reserved.

Serum Zinc and β D Glucuronidase Enzyme Level in Type 2 Diabetes Mellitus with Periodontitis.

PubMed

Pushparani, D S

2016-01-01

The exact mechanism by which nutritional deficiency and lysosomal enzyme change, modify periodontal destruction has not yet been precisely defined. The study aimed to determine the serum zinc and β D glucuronidase enzyme level in the selected groups and how its increase or decrease levels are related to type 2 diabetes mellitus (T2DM) with periodontitis when compared to other groups. Six hundred subjects were selected and are categorized into four groups as Group I (control healthy subjects, n=150), Group II (T2DM with periodontitis, n=150), Group III (T2DM without periodontitis, n=150) and Group IV (Non-DM with periodontitis, n=150). The lab investigations included measuring fasting blood glucose, serum zinc and β D- glucuronidase levels. In the results, the level of serum zinc was found to be lesser in group III subjects and the activity of serum β D glucuronidase was found to be elevated nine times in group III (T2DM with periodontitis) and two times elevated in group II (T2DM without periodontitis) and group IV (Non-DM with periodontitis), when compared to control. Zinc has been reported to reduce the stabilization of lysosomal membranes. Periodontitis has been taken as the prime condition in this study and categorized as experimental groups. Perturbations in mineral metabolism are more pronounced in diabetic populations. When the level of zinc is decreased, the structural integrity of lysosomal membrane has been lost and it would have caused for the increased release of β D glucuronidase in T2DM with periodontitis.

Phi Delta Kappa Viewpoint.

ERIC Educational Resources Information Center

Phi Delta Kappa, Trenton, NJ. Trenton Area Chapter.

This collection of articles on aspects of educational research, service, and leadership, are all written by members the Trenton (New Jersey) Area Chapter of Phi Delta Kappa. "Extra Year Programs: The K-1 Transition," by Richard Graja, reports on a study of 210 families regarding the Extra Year program, an opportunity for children to…

Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

PubMed

Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

2018-01-24

Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

NMR study on the network structure of a mixed gel of kappa and iota carrageenans.

PubMed

Hu, Bingjie; Du, Lei; Matsukawa, Shingo

2016-10-05

The temperature dependencies of the (1)H T2 and diffusion coefficient (D) of a mixed solution of kappa-carrageenan and iota-carrageenan were measured by NMR. Rheological and NMR measurements suggested an exponential formation of rigid aggregates of kappa-carrageenan and a gradual formation of fine aggregates of iota-carrageenan during two step increases of G'. The results also suggested that longer carrageenan chains are preferentially involved in aggregation, thus resulting in a decrease in the average Mw of solute carrageenans. The results of diffusion measurements for poly(ethylene oxide) (PEO) suggested that kappa-carrageenan formed thick aggregates that decreased hindrance to PEO diffusion by decreasing the solute kappa-carrageenan concentration in the voids of the aggregated chains, and that iota-carrageenan formed fine aggregates that decreased the solute iota-carrageenan concentration less. DPEO in a mixed solution of kappa-carrageenan and iota-carrageenan suggested two possibilities for the microscopic network structure: an interpenetrating network structure, or micro-phase separation. Copyright © 2016. Published by Elsevier Ltd.

Single-layer ZnMN2 (M = Si, Ge, Sn) zinc nitrides as promising photocatalysts.

PubMed

Bai, Yujie; Luo, Gaixia; Meng, Lijuan; Zhang, Qinfang; Xu, Ning; Zhang, Haiyang; Wu, Xiuqiang; Kong, Fanjie; Wang, Baolin

2018-05-30

Searching for two-dimensional semiconductor materials that are suitable for visible-light photocatalytic water splitting provides a sustainable solution to deal with the future energy crisis and environmental problems. Herein, based on first-principles calculations, single-layer ZnMN2 (M = Si, Ge, Sn) zinc nitrides are proposed as efficient photocatalysts for water splitting. Stability analyses show that the single-layer ZnMN2 zinc nitrides exhibit energetic and dynamical stability. The electronic properties reveal that all of the single-layer ZnMN2 zinc nitrides are semiconductors. Interestingly, single-layer ZnSnN2 is a direct band gap semiconductor with a desirable band gap (1.74 eV), and the optical adsorption spectrum confirms its optical absorption in the visible light region. The hydrogen evolution reaction (HER) calculations show that the catalytic activity for single-layer ZnMN2 (M = Ge, Sn) is better than that of single-layer ZnSiN2. Furthermore, the band gaps and band edge positions for the single-layer ZnMN2 zinc nitrides can be effectively tuned by biaxial strain. Especially, single-layer ZnGeN2 can be effectively tuned to match better with the redox potentials of water and enhance the light absorption in the visible light region at a tensile strain of 5%, which is confirmed by the corresponding optical absorption spectrum. Our results provide guidance for experimental synthesis efforts and future searches for single-layer materials suitable for photocatalytic water splitting.

Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

NASA Astrophysics Data System (ADS)

Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

2006-07-01

Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

Zinc Enzymes.

ERIC Educational Resources Information Center

Bertini, I.; And Others

1985-01-01

Discusses the role of zinc in various enzymes concerned with hydration, hydrolysis, and redox reactions. The binding of zinc to protein residues, properties of noncatalytic zinc(II) and catalytic zinc, and the reactions catalyzed by zinc are among the topics considered. (JN)

Zinc: an essential but elusive nutrient123

PubMed Central

King, Janet C

2011-01-01

Zinc is essential for multiple aspects of metabolism. Physiologic signs of zinc depletion are linked with diverse biochemical functions rather than with a specific function, which makes it difficult to identify biomarkers of zinc nutrition. Nutrients, such as zinc, that are required for general metabolism are called type 2 nutrients. Protein and magnesium are examples of other type 2 nutrients. Type 1 nutrients are required for one or more specific functions: examples include iron, vitamin A, iodine, folate, and copper. When dietary zinc is insufficient, a marked reduction in endogenous zinc loss occurs immediately to conserve the nutrient. If zinc balance is not reestablished, other metabolic adjustments occur to mobilize zinc from small body pools. The location of those pools is not known, but all cells probably have a small zinc reserve that includes zinc bound to metallothionein or zinc stored in the Golgi or in other organelles. Plasma zinc is also part of this small zinc pool that is vulnerable to insufficient intakes. Plasma zinc concentrations decline rapidly with severe deficiencies and more moderately with marginal depletion. Unfortunately, plasma zinc concentrations also decrease with a number of conditions (eg, infection, trauma, stress, steroid use, after a meal) due to a metabolic redistribution of zinc from the plasma to the tissues. This redistribution confounds the interpretation of low plasma zinc concentrations. Biomarkers of metabolic zinc redistribution are needed to determine whether this redistribution is the cause of a low plasma zinc rather than poor nutrition. Measures of metallothionein or cellular zinc transporters may fulfill that role. PMID:21715515

Polymorphic one-dimensional (N2H4)2ZnTe: soluble precursors for the formation of hexagonal or cubic zinc telluride.

PubMed

Mitzi, David B

2005-10-03

Two hydrazine zinc(II) telluride polymorphs, (N2H4)2ZnTe, have been isolated, using ambient-temperature solution-based techniques, and the crystal structures determined: alpha-(N2H4)2ZnTe (1) [P21, a = 7.2157(4) Angstroms, b = 11.5439(6) Angstroms, c = 7.3909(4) Angstroms, beta = 101.296(1) degrees, Z = 4] and beta-(N2H4)2ZnTe (2) [Pn, a = 8.1301(5) Angstroms, b = 6.9580(5) Angstroms, c = 10.7380(7) Angstroms, beta = 91.703(1) degrees, Z = 4]. The zinc atoms in 1 and 2 are tetrahedrally bonded to two terminal hydrazine molecules and two bridging tellurium atoms, leading to the formation of extended one-dimensional (1-D) zinc telluride chains, with different chain conformations and packings distinguishing the two polymorphs. Thermal decomposition of (N2H4)2ZnTe first yields crystalline wurtzite (hexagonal) ZnTe at temperatures as low as 200 degrees C, followed by the more stable zinc blende (cubic) form at temperatures above 350 degrees C. The 1-D polymorphs are soluble in hydrazine and can be used as convenient precursors for the low-temperature solution processing of p-type ZnTe semiconducting films.

Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway.

PubMed

Bhui, Kulpreet; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer

2009-09-18

Chemoprevention impels the pursuit for either single targeted or cocktail of multi-targeted agents. Bromelain, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of pineapple (Ananas cosmosus), endowed with anti-inflammatory, anti-invasive and anti-metastatic properties. Herein, we report the anti tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model. Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse. Preventive effect was also comprehended in terms of reduction in tumor volume up to a tune of approximately 65%. Components of the cell signaling pathways, connecting proteins involved in cell death were targeted. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2. A marked inhibition in cyclooxygenase-2 (Cox-2) expression and inactivation of nuclear factor-kappa B (NF-kappaB) was recorded, as phosphorylation and consequent degradation of I kappa B alpha was blocked by bromelain. Also, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity. The basis of anti tumor-initiating activity of bromelain was revealed by its time dependent reduction in DNA nick formation and increase in percentage prevention. Thus, modulation of inappropriate cell signaling cascades driven by bromelain is a coherent approach in achieving chemoprevention.

TRIM45 negatively regulates NF-{kappa}B-mediated transcription and suppresses cell proliferation

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

Shibata, Mio; Sato, Tomonobu; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638

2012-06-22

Highlights: Black-Right-Pointing-Pointer NF-{kappa}B plays an important role in cell survival and carcinogenesis. Black-Right-Pointing-Pointer TRIM45 negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription. Black-Right-Pointing-Pointer TRIM45 overexpression suppresses cell growth. Black-Right-Pointing-Pointer TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth. -- Abstract: The NF-{kappa}B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-{kappa}B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-{kappa}B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one ofmore » the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-{kappa}B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth.« less

Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-kappa B signaling pathways in murine RAW 264.7 macrophages.

PubMed

Aga, Mini; Watters, Jyoti J; Pfeiffer, Zachary A; Wiepz, Gregory J; Sommer, Julie A; Bertics, Paul J

2004-04-01

Extracellular nucleotides such as ATP are present in abundance at sites of inflammation and tissue damage, and these agents exert a potent modulatory effect on macrophage/monocyte function via the nucleotide receptor P2X(7). In this regard, after exposure to bacterial LPS, P2X(7) activation augments expression of the inducible nitric oxide (NO) synthase and production of NO in macrophages. Because P2X(7) has been reported to stimulate certain members of the MAP kinase family (ERK1/2) and can enhance the DNA-binding activity of NF-kappa B, we tested the hypothesis that LPS and nucleotides regulate NF-kappa B-dependent inflammatory events via cross talk with MAPK-associated pathways. In this regard, the present studies revealed that cotreatment of macrophages with LPS and the P2X(7)-selective ligand 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) results in the cooperative activation of NF-kappa B DNA-binding activity and a sustained attenuation of levels of the NF-kappa B inhibitory protein I kappa B alpha. Interestingly, a persistent reduction in I kappa B alpha levels is also observed when the MEK1/2 inhibitor U0126 is coadministered with LPS, suggesting that components of the MEK/ERK pathway are involved in regulating I kappa B alpha protein expression and/or turnover. The observation that U0126 and BzATP exhibit overlapping actions with respect to LPS-induced changes in I kappa B alpha levels is supported by the finding that Ras activation, which is upstream of MEK/ERK activation, is reduced upon macrophage cotreatment with BzATP and LPS compared with the effects of BzATP treatment alone. These data are consistent with the concept that the Ras/MEK/ERK pathways are involved in regulating NF-kappa B/I kappa B-dependent inflammatory mediator production and suggest a previously unidentified mechanism by which nucleotides can modulate LPS-induced action via cross talk between NF-kappa B and Ras/MEK/MAPK-associated pathways.

