Post-transcriptional gene expression control by NANOS is up-regulated and functionally important in pRb-deficient cells

PubMed Central

Miles, Wayne O; Korenjak, Michael; Griffiths, Lyra M; Dyer, Michael A; Provero, Paolo; Dyson, Nicholas J

2014-01-01

Inactivation of the retinoblastoma tumor suppressor (pRb) is a common oncogenic event that alters the expression of genes important for cell cycle progression, senescence, and apoptosis. However, in many contexts, the properties of pRb-deficient cells are similar to wild-type cells suggesting there may be processes that counterbalance the transcriptional changes associated with pRb inactivation. Therefore, we have looked for sets of evolutionary conserved, functionally related genes that are direct targets of pRb/E2F proteins. We show that the expression of NANOS, a key facilitator of the Pumilio (PUM) post-transcriptional repressor complex, is directly repressed by pRb/E2F in flies and humans. In both species, NANOS expression increases following inactivation of pRb/RBF1 and becomes important for tissue homeostasis. By analyzing datasets from normal retinal tissue and pRb-null retinoblastomas, we find a strong enrichment for putative PUM substrates among genes de-regulated in tumors. These include pro-apoptotic genes that are transcriptionally down-regulated upon pRb loss, and we characterize two such candidates, MAP2K3 and MAP3K1, as direct PUM substrates. Our data suggest that NANOS increases in importance in pRb-deficient cells and helps to maintain homeostasis by repressing the translation of transcripts containing PUM Regulatory Elements (PRE). PMID:25100735

Post-transcriptional gene expression control by NANOS is up-regulated and functionally important in pRb-deficient cells.

PubMed

Miles, Wayne O; Korenjak, Michael; Griffiths, Lyra M; Dyer, Michael A; Provero, Paolo; Dyson, Nicholas J

2014-10-01

Inactivation of the retinoblastoma tumor suppressor (pRb) is a common oncogenic event that alters the expression of genes important for cell cycle progression, senescence, and apoptosis. However, in many contexts, the properties of pRb-deficient cells are similar to wild-type cells suggesting there may be processes that counterbalance the transcriptional changes associated with pRb inactivation. Therefore, we have looked for sets of evolutionary conserved, functionally related genes that are direct targets of pRb/E2F proteins. We show that the expression of NANOS, a key facilitator of the Pumilio (PUM) post-transcriptional repressor complex, is directly repressed by pRb/E2F in flies and humans. In both species, NANOS expression increases following inactivation of pRb/RBF1 and becomes important for tissue homeostasis. By analyzing datasets from normal retinal tissue and pRb-null retinoblastomas, we find a strong enrichment for putative PUM substrates among genes de-regulated in tumors. These include pro-apoptotic genes that are transcriptionally down-regulated upon pRb loss, and we characterize two such candidates, MAP2K3 and MAP3K1, as direct PUM substrates. Our data suggest that NANOS increases in importance in pRb-deficient cells and helps to maintain homeostasis by repressing the translation of transcripts containing PUM Regulatory Elements (PRE). © 2014 The Authors.

THE ROLE OF THE RETINOBLASTOMA/E2F1 TUMOR SUPPRESSOR PATHWAY IN THE LESION RECOGNITION STEP OF NUCLEOTIDE EXCISION REPAIR

PubMed Central

Lin, Patrick S.; McPherson, Lisa A.; Chen, Aubrey Y.; Sage, Julien; Ford, James M.

2009-01-01

The retinoblastoma Rb/E2F tumor suppressor pathway plays a major role in the regulation of mammalian cell cycle progression. The pRb protein, along with closely related proteins p107 and p130, exerts its anti-proliferative effects by binding to the E2F family of transcription factors known to regulate essential genes throughout the cell cycle. We sought to investigate the role of the Rb/E2F1 pathway in the lesion recognition step of nucleotide excision repair (NER) in mouse embryonic fibroblasts (MEFs). Rb−/−;p107−/−;p130−/− MEFs repaired both cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PPs) at higher efficiency than did wildtype cells following UV-C irradiation. The expression of damaged DNA binding gene DDB2 involved in the DNA lesion recognition step was elevated in the Rb family-deficient MEFs. To determine if the enhanced DNA repair in the absence of the Rb gene family is due to the derepression of E2F1, we assayed the ability of E2F1-deficient cells to repair damaged DNA and demonstrated that E2F1−/− MEFs are impaired for the removal of both CPDs and 6-4PPs. Furthermore, wildtype cells induced a higher expression of DDB2 and xeroderma pigmentosum gene XPC transcript levels than did E2F1−/− cells following UV-C irradiation. Using an E2F SiteScan algorithm, we uncovered a putative E2F-responsive element in the XPC promoter upstream of the transcription start site. We showed with chromatin immunoprecipitation assays the binding of E2F1 to the XPC promoter in a UV-dependent manner, suggesting that E2F1 is a transcriptional regulator of XPC. Our study identifies a novel E2F1 gene target and further supports the growing body of evidence that the Rb/E2F1 tumor suppressor pathway is involved in the regulation of the DNA lesion recognition step of nucleotide excision repair. PMID:19376752

Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family

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

Liban, Tyler J.; Medina, Edgar M.; Tripathi, Sarvind

The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD–CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences formore » different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein–E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.« less

Tandem E2F Binding Sites in the Promoter of the p107 Cell Cycle Regulator Control p107 Expression and Its Cellular Functions

PubMed Central

Burkhart, Deborah L.; Wirt, Stacey E.; Zmoos, Anne-Flore; Kareta, Michael S.; Sage, Julien

2010-01-01

The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells. PMID:20585628

Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.

PubMed

Ferrari, Roberto; Gou, Dawei; Jawdekar, Gauri; Johnson, Sarah A; Nava, Miguel; Su, Trent; Yousef, Ahmed F; Zemke, Nathan R; Pellegrini, Matteo; Kurdistani, Siavash K; Berk, Arnold J

2014-11-12

Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians.

PubMed

Zhu, Shu Jun; Pearson, Bret J

2013-01-15

Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are well known for their regenerative abilities, which rely on a large population of pluripotent adult stem cells. However, the mechanisms by which planarians maintain a precise population of adult stem cells while balancing proliferation and cell death, remain to be elucidated. Here we have identified, characterized, and functionally tested the core Retinoblastoma (Rb) pathway components in planarian adult stem cell biology. The Rb pathway is an ancient and conserved mechanism of proliferation control from plants to animals and is composed of three core components: an Rb protein, and a transcription factor heterodimer of E2F and DP proteins. Although the planarian genome contains all components of the Rb pathway, we found that they have undergone gene loss from the ancestral state, similar to other species in their phylum. The single Rb homolog (Smed-Rb) was highly expressed in planarian stem cells and was required for stem cell maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show that planarians and their phylum have undergone the most severe reduction in E2F genes observed thus far, and the single remaining E2F was predicted to be a repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper-proliferation. Finally, we showed that known Rb-interacting genes in other systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar to Rb in expression and phenotypes when knocked down by RNAi, suggesting that these established interactions with Rb may also be conserved in planarians. Together, these results showed that planarians use the conserved components of the Rb tumor suppressor pathway to control proliferation and cell survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Papillomavirus E7 protein binding to the retinoblastoma protein is not required for viral induction of warts.

PubMed Central

Defeo-Jones, D; Vuocolo, G A; Haskell, K M; Hanobik, M G; Kiefer, D M; McAvoy, E M; Ivey-Hoyle, M; Brandsma, J L; Oliff, A; Jones, R E

1993-01-01

Human papillomaviruses (HPVs) are the etiologic agents responsible for benign epithelial proliferative disorders including genital warts and are a contributory factor in the pathogenesis of cervical cancer. HPVs demonstrate strict species and cell-type specificity, which is manifested by the inability of these viruses to induce disease in any species other than humans. The natural history of HPV infection in humans is closely mimicked by cottontail rabbit papillomavirus (CRPV) infection in domestic laboratory rabbits. The CRPV E7 gene is known to play an essential role in virus-mediated induction of papillomas. We now show by mutational analysis that the CRPV E7 protein's biochemical and biological properties, including binding to the retinoblastoma suppressor protein (pRB), transcription factor E2F transactivation of the adenovirus E2 promoter, disruption of pRB-E2F complexes, and cellular transformation as measured by growth in soft agar, mimic those of the HPV E7 protein. Intradermal injection of CRPV DNA lacking E7 gene sequences critical for the binding of the CRPV E7 protein to pRB induced papillomas in rabbits. These studies indicate that E7 protein binding to pRB is not required in the molecular pathogenesis of virally induced warts and suggest that other properties intrinsic to the E7 protein are necessary for papilloma formation. Images PMID:8380462

The DREAM complex: Master coordinator of cell cycle dependent gene expression

PubMed Central

Sadasivam, Subhashini; DeCaprio, James A.