Zinc

MedlinePlus

... Using toothpastes containing zinc, with or without an antibacterial agent, appears to prevent plaque and gingivitis. Some ... is some evidence that zinc has some antiviral activity against the herpes virus. Low zinc levels can ...

Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

PubMed

Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia; Buck, Isabelle; Teiten, Marie-Hélène; Daubeuf, Sandrine; Eifes, Serge; Dicato, Mario; Aggarwal, Bharat B; Visvikis, Athanase; Diederich, Marc

2009-02-01

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions.

Gigantol isolated from the whole plants of Cymbidium goeringii inhibits the LPS-induced iNOS and COX-2 expression via NF-kappaB inactivation in RAW 264.7 macrophages cells.

PubMed

Won, Jong-Heon; Kim, Ji-Yeon; Yun, Kyung-Jin; Lee, Jin-Hee; Back, Nam-In; Chung, Hae-Gon; Chung, Sun A; Jeong, Tae-Sook; Choi, Myung-Sook; Lee, Kyung-Tae

2006-10-01

During our efforts to find bioactive natural products with anti-inflammatory activity, we isolated gigantol from the whole plants of Cymbidium goeringii (Orchidaceae) by activity-guided chromatographic fractionation. Gigantol was found to have potent inhibitory effects on LPS-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) production in RAW 264.7 cells. Consistent with these findings, gigantol suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in RAW 264.7 cells in a concentration-dependent manner. Our data also indicate that gigantol is a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) release and influenced the mRNA expression levels of these cytokines in a dose-dependent manner. Furthermore, a reporter gene assay for nuclear factor kappa B (NF-kappaB) and an electromobility shift assay (EMSA) demonstrated that gigantol effectively inhibited the activation of NF-kappaB, which is necessary for the expression of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6. Thus, our studies suggest that gigantol inhibits LPS-induced iNOS and COX-2 expression by blocking NF- kappaB activation.

Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

PubMed

Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

2007-03-21

Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

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

Xue, Xia; Center for New Drugs Evaluation, Shandong University, Jinan 250012; Qu, Xian-Jun

Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at dosesmore » of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-{kappa}B p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 {+-} 0.7 to 1.2 {+-} 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-{kappa}B p65.« less

Status of zinc injection in PWRs

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

Bergmann, C.A.

1995-03-01

Based on laboratory and other studies, it was concluded that zinc addition in a PWR primary coolant should result in reduced Alloy 600 PWSCC and general corrosion rates of the materials of construction. Because of these positive results, a Westinghouse Owner`s Subgroup, EPRI, and Westinghouse provided funds to continue the development and application of zinc in an operating plant. As part of the program, Southern Operating Nuclear Company agreed to operate the Farley 2 plant with zinc addition as a demonstration test of the effectiveness of zinc. Since zinc is incorporated in the corrosion oxide film on the primary systemmore » surfaces and Farley 2 is a mature plant, it was estimated that about 10 kgs of zinc would be needed to condition the plant before an equilibrium value in the coolant would be reached. The engineered aspects of a Zinc Addition and Monitoring System (ZAMS) considered such items as the constitutents, location, sizing and water supply of the ZAMS. Baseline data such as the PWSCC history of the Alloy 600 steam generator tubing, fuel oxide thickness, fuel crud deposits, radiation levels, and RCP seal leak-off rates were obtained before zinc addition is initiated. This presentation summarizes some of the work performed under the program, and the status of zinc injection in the Farley 2 plant.« less

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

PubMed

Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

2018-01-01

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Highly Durable Na2V6O16·1.63H2O Nanowire Cathode for Aqueous Zinc-Ion Battery.

PubMed

Hu, Ping; Zhu, Ting; Wang, Xuanpeng; Wei, Xiujuan; Yan, Mengyu; Li, Jiantao; Luo, Wen; Yang, Wei; Zhang, Wencui; Zhou, Liang; Zhou, Zhiqiang; Mai, Liqiang

2018-03-14

Rechargeable aqueous zinc-ion batteries are highly desirable for grid-scale applications due to their low cost and high safety; however, the poor cycling stability hinders their widespread application. Herein, a highly durable zinc-ion battery system with a Na 2 V 6 O 16 ·1.63H 2 O nanowire cathode and an aqueous Zn(CF 3 SO 3 ) 2 electrolyte has been developed. The Na 2 V 6 O 16 ·1.63H 2 O nanowires deliver a high specific capacity of 352 mAh g -1 at 50 mA g -1 and exhibit a capacity retention of 90% over 6000 cycles at 5000 mA g -1 , which represents the best cycling performance compared with all previous reports. In contrast, the NaV 3 O 8 nanowires maintain only 17% of the initial capacity after 4000 cycles at 5000 mA g -1 . A single-nanowire-based zinc-ion battery is assembled, which reveals the intrinsic Zn 2+ storage mechanism at nanoscale. The remarkable electrochemical performance especially the long-term cycling stability makes Na 2 V 6 O 16 ·1.63H 2 O a promising cathode for a low-cost and safe aqueous zinc-ion battery.

Highly condensed fluorinated methacrylate hybrid material for transparent low-kappa passivation layer in LCD-TFT.

PubMed

Oh, Ji-Hoon; Kwak, Seung-Yeon; Yang, Seung-Cheol; Bae, Byeong-Soo

2010-03-01

Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation.

Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

PubMed

Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

1990-11-01

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia.

Measuring agreement of multivariate discrete survival times using a modified weighted kappa coefficient.

PubMed

Guo, Ying; Manatunga, Amita K

2009-03-01

Assessing agreement is often of interest in clinical studies to evaluate the similarity of measurements produced by different raters or methods on the same subjects. We present a modified weighted kappa coefficient to measure agreement between bivariate discrete survival times. The proposed kappa coefficient accommodates censoring by redistributing the mass of censored observations within the grid where the unobserved events may potentially happen. A generalized modified weighted kappa is proposed for multivariate discrete survival times. We estimate the modified kappa coefficients nonparametrically through a multivariate survival function estimator. The asymptotic properties of the kappa estimators are established and the performance of the estimators are examined through simulation studies of bivariate and trivariate survival times. We illustrate the application of the modified kappa coefficient in the presence of censored observations with data from a prostate cancer study.

Influence of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) on zinc electrodeposition

NASA Astrophysics Data System (ADS)

Lehr, I. L.; Saidman, S. B.

2012-03-01

This work is a study of the electrodeposition of zinc onto SAE 4140 steel electrodes using solutions containing zinc sulfate and bis(2-ethylhexyl) sodium sulfosuccinate (AOT). The influence of different parameters such as electrolyte concentration, electrodeposition time and temperature on the morphology of the electrodeposits was analyzed. The deposits were characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction. The variation of open circuit potential over time in chloride solutions was also evaluated. The nucleation-growth process and consequently the morphology of the electrodeposits are modified in the presence of AOT. The surfactant induces the formation of a porous deposit.

NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach.

PubMed

Amit, Sharon; Ben-Neriah, Yinon

2003-02-01

Nuclear factor-kappa B (NF-kappaB) activation relies primarily on ubiquitin-mediated degradation of its inhibitor IkappaB. NF-kappaB plays an important role in many aspects of tumor development, progression, and therapy. Some types of cancer are characterized by constitutive NF-kappaB activity, whereas in others such activity is induced following chemotherapy. NF-kappaB-harboring tumors are generally resistant to chemotherapy and their eradication requires NF-kappaB inhibition. Here we describe the mechanisms of NF-kappaB activation in normal and tumor cells, review prevalent notions regarding the factor's contribution to tumorigenicity and discuss present and future options for NF-kappaB inhibition in cancer. The ubiquitination-mediated activation of NF-kappaB is intersected by another cancer-associated protein, beta-catenin. We, therefore, compare the related activation pathways and discuss the possibility of differential targeting of the involved ubiquitination machinery. Copyright 2002 Elsevier Science Ltd.

Mechanisms for kappa reduction and color removal by xylanases

Treesearch

Thomas W. Jeffries; Mark Davis; Brian Rosin; Larry L. Landucci

1998-01-01

Xylanases reduce kappa and release UV- and visibly absorptive materials from kraft pulps. The extents of these actions depend on the origin and processing of the pulp, access of enzymes to the substrate, and the natures of the enzymes. Hexeneuronic acid (HexA) is a component of kraft pulp xylans that accounts for a fraction of the kappa content. It absorbs strongly in...

Ion and electron Kappa distribution functions in the plasma sheet.

NASA Astrophysics Data System (ADS)

Moya, P. S.; Stepanova, M. V.; Espinoza, C.; Antonova, E. E.; Valdivia, J. A.

2017-12-01

We present a study of ion and electron flux spectra in the Earth's plasma sheet using kappa distribution functions. Satellite data from the THEMIS mission were collected for thousands of crossings through the plasma sheet, between 7 and 35 Re and during the years 2008-2009. The events were separated according to the geomagnetic activity at the time. Our results show the distribution of the kappa index and characteristic energies across the plasma sheet and its evolution with distance to Earth for quiet times and for the substorm expansion and recovery phases. For the ions, it is observed that the kappa values tend to decrease outwards and that this effect is more significant in the dusk sector, where the smallest values are found for distances beyond 15 Re. The main effect of the substorms appears as an enhancement of this behavior. The electrons show a much more homogeneous distribution in quiet times, with a mild tendency for larger kappa values at larger distances. During substorms, the kappa values tend to equalize and appear very homogenous during expansion. However, they exhibit a significant increase in the dusk sector during the recovery substorm phase. Finally, we observe that the characteristic energy of the particles during substorms increases and concentrate at distances less than 15 Re.

Zinc Levels in Left Ventricular Hypertrophy.

PubMed

Huang, Lei; Teng, Tianming; Bian, Bo; Yao, Wei; Yu, Xuefang; Wang, Zhuoqun; Xu, Zhelong; Sun, Yuemin

2017-03-01

Zinc is one of the most important trace elements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and left ventricular hypertrophy (LVH). A total of 519 patients was enrolled and their serum zinc levels were measured in this study. We performed analyses on the relationship between zinc levels and LVH and the four LV geometry pattern patients: normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH. We performed further linear and multiple regression analyses to confirm the relationship between zinc and left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). Our data showed that zinc levels were 710.2 ± 243.0 μg/L in the control group and were 641.9 ± 215.2 μg/L in LVH patients. We observed that zinc levels were 715 ± 243.5 μg/L, 694.2 ± 242.7 μg/L, 643.7 ± 225.0 μg/L, and 638.7 ± 197.0 μg/L in normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH patients, respectively. We further found that there was a significant inverse linear relationship between zinc and LVM (p = 0.001) and LVMI (p = 0.000) but did not show a significant relationship with RWT (p = 0.561). Multiple regression analyses confirmed that the linear relationship between zinc and LVM and LVMI remained inversely significant. The present study revealed that serum zinc levels were significantly decreased in the LVH patients, especially in the eccentric LVH and concentric LVH patients. Furthermore, zinc levels were significantly inversely correlated with LVM and LVMI.

Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

PubMed

Alexander, George; Carlsen, Harald; Blomhoff, Rune

2006-04-01

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

[Improvement in zinc nutrition due to zinc transporter-targeting strategy].

PubMed

Kambe, Taiho

2016-07-01

Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

PubMed

Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis.

PubMed

Oakley, Fiona; Meso, Muriel; Iredale, John P; Green, Karen; Marek, Carylyn J; Zhou, Xiaoying; May, Michael J; Millward-Sadler, Harry; Wright, Matthew C; Mann, Derek A

2005-01-01

Resolution of liver fibrosis is associated with clearance of hepatic myofibroblasts by apoptosis; development of strategies that promote this process in a selective way is therefore important. The aim of this study was to determine whether the inhibitor of kappaB kinase suppressor sulfasalazine stimulates hepatic myofibroblast apoptosis and recovery from fibrosis. Hepatic myofibroblasts were generated by culture activation of rat and human hepatic stellate cells. Fibrosis was established in rat livers by chronic injury with carbon tetrachloride followed by recovery with or without sulfasalazine (150 mg/kg) treatment. Treatment of hepatic stellate cells with sulfasalazine (0.5-2.0 mmol/L) induced apoptosis of activated rat and human hepatic stellate cells. A single in vivo administration of sulfasalazine promoted accelerated recovery from fibrosis as assessed by improved fibrosis score, selective clearance of smooth muscle alpha-actin-positive myofibroblasts, reduced hepatic procollagen I and tissue inhibitor of metalloproteinase 1 messenger RNA expression, and increased matrix metalloproteinase 2 activity. Mechanistic studies showed that sulfasalazine selectively blocks nuclear factor-kappaB-dependent gene transcription, inhibits hepatic stellate cell expression of Gadd45beta, stimulates phosphorylation of Jun N-terminal kinase 2, and promotes apoptosis by a mechanism that is prevented by the Jun N-terminal kinase inhibitor SP600125. As further evidence for a survival role for the inhibitor of kappaB kinase/nuclear factor-kappaB pathway in activated hepatic stellate cells, a highly selective cell-permeable peptide inhibitor of kappaB kinase activation also stimulated hepatic stellate cell apoptosis via a Jun N-terminal kinase-dependent mechanism. Inhibition of the inhibitor of kappaB kinase/nuclear factor-kappaB pathway is sufficient to increase the rate at which activated hepatic stellate cells undergo apoptosis both in vitro and in vivo, and drugs that

(/sup 3/H)Ethylketocyclazocine binding to mouse brain membranes: evidence for a kappa opioid receptor type

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

Garzon, J.; Sanchez-Blazquez, P.; Lee, N.M.

1984-10-01

The binding of the putative kappa agonist ethylketocyclazocine (EKC) to synaptosomal membranes of mouse brain was studied. This benzomorphan was able to bind to different opioid receptors. A portion of this binding was not inhibited by the agonist naloxone, even at high concentrations (10 microM). This population of receptors, to which opioate alkaloids and opiod peptides display very low affinity, is probably the sigma receptor. Another class of binding sites was identified by the simultaneous addition of the selective agonists Sandoz FK-33824 and D-Ala2-D-Leu5-enkephalin, which blocked the access of EKC to mu and delta opioid receptors, respectively, leaving a portionmore » of naloxone-displaceable benzomorphan binding still detectable. Analysis of this remaining binding revealed a small population of receptors of high affinity, the kappa receptor. Therefore, EKC binds to the mu, delta, kappa and sigma receptors in the mouse brain, with similar affinities for the mu and kappa (0.22 and 0.15 nM). These results confirm the existence of a kappa opioid receptor type in the mouse brain.« less

The biological inorganic chemistry of zinc ions.

PubMed

Krężel, Artur; Maret, Wolfgang

2016-12-01

The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the "mobile" zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn 2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn 2+ differs from s-block cations such as Ca 2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is

Zinc for the common cold.

PubMed

Singh, Meenu; Das, Rashmi R

2013-06-18

The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance. In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov. Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. Two review authors independently extracted data and assessed trial quality. Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a

Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture.

PubMed

Dagher, Zeina; Garçon, Guillaume; Billet, Sylvain; Verdin, Anthony; Ledoux, Frédéric; Courcot, Dominique; Aboukais, Antoine; Shirali, Pirouz

2007-01-01

To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM(2.5) air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short-term studies have shown them to cause dose-dependent and time-dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor-kappa B (NF-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM-exposed L132 cells, there were concentration- and/or time-dependent increases in nuclear p65 and cytoplasmic IkB-alpha phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM(2.5) were involved in the activation of the NF-kappaB/IkappaB complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells. (c) 2007 John Wiley & Sons, Ltd.

Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

PubMed

Baud, Véronique; Karin, Michael

2009-01-01

Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

Interaction of zinc with dental mineral.

PubMed

Ingram, G S; Horay, C P; Stead, W J

1992-01-01

As some currently available toothpastes contain zinc compounds, the reaction of zinc with dental mineral and its effect on crystal growth rates were studied using three synthetic calcium-deficient hydroxyapatites (HAP) as being representative of dental mineral. Zinc was readily acquired by all HAP samples in the absence of added calcium, the amount adsorbed being proportional to the HAP surface area; about 9 mumol Zn/m2 was adsorbed at high zinc concentrations. As zinc was acquired, calcium was released, consistent with 1:1 Ca:Zn exchange. Soluble calcium reduced zinc uptake and similarly, calcium post-treatment released zinc. Pretreatment of HAP with 0.5 mM zinc reduced its subsequent ability to undergo seeded crystal growth, as did extracts of a toothpaste containing 0.5% zinc citrate, even in the presence of saliva. The reverse reaction, i.e. displacement of adsorbed zinc by salivary levels of calcium, however, indicates the mechanism by which zinc can reduce calculus formation in vivo by inhibiting plaque mineralisation without adversely affecting the anti-caries effects of fluoride.

Impact of Cadmium on Intracellular Zinc Levels in HepG2 Cells: Quantitative Evaluations and Molecular Effects.

PubMed

Urani, Chiara; Melchioretto, Pasquale; Bruschi, Maurizio; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura

2015-01-01

Cadmium is classified as a human carcinogen, and its disturbance in zinc homeostasis has been well established. However, its extent as well as molecular mechanisms involved in cadmium carcinogenesis has yet to be fully clarified. To this end, we used the zinc specific probe Zinquin to visualize and to quantitatively evaluate changes in the concentration of labile zinc, in an in vitro model of human hepatic cells (HepG2) exposed to cadmium. A very large increase (+93%) of intracellular labile zinc, displaced by cadmium from the zinc proteome, was measured when HepG2 were exposed to 10 µM cadmium for 24 hrs. Microarray expression profiling showed that in cells, featuring an increase of labile zinc after cadmium exposure, one of the top regulated genes is Snail1 (+3.6), which is included in the adherens junction pathway and linked to cancer. In the same pathway MET, TGF-βR, and two members of the Rho-family GTPase, Rac, and cdc42 all implicated in the loss of adherence features and acquisition of migratory and cancer properties were regulated, as well. The microRNAs analysis showed a downregulation of miR-34a and miR-200a, both implicated in the epithelial-mesenchymal transition. These microRNAs results support the role played by zinc in affecting gene expression at the posttranscriptional level.

An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

PubMed Central

Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

2016-01-01

The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

Nomogram for sample size calculation on a straightforward basis for the kappa statistic.

PubMed

Hong, Hyunsook; Choi, Yunhee; Hahn, Seokyung; Park, Sue Kyung; Park, Byung-Joo

2014-09-01

Kappa is a widely used measure of agreement. However, it may not be straightforward in some situation such as sample size calculation due to the kappa paradox: high agreement but low kappa. Hence, it seems reasonable in sample size calculation that the level of agreement under a certain marginal prevalence is considered in terms of a simple proportion of agreement rather than a kappa value. Therefore, sample size formulae and nomograms using a simple proportion of agreement rather than a kappa under certain marginal prevalences are proposed. A sample size formula was derived using the kappa statistic under the common correlation model and goodness-of-fit statistic. The nomogram for the sample size formula was developed using SAS 9.3. The sample size formulae using a simple proportion of agreement instead of a kappa statistic and nomograms to eliminate the inconvenience of using a mathematical formula were produced. A nomogram for sample size calculation with a simple proportion of agreement should be useful in the planning stages when the focus of interest is on testing the hypothesis of interobserver agreement involving two raters and nominal outcome measures. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling the temporal variability of zinc concentrations in zinc roof runoff-experimental study and uncertainty analysis.

PubMed

Sage, Jérémie; El Oreibi, Elissar; Saad, Mohamed; Gromaire, Marie-Christine

2016-08-01

This study investigates the temporal variability of zinc concentrations from zinc roof runoff. The influence of rainfall characteristics and dry period duration is evaluated by combining laboratory experiment on small zinc sheets and in situ measurements under real weather conditions from a 1.6-m(2) zinc panel. A reformulation of a commonly used conceptual runoff quality model is introduced and its ability to simulate the evolution of zinc concentrations is evaluated. A systematic and sharp decrease from initially high to relatively low and stable zinc concentrations after 0.5 to 2 mm of rainfall is observed for both experiments, suggesting that highly soluble corrosion products are removed at early stages of runoff. A moderate dependence between antecedent dry period duration and the magnitude of zinc concentrations at the beginning of a rain event is evidenced. Contrariwise, results indicate that concentrations are not significantly influenced by rainfall intensities. Simulated rainfall experiment nonetheless suggests that a slight effect of rainfall intensities may be expected after the initial decrease of concentrations. Finally, this study shows that relatively simple conceptual runoff quality models may be adopted to simulate the variability of zinc concentrations during a rain event and from a rain event to another.

Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

PubMed Central

Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

1990-01-01

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia. Images PMID:1976820

Improved electrolyte for zinc-bromine flow batteries

NASA Astrophysics Data System (ADS)

Wu, M. C.; Zhao, T. S.; Wei, L.; Jiang, H. R.; Zhang, R. H.

2018-04-01

Conventional zinc bromide electrolytes offer low ionic conductivity and often trigger severe zinc dendrite growth in zinc-bromine flow batteries. Here we report an improved electrolyte modified with methanesulfonic acid, which not only improves the electrolyte conductivity but also ameliorates zinc dendrite. Experimental results also reveal that the kinetics and reversibility of Zn2+/Zn and Br2/Br- are improved in this modified electrolyte. Moreover, the battery's internal resistance is significantly reduced from 4.9 to 2.0 Ω cm2 after adding 1 M methanesulfonic acid, thus leading to an improved energy efficiency from 64% to 75% at a current density of 40 mA cm-2. More impressively, the battery is capable of delivering an energy efficiency of about 78% at a current density of as high as 80 mA cm-2 when the electrode is replaced by a thermally treated one. Additionally, zinc dendrite growth is found to be effectively suppressed in methanesulfonic acid supported media, which, as a result, enables the battery to be operated for 50 cycles without degradation, whereas the one without methanesulfonic acid suffers from significant decay after only 40 cycles, primarily due to severe zinc dendrite growth. These superior results indicate methanesulfonic acid is a promising supporting electrolyte for zinc-bromine flow batteries.