2014-01-01

Preface The dimerization partner (DP), retinoblastoma (RB)-like, E2F and MuvB (DREAM) complex provides a previously unsuspected unifying role in the cell cycle by directly linking p130, p107, E2F, BMYB and FOXM1. DREAM mediates gene repression during G0 and coordinates periodic gene expression with peaks during G1/S and G2/M. Perturbations in DREAM regulation shift the balance from quiescence towards proliferation and contribute to increased mitotic gene expression levels frequently observed in cancers with poor prognosis. PMID:23842645

Pumilio and nanos RNA-binding proteins counterbalance the transcriptional consequences of RB1 inactivation

PubMed Central

Miles, Wayne O; Dyson, Nicholas J

2014-01-01

The ability of the retinoblastoma protein (RB) tumor suppressor to repress transcription stimulated by the E2 promoter binding factors (E2F) is integral to its biological functions. Our recent report described a conserved feedback mechanism mediated by the RNA-binding proteins Pumilio and Nanos that increases in importance following RB loss and helps cells to tolerate deregulated E2F. PMID:27308363

Pumilio and nanos RNA-binding proteins counterbalance the transcriptional consequences of RB1 inactivation.

PubMed

Miles, Wayne O; Dyson, Nicholas J

2014-01-01

The ability of the retinoblastoma protein (RB) tumor suppressor to repress transcription stimulated by the E2 promoter binding factors (E2F) is integral to its biological functions. Our recent report described a conserved feedback mechanism mediated by the RNA-binding proteins Pumilio and Nanos that increases in importance following RB loss and helps cells to tolerate deregulated E2F.

Magnetic Trapping of Atomic Nitrogen (14N) and Cotrapping of NH (X3sigma)

DTIC Science & Technology

2008-11-12

online Diagram of trapping apparatus. The...rb .u ni ts ) Wave number - 48375 (cm-1) In te gr at ed N itr og en F lu or es ce nc e (a rb .u ni ts ) FIG. 2. Color online Integrated nitrogen...nsec) N F lu or es ce nc e (a rb .u ni ts ) (a) (b) N H F lu or es ce nc e (a rb .u ni ts ) FIG. 4. Color online Cotrapping of N and NH, a

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

DTIC Science & Technology

2017-10-01

interaction will lead to enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified...relevant for CCNE1-amplified ovarian tumors which are dependent on hyperactive HR and are sensitive to suppression of BRCA1. 15. SUBJECT TERMS Ovarian...enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third

Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells.

PubMed

Kranenburg, O; Scharnhorst, V; Van der Eb, A J; Zantema, A

1995-10-01

Studies on the molecular mechanisms underlying neuronal differentiation are frequently performed using cell lines established from neuroblastomas. In this study we have used mouse N1E-115 neuroblastoma cells that undergo neuronal differentiation in response to DMSO. During differentiation, cyclin-dependent kinase (cdk) activities decline and phosphorylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss of cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27KIP1 and concurrent loss of cdk4 phosphorylation. Moreover, neuronal differentiation can be induced by overexpression of p27KIP1 or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differentiation.

Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells

PubMed Central

1995-01-01

Studies on the molecular mechanisms underlying neuronal differentiation are frequently performed using cell lines established from neuroblastomas. In this study we have used mouse N1E-115 neuroblastoma cells that undergo neuronal differentiation in response to DMSO. During differentiation, cyclin-dependent kinase (cdk) activities decline and phosphorylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss of cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27KIP1 and concurrent loss of cdk4 phosphorylation. Moreover, neuronal differentiation can be induced by overexpression of p27KIP1 or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differentiation. PMID:7559779

HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4+ T cells

PubMed Central

Kawatsuki, A; Yasunaga, J-i; Mitobe, Y; Green, PL; Matsuoka, M

2016-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that induces a fatal T-cell malignancy, adult T-cell leukemia (ATL). Among several regulatory/accessory genes in HTLV-1, HTLV-1 bZIP factor (HBZ) is the only viral gene constitutively expressed in infected cells. Our previous study showed that HBZ functions in two different molecular forms, HBZ protein and HBZ RNA. In this study, we show that HBZ protein targets retinoblastoma protein (Rb), which is a critical tumor suppressor in many types of cancers. HBZ protein interacts with the Rb/E2F-1 complex and activates the transcription of E2F-target genes associated with cell cycle progression and apoptosis. Mouse primary CD4+ T cells transduced with HBZ show accelerated G1/S transition and apoptosis, and importantly, T cells from HBZ transgenic (HBZ-Tg) mice also demonstrate enhanced cell proliferation and apoptosis. To evaluate the functions of HBZ protein alone in vivo, we generated a new transgenic mouse strain that expresses HBZ mRNA altered by silent mutations but encoding intact protein. In these mice, the numbers of effector/memory and Foxp3+ T cells were increased, and genes associated with proliferation and apoptosis were upregulated. This study shows that HBZ protein promotes cell proliferation and apoptosis in primary CD4+ T cells through activation of the Rb/E2F pathway, and that HBZ protein also confers onto CD4+ T-cell immunophenotype similar to those of ATL cells, suggesting that HBZ protein has important roles in dysregulation of CD4+ T cells infected with HTLV-1. PMID:26804169

The DREAM complex through its subunit Lin37 cooperates with Rb to initiate quiescence

PubMed Central

Mages, Christina FS; Wintsche, Axel; Bernhart, Stephan H

2017-01-01

The retinoblastoma Rb protein is an important factor controlling the cell cycle. Yet, mammalian cells carrying Rb deletions are still able to arrest under growth-limiting conditions. The Rb-related proteins p107 and p130, which are components of the DREAM complex, had been suggested to be responsible for a continued ability to arrest by inhibiting E2f activity and by recruiting chromatin-modifying enzymes. Here, we show that p130 and p107 are not sufficient for DREAM-dependent repression. We identify the MuvB protein Lin37 as an essential factor for DREAM function. Cells not expressing Lin37 proliferate normally, but DREAM completely loses its ability to repress genes in G0/G1 while all remaining subunits, including p130/p107, still bind to target gene promoters. Furthermore, cells lacking both Rb and Lin37 are incapable of exiting the cell cycle. Thus, Lin37 is an essential component of DREAM that cooperates with Rb to induce quiescence. PMID:28920576

THE E2/FRB PATHWAY REGULATION OF DNA REPLICATION AND PROTEIN BIOSYNTHESIS

EPA Science Inventory

The E2F/Rb pathway plays a pivotal role in the control of cell cycle progression and regulates the expression of genes required for Gl/S transition. Our study examines the genomic response in Drosophila embryos after overexpression and mutation of E2F/Rb pathway molecules. Hierar...

Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

PubMed Central

Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin; Hawley, Teresa; Catron, Mackenzie; Lichauco, Arturo; Cabrera-Luque, Juan; Yuen, Tracy; Rowitch, David; Gallo, Vittorio

2016-01-01

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI. PMID:27991597

Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

PubMed

Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

Signalling In The Epidermis: The E2f Cell Cycle Regulatory Pathway In Epidermal Morphogenesis, Regeneration And Transformation

PubMed Central

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis. PMID:15951853

Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.

PubMed

Naqsh e Zahra, Syeda; Khattak, Naureen Aslam; Mir, Asif

2013-01-01

Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely to be provide a gateway for developing computer aided drug designing.

A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer.

PubMed

Malorni, Luca; Piazza, Silvano; Ciani, Yari; Guarducci, Cristina; Bonechi, Martina; Biagioni, Chiara; Hart, Christopher D; Verardo, Roberto; Di Leo, Angelo; Migliaccio, Ilenia

2016-09-13

Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.

Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis

PubMed Central

Mori, Munemasa; Hazan, Renin; Danielian, Paul S.; Mahoney, John E.; Li, Huijun; Lu, Jining; Miller, Emily S.; Zhu, Xueliang; Lees, Jacqueline A.; Cardoso, Wellington V.

2017-01-01

Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4. After inducing a transcriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis. Thus, E2f4 integrates nuclear and previously unsuspected cytoplasmic events of centriole amplification, providing new perspectives for the understanding of normal ciliogenesis, ciliopathies and cancer. PMID:28675157

DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

PubMed

Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

2007-04-01

The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

Structural and Biochemical Insights into MLL1 Core Complex Assembly

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

Avdic, Vanja; Zhang, Pamela; Lanouette, Sylvain

2012-05-02

Histone H3 Lys-4 methylation is predominantly catalyzed by a family of methyltransferases whose enzymatic activity depends on their interaction with a three-subunit complex composed of WDR5, RbBP5, and Ash2L. Here, we report that a segment of 50 residues of RbBP5 bridges the Ash2L C-terminal domain to WDR5. The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5s {beta}-propeller domain. RbBP5 engages in several hydrogen bonds and van der Waals contacts within a V-shaped cleft formed by the junction of two blades on WDR5. Mutational analysesmore » of both the WDR5 V-shaped cleft and RbBP5 residues reveal that the interactions between RbBP5 and WDR5 are important for the stimulation of MLL1 methyltransferase activity. Overall, this study provides the structural basis underlying the formation of the WDR5-RbBP5 subcomplex and further highlight the crucial role of WDR5 in scaffolding the MLL1 core complex.« less

Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.