A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity.

PubMed

Richards, Christopher D; Warr, Coral G; Burke, Richard

2017-01-01

Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The Drosophila zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised Drosophila zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of Zip88E presented here indicates that Zip88E may instead play a role in detecting and responding to zinc toxicity. Larvae homozygous for a null Zip88E allele are viable yet display heightened sensitivity to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied by an overall decrease in Metallothionein B transcription throughout the larval midgut. A Zip88E reporter gene is expressed only in the salivary glands, a handful of enteroendocrine cells at the boundary between the anterior and middle midgut regions, and in two parallel strips of sensory cell projections connecting to the larval ventral ganglion. Zip88E expression solely in this restricted subset of cells is sufficient to rescue the Zip88E mutant phenotype. Together, our data suggest that Zip88E may be functioning in a small subset of cells to detect excessive zinc levels and induce a systemic response to reduce dietary zinc absorption and hence protect against toxicity.

Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

PubMed

Liao, C L; Lin, Y L; Wu, B C; Tsao, C H; Wang, M C; Liu, C I; Huang, Y L; Chen, J H; Wang, J P; Chen, L K

2001-09-01

Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation.

PubMed

Hsuan, S L; Kannan, M S; Jeyaseelan, S; Prakash, Y S; Malazdrewich, C; Abrahamsen, M S; Sieck, G C; Maheswaran, S K

1999-05-01

In bovine alveolar macrophages (BAMs), exposure to leukotoxin (Lkt) and endotoxin (LPS) from Pasteurella haemolytica results in expression of inflammatory cytokine genes and intracellular calcium ([Ca2+]i) elevation. Leukotoxin from P. haemolytica interacts only with leukocytes and platelets from ruminant species. Upregulation of cytokine genes in different cells by LPS involves activation of the transcription factor NF-kappaB (NF-kappaB), resulting in its translocation from the cytoplasm to the nucleus. Using immunocytochemical staining and confocal imaging, we studied whether NF-kappaB activation represents a common mechanism for the expression of multiple cytokine genes in BAMs (Lkt-susceptible cells) stimulated with Lkt and LPS. Bovine pulmonary artery endothelial cells and porcine alveolar macrophages were used as nonsusceptible cells. The role of Ca2+ and tyrosine kinases in NF-kappaB activation and inflammatory cytokine gene expression was studied, since an inhibitor of tyrosine kinases attenuates LPS-induced [Ca2+]i elevation in BAMs. The results are summarized as follows: (a) Lkt induced NF-kappaB activation and [Ca2+]i elevation only in BAMs, while LPS effects were demonstrable in all cell types; (b) chelation of [Ca2+]i blocked NF-kappaB activation and IL-1beta, TNFalpha, and IL-8 mRNA expression; and (c) tyrosine kinase inhibitor herbimycin A blocked expression of all three cytokine genes in BAMs stimulated with Lkt, while only the expression of IL-1beta was blocked in BAMs stimulated with LPS. We conclude that cytokine gene expression in BAMs requires NF-kappaB activation and [Ca2+]i elevation, and Lkt effects exhibit cell type- and species specificity. Copyright 1999 Academic Press.

Improved zinc electrode and rechargeable zinc-air battery

DOEpatents

Ross, P.N. Jr.

1988-06-21

The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

Serum thymulin in human zinc deficiency.

PubMed Central

Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

1988-01-01

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

Improved colorimetric determination of serum zinc.

PubMed

Johnson, D J; Djuh, Y Y; Bruton, J; Williams, H L

1977-07-01

We show how zinc may easily be quantified in serum by first using an optimum concentration of guanidine hydrochloride to cause release of zinc from proteins, followed by complexation of released metals with cyanide. The cyanide complex of zinc is preferentially demasked with chloral hydrate, followed by a colorimetric reaction between zinc and 4-(2-pyridylazo)resorcinol. This is a sensitive water-soluble ligand; its complex with zinc has an absorption maximum at 497 nm. Values found by this technique compare favorably with those obtained by atomic absorption spectroscopy.

Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys.

PubMed

Schindler, Charles W; Graczyk, Zofi; Gilman, Joanne P; Negus, S Stevens; Bergman, Jack; Mello, Nancy K; Goldberg, Steven R

2007-12-08

As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

Factors influencing zinc status of apparently healthy indians.

PubMed

Agte, Vaishali V; Chiplonkar, Shashi A; Tarwadi, Kirtan V

2005-10-01

To identify dietary, environmental and socio-economic factors associated with mild zinc deficiency, three zinc status indices; erythrocyte membrane zinc (RBCMZn), plasma zinc and super oxide dismutase (SOD) were assessed in free living and apparently healthy Indian population. Dietary patterns of 232 men and 223 women (20-65 yr) from rural, industrial and urban regions of Western India were evaluated by food frequency questionnaire. RBCMZn was estimated using atomic absorption spectrometry, hemoglobin and serum ceruloplasmin by spectrophotometer. On a sub sample (48 men and 51 women) plasma zinc and SOD were also assessed. Mean RBCMZn was 0.5 +/- 0.1 micromols/g protein with 46% individuals showing zinc deficiency. Mean plasma zinc was 0.98 +/- 0.12 microg/mL with 25% men and 2.5% women having values below normal range. Mean SOD was 0.97 +/- 0.1 (u/mL cells). A significant positive correlation was observed between intakes of green leafy vegetables, other vegetables and milk products with RBCMZn status (p < 0.05). But these were not correlated with plasma zinc (p > 0.2). Cereal and legume intakes were negatively correlated with RBCMZn (p < 0.05) but positively correlated with plasma zinc (p < 0.05) and not correlated with SOD (p > 0.2). Fruit and other vegetable intake were positively correlated with SOD (p < 0.05) alone. Logistic regression analyses revealed that RBCMZn was positively associated with intakes of beta-carotene, zinc and environmental conditions and negatively associated with family size (p < 0.05). Plasma zinc indicated positive association with zinc, thiamin and riboflavin intakes (p < 0.05) and SOD showed negative association with iron and family size. RBCMZn was a more sensitive indicator of long-term zinc status than plasma zinc and SOD. Prominent determinants of zinc status were intakes of beta-carotene and zinc along with environmental conditions and family size.

Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

DOEpatents

Adler, Thomas C.; McLarnon, Frank R.; Cairns, Elton J.

1995-01-01

An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing one or more hydroxides having the formula M(OH), one or more fluorides having the formula MF, and one or more carbonates having the formula M.sub.2 CO.sub.3, where M is a metal selected from the group consisting of alkali metals. The electrolyte inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics.

SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

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

Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin

2012-03-09

Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistancemore » in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.« less

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2.

PubMed

Joshua, Ifeoluwapo Matthew; Höfken, Thomas

2017-04-05

Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae . These proteins also control adaptations to anaerobic growth, sterol biosynthesis as well as filamentation and mating. Orthologs of these zinc cluster proteins have been identified in several species of Candida . Upc2 plays a critical role in antifungal resistance in these important human fungal pathogens. Upc2 is therefore an interesting potential target for novel antifungals. In this review we discuss the functions, mode of actions and regulation of Ecm22, Upc2, Sut1 and Sut2 in budding yeast and Candida .

Structure of new carotenoids with the 6-oxo-kappa end group from the fruits of paprika, Capsicum annuum.

PubMed

Maoka, Takashi; Akimoto, Naoshige; Fujiwara, Yasuhiro; Hashimoto, Keiji

2004-01-01

New carotenoids 1 and 2 were isolated as minor components from the ripe fruits of paprika (Capsicum annuum). The structures of 1 and 2 were determined to be (3R,5'R)-3-hydroxy-beta,kappa-caroten-6'-one and (5'R)-3,4-didehydro-beta,kappa-caroten-6'-one, respectively, from UV-vis, NMR, CD, HRFABMS, and FABMS/MS spectra.

Angle Kappa Measurements: Normal Values in Healthy Iranian Population Obtained With the Orbscan II

PubMed Central

Gharaee, Hamid; Shafiee, Masoud; Hoseini, Rafie; Abrishami, Mojtaba; Abrishami, Yalda; Abrishami, Mostafa

2014-01-01

Background: The angle kappa is important in proper centration of corneal ablation in keratorefractive surgery. Orbscan II device is widely used preoperatively in photoablation surgeries and can be used to measure the angle kappa. Objectives: This study aimed to determine the mean angle kappa and its intercepts in healthy young Iranian adults. Patients and Methods: In this cross-sectional study, orthotropic patients (age range, 18-35 years) who were referred to the Khatam Eye Hospital (Mashhad, Iran) were included. Exclusion criteria were as follows: history of any eye deviation or strabismus with or without orthoptic or surgical treatment; any intraocular, corneal, or keratorefractive surgery; contact lens use; any corneal anomaly; any ophthalmic or systemic drug consumption; and hyperopic spherical refraction > + 3.00 diopters (D), spherical refraction > -5.00 D, or cylindrical refraction > 2.00 D. All of the parameters were measured by the same operator through an Orbscan II device. Results: A total of 977 healthy participants who aged 18 to 45 years were included consecutively. The study population consisted of 614 females and 363 males. The average angle kappa was 5.00º ± 1.36º at 240.21º ± 97.17º in males and 4.97º ± 1.30º at 244.22º ± 94.39º in females (P = 0.63). The average horizontal (x-axis) angle kappa was -0.02º ± 0.49º, with a mean of -0.02º ± 0.50º in males and -0.02º ± 0.49º in females (P = 0.93). The average vertical (y-axis) angle kappa was -0.09º ± 0.32º, with a mean of -0.09º ± 0.33º in males and -0.09º ± 0.32º in females (P = 0.74). Conclusions: By using the normal angle kappa determined in this study, pseudodeviations can be identified more precisely in those who might undergo keratorefractive surgery. PMID:25763261

Chronic intermittent hypoxia activates nuclear factor-{kappa}B in cardiovascular tissues in vivo

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

Greenberg, Harly; Ye Xiaobing; Wilson, David

2006-05-05

Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-{kappa}B pathway. We demonstrated that exposure of mice to CIH activated NF-{kappa}B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-{kappa}B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminatedmore » by nocturnal CPAP therapy. The elevated NF-{kappa}B activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-{kappa}B-dependent gene product. Thus, CIH-mediated NF-{kappa}B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.« less

15-Deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2} down-regulates CXCR4 on carcinoma cells through PPAR{gamma}- and NF{kappa}B-mediated pathways

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

Richard, Cynthia Lee; Lowthers, Erica Lauren; Blay, Jonathan

2007-10-01

The chemokine receptor CXCR4 plays a key role in the metastasis of colorectal cancer and its growth at metastatic sites. Here, we have investigated the mechanisms by which CXCR4 on cancer cells might be regulated by eicosanoids present within the colorectal tumor microenvironment. We show that prostaglandins PGE{sub 2}, PGA{sub 2}, PGD{sub 2}, PGJ{sub 2} and 15dPGJ{sub 2} each down-regulates CXCR4 receptor expression on human colorectal carcinoma cells to differing degrees. The most potent of these were PGD{sub 2} and its metabolites PGJ{sub 2} and 15dPGJ{sub 2}. Down-regulation was most rapid with the end-product 15dPGJ{sub 2} and was accompanied bymore » a marked reduction in CXCR4 mRNA. 15dPGJ{sub 2} is known to be a ligand for the nuclear receptor PPAR{gamma}. Down-regulation of CXCR4 was also observed with the PPAR{gamma} agonist rosiglitazone, while 15dPGJ{sub 2}-induced CXCR4 down-regulation was substantially diminished by the PPAR{gamma} antagonists GW9662 and T0070907. These data support the involvement of PPAR{gamma}. However, the 15dPGJ{sub 2} analogue CAY10410, which can act on PPAR{gamma} but which lacks the intrinsic cyclopentenone structure found in 15dPGJ{sub 2}, down-regulated CXCR4 substantially less potently than 15dPGJ{sub 2}. The cyclopentenone grouping is known to inhibit the activity of NF{kappa}B. Consistent with an additional role for NF{kappa}B, we found that the cyclopentenone prostaglandin PGA{sub 2} and cyclopentenone itself could also down-regulate CXCR4. Immunolocalization studies showed that the cellular context was sufficient to trigger a focal nuclear pattern of NF{kappa}B p50 and that 15dPGJ{sub 2} interfered with this p50 nuclear localization. These data suggest that 15dPGJ{sub 2} can down-regulate CXCR4 on cancer cells through both PPAR{gamma} and NF{kappa}B. 15dPGJ{sub 2}, present within the tumor microenvironment, may act to down-regulate CXCR4 and impact upon the overall process of tumor expansion.« less

Solubilization of insoluble zinc compounds by Gluconacetobacter diazotrophicus and the detrimental action of zinc ion (Zn2+) and zinc chelates on root knot nematode Meloidogyne incognita.

PubMed

Saravanan, V S; Kalaiarasan, P; Madhaiyan, M; Thangaraju, M

2007-03-01

To examine the zinc (Zn) solubilization potential and nematicidal properties of Gluconacetobacter diazotrophicus. Atomic Absorption Spectrophotometer, Differential Pulse Polarography and Gas Chromatography Coupled Mass Spectrometry were used to estimate the total Zn and Zn(2+) ions and identify the organic acids present in the culture supernatants. The effect of culture filtrate of Zn-amended G. diazotrophicus PAl5 on Meloidogyne incognita in tomato was examined under gnotobiotic conditions. Gluconacetobacter diazotrophicus PAl5 effectively solubilized the Zn compounds tested and 5-ketogluconic acid was identified as the major organic acid aiding the solubilization of zinc oxide. The presence of Zn compounds in the culture filtrates of G. diazotrophicus enhanced the mortality and reduced the root penetration of M. incognita under in vitro conditions. 5-ketogluconic acid produced by G. diazotrophicus mediated the solubilization process and the available Zn(2+) ions enhanced the nematicidal activity of G. diazotrophicus against M. incognita. Zn solubilization and enhanced nematicidal activity of Zn-amended G. diazotrophicus provides the possibility of exploiting it as a plant growth promoting bacteria.

21 CFR 73.1991 - Zinc oxide.

Code of Federal Regulations, 2010 CFR

2010-04-01

... amounts consistent with good manufacturing practice. (d) Labeling. The color additive and any mixtues... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc...). It is principally composed of Zn. (2) Color additive mixtures for drug use made with zinc oxide may...

EWS-FLI1 inhibits TNF{alpha}-induced NF{kappa}B-dependent transcription in Ewing sarcoma cells

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

Lagirand-Cantaloube, Julie, E-mail: julie.cantaloube@crbm.cnrs.fr; Laud, Karine, E-mail: karine.laud@curie.fr; Institut Curie, Genetique et biologie des cancers, Paris

2010-09-03

Research highlights: {yields} EWS-FLI1 interferes with TNF-induced activation of NF{kappa}B in Ewing sarcoma cells. {yields} EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NF{kappa}B binding to DNA. {yields} EWS-FLI1 reduces TNF-stimulated NF{kappa}B-dependent transcriptional activation. {yields} Constitutive NF{kappa}B activity is not affected by EWS-FLI1. {yields} EWS-FLI1 physically interacts with NF{kappa}B p65 in vivo. -- Abstract: Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NF{kappa}B) is a tightly regulated transcription factor controllingmore » cell survival, proliferation and differentiation, as well as tumorigenesis. NF{kappa}B activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NF{kappa}B activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NF{kappa}B basal activity, but impairs TNF-induced NF{kappa}B-driven transcription, at least in part through inhibition of NF{kappa}B binding to DNA. We detected an in vivo physical interaction between the fusion protein and NF{kappa}B p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NF{kappa}B.« less

Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

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

Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.

Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an importantmore » role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

PubMed

Giardina, G; Clarke, G D; Dondio, G; Petrone, G; Sbacchi, M; Vecchietti, V

1994-10-14

This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

Method of capturing or trapping zinc using zinc getter materials

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

Hunyadi Murph, Simona E.; Korinko, Paul S.

2017-07-11

A method of trapping or capturing zinc is disclosed. In particular, the method comprises a step of contacting a zinc vapor with a zinc getter material. The zinc getter material comprises nanoparticles and a metal substrate.

Zinc for the common cold.

PubMed

Singh, Meenu; Das, Rashmi R

2011-02-16

The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. To assess the effect of zinc on common cold symptoms. We searched CENTRAL (2010, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010) and EMBASE (1974 to June 2010). Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. Two review authors independently extracted data and assessed trial quality. We included 13 therapeutic trials (966 participants) and two preventive trials (394 participants). Intake of zinc is associated with a significant reduction in the duration (standardized mean difference (SMD) -0.97; 95% confidence interval (CI) -1.56 to -0.38) (P = 0.001), and severity of common cold symptoms (SMD -0.39; 95% CI -0.77 to -0.02) (P = 0.04). There was a significant difference between the zinc and control group for the proportion of participants symptomatic after seven days of treatment (OR 0.45; 95% CI 0.2 to 1.00) (P = 0.05). The incidence rate ratio (IRR) of developing a cold (IRR 0.64; 95% CI 0.47 to 0.88) (P = 0.006), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.59; 95% CI 0.97 to 2.58) (P = 0.06), bad taste (OR 2.64; 95% CI 1.91 to 3.64) (P < 0.00001) and nausea (OR 2.15; 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. Zinc administered within 24 hours of onset of symptoms reduces the duration and severity of the common cold in healthy people. When supplemented for at least five months, it reduces cold

Application of iota and kappa carrageenans to traditional several food using modified cassava flour

NASA Astrophysics Data System (ADS)

Al-Baarri, A. N.; Legowo, A. M.; Rizqiati, H.; Widayat; Septianingrum, A.; Sabrina, H. N.; Arganis, L. M.; Saraswati, R. O.; Mochtar, Rr C. P. R.

2018-01-01

Carrageenan has been known well as hydrocolloids that forming viscous dispersions and gels when dispersed in water. The carrageenan has not been widely applied to traditional foods. Therefore, the aim of this research was to determine the effect of kappa and iota carrageenans in traditional food models using modified cassava flour, sugar, and coconut milk. The textural properties, i.e. hardness, cohesiveness, springiness and adhesiveness have been measured using texture analyzer. The study indicated that traditional food models added kappa carrageenan at 2% generated remarkably higher in the hardness, cohesiveness, and springiness than those added iota carrageenan. On the other hand, the reserve result were found in the adhesiveness parameter. As conclusion, kappa carrageenan scan be potentially used for producing traditional foods based on the hard-texture-oriented foods whereas iota carrageenan can be used for the traditional foods with better adhesiveness.

Transcription factor NF-kappaB participates in regulation of epithelial cell turnover in the colon.

PubMed

Inan, M S; Tolmacheva, V; Wang, Q S; Rosenberg, D W; Giardina, C

2000-12-01

The transcription factor nuclear factor (NF)-kappaB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-kappaB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-kappaB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-kappaB1 (p50) knockout mice were used to study the role of NF-kappaB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-kappaB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-kappaB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-alpha and nerve growth factor-alpha genes at elevated levels, with in situ hybridization localizing some of the TNF-alpha expression to epithelial cells. TNF-alpha is NF-kappaB regulated, and its upregulation in NF-kappaB1 knockouts may result from an alleviation of p50-p50 repression. NF-kappaB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

Zinc titanate sorbents

DOEpatents

Gupta, R.P.; Gangwal, S.K.; Jain, S.C.

1998-02-03

The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750 to about 950 C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 microns, and about 1 part titanium dioxide having a median particle size of less than about 1 micron. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

Zinc titanate sorbents

DOEpatents

Gupta, Raghubir P.; Gangwal, Santosh K.; Jain, Suresh C.

1998-01-01

The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750.degree. C. to about 950.degree. C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 .mu., and about 1 part titanium dioxide having a median particle size of less than about 1 .mu.. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: acrodermatitis enteropathica and transient neonatal zinc deficiency as examples.

PubMed

Kasana, Shakhenabat; Din, Jamila; Maret, Wolfgang

2015-01-01

Discovering genetic causes of zinc deficiency has been a remarkable scientific journey. It started with the description of a rare skin disease, its treatment with various agents, the successful therapy with zinc, and the identification of mutations in a zinc transporter causing the disease. The journey continues with defining the molecular and cellular pathways that lead to the symptoms caused by zinc deficiency. Remarkably, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency. One is ZIP4, which is involved in intestinal zinc uptake. Its mutations can cause acrodermatitis enteropathica (AE) with autosomal recessive inheritance. The other one is ZnT2, the transporter responsible for supplying human milk with zinc. Mutations in this transporter cause transient neonatal zinc deficiency (TNZD) with symptoms similar to AE but with autosomal dominant inheritance. The two diseases can be distinguished in affected infants. AE is fatal if zinc is not supplied to the infant after weaning, whereas TNZD is a genetic defect of the mother limiting the supply of zinc in the milk, and therefore the infant usually will obtain enough zinc once weaned. Although these diseases are relatively rare, the full functional consequences of the numerous mutations in ZIP4 and ZnT2 and their interactions with dietary zinc are not known. In particular, it remains unexplored whether some mutations cause milder disease phenotypes or increase the risk for other diseases if dietary zinc requirements are not met or exceeded. Thus, it is not known whether widespread zinc deficiency in human populations is based primarily on a nutritional deficiency or determined by genetic factors as well. This consideration becomes even more significant with regard to mutations in the other 22 human zinc transporters, where associations with a range of diseases, including diabetes, heart disease, and mental illnesses have been observed

The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

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

Nam, Seon Young; Chung, Hee-Yong

2005-10-21

In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

Implication of zinc excess on soil health.