PubMed

Alqarni, Saad S M; Murthy, Andal; Zhang, Wei; Przewloka, Marcin R; Silva, Ana P G; Watson, Aleksandra A; Lejon, Sara; Pei, Xue Y; Smits, Arne H; Kloet, Susan L; Wang, Hongxin; Shepherd, Nicholas E; Stokes, Philippa H; Blobel, Gerd A; Vermeulen, Michiel; Glover, David M; Mackay, Joel P; Laue, Ernest D

2014-08-08

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular pathways: regulation of metabolism by RB.

PubMed

Clem, Brian F; Chesney, Jason

2012-11-15

The discovery of the retinoblastoma (RB-1) gene as a tumor suppressor that is disrupted in a majority of human cancers either via direct or indirect genetic alterations has resulted in increased interest in its functions and downstream effectors. Although the canonical pathway that links this tumor suppressor to human cancers details its interaction with the E2F transcription factors and cell-cycle progression, recent studies have shown an essential role for RB-1 in the suppression of glycolytic and glutaminolytic metabolism. Characterization of the precise metabolic transporters and enzymes suppressed by the RB-E2F axis should enable the identification of small molecule antagonists that have selective and potent antitumor properties. ©2012 AACR.

Elliptic Integrals in the Minkowski Plane

DTIC Science & Technology

1991-05-09

factorial Pochhammer notation F(a + k) (a)k - (a) Let F(a, b , c denote the hypergeometric function. Assume c - a - b = d , where d is a positive...integer. Then in a neighborhood of C = 1 , ((d) F(a+ b+d) d-1 (a)n (b)n )n(22) F(a , b , a + b + d , () = E~ )rb+ 0-’)n( ) r(a +d) r(b +d) n =O0( ’d’ n...axes a , b and eccentriaty e = c where c = Ta2 - b2 . Let P denote one of the foci of the ellipse. Then (26) 1 1 1 2 and(26) ar+(K, P) 2 -er F(- 1

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

PubMed Central

Andrejka, Laura; Wen, Hong; Ashton, Jonathan; Grant, Megan; Iori, Kevin; Wang, Amy; Manak, J. Robert; Lipsick, Joseph S.

2011-01-01

Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within the same highly conserved multiprotein transcriptional repressor complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as Drosophila Rb E2F and Myb-interacting proteins (dREAM). We now report that the animal-specific C terminus of Drosophila Myb but not the more highly conserved N-terminal DNA-binding domain is necessary and sufficient for (i) adult viability, (ii) proper localization to chromosomes in vivo, (iii) regulation of gene expression in vivo, and (iv) interaction with the highly conserved core of the MuvB/dREAM transcriptional repressor complex. In addition, we have identified a conserved peptide motif that is required for this interaction. Our results imply that an ancient function of Myb in regulating G2/M genes in both plants and animals appears to have been transferred from the DNA-binding domain to the animal-specific C-terminal domain. Increased expression of B-MYB/MYBL2, the human ortholog of Drosophila Myb, correlates with poor prognosis in human patients with breast cancer. Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics. PMID:21969598

Comparison of the fluorescence kinetics of detergent-solubilized and membrane-reconstituted LH2 complexes from Rps. acidophila and Rb. sphaeroides.

PubMed

Pflock, Tobias; Dezi, Manuela; Venturoli, Giovanni; Cogdell, Richard J; Köhler, Jürgen; Oellerich, Silke

2008-01-01

Picosecond time-resolved fluorescence spectroscopy has been used in order to compare the fluorescence kinetics of detergent-solubilized and membrane-reconstituted light-harvesting 2 (LH2) complexes from the purple bacteria Rhodopseudomonas (Rps.) acidophila and Rhodobacter (Rb.) sphaeroides. LH2 complexes were reconstituted in phospholipid model membranes at different lipid:protein-ratios and all samples were studied exciting with a wide range of excitation densities. While the detergent-solubilized LH2 complexes from Rps. acidophila showed monoexponential decay kinetics (tau(f )= 980 ps) for excitation densities of up to 3.10(13) photons/(pulse.cm(2)), the membrane-reconstituted LH2 complexes showed multiexponential kinetics even at low excitation densities and high lipid:protein-ratios. The latter finding indicates an efficient clustering of LH2 complexes in the phospholipid membranes. Similar results were obtained for the LH2 complexes from Rb. sphaeroides.

Novel functions for the transcription factor E2F4 in development and disease

PubMed Central

Sage, Julien

2016-01-01

ABSTRACT The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration. PMID:27753528

Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.

PubMed

Khan, Mateen A; Ma, Jia; Walden, William E; Merrick, William C; Theil, Elizabeth C; Goss, Dixie J

2014-06-01

Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance of kinetics and stability, we now report rapid rates of protein/RNA complex assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response kinetics that coincide with the different iron responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so that at 50 µM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which suggests that both rate of assembly and stability of the complexes are important, and that allows this regulatory system to respond rapidly to change in cellular iron. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

PubMed

Lee, Tae J; Yao, Guang; Bennett, Dorothy C; Nevins, Joseph R; You, Lingchong

2010-09-21

The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.

Protection of Medical Equipment against Electromagnetic Pulse (EMP): phase I

DTIC Science & Technology

1986-06-12

case condition. The current in the power cord path due to the EMP pin threat is computed frorn: VEMP I(RS+RBI +RB2+RL+RB3 +ZC+RB4+R+RB5 R +RB6 + RB 7...base-emitter, causing darage. 44 I NN4154 100 B-C vEMP _ 2N4401 S B-E 2N4401 270 Figure 7.5 ESA: Patient monitor path to ground. 45 7.1.3 Foot Switch...computed from: VEMP Z Rs. RB) VVBD (7.5) 1800 = l(100 25) + 50 (7.6) The resulting threat current is 14A. The rectifier diode threshold is 3.7A at f

MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes.

PubMed

Wu, Jiangbin; Lv, Qing; He, Jie; Zhang, Haoxiang; Mei, Xueshuang; Cui, Kai; Huang, Nunu; Xie, Weidong; Xu, Naihan; Zhang, Yaou

2014-10-11

Accelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control. Overexpression of miR-188 inhibits cell proliferation, tumor colony formation and G1/S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G1/S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation. This study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G1/S related cyclin/CDKs and Rb/E2F signaling pathway.

RB Loss Promotes Prostate Cancer Metastasis

PubMed Central

Thangavel, Chellappagounder; Boopathi, Ettickan; Liu, Yi; Haber, Alex; Ertel, Adam; Bhardwaj, Anshul; Addya, Sankar; Williams, Noelle; Ciment, Stephen J.; Cotzia, Paolo; Dean, Jeffry L.; Snook, Adam; McNair, Chris; Price, Matt; Hernandez, James R.; Zhao, Shuang G.; Birbe, Ruth; McCarthy, James B.; Turley, Eva A.; Pienta, Kenneth J.; Feng, Felix Y.; Dicker, Adam P.; Knudsen, Karen E.; Den, Robert B.

2017-01-01

RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. PMID:27923835

Inhibition of E2F1 activity and cell cycle progression by arsenic via retinoblastoma protein.

PubMed

Sheldon, Lynn A

2017-01-01

The regulation of cell cycle progression by steroid hormones and growth factors is important for maintaining normal cellular processes including development and cell proliferation. Deregulated progression through the G1/S and G2/M cell cycle transitions can lead to uncontrolled cell proliferation and cancer. The transcription factor E2F1, a key cell cycle regulator, targets genes encoding proteins that regulate cell cycle progression through the G1/S transition as well as proteins important in DNA repair and apoptosis. E2F1 expression and activity is inhibited by inorganic arsenic (iAs) that has a dual role as a cancer therapeutic and as a toxin that leads to diseases including cancer. An understanding of what underlies this dichotomy will contribute to understanding how to use iAs as a more effective therapeutic and also how to treat cancers that iAs promotes. Here, we show that quiescent breast adenocarcinoma MCF-7 cells treated with 17-β estradiol (E2) progress through the cell cycle, but few cells treated with E2 + iAs progress from G1 into S-phase due to a block in cell cycle progression. Our data support a model in which iAs inhibits the dissociation of E2F1 from the tumor suppressor, retinoblastoma protein (pRB) due to changes in pRB phosphorylation which leads to decreased E2F1 transcriptional activity. These findings present an explanation for how iAs can disrupt cell cycle progression through E2F1-pRB and has implications for how iAs acts as a cancer therapeutic as well as how it may promote tumorigenesis through decreased DNA repair.

Proteomic analysis of the gamma human papillomavirus type 197 E6 and E7 associated cellular proteins

PubMed Central

Grace, Miranda; Munger, Karl

2016-01-01

Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing. To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex. Despite lacking a canonical retinoblastoma (RB1) tumor suppressor binding site, HPV197 E7 binds RB1 and activates E2F transcription. Hence, HPV197 E6 and E7 proteins interact with a similar set of cellular proteins as E6 and E7 proteins encoded by HPVs that have been linked to human carcinogenesis and/or have transforming activities in vitro. PMID:27771561

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

PubMed Central

Lorz, Corina; García-Escudero, Ramón; Segrelles, Carmen; Garín, Marina I.; Ariza, José M.; Santos, Mirentxu; Ruiz, Sergio; Lara, María F.; Martínez-Cruz, Ana B.; Costa, Clotilde; Buitrago-Pérez, Águeda; Saiz-Ladera, Cristina; Dueñas, Marta

2010-01-01

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis. Electronic supplementary material The online version of this article (doi:10.1007/s12015-010-9139-0) contains supplementary material, which is available to authorized users. PMID:20376578

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

PubMed Central

Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

2008-01-01

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

COMPLEX FLUORIDES OF PLUTONIUM AND AN ALKALI METAL

DOEpatents

Seaborg, G.T.

1960-08-01

A method is given for precipitating alkali metal plutonium fluorides. such as KPuF/sub 5/, KPu/sub 2/F/sub 9/, NaPuF/sub 5/, and RbPuF/sub 5/, from an aqueous plutonium(IV) solution by adding hydrogen fluoride and alkali-metal- fluoride.

Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

PubMed Central

Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

2012-01-01

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation.

PubMed

Jones, Robert A; Robinson, Tyler J; Liu, Jeff C; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E D; Pellecchia, Giovanna; Fell, Victoria L; Bae, SooIn; Muthuswamy, Lakshmi; Datti, Alessandro; Egan, Sean E; Jiang, Zhe; Leone, Gustavo; Bader, Gary D; Schimmer, Aaron; Zacksenhaus, Eldad

2016-10-03

Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low-like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration-approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC.

RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation

PubMed Central

Jones, Robert A.; Robinson, Tyler J.; Liu, Jeff C.; Shrestha, Mariusz; Voisin, Veronique; Ju, YoungJun; Chung, Philip E.D.; Pellecchia, Giovanna; Fell, Victoria L.; Bae, SooIn; Muthuswamy, Lakshmi; Egan, Sean E.; Jiang, Zhe; Leone, Gustavo; Bader, Gary D.; Schimmer, Aaron

2016-01-01

Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low–like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration–approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC. PMID:27571409

Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

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

Kurayoshi, Kenta; Ozono, Eiko; Iwanaga, Ritsuko

Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicidemore » gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter is activated by E2F only in cancer cells and therefore may be more cancer cell-specific than E2F1 promoter to drive gene expression. We show here that the ARF promoter has lower activity in normal growing fibroblasts and shows higher cancer cell-specificity compared to the E2F1 promoter. We also demonstrate that adenovirus expressing HSV-TK under the control of the ARF promoter shows lower cytotoxicity than that of the E2F1 promoter, in normal growing fibroblasts but has equivalent cytotoxicity in cancer cell lines. These results suggest that the ARF promoter, which is specifically activated by deregulated E2F activity, is an excellent candidate to drive therapeutic cytotoxic gene expression, specifically in cancer cells.« less

Inhibition of Retinoblastoma Protein Inactivation

DTIC Science & Technology

2017-11-01

SUBJECT TERMS cell cycle, Retinoblastoma protein, E2F transcription factor, high throughput screen, drug discovery, x-ray crystallography 16. SECURITY...screening by x-ray crystallography . 2.0 KEYWORDS Retinoblastoma (Rb) pathway, E2F transcription factor, cancer, cell-cycle inhibition, activation...modulation, inhibition, high throughput screening, fragment-based screening, x-ray crystallography . 3.0 ACCOMPLISHMENTS Summary: We

Erratum to: Magnetic field-induced modification of selection rules for Rb D2 line monitored by selective reflection from a vapor nanocell. Eur. Phys. J. D 71: 216 (2017), DOI: 10.1140/epjd/e2017-80291-6

NASA Astrophysics Data System (ADS)

Klinger, Emmanuel; Sargsyan, Armen; Tonoyan, Ara; Hakhumyan, Grant; Papoyan, Aram; Leroy, Claude; Sarkisyan, David

2018-01-01

The two technical points below are corrected by this erratum: 1. The publisher apologizes for a technical problem occurring in the scale numbering of Figure 2. The figure is corrected below. [Figure not available: see fulltext.] 2. Page 6, line 14 of the Conclusion section " F g = 2, m F = -3 → F e = 4, m F = -2" should be replaced by " F g = 2, m F = -2 → F e = 4, m F = -1".

Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.

PubMed

Avdulov, Svetlana; Li, Shunan; Michalek, Van; Burrichter, David; Peterson, Mark; Perlman, David M; Manivel, J Carlos; Sonenberg, Nahum; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2004-06-01

Common human malignancies acquire derangements of the translation initiation complex, eIF4F, but their functional significance is unknown. Hypophosphorylated 4E-BP proteins negatively regulate eIF4F assembly by sequestering its mRNA cap binding component eIF4E, whereas hyperphosphorylation abrogates this function. We found that breast carcinoma cells harbor increases in the eIF4F constituent eIF4GI and hyperphosphorylation of 4E-BP1 which are two alterations that activate eIF4F assembly. Ectopic expression of eIF4E in human mammary epithelial cells enabled clonal expansion and anchorage-independent growth. Transfer of 4E-BP1 phosphorylation site mutants into breast carcinoma cells suppressed their tumorigenicity, whereas loss of these 4E-BP1 phosphorylation site mutants accompanied spontaneous reversion to a malignant phenotype. Thus, eIF4F activation is an essential component of the malignant phenotype in breast carcinoma.

The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth.

PubMed

Brehm, A; Nielsen, S J; Miska, E A; McCance, D J; Reid, J L; Bannister, A J; Kouzarides, T

1999-05-04

E7 is the main transforming protein of human papilloma virus type 16 (HPV16) which is implicated in the formation of cervical cancer. The transforming activity of E7 has been attributed to its interaction with the retinoblastoma (Rb) tumour suppressor. However, Rb binding is not sufficient for transformation by E7. Mutations within a zinc finger domain, which is dispensable for Rb binding, also abolish E7 transformation functions. Here we show that HPV16 E7 associates with histone deacetylase in vitro and in vivo, via its zinc finger domain. Using a genetic screen, we identify Mi2beta, a component of the recently identified NURD histone deacetylase complex, as a protein that binds directly to the E7 zinc finger. A zinc finger point mutant which is unable to bind Mi2beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells. Our results suggest that the binding to a histone deacetylase complex is an important parameter for the growthpromoting activity of the human papilloma virus E7 protein. This provides the first indication that viral oncoproteins control cell proliferation by targeting deacetylation pathways.

RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells.

PubMed

Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland

2016-05-31

The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.

E2F transcription factors and digestive system malignancies: how much do we know?

PubMed

Evangelou, Konstantinos; Havaki, Sophia; Kotsinas, Athanassios

2014-08-07

The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell's fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ''Letter to the Editor'', we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.

Inhibition of Retinoblastoma Protein Inactivation

DTIC Science & Technology

2016-09-01

Retinoblastoma protein, E2F transcription factor, high throughput screen, drug discovery, x-ray crystallography 16. SECURITY CLASSIFICATION OF: 17...developed a method to perform fragment based screening by x-ray crystallography . 2.0 KEYWORDS Retinoblastoma (Rb) pathway, E2F transcription factor...cancer, cell-cycle inhibition, activation, modulation, inhibition, high throughput screening, fragment-based screening, x-ray crystallography

Hedgehog-mediated regulation of PPARγ controls metabolic patterns in neural precursors and shh-driven medulloblastoma.

PubMed

Bhatia, Bobby; Potts, Chad R; Guldal, Cemile; Choi, SunPhil; Korshunov, Andrey; Pfister, Stefan; Kenney, Anna M; Nahlé, Zaher A

2012-04-01

Sonic hedgehog (Shh) signaling is critical during development and its aberration is common across the spectrum of human malignancies. In the cerebellum, excessive activity of the Shh signaling pathway is associated with the devastating pediatric brain tumor medulloblastoma. We previously demonstrated that exaggerated de novo lipid synthesis is a hallmark of Shh-driven medulloblastoma and that hedgehog signaling inactivates the Rb/E2F tumor suppressor complex to promote lipogenesis. Indeed, such Shh-mediated metabolic reprogramming fuels tumor progression, in an E2F1- and FASN-dependent manner. Here, we show that the nutrient sensor PPARγ is a key component of the Shh metabolic network, particularly its regulation of glycolysis. Our data show that in primary cerebellar granule neural precursors (CGNPs), proposed medulloblastoma cells-of-origin, Shh stimulation elicits a marked induction of PPARγ alongside major glycolytic markers. This is also documented in the actively proliferating Shh-responsive CGNPs in the developing cerebellum, and PPARγ expression is strikingly elevated in Shh-driven medulloblastoma in vivo. Importantly, pharmacological blockade of PPARγ and/or Rb inactivation inhibits CGNP proliferation, drives medulloblastoma cell death and extends survival of medulloblastoma-bearing animals in vivo. This coupling of mitogenic Shh signaling to a major nutrient sensor and metabolic transcriptional regulator define a novel mechanism through which Shh signaling engages the nutrient sensing machinery in brain cancer, controls the cell cycle, and regulates the glycolytic index. This also reveals a dominant role of Shh in the etiology of glucose metabolism in medulloblastoma and underscores the function of the Shh → E2F1 → PPARγ axis in altering substrate utilization patterns in brain cancers in favor of tumor growth. These findings emphasize the value of PPARγ downstream of Shh as a global therapeutic target in hedgehog-dependent and/or Rb-inactivated tumors.

Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine

PubMed Central

Singh, Sandeep; Davis, Rebecca; Alamanda, Vignesh; Pireddu, Roberta; Pernazza, Daniel; Sebti, Said; Lawrence, Nicholas; Chellappan, Srikumar

2010-01-01

Metastatic melanoma is an aggressive cancer with very low response rate against conventional chemotherapeutic agents such as dacarbazine (DTIC). Inhibitor of Rb-Raf-1 interaction (RRD-251) was tested against the melanoma cell lines SK-MEL-28, SK-MEL-5 and SK-MEL-2. RRD-251 was found to be a potent inhibitor of melanoma cell proliferation, irrespective of V600E B-Raf mutation status of the cell lines. In a SK-MEL-28 xenograft experiment, RRD-251 exerted a significant suppression of tumor growth compared to vehicle (p=0.003). Similar to in vitro effects, tumors from RRD-251 treated animals showed decreased Rb-Raf-1 interaction in vivo. Growth suppressive effects of RRD-251 were associated with induction of apoptosis as well as a G1 arrest, with an accompanying decrease in S-phase cells. RRD-251 inhibited Rb phosphorylation, and downregulated E2F1 protein levels in these cells. Real-time PCR analysis showed that RRD-251 caused downregulation of cell cycle regulatory genes thymidylate synthase (TS) and cdc6 as well as anti-apoptotic gene Mcl-1. Combinatorial treatment of RRD-251 and DTIC resulted in a significantly higher apoptosis in DTIC resistant cell lines SK-MEL-28 and SK-MEL-5, as revealed by increased Caspase-3 activity and PARP cleavage. Since aberrant Rb/E2F pathway is associated with melanoma progression and resistance to apoptosis, these results suggest that the Rb-Raf-1 inhibitor could be an effective agent for melanoma treatment, either alone or in combination with DTIC. PMID:21139044

Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine.

PubMed

Singh, Sandeep; Davis, Rebecca; Alamanda, Vignesh; Pireddu, Roberta; Pernazza, Daniel; Sebti, Said; Lawrence, Nicholas; Chellappan, Srikumar

2010-12-01

Metastatic melanoma is an aggressive cancer with very low response rate against conventional chemotherapeutic agents such as dacarbazine (DTIC). Inhibitor of Rb-Raf-1 interaction RRD-251 was tested against the melanoma cell lines SK-MEL-28, SK-MEL-5, and SK-MEL-2. RRD-251 was found to be a potent inhibitor of melanoma cell proliferation, irrespective of V600E B-Raf mutation status of the cell lines. In a SK-MEL-28 xenograft experiment, RRD-251 exerted a significant suppression of tumor growth compared with vehicle (P = 0.003). Similar to in vitro effects, tumors from RRD-251-treated animals showed decreased Rb-Raf-1 interaction in vivo. Growth suppressive effects of RRD-251 were associated with induction of apoptosis as well as a G(1) arrest, with an accompanying decrease in S-phase cells. RRD-251 inhibited Rb phosphorylation and downregulated E2F1 protein levels in these cells. Real-time PCR analysis showed that RRD-251 caused downregulation of cell-cycle regulatory genes thymidylate synthase (TS) and cdc6 as well as the antiapoptotic gene Mcl-1. Combinatorial treatment of RRD-251 and DTIC resulted in a significantly higher apoptosis in DTIC resistant cell lines SK-MEL-28 and SK-MEL-5, as revealed by increased caspase-3 activity and PARP cleavage. Because aberrant Rb/E2F pathway is associated with melanoma progression and resistance to apoptosis, these results suggest that the Rb-Raf-1 inhibitor could be an effective agent for melanoma treatment, either alone or in combination with DTIC. ©2010 AACR.

Ectopic expression of necdin induces differentiation of mouse neuroblastoma cells.

PubMed

Kobayashi, Masakatsu; Taniura, Hideo; Yoshikawa, Kazuaki

2002-11-01

Necdin is expressed predominantly in postmitotic neurons, and ectopic expression of this protein strongly suppresses cell growth. Necdin has been implicated in the pathogenesis of Prader-Willi syndrome, a human neurodevelopmental disorder associated with genomic imprinting. Here we demonstrate that ectopic expression of necdin induces a neuronal phenotype in neuroblastoma cells. Necdin was undetectable in mouse neuroblastoma N1E-115 cells under undifferentiated and differentiated conditions. N1E-115 cells transfected with necdin cDNA showed morphological differentiation such as neurite outgrowth and expression of the synaptic marker proteins synaptotagmin and synaptophysin. In addition, Western blot analysis of the retinoblastoma protein (Rb) family members Rb, p130, and p107 revealed that necdin cDNA transfectants contained an increased level of p130 and a reduced level of p107, a pattern seen in differentiated G(0) cells. The transcription factors E2F1 and E2F4 physically interacted with necdin via their carboxyl-terminal transactivation domains, but only E2F1 abrogated necdin-induced growth arrest and neurite outgrowth of neuroblastoma cells. Overexpression of E2F1 in differentiated N1E-115 cells induced apoptosis, which was antagonized by co-expression of necdin. These results suggest that necdin promotes the differentiation and survival of neurons through its antagonistic interactions with E2F1.

Synthesis and structure resolution of RbLaF4.

PubMed

Rollet, Anne-Laure; Allix, Mathieu; Veron, Emmanuel; Deschamps, Michael; Montouillout, Valérie; Suchomel, Matthew R; Suard, Emmanuelle; Barre, Maud; Ocaña, Manuel; Sadoc, Aymeric; Boucher, Florent; Bessada, Catherine; Massiot, Dominique; Fayon, Franck

2012-02-20

The synthesis and structure resolution of RbLaF(4) are described. RbLaF(4) is synthesized by solid-state reaction between RbF and LaF(3) at 425 °C under a nonoxidizing atmosphere. Its crystal structure has been resolved by combining neutron and synchrotron powder diffraction data refinements (Pnma,a = 6.46281(2) Å, b = 3.86498(1) Å, c = 16.17629(4) Å, Z = 4). One-dimensional (87)Rb, (139)La, and (19)F MAS NMR spectra have been recorded and are in agreement with the proposed structural model. Assignment of the (19)F resonances is performed on the basis of both (19)F-(139)La J-coupling multiplet patterns observed in a heteronuclear DQ-filtered J-resolved spectrum and (19)F-(87)Rb HMQC MAS experiments. DFT calculations of both the (19)F isotropic chemical shieldings and the (87)Rb, (139)La electric field gradient tensors using the GIPAW and PAW methods implemented in the CASTEP code are in good agreement with the experimental values and support the proposed structural model. Finally, the conductivity of RbLaF(4) and luminescence properties of Eu-doped LaRbF(4) are investigated.

First-principles calculations of two cubic fluoropervskite compounds: RbFeF3 and RbNiF3

NASA Astrophysics Data System (ADS)

Mubarak, A. A.; Al-Omari, Saleh

2015-05-01

We present first-principles calculations of the structural, elastic, electronic, magnetic and optical properties for RbFeF3 and RbNiF3. The full-potential linear augmented plan wave (FP-LAPW) method within the density functional theory was utilized to perform the present calculations. We employed the generalized gradient approximation as exchange-correlation potential. It was found that the calculated analytical lattice parameters agree with previous studies. The analysis of elastic constants showed that the present compounds are elastically stable and anisotropic. Moreover, both compounds are classified as a ductile compound. The calculations of the band structure and density functional theory revealed that the RbFeF3 compound has a half-metallic behavior while the RbNiF3 compound has a semiconductor behavior with indirect (M-Γ) band gap. The ferromagnetic behavior was studied for both compounds. The optical properties were calculated for the radiation of up to 40 eV. A beneficial optics technology is predicted as revealed from the optical spectra.

The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth.