PubMed

Wyszkowska, Jadwiga; Boros-Lajszner, Edyta; Borowik, Agata; Baćmaga, Małgorzata; Kucharski, Jan; Tomkiel, Monika

2016-01-01

This study was undertaken to evaluate zinc's influence on the resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease. The experiment was conducted in a greenhouse of the University of Warmia and Mazury (UWM) in Olsztyn, Poland. Plastic pots were filled with 3 kg of sandy loam with pHKCl - 7.0 each. The experimental variables were: zinc applied to soil at six doses: 100, 300, 600, 1,200, 2,400 and 4,800 mg of Zn(2+) kg(-1) in the form of ZnCl2 (zinc chloride), and species of plant: oat (Avena sativa L.) cv. Chwat and white mustard (Sinapis alba) cv. Rota. Soil without the addition of zinc served as the control. During the growing season, soil samples were subjected to microbiological analyses on experimental days 25 and 50 to determine the abundance of organotrophic bacteria, actinomyces and fungi, and the activity of dehydrogenases, catalase and urease, which provided a basis for determining the soil resistance index (RS). The physicochemical properties of soil were determined after harvest. The results of this study indicate that excessive concentrations of zinc have an adverse impact on microbial growth and the activity of soil enzymes. The resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease decreased with an increase in the degree of soil contamination with zinc. Dehydrogenases were most sensitive and urease was least sensitive to soil contamination with zinc. Zinc also exerted an adverse influence on the physicochemical properties of soil and plant development. The growth of oat and white mustard plants was almost completely inhibited in response to the highest zinc doses of 2,400 and 4,800 mg Zn(2+) kg(-1).

Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.

PubMed Central

Goodhardt, M; Babinet, C; Lutfalla, G; Kallenbach, S; Cavelier, P; Rougeon, F

1989-01-01

We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged kappa transgene. Furthermore, unlike endogenous kappa genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage- and lineage- specific regulation of Ig kappa light chain gene rearrangement in vivo. Images PMID:2508061

Effect of modifying agents on the hydrophobicity and yield of zinc borate synthesized by zinc oxide

NASA Astrophysics Data System (ADS)

Acarali, Nil Baran; Bardakci, Melek; Tugrul, Nurcan; Derun, Emek Moroydor; Piskin, Sabriye

2013-06-01

The aim of this study was to synthesize zinc borate using zinc oxide, reference boric acid, and reference zinc borate (reference ZB) as the seed, and to investigate the effects of modifying agents and reaction parameters on the hydrophobicity and yield, respectively. The reaction parameters include reaction time (1-5 h), reactant ratio (H3BO3/ZnO by mass: 2-5), seed ratio (seed crystal/(H3BO3+ZnO) by mass: 0-2wt%), reaction temperature (50-120°C), cooling temperature (10-80°C), and stirring rate (400-700 r/min); the modifying agents involve propylene glycol (PG, 0-6wt%), kerosene (1wt%-6wt%), and oleic acid (OA, 1wt%-6wt%) with solvents (isopropyl alcohol (IPA), ethanol, and methanol). The results of reaction yield obtained from either magnetically or mechanically stirred systems were compared. Zinc borate produced was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and contact angle tests to identify the hydrophobicity. In conclusion, zinc borate is synthesized successfully under the optimized reaction conditions, and the different modifying agents with various solvents affect the hydrophobicity of zinc borate.

The Zinc Transporter Zip5 (Slc39a5) Regulates Intestinal Zinc Excretion and Protects the Pancreas against Zinc Toxicity

PubMed Central

Geiser, Jim; De Lisle, Robert C.; Andrews, Glen K.

2013-01-01

Background ZIP5 localizes to the baso-lateral membranes of intestinal enterocytes and pancreatic acinar cells and is internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. These cell-types are thought to control zinc excretion from the body. The baso-lateral localization and zinc-regulation of ZIP5 in these cells are unique among the 14 members of the Slc39a family and suggest that ZIP5 plays a role in zinc excretion. Methods/Principal Findings We created mice with floxed Zip5 genes and deleted this gene in the entire mouse or specifically in enterocytes or acinar cells and then examined the effects on zinc homeostasis. We found that ZIP5 is not essential for growth and viability but total knockout of ZIP5 led to increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of-function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally, loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation of 67zinc. Retention of pancreatic 67zinc was impaired in these mice but the absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and exacerbated the formation of large cytoplasmic vacuoles containing secretory protein in acinar cells. Conclusions These studies demonstrate that ZIP5 participates in the control of zinc excretion in mice. Specifically, they reveal a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in acinar cells to protect against zinc-induced acute pancreatitis and attenuate the process of zymophagy. This suggests that it may play a role in autophagy. PMID:24303081

The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

PubMed

Butelman, Eduardo R; Rus, Szymon; Prisinzano, Thomas E; Kreek, Mary Jeanne

2010-06-01

The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

Zinc in innate and adaptive tumor immunity

PubMed Central

2010-01-01

Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order. PMID:21087493

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

PubMed

Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

1998-05-01

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription

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

Wang Jian; Tan Juan; Zhang Xihui

2010-05-10

Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may bemore » responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription.« less

BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription.

PubMed

Wang, Jian; Tan, Juan; Zhang, Xihui; Guo, Hongyan; Zhang, Qicheng; Guo, Tingting; Geng, Yunqi; Qiao, Wentao

2010-05-10

Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may be responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription. Copyright 2010 Elsevier Inc. All rights reserved.

Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure.

PubMed

Benyhe, S; Márki, A; Nachtsheim, Corina; Holzgrabe, Ulrike; Borsodi, Anna

2003-01-01

Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent kappa-opioid receptor specific agonists. One lead molecule of this series. called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3.7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [3H]U-69.593 binding sites in guinea pig cerebellar membranes which known to be a good source for kappa1 receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic kappa-selective benzomorphan compound; when compared to the arylacetamide structure of U-69.593, a specific kappa1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.

Biphasic zinc compartmentalisation in a human fungal pathogen.

PubMed

Crawford, Aaron C; Lehtovirta-Morley, Laura E; Alamir, Omran; Niemiec, Maria J; Alawfi, Bader; Alsarraf, Mohammad; Skrahina, Volha; Costa, Anna C B P; Anderson, Andrew; Yellagunda, Sujan; Ballou, Elizabeth R; Hube, Bernhard; Urban, Constantin F; Wilson, Duncan

2018-05-01

Nutritional immunity describes the host-driven manipulation of essential micronutrients, including iron, zinc and manganese. To withstand nutritional immunity and proliferate within their hosts, pathogenic microbes must express efficient micronutrient uptake and homeostatic systems. Here we have elucidated the pathway of cellular zinc assimilation in the major human fungal pathogen Candida albicans. Bioinformatics analysis identified nine putative zinc transporters: four cytoplasmic-import Zip proteins (Zrt1, Zrt2, Zrt3 and orf19.5428) and five cytoplasmic-export ZnT proteins (orf19.1536/Zrc1, orf19.3874, orf19.3769, orf19.3132 and orf19.52). Only Zrt1 and Zrt2 are predicted to localise to the plasma membrane and here we demonstrate that Zrt2 is essential for C. albicans zinc uptake and growth at acidic pH. In contrast, ZRT1 expression was found to be highly pH-dependent and could support growth of the ZRT2-null strain at pH 7 and above. This regulatory paradigm is analogous to the distantly related pathogenic mould, Aspergillus fumigatus, suggesting that pH-adaptation of zinc transport may be conserved in fungi and we propose that environmental pH has shaped the evolution of zinc import systems in fungi. Deletion of C. albicans ZRT2 reduced kidney fungal burden in wild type, but not in mice lacking the zinc-chelating antimicrobial protein calprotectin. Inhibition of zrt2Δ growth by neutrophil extracellular traps was calprotectin-dependent. This suggests that, within the kidney, C. albicans growth is determined by pathogen-Zrt2 and host-calprotectin. As well as serving as an essential micronutrient, zinc can also be highly toxic and we show that C. albicans deals with this potential threat by rapidly compartmentalising zinc within vesicular stores called zincosomes. In order to understand mechanistically how this process occurs, we created deletion mutants of all five ZnT-type transporters in C. albicans. Here we show that, unlike in Saccharomyces cerevisiae, C

The kappa-opiate receptor impacts the pathophysiology and behavior of substance use.

PubMed

Mysels, David; Sullivan, Maria A

2009-01-01

There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology.

Electrodeposition of zinc hydroxysulfate nanosheets and reduction to zinc metal microdendrites on polypyrrole films.

PubMed

Andreoli, Enrico; Rooney, Denise A; Redington, Wynette; Gunning, Robert; Breslin, Carmel B

2012-01-01

Nanothin sheets made of zinc sulfate hydroxide hydrate, ZnSO4[Zn(OH)2]3 x 5H2O, are easily and quickly prepared using an innovative electrochemical route onto polypyrrole-polystyrene sulfonate (PPy-PSS) films. The sheets are characterized using a range of experimental techniques. The deposits are formed on the film surface with instantaneous nucleation to grow into a network of entangled nanosheets. The effect of the experimental conditions on the deposition is reported. Interestingly, the formation of the nanosheets is observed on PPy-PSS films only, and not on films doped with other sulfate/sulfonate dopants. The zinc nanosheets can be easily electrochemically reduced to metallic zinc microdentrites.

Polycystin-1 promotes PKC{alpha}-mediated NF-{kappa}B activation in kidney cells

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

Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky

2006-11-17

Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-{kappa}B signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293{sup CTT}), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-{kappa}B nuclear levels and NF-{kappa}B-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-{kappa}B promoter activation was mediated by PKC{alpha}more » because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293{sup CTT} cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-{kappa}B inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKC{alpha}-mediated NF-{kappa}B signalling and cell survival.« less

Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry.

PubMed

Barnidge, David R; Dasari, Surendra; Ramirez-Alvarado, Marina; Fontan, Adrian; Willrich, Maria A V; Tschumper, Renee C; Jelinek, Diane F; Snyder, Melissa R; Dispenzieri, Angela; Katzmann, Jerry A; Murray, David L

2014-11-07

We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses.

Long Life, High Energy Silver-Zinc Batteries

NASA Technical Reports Server (NTRS)

Kainthla, Ramesh; Coffey, Brendan

2003-01-01

This viewgraph presentation includes: 1) an introduction to RBC Technologies; 2) Rechargeable Zinc Alkaline (RZA(tm)) Systems which include MnO2/Zn, Ni/Zn, Ag/Zn, and Zn/Air; and 3) RZA Silver/Zinc Battery Developments. Conclusions include the following: 1)Issues with long term wet life and cycle life of the silver/zinc battery system are being overcome through the use of new anode formulations and separator designs; 2) Performance may exceed 200 cycles to 80% of initial capacity and ultimate wet-life of > 36 months; and 3) Rechargeable silver/zinc batteries available in prismatic and cylindrical formats may provide a high energy, high power alternative to lithium-ion in military/aerospace applications.

Effects of dietary supplementation with tribasic zinc sulfate or zinc sulfate on growth performance, zinc content and expression of zinc transporters in young pigs.