PubMed Central

Brehm, A; Nielsen, S J; Miska, E A; McCance, D J; Reid, J L; Bannister, A J; Kouzarides, T

1999-01-01

E7 is the main transforming protein of human papilloma virus type 16 (HPV16) which is implicated in the formation of cervical cancer. The transforming activity of E7 has been attributed to its interaction with the retinoblastoma (Rb) tumour suppressor. However, Rb binding is not sufficient for transformation by E7. Mutations within a zinc finger domain, which is dispensable for Rb binding, also abolish E7 transformation functions. Here we show that HPV16 E7 associates with histone deacetylase in vitro and in vivo, via its zinc finger domain. Using a genetic screen, we identify Mi2beta, a component of the recently identified NURD histone deacetylase complex, as a protein that binds directly to the E7 zinc finger. A zinc finger point mutant which is unable to bind Mi2beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells. Our results suggest that the binding to a histone deacetylase complex is an important parameter for the growthpromoting activity of the human papilloma virus E7 protein. This provides the first indication that viral oncoproteins control cell proliferation by targeting deacetylation pathways. PMID:10228159

Role of Acentric Displacements on the Crystal Structure and Second-Harmonic Generating Properties of RbPbCO3F and CsPbCO3F

PubMed Central

2015-01-01

Two lead fluorocarbonates, RbPbCO3F and CsPbCO3F, were synthesized and characterized. The materials were synthesized through solvothermal and conventional solid-state techniques. RbPbCO3F and CsPbCO3F were structurally characterized by single-crystal X-ray diffraction and exhibit three-dimensional (3D) crystal structures consisting of corner-shared PbO6F2 polyhedra. For RbPbCO3F, infrared and ultraviolet–visible spectroscopy and thermogravimetric and differential thermal analysis measurements were performed. RbPbCO3F is a new noncentrosymmetric material and crystallizes in the achiral and nonpolar space group P6̅m2 (crystal class 6̅m2). Powder second-harmonic generation (SHG) measurements on RbPbCO3F and CsPbCO3F using 1064 nm radiation revealed an SHG efficiency of approximately 250 and 300 × α-SiO2, respectively. Charge constants d33 of approximately 72 and 94 pm/V were obtained for RbPbCO3F and CsPbCO3F, respectively, through converse piezoelectric measurements. Electronic structure calculations indicate that the nonlinear optical response originates from the distorted PbO6F2 polyhedra, because of the even–odd parity mixing of the O 2p states with the nearly spherically symmetric 6s electrons of Pb2+. The degree of inversion symmetry breaking is quantified using a mode-polarization vector analysis and is correlated with cation size mismatch, from which it is possible to deduce the acentric properties of 3D alkali-metal fluorocarbonates. PMID:24867361

Breakpoint structure of the Anopheles gambiae 2Rb chromosomal inversion.

PubMed

Lobo, Neil F; Sangaré, Djibril M; Regier, Allison A; Reidenbach, Kyanne R; Bretz, David A; Sharakhova, Maria V; Emrich, Scott J; Traore, Sekou F; Costantini, Carlo; Besansky, Nora J; Collins, Frank H

2010-10-25

Alternative arrangements of chromosome 2 inversions in Anopheles gambiae are important sources of population structure, and are associated with adaptation to environmental heterogeneity. The forces responsible for their origin and maintenance are incompletely understood. Molecular characterization of inversion breakpoints provides insight into how they arose, and provides the basis for development of molecular karyotyping methods useful in future studies. Sequence comparison of regions near the cytological breakpoints of 2Rb allowed the molecular delineation of breakpoint boundaries. Comparisons were made between the standard 2R+b arrangement in the An. gambiae PEST reference genome and the inverted 2Rb arrangements in the An. gambiae M and S genome assemblies. Sequence differences between alternative 2Rb arrangements were exploited in the design of a PCR diagnostic assay, which was evaluated against the known chromosomal banding pattern of laboratory colonies and field-collected samples from Mali and Cameroon. The breakpoints of the 7.55 Mb 2Rb inversion are flanked by extensive runs of the same short (72 bp) tandemly organized sequence, which was likely responsible for chromosomal breakage and rearrangement. Application of the molecular diagnostic assay suggested that 2Rb has a single common origin in An. gambiae and its sibling species, Anopheles arabiensis, and also that the standard arrangement (2R+b) may have arisen twice through breakpoint reuse. The molecular diagnostic was reliable when applied to laboratory colonies, but its accuracy was lower in natural populations. The complex repetitive sequence flanking the 2Rb breakpoint region may be prone to structural and sequence-level instability. The 2Rb molecular diagnostic has immediate application in studies based on laboratory colonies, but its usefulness in natural populations awaits development of complementary molecular tools.

Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G1 by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter

PubMed Central

Cicatiello, Luigi; Addeo, Raffaele; Sasso, Annarita; Altucci, Lucia; Petrizzi, Valeria Belsito; Borgo, Raphaelle; Cancemi, Massimo; Caporali, Simona; Caristi, Silvana; Scafoglio, Claudio; Teti, Diana; Bresciani, Francesco; Perillo, Bruno; Weisz, Alessandro

2004-01-01

Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G1-phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids through a mechanism(s) that is not fully elucidated. We report here that CCND1 promoter activation by estrogens in human breast cancer cells is mediated by recruitment of a c-Jun/c-Fos/estrogen receptor α complex to the tetradecanoyl phorbol acetate-responsive element of the gene, together with Oct-1 to a site immediately adjacent. This process coincides with the release from the same DNA region of a transcriptional repressor complex including Yin-Yang 1 (YY1) and histone deacetylase 1 and is sufficient to induce the assembly of the basal transcription machinery on the promoter and to lead to initial cyclin D1 accumulation in the cell. Later on in estrogen stimulation, the cyclin D1/Cdk4 holoenzyme associates with the CCND1 promoter, where E2F and pRb can also be found, contributing to the long-lasting gene enhancement required to drive G1-phase completion. Interestingly, progesterone triggers similar regulatory events through its own NRs, suggesting that the gene regulation cascade described here represents a crossroad for the transcriptional control of G1-phase progression by different classes of NRs. PMID:15282324

Red-emitting phosphor Rb2TiF6:Mn4+ with high thermal-quenching resistance for wide color-gamut white light-emitting diodes

NASA Astrophysics Data System (ADS)

Wang, Zhengliang; Yang, Zhiyu; Tan, Huiying; Brik, Mikhail G.; Zhou, Qiang; Chen, Guo; Liang, Hongbin

2017-10-01

Red-emitting phosphor plays a critical role in improving performance of the phosphor-converted white light-emitting diodes (pc-WLEDs). Herein, a red-emitting phosphor, Rb2TiF6:Mn4+, was synthesized via the ion exchange method under mild condition. The crystal structure and morphology were characterized by the powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The Rietveld refinements of Rb2TiF6:Mn4+ indicate that this sample is of single phase with hexagonal crystal structure. The as-prepared Rb2TiF6:Mn4+ has sharp red emissions with broad excitation band at ∼460 nm. The luminescent behavior of Mn4+ was discussed in detail. The temperature-dependent emission spectra of Rb2TiF6:Mn4+ indicate that this phosphor shares high thermal quenching resistance and excellent color stability. A series of WLEDs with tunable color rendering index and color temperature were fabricated by combining commercial Y3Al5O12:Ce3+ and Rb2TiF6:Mn4+ on blue GaN-LED chips. With the addition of Rb2TiF6:Mn4+, WLED with wide gamut was obtained with low color temperature (3123 K), high color rendering index (91.5) and high luminous efficacy (187.9 lm/W). These findings show this phosphor could be a promising commercial red phosphor in wide color-gamut WLEDs.

Differentiation-associated microRNAs antagonize the Rb–E2F pathway to restrict proliferation

PubMed Central

Marzi, Matteo J.; Puggioni, Eleonora M. R.; Dall'Olio, Valentina; Bucci, Gabriele; Bernard, Loris; Bianchi, Fabrizio; Crescenzi, Marco

2012-01-01

The cancer-associated loss of microRNA (miRNA) expression leads to a proliferative advantage and aggressive behavior through largely unknown mechanisms. Here, we exploit a model system that recapitulates physiological terminal differentiation and its reversal upon oncogene expression to analyze coordinated mRNA/miRNA responses. The cell cycle reentry of myotubes, forced by the E1A oncogene, was associated with a pattern of mRNA/miRNA modulation that was largely reciprocal to that induced during the differentiation of myoblasts into myotubes. The E1A-induced mRNA response was preponderantly Retinoblastoma protein (Rb)-dependent. Conversely, the miRNA response was mostly Rb-independent and exerted through tissue-specific factors and Myc. A subset of these miRNAs (miR-1, miR-34, miR-22, miR-365, miR-29, miR-145, and Let-7) was shown to coordinately target Rb-dependent cell cycle and DNA replication mRNAs. Thus, a dual level of regulation—transcriptional regulation via Rb–E2F and posttranscriptional regulation via miRNAs—confers robustness to cell cycle control and provides a molecular basis to understand the role of miRNA subversion in cancer. PMID:23027903

Retinoblastoma protein (pRB) was significantly phosphorylated through a Ras-to-MAPK pathway in mutant K-ras stably transfected human adrenocortical cells.