PubMed

Deng, Bo; Zhou, Xihong; Wu, Jie; Long, Ciming; Yao, Yajun; Peng, Hongxing; Wan, Dan; Wu, Xin

2017-10-01

An experiment was conducted to compare the effects of zinc sulfate (ZS) and tribasic zinc sulfate (TBZ) as sources of supplemental zinc on growth performance, serum zinc (Zn) content and messenger RNA (mRNA) expression of Zn transporters (ZnT1/ZnT2/ZnT5/ZIP4/DMT1) of young growing pigs. A total of 96 Duroc × Landrace × Yorkshire pigs were randomly allotted to two treatments and were fed a basal diet supplemented with 100 mg/kg Zn from either ZS or TBZ for 28 days. Feed : gain ratio in pigs fed TBZ were lower (P < 0.05) than pigs fed ZS, and average daily weight gain tended to increase (0.05 ≤ P ≤ 0.10) in pigs fed TBZ. Compared with pigs fed ZS, pigs fed TBZ had a higher CuZn-superoxide dismutase and Zn content in serum (P < 0.05) while they had a lower Zn content in feces (P < 0.05). In addition, ZIP4 mRNA expression of zinc transporter in either duodenum or jejunum of pigs fed TBZ were higher (P < 0.05) than pigs fed ZS. These results indicate that TBZ is more effective in serum Zn accumulation and intestinal Zn absorption, and might be a potential substitute for ZS in young growing pigs. © 2017 Japanese Society of Animal Science.

Morphology control of zinc regeneration for zinc-air fuel cell and battery

NASA Astrophysics Data System (ADS)

Wang, Keliang; Pei, Pucheng; Ma, Ze; Xu, Huachi; Li, Pengcheng; Wang, Xizhong

2014-12-01

Morphology control is crucial both for zinc-air batteries and for zinc-air fuel cells during zinc regeneration. Zinc dendrite should be avoided in zinc-air batteries and zinc pellets are yearned to be formed for zinc-air fuel cells. This paper is mainly to analyze the mechanism of shape change and to control the zinc morphology during charge. A numerical three-dimensional model for zinc regeneration is established with COMSOL software on the basis of ionic transport theory and electrode reaction electrochemistry, and some experiments of zinc regeneration are carried out. The deposition process is qualitatively analyzed by the kinetics Monte Carlo method to study the morphological change from the electrocrystallization point of view. Morphological evolution of deposited zinc under different conditions of direct currents and pulse currents is also investigated by simulation. The simulation shows that parametric variables of the flowing electrolyte, the surface roughness and the structure of the electrode, the charging current and mode affect morphological evolution. The uniform morphology of deposited zinc is attained at low current, pulsating current or hydrodynamic electrolyte, and granular morphology is obtained by means of an electrode of discrete columnar structure in combination with high current and flowing electrolyte.

Corrective recombination of mouse immunoglobulin kappa alleles in Abelson murine leukemia virus-transformed pre-B cells.

PubMed Central

Feddersen, R M; Van Ness, B G

1990-01-01

Previous characterization of mouse immunoglobulin kappa gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single kappa allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single kappa allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the kappa locus during cell culture. Clonal cell lines which had rearranged one kappa allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed kappa protein, were isolated and examined for further kappa rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive kappa gene, occur with a significant frequency (6 of 17 kappa-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed. Images PMID:2153918

Fatigue of die cast zinc alloys

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

Schrems, K.K.; Dogan, O.N.; Goodwin, F.E.

2006-04-01

The rotating bending fatigue limit of die cast zinc alloy 2, alloy 3, alloy 5, AcuZinc 5, and ZA-8 were determined as a part of an on-going program by ILZRO into the mechanical properties of die cast zinc. The stress-life (S-N) curves of alloys 3, 5, AcuZinc 5, and ZA-8 were determined previously. This presentation reports the results of the S-N curve for Alloy 2 and the calculated fatigue limits for all five alloys. During the previous stress-life testing, the samples were stopped at 10 million cycles and the fatigue limit for alloy 3, alloy 5, and AcuZinc 5 appearedmore » to be higher and the fatigue limit for ZA-8 appeared to be lower than the values reported in the literature. This was further investigated in alloy 5 and ZA-8 by testing continuous cast bulk alloy 5 and ZA-8.« less

Role of H2O2 in the Oxidative Effects of Zinc Exposure in Human Airway Epithelial Cells

EPA Science Inventory

Human exposure to particulate matter (PM) is a global environmental health concern. Zinc (Zn(2+)) is a ubiquitous respiratory toxicant that has been associated with PM health effects. However, the molecular mechanism of Zn(2+) toxicity is not fully understood. H202 and Zn(2+) hav...

Low-temperature solution-processed zinc oxide field effect transistor by blending zinc hydroxide and zinc oxide nanoparticle in aqueous solutions

NASA Astrophysics Data System (ADS)

Shin, Hyeonwoo; Kang, Chan-mo; Baek, Kyu-Ha; Kim, Jun Young; Do, Lee-Mi; Lee, Changhee

2018-05-01

We present a novel methods of fabricating low-temperature (180 °C), solution-processed zinc oxide (ZnO) transistors using a ZnO precursor that is blended with zinc hydroxide [Zn(OH)2] and zinc oxide hydrate (ZnO • H2O) in an ammonium solution. By using the proposed method, we successfully improved the electrical performance of the transistor in terms of the mobility (μ), on/off current ratio (I on/I off), sub-threshold swing (SS), and operational stability. Our new approach to forming a ZnO film was systematically compared with previously proposed methods. An atomic forced microscopic (AFM) image and an X-ray photoelectron spectroscopy (XPS) analysis showed that our method increases the ZnO crystallite size with less OH‑ impurities. Thus, we attribute the improved electrical performance to the better ZnO film formation using the blending methods.

Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-{beta}

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

Zhao, Haige; Hiroi, Toyoko; Hansen, Baranda S.

2009-11-27

Vascular endothelial cells respond to biomechanical forces, such as cyclic stretch and shear stress, by altering gene expression. Since endothelial-derived prostanoids, such as prostacyclin and thromboxane A{sub 2}, are key mediators of endothelial function, we investigated the effects of cyclic stretch on the expression of genes in human umbilical vein endothelial cells controlling prostanoid synthesis: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS) and thromboxane A{sub 2} synthase (TXAS). COX-2 and TXAS mRNAs were upregulated by cyclic stretch for 24 h. In contrast, PGIS mRNA was decreased and stretch had no effect on COX-1 mRNA expression. We further show that stretch-inducedmore » upregulation of COX-2 is mediated by activation of the NF-{kappa}{beta} signaling pathway.« less

BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of Cot kinase gene expression in T-lymphocytes.

PubMed

Cismasiu, Valeriu B; Duque, Javier; Paskaleva, Elena; Califano, Danielle; Ghanta, Sailaja; Young, Howard A; Avram, Dorina

2009-01-15

BCL11B is a transcriptional regulator with an important role in T-cell development and leukaemogenesis. We demonstrated recently that BCL11B controls expression from the IL (interleukin)-2 promoter through direct binding to the US1 (upstream site 1). In the present study, we provide evidence that BCL11B also participates in the activation of IL-2 gene expression by enhancing NF-kappaB (nuclear factor kappaB) activity in the context of TCR (T-cell receptor)/CD28-triggered T-cell activation. Enhanced NF-kappaB activation is not a consequence of BCL11B binding to the NF-kappaB response elements or association with the NF-kappaB-DNA complexes, but rather the result of higher translocation of NF-kappaB to the nucleus caused by enhanced degradation of IkappaB (inhibitor of NF-kappaB). The enhanced IkappaB degradation in cells with increased levels of BCL11B was specific for T-cells activated through the TCR, but not for cells activated through TNFalpha (tumour necrosis factor alpha) or UV light, and was caused by increased activity of IkappaB kinase, as indicated by its increase in phosphorylation. As BCL11B is a transcription factor, we investigated whether the expression of genes upstream of IkappaB kinase in the TCR/CD28 signalling pathway was affected by increased BCL11B expression, and found that Cot (cancer Osaka thyroid oncogene) kinase mRNA levels were elevated. Cot kinase is known to promote enhanced IkappaB kinase activity, which results in the phosphorylation and degradation of IkappaB and activation of NF-kappaB. The implied involvement of Cot kinase in BCL11B-mediated NF-kappaB activation in response to TCR activation is supported by the fact that a Cot kinase dominant-negative mutant or Cot kinase siRNA (small interfering RNA) knockdown blocked BCL11B-mediated NF-kappaB activation. In support of our observations, in the present study we report that BCL11B enhances the expression of several other NF-kappaB target genes, in addition to IL-2. In addition, we

Carbon Dioxide Electroreduction using a Silver-Zinc Alloy [CO 2 Electroreduction on a Ag-Zn Alloy

DOE PAGES

Hatsukade, Toru; Kuhl, Kendra P.; Cave, Etosha R.; ...

2017-02-20

We report on CO 2 electroreduction activity and selectivity of a polycrystalline AgZn foil in aqueous bicarbonate electrolyte. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) measurements show that the alloy foil was slightly enriched in zinc both at the surface and in the bulk, with a surface alloy composition of 61.3±5.4 at % zinc and with Ag 5Zn 8 as the most prominent bulk phase. AgZn is active for CO 2 reduction; CO is the main product, likely due to the weak CO binding energy of the surface, with methane and methanol emerging as minor products. Compared to puremore » silver and pure zinc foils, enhancements in activity and selectivity for methane and methanol are observed. A five-fold increase is observed in the combined partial current densities for methane and methanol at –1.43 V vs. the reversible hydrogen electrode (RHE), representing a four- to six-fold increase in faradaic efficiency. Here, such enhancements indicate the existence of a synergistic effect between silver and zinc at the surface of the alloy that contributes to the enhanced formation of further reduced products.« less

Production of zinc pellets

DOEpatents

Cooper, J.F.

1996-11-26

Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries. 6 figs.

Production of zinc pellets

DOEpatents

Cooper, John F.

1996-01-01

Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries.

Molecular genetic analysis of the V kappa Ser group associated with two mouse light chain genetic markers. Complementary DNA cloning and southern hybridization analysis

PubMed Central

1985-01-01

Previous studies (21) have shown that two mouse kappa light (L) chain variable (V) region polymorphisms, the IB-peptide and Efla markers, reflect expression of a characteristic group of V kappa regions, called V kappa Ser, by some inbred strains and not others. Expression of V kappa Ser is controlled by a locus on chromosome 6, the chromosome that contains the kappa locus. To further characterize this V kappa group and begin to analyze the basis for its strain-specific expression, full- length complementary DNA (cDNA) copies were produced of L chain mRNA from the M75 myeloma that had been induced in the C.C58 strain of mice, and which produces a V kappa Ser L chain. The C.C58 strain is congenic with BALB/cAn, differing in the region of chromosome 6 that controls expression of the V kappa polymorphisms and the Lyt-2 and Lyt-3 T cell alloantigens. The complete nucleotide sequence of this cloned cDNA was determined and compared with the nucleotide sequences the most closely related BALB/c myeloma L chains known. Results indicated significant differences throughout the variable region, but particularly toward the 5' portion of the sequence. A probe corresponding to 200 bp of the 5' end of the cloned V kappa Ser cDNA was used in Southern hybridizations of restriction digests of liver DNA from a number of inbred, recombinant, and recombinant inbred strains. Under stringent hybridization conditions, one strongly-hybridizing fragment was observed in Bam HI, Hind III, and Eco RI digests, and based on the size of the fragments, strains could be organized into two groups. The presence of strongly hybridizing Bam HI, Hind III, and Eco RI fragments of 3.2, 2.8, and 2.1 kb, respectively, was found to correlate completely with expression by the strain of the IB-peptide and Efla markers. All nonexpressor strains yielded hybridizing fragments of 7.8, 8.4, and 2.8 kb, respectively. Possible explanations for strain- specific expression of V kappa Ser-associated phenotypic markers are

40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid (H3BO2), zinc salt. 721.3032 Section 721.3032 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3032 Boric acid (H3BO2),...