PubMed

Chen, Y-F; Chiu, H-H; Wu, C-H; Wang, J-Y; Chen, F-M; Tzou, W-H; Shin, S-J; Lin, S-R

2003-10-01

Our previous studies have shown that the cell proliferation rate, mRNA levels of p450scc, p450c17, and 3betaHSD, and secretion of cortisol were significantly increased in human adrenocortical cells stably transfected with mutated K-ras expression plasmid "pK568MRSV" after being inducted with IPTG. In addition, the increased level was a time-dependent manner. However, the levels of p450, p450scc, p450c17, 3betaHSD, cortisol, and cell proliferation rate were inhibited by a MEK phospholation inhibitor, PD098059. The above results prove that mutated K-ras oncogene is able to regulate tumorigenesis and steroidogenesis through a Ras-RAF-MEK-MAPK signal transduction pathway. The aim of this study was to investigate regulated factors in this pathway and also examine whether the other signal transduction pathways or other moles involved in tumorigenesis or steroidogenesis. In the first year, we analyzed gene profiles of mutant K-ras-transfected adrenocortical cells by DNA microarray to determine the gene expression related to cell cycle, signal transduction, apoptosis, tumorigenesis, steroidogenesis, and other expressed sequence tag. After being affected by the K-ras mutant, gene expression was significantly increased in some upregulated genes. Human zinc-finger protein 22 increased by 28.5 times, Osteopontin increased by 5.8 times, LIM domain Kinase 2 (LIMK2) increased by 3.3 times, Homo sapiens dual-specificity tyrosine-(Y)-phosphorylation regulated Kinase 2 (DYRK2) increased by 2.2 times, and human syntaxin 3 increased by two times. On the other hand, significant decreases in gene expression were also observed in some downregulated genes. Retinoblastoma binding protein 1 (RBBP1) decreased by four times, Homo sapiens craniofacial development protein 1 (CFDP1) decreased by 2.4 times, DAP Kinase-related apoptosis-inducing protein Kinase 1 (DRAK1) decreased by 2.3 times, SKI-interacting protein (SKIP) decreased by 2.2 times, and human poly(A)-Binding protein (PABP) decreased by 2.1 times. In all significant differentially expressed genes, preliminary analysis by bioinformatics revealed that after induced K-ras mutant expression by isopropyl thiogalctoside (IPTG), the downregulation of RBBP1 gene was most correlated to cell proliferation. RBBP1 can bind with RB/E2F to form a mSIN3-HDAC complex, which induces cell cycle arrest in the G1/G0 stage by repressing transcription of E2F-regulated genes. The result of a Northern blot showed that RBBP1 were inhibited after an induction of IPTG for 36 h. Another Northern blot analysis proved that mRNA levels of cyclin D1 and c-myc increased in proportion to K-ras expression. Finally, Western blot was carried out, and the results showed that phosphorylated pRB also increased. Taken together, we infer that the mutant K-ras oncogene promoted the cells to proceed to the G1/S stage by the inhibiting the formation of RB/RBBP1-dependent repressor complex from binding with the SIN3-HDAC complex, which resulted in the acetylation of histone to active transcription of E2F-regulated genes. However, the roles of the other differentially expressed genes involved in cell proliferation, cell morphologic change, tumorigenesis, or steroidogenesis still need further investigation.

Evidence for Chemical and Electronic Nonuniformities in the Formation of the Interface of RbF-Treated Cu(In,Ga)Se2 with CdS.

PubMed

Nicoara, Nicoleta; Kunze, Thomas; Jackson, Philip; Hariskos, Dimitrios; Duarte, Roberto Félix; Wilks, Regan G; Witte, Wolfram; Bär, Marcus; Sadewasser, Sascha

2017-12-20

We report on the initial stages of CdS buffer layer formation on Cu(In,Ga)Se 2 (CIGSe) thin-film solar cell absorbers subjected to rubidium fluoride (RbF) postdeposition treatment (PDT). A detailed characterization of the CIGSe/CdS interface for different chemical bath deposition (CBD) times of the CdS layer is obtained from spatially resolved atomic and Kelvin probe force microscopy and laterally integrating X-ray spectroscopies. The observed spatial inhomogeneity in the interface's structural, chemical, and electronic properties of samples undergoing up to 3 min of CBD treatments is indicative of a complex interface formation including an incomplete coverage and/or nonuniform composition of the buffer layer. It is expected that this result impacts solar cell performance, in particular when reducing the CdS layer thickness (e.g., in an attempt to increase the collection in the ultraviolet wavelength region). Our work provides important findings on the absorber/buffer interface formation and reveals the underlying mechanism for limitations in the reduction of the CdS thickness, even when an alkali PDT is applied to the CIGSe absorber.

Light, rest mass and electric charge quanta all formed by neutrinos?

NASA Astrophysics Data System (ADS)

Chen, Shao-Guang

In high energy physics experiments the electric charge and rest mass of particles can commonly transform into the photons, vice versa. Its reason QFT can only give a vague answer: based on the particle creation and annihilation operators. There are not more clear answers or conjecture? At least, light, electric charge and rest mass should have a collective structure component, if not, the transformation is unable understanding. An elementary answer is that neutrino and antineutrino as their collective structure component. In the paper ‘Chen Qiliang & Wang Bin, The formation and characteristics of Chen Shaoguang's formula, China Science &Technology Overview 127101-103 (2011)’, the lowest energy state vertical polarized left spin 1/2 neutrino and right spin 1/2 antineutrino are just the left, right advance unit quanta la _{0}nuυ, ra nuυ _{0} and left, right back unit quanta lb (0) nuυ, rb nuυ (0) , it again compose into spin 1 unit photon la-ra _{0}nuυnuυ _{0} and back-photon lb-rb (0) nuυnuυ (0) , spin 0 unit rest mass ra-rb nuυ _{0}nuυ (0) and anti-mass la-lb _{0}nuυ (0) nuυ, spin 0 unit positive charge la-rb _{0}nuυnuυ (0) and negative charge ra-lb nuυ _{0} (0) nuυ. The physical vacuum is the even collocation of non-combinational nuυ _{0} or _{0}nuυ. It accord to the high energy physics experimental results of the transformation among the photons, masses quanta and charges quanta. In my paper ‘Quanta turn-advance ism, China Science && Technology Overview 131 192-210 (2011)’, QFT four-dimensional uncertainty principle and momentum-energy conservation law had been generalized as a five-dimensional equations: de Broglie wavelength as a position vector \\underline{q}= (i c t, r, s), momentum \\underline{P} = (i E / c, P, U c), \\underline{q} = i h / \\underline{P}, \\underline{q} \\underline{q} = 0, \\underline{P} \\underline{P} = 0, Sigma∑ \\underline{P} = \\underline{P} (0) . The five-dimensional time-space-spin had been quantized as a non-dot model basic cell. QFT is no longer with divergence difficulty by the non-dot model. It is mathematically easy that from five-dimensional equations deduce out the Dirac, Klein-Gordan, Maxwell equations and Lorentz force formula, but appear some new results. The interactions between _{0}nuυ, nuυ _{0}, (0) nuυ, nuυ (0) , i.e., force f = ± ( h c / 2 r (3) ) r cos thetaθ for r not equal to 0 and f = 0 for r = 0, f as the magnetic force makes the photons, rest mass and charge quanta automatically come into being and stabilize. CMB photon can be produced from many spin 1 unit photons by its statistical attraction. The explanation of abnormal magnetic moment and Lamb shift is more natural and simple only with the spin — the conjunction between turn and advance. Many testable results had been obtained. The la, ra, lb, rb exist on each direction of i, j, k, its mathematical describe is with five-dimension unit place vector \\underline{q} = (i c t, r, s) and momentum \\underline{P} = (i E t /c, P, U c). The left spin s is real number and right spin s is imaginary number, positive direction advance r is i (or j, k) and back direction advance r is -i (or -j, -k). For four la, ra, lb, rb the t and E are all the same, but P only absolute value are the same and turn- quantity U with the external interaction has the difference of left turn U = e and right turn U = \\underline{e}. Such as in i direction we get that la: \\underline{q} = (i c t, r, 0, 0, s ), \\underline{P} = (i E/c, P, 0, 0 , e c); ra: \\underline{q} = (i c t, r, 0, 0, i s), \\underline{P} = (i E/c, P, 0, 0, \\underline{e} c); lb: \\underline{q}=(i c t, - r, 0, 0, -s), \\underline{P} = (i E/c, -P, 0, 0, -e c); {rb}: \\underline{q} = (i c t, - r, 0, 0, - i s), \\underline{P} = (i E/c, -P, 0, 0, - \\underline{e} c); la-ra : \\underline{q} = (i 2 c t, 2 r, (1+i) s), \\underline{P} = ( i 2 E/c, 2 P, (e + \\underline{e}) c); lb-rb : \\underline{q} = (i 2 c t,-2 r, -(1 + i) s), \\underline{P} = (i 2 E/c, -2 P, -(e + \\underline{e}) c); ra-rb: \\underline{q} = (i c 2 t, 0, (i - i) s ), \\underline{P} = (i 2 E/c, 0, (\\underline{e} - \\underline{e}) c); la-lb: \\underline{q} = (i 2 c t, 0, (s - s)), \\underline{P} = (i 2 E/c, 0, (e - e) c); la-rb : \\underline{q} = (i c 2 t, 0, ( 1 - i ) s), \\underline{P} = (i 2 E/c, 0 , (e - \\underline{e}) c); ra-lb: \\underline{q} = (i 2 c t, 0, (i - 1 ) s), \\underline{P} = (i 2 E/c, 0, (\\underline{e} - e) c). Because of the vertical polarization of neutrinos, when momentum in reverse the turn-quantity also from left to right or from right to left, we get: \\underline{e} = - e. The turn-quantity U of la-rb or ra-lb equal to 2 e or -2 e, so that the turn-quantity U is just the electric quantity q, also is the reason that it call as the positive or negative charge quantum. The ra-rb or la-lb to be called the rest mass or the anti-mass quantum for its momentum and turn-quantity all equal to zero, it is at the absolute rest and absolute non-external-interaction (the gravitation caused by the ra or la inside bodies). The la-ra or lb-rb has the momentum 2 P or - 2 P and turn-quantity (e + \\underline{e}) or - (e + \\underline{e}) and is a pure momentum without external-interaction (the ra or la is the momentum with external-interaction), so to be called as the photon or back-photon. In the right turn Milky Way the number of right turn ra-rb much exceed the number of left turn la-lb, so ra-rb as the rest mass and la-lb as the anti-mass, and the physical vacuum is composed by right turn ra. But the number of la-rb and ra-lb at the same, who call as negative charge all ok, I take ra-lb as the negative charge. In a simple model the fifth-dimensional turn-quantity U c with the momentum P average share the general energy for ra , la, la-ra and lb-rb, but for the charge quanta la-rb and ra-lb the general energy all in the electric quantity q. For ra-rb quantum though the external-interaction of ra and rb to be counteracted and leads to its turn-quantity U = (e - e) = 0, but the general energy unable vanish and corresponding to the absolute values of turn-quantity [ e ] + [ - e ]= [ U ]. So the absolute value of turn-quantity [ U ] is called as the rest mass. The recombination: la-ra + lb-rb = la+ ra + lb + rb = la-lb + ra-rb = la+ ra +lb + rb = la-rb +ra-lb accord to the transformation among the photons, masses quanta and charges quanta. Furthermore, we get the light, charge and rest mass all come from the same ‘non-dot model’ basic cell turn-advance quanta. From \\underline{P} • \\underline{P} = 0 we get the rest mass of la or ra: m (0) = [ e ] = [ P/c ] = ±± (1/2 (1/2) ) E/c (2) ; the electric quantity of unit charge quanta la-rb or ra-lb q _{0} = 2 (1/2) 2 q (0) , q (0) is the electric quantity of unit turn-advance quanta. The ±± symbol shows that when m (0) to take positive value then the neutrinos and antineutrinos all have positive and negative energy level, when the energy E to take positive value then e to take positive value then \\underline{e} must take negative value. In the quantized inconsecutive time-space-spin with momentum and turn-quantity as the coordinates drawing the momentum-turn graphics are some points with certain distance. The rest mass m _{0} is the lowest energy state advance-back neutrinos pair ra-rb, when j direction have 2n ra or rb the i , k directions must have (2n-1), (2n+1) ra or rb for i, j, k three directions all matching into pair to eliminate the external interaction of electric quantity q (0) in ra. The spatial rest mass is: (n) m _{0} = (2n-1) 2n (2n+1) m (0) = 6, 60, 210, 504, 990 and 1716 m (0) . According to the uncertainty principle n large rest mass layer is more little and at the inside layer of particle. The spatial unit charge quanta e or \\underline{e} are composed by nine one-dimensional unit charge quanta la-rb or ra-lb because of the vertical polarization at each spatial direction there is only three states: the left, the right and the middle of left-right balance.

Enhance tumor radiosensitivity by intracellular delivery of eukaryotic translation initiation factor 4E binding proteins.

PubMed

Tian, Shuang; Li, Xiu-Li; Shi, Mei; Yao, Yuan-Qing; Li, Li-Wen; Xin, Xiao-Yan

2011-02-01

PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3-kinase)/Akt/mTOR (mammalian target of rapamycin) signaling pathway, which is commonly dysregulated in a broad array of human malignancies, controls the assembly of eukaryotic translation initiation factor 4F (eIF4F) complex through regulation of eIF4E binding proteins (4E-BPs) phosphorylation. And accumulated data over the past two decades implicated eIF4F complex as one of the promising targets for anticancer therapy. It has been confirmed that the translation initiation of mRNA coding for hypoxia-inducible factor-1α (HIF-1α) and survivin, which had been considered as the two major determinants of tumor radiosensitivity, are both controlled by eIF4F complex. Also, eIF4F complex controls the expression of VEGF and bFGF, the two well-known pro-angiogenic factors involved in developing radioresistance. Therefore eIF4F complex plays a pivotal role in regulation of radiosensitivity. In this article, we postulate that cell-permeable, phosphorylation-defective 4E-BP fusion proteins, which could be prepared by substituting the mTOR recognition motif located in N-terminal of 4E-BPs with protein transduction domain from HIV-1 TAT, HSV-1 VP22 or PTD4, could not only inhibit tumor growth but also enhance tumor response to radiation therapy through disruption of eIF4F complex assembly. In our opinion, the recombinant fusion proteins are superior to mTOR inhibitors for they do not cause immunosuppression, do not lead to Akt activation, and could be easily prepared by prokaryotic expression. If the hypothesis was proved to be practical, the cell-permeable, phosphorylation-defective 4E-BP fusion proteins would be widely used in clinical settings to improve tumor response to radiotherapy in the near future. Copyright © 2010 Elsevier Ltd. All rights reserved.

Two novel nonlinear optical carbonates in the deep-ultraviolet region: KBeCO3F and RbAlCO3F2

PubMed Central

Kang, Lei; Lin, Zheshuai; Qin, Jingui; Chen, Chuangtian

2013-01-01

With the rapid developments of the all-solid-state deep-ultraviolet (deep-UV) lasers, the good nonlinear optical (NLO) crystal applied in this spectral region is currently lacking. Here, we design two novel NLO carbonates KBeCO3F and RbAlCO3F2 from the first-principles theory implemented in the molecular engineering expert system especially for NLO crystals. Both structurally stable crystals possess very large energy band gaps and optical anisotropy, so they would become the very promising deep-UV NLO crystals alternative to KBBF. Recent experimental results on MNCO3F (M = K, Rb, Cs; N = Ca, Sr, Ba) not only confirm our calculations, but also suggest that the synthesis of the KBeCO3F and RbAlCO3F2 crystals is feasible. PMID:23455618

Structure of a human cap-dependent 48S translation pre-initiation complex

PubMed Central

Eliseev, Boris; Yeramala, Lahari; Leitner, Alexander; Karuppasamy, Manikandan; Raimondeau, Etienne; Huard, Karine; Alkalaeva, Elena; Aebersold, Ruedi

2018-01-01

Abstract Eukaryotic translation initiation is tightly regulated, requiring a set of conserved initiation factors (eIFs). Translation of a capped mRNA depends on the trimeric eIF4F complex and eIF4B to load the mRNA onto the 43S pre-initiation complex comprising 40S and initiation factors 1, 1A, 2, 3 and 5 as well as initiator-tRNA. Binding of the mRNA is followed by mRNA scanning in the 48S pre-initiation complex, until a start codon is recognised. Here, we use a reconstituted system to prepare human 48S complexes assembled on capped mRNA in the presence of eIF4B and eIF4F. The highly purified h-48S complexes are used for cross-linking/mass spectrometry, revealing the protein interaction network in this complex. We report the electron cryo-microscopy structure of the h-48S complex at 6.3 Å resolution. While the majority of eIF4B and eIF4F appear to be flexible with respect to the ribosome, additional density is detected at the entrance of the 40S mRNA channel which we attribute to the RNA-recognition motif of eIF4B. The eight core subunits of eIF3 are bound at the 40S solvent-exposed side, as well as the subunits eIF3d, eIF3b and eIF3i. elF2 and initiator-tRNA bound to the start codon are present at the 40S intersubunit side. This cryo-EM structure represents a molecular snap-shot revealing the h-48S complex following start codon recognition. PMID:29401259

Synthesis and characterization of new fluoride-containing manganese vanadates A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} (A=Rb, Cs) and Mn{sub 2}VO{sub 4}F

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

Sanjeewa, Liurukara D.; McGuire, Michael A.; Smith Pellizzeri, Tiffany M.

2016-09-15

Large single crystals of A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} (A=Rb, Cs) and Mn{sub 2}VO{sub 4}F were grown using a high-temperature (~600 °C) hydrothermal technique. Single crystal X-ray diffraction and powder X-ray diffraction were utilized to characterize the structures, which both possess MnO{sub 4}F{sub 2} building blocks. The A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} series crystallizes as a new structure type in space group Pbcn (No. 60), Z=4 (Rb{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2}: a=7.4389(17) Å, b=11.574(3) Å, c=10.914(2) Å; Cs{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2}: a=7.5615(15) Å, b=11.745(2) Å, c=11.127(2) Å). The structure is composed of zigzag chains ofmore » edge-sharing MnO{sub 4}F{sub 2} units running along the a-axis, and interconnected through V{sub 2}O{sub 7} pyrovanadate groups. Temperature dependent magnetic susceptibility measurements on this interesting one-dimensional