40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid (H3BO2), zinc salt. 721.3032 Section 721.3032 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3032 Boric acid (H3BO2),...

40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid (H3BO2), zinc salt. 721.3032 Section 721.3032 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3032 Boric acid (H3BO2),...

Infantile zinc deficiency: Association with autism spectrum disorders

PubMed Central

Yasuda, Hiroshi; Yoshida, Kazuya; Yasuda, Yuichi; Tsutsui, Toyoharu

2011-01-01

Elucidation of the pathogenesis and effective treatment of autism spectrum disorders is one of the challenges today. In this study, we examine hair zinc concentrations for 1,967 children with autistic disorders (1,553 males and 414 females), and show considerable association with zinc deficiency. Histogram of hair zinc concentration was non-symmetric with tailing in lower range, and 584 subjects were found to have lower zinc concentrations than −2 standard deviation level of its reference range (86.3–193ppm). The incidence rate of zinc deficiency in infant group aged 0–3 year-old was estimated 43.5 % in male and 52.5 % in female. The lowest zinc concentration of 10.7 ppm was detected in a 2-year-old boy, corresponding to about 1/12 of the control mean level. These findings suggest that infantile zinc deficiency may epigenetically contribute to the pathogenesis of autism and nutritional approach may yield a novel hope for its treatment and prevention. PMID:22355646

Zinc Signals and Immunity.

PubMed

Maywald, Martina; Wessels, Inga; Rink, Lothar

2017-10-24

Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

Zinc Signals and Immunity

PubMed Central

Maywald, Martina; Wessels, Inga; Rink, Lothar

2017-01-01

Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as “zinc waves”, and late homeostatic zinc signals regarding prolonged changes in intracellular zinc. PMID:29064429

NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia.

PubMed

Jang, Pil-Geum; Namkoong, Cherl; Kang, Gil Myoung; Hur, Man-Wook; Kim, Seung-Whan; Kim, Geun Hyang; Kang, Yeoungsup; Jeon, Min-Jae; Kim, Eun Hee; Lee, Myung-Shik; Karin, Michael; Baik, Ja-Hyun; Park, Joong-Yeol; Lee, Ki-Up; Kim, Young-Bum; Kim, Min-Seon

2010-03-26

Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-kappaB (NF-kappaB), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus. In parallel, administration of LPS and Tat increased hypothalamic pro-inflammatory cytokine production, which was abrogated by inhibition of hypothalamic NF-kappaB. In vitro, NF-kappaB activation directly stimulated the transcriptional activity of pro-opiomelanocortin (POMC), a precursor of anorexigenic melanocortin, and mediated the stimulatory effects of LPS, Tat, and pro-inflammatory cytokines on POMC transcription, implying the involvement of NF-kappaB in controlling feeding behavior. Consistently, hypothalamic injection of LPS and Tat caused a significant reduction in food intake and body weight, which was prevented by blockade of NF-kappaB and melanocortin. Furthermore, disruption of I kappaB kinase-beta, an upstream kinase of NF-kappaB, in POMC neurons attenuated LPS- and Tat-induced anorexia. These findings suggest that infection-associated anorexia and weight loss are mediated via NF-kappaB activation in hypothalamic POMC neurons. In addition, hypothalamic NF-kappaB was activated by leptin, an important anorexigenic hormone, and mediates leptin-stimulated POMC transcription, indicating that hypothalamic NF-kappaB also serves as a downstream signaling pathway of leptin.

Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-kappaB activation.

PubMed

Selvaraj, Suresh K; Prasadarao, Nemani V

2005-08-01

Phagocytes are well-known effectors of the innate immune system to produce proinflammatory cytokines and chemokines such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8 during infections. Here, we show that infection of monocytes with wild-type Escherichia coli K1, which causes meningitis in neonates, suppresses the production of cytokines and chemokines (TNF-alpha, regulated on activation, normal T expressed and secreted, macrophage-inflammatory protein-1beta, IL-1beta, and IL-8). In contrast, infection of monocytes with a mutant E. coli, which lacks outer membrane protein A (OmpA- E. coli) resulted in robust production of cytokines and chemokines. Wild-type E. coli K1 (OmpA+ E. coli) prevented the phosphorylation and its degradation of inhibitor of kappaB, thereby blocking the translocation of nuclear factor (NF)-kappaB to the nucleus. OmpA+ E. coli-infected cells, subsequently subjected to lipopolysaccharide challenge, were crippled severely in their ability to activate NF-kappaB to induce cytokine/chemokine production. Selective inhibitors of the extracellular signal-regulated kinase (ERK) 1/2 pathway and p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase, significantly reduced the activation of NF-kappaB and the production of cytokines and chemokines induced by OmpA- E. coli, indicating a role for these kinases in the NF-kappaB/cytokine pathway. It is interesting that the phosphorylation of ERK 1/2 and p38 MAPK was notably reduced in monocytes infected with OmpA+ E. coli when compared with monocytes infected with OmpA- E. coli, suggesting that the modulation of upstream events common for NF-kappaB and MAPKs by the bacterium is possible. The ability of OmpA+ E. coli K1 to inhibit the macrophage response temporarily may enable bacterial survival and growth within the host for the onset of meningitis by E. coli K1.

Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

PubMed

Kogan, Samuel; Sood, Aditya; Garnick, Mark S

2017-04-01

Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

Process for preparing zinc oxide-based sorbents

DOEpatents

Gangwal, Santosh Kumar [Cary, NC; Turk, Brian Scott [Durham, NC; Gupta, Raghubir Prasad [Durham, NC

2011-06-07

The disclosure relates to zinc oxide-based sorbents, and processes for preparing and using them. The sorbents are preferably used to remove one or more reduced sulfur species from gas streams. The sorbents comprise an active zinc component, optionally in combination with one or more promoter components and/or one or more substantially inert components. The active zinc component is a two phase material, consisting essentially of a zinc oxide (ZnO) phase and a zinc aluminate (ZnAl.sub.2O.sub.4) phase. Each of the two phases is characterized by a relatively small crystallite size of typically less than about 500 Angstroms. Preferably the sorbents are prepared by converting a precursor mixture, comprising a precipitated zinc oxide precursor and a precipitated aluminum oxide precursor, to the two-phase, active zinc oxide containing component.

Zinc

MedlinePlus

... Guidelines for Americans and the U.S. Department of Agriculture's MyPlate . Where can I find out more about ... on food sources of zinc: U.S. Department of Agriculture's (USDA’s) National Nutrient Database Nutrient List for zinc ( ...

Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

PubMed Central

Niederman, T M; Garcia, J V; Hastings, W R; Luria, S; Ratner, L

1992-01-01

Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W. C. Greene, N. Engl. J. Med. 324:308-317, 1991; S. M. Schnittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T. Folks, D. M. Powell, M. M. Lightfoote, S. Benn, M. A. Martin, and A. S. Fauci, Science 231:600-602, 1986; D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G. Nabel and D. Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T-cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex. Images PMID:1527859

High-frequency expression of a conserved kappa light-chain variable-region gene in chronic lymphocytic leukemia

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

Kipps, T.J.; Fong, S.; Tomhave, E.

Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a cross reactive idiotype on 48% of human IgM RF paraproteins, but does not react with IgM paraproteins without RF activity or substantially with normal pooled immunoglobulin. The 17.109-reactive idiotype is a marker for a kappa III variable-region gene, designated V/sub kappa/RF, that is conserved in outbred human populations. In a limited study of 31 CLL patients, the leukemic cells from 5 of 20 patients with kappa light chain-expressingmore » CLL were recognized by the 17.109 monoclonal antibody. Despite having malignant cells specifically reactive with this antibody, patients with 17.109-positive CLL did not have elevated serum levels of circulating antibody bearing 17.109-reactive determinants. Total RNAs isolated from the CLL B lymphocytes, or from hybridomas produced by fusing the CLL cells with the WI-L2-729-HF/sub 2/ cell line, were fractionated electrophoretically and examined by blot hybridization. Under stringent hybridization conditions capable of discerning a single base-pair mismatch, RNA from the 17.109-idiotype-positive CLL cells hybridized to synthetic oligonucleotide probes corresponding to framework and complementary-determining regions in the V/sub kappa/RF gene. The high frequency of the 17.109-associated idiotype and the V/sub kappa/RF gene in CLL suggests that the disease may arise from B lymphocytes that express a restricted set of inherited immunoglobulin variable-region genes with little or no somatic mutation.« less

Selectivity shifting behavior of Pd nanoparticles loaded zinc stannate/zinc oxide (Zn2SnO4/ZnO) nanowires sensors

NASA Astrophysics Data System (ADS)

Arafat, M. M.; Ong, J. Y.; Haseeb, A. S. M. A.

2018-03-01

In this research, the gas sensing behavior of Pd nanoparticles loaded zinc stannate/zinc oxide (Zn2SnO4/ZnO) nanowires were investigated. The Zn2SnO4/ZnO nanowires were grown on Au interdigitated alumina substrate by carbon assisted thermal evaporation process. Pd nanoparticles were loaded on the Zn2SnO4/ZnO nanowires by wet reduction process. The nanowires were characterized by X-ray diffractometer, field emission scanning electron microscope and energy dispersive X-ray spectroscope. The Zn2SnO4/ZnO and Pd nanoparticles loaded Zn2SnO4/ZnO nanowires were investigated for detecting H2, H2S and C2H5OH gases in N2 background. Results revealed that the average diameter and length of as-grown Zn2SnO4/ZnO nanowires were 74 nm and 30 μm, respectively. During wet reduction process,Pd particles having size of 20-60 nm were evenly distributed on the Zn2SnO4/ZnO nanowires. The Zn2SnO4/ZnO nanowires based sensors showed selective response towards C2H5OH whereas Pd nanoparticles loaded Zn2SnO4/ZnO nanowires showed selective response towards H2. The recovery time of the sensors reduced with Pd loading on Zn2SnO4/ZnO nanowires. A mechanism is proposed to elucidate the gas sensing mechanism of Pd nanoparticles loaded Zn2SnO4/ZnO nanowires.

Serum zinc, copper, retinol-binding protein, prealbumin, and ceruloplasmin concentrations in infants receiving intravenous zinc and copper supplementation.

PubMed

Lockitch, G; Godolphin, W; Pendray, M R; Riddell, D; Quigley, G

1983-02-01

One hundred twenty-seven newborn infants requiring parenteral nutrition were randomly assigned to receive differing amounts of zinc (40 to 400 micrograms/kg/day) and copper (20 or 40 micrograms/kg/day) supplementation within five birth weight groups (600 to 2,500 gm). The serum zinc concentration remained relatively constant in the group receiving the most zinc supplementation after two weeks of therapy, but declined sharply in the groups receiving less supplementation. No effect of increased copper intake was noted on ceruloplasmin values, but a difference in serum copper concentrations was noted at two weeks. No correlation was noted between serum zinc and copper values or among those for serum zinc, retinol-binding protein, and prealbumin. Reference ranges were defined for serum zinc, copper, retinol-binding protein, prealbumin, and ceruloplasmin in the preterm infant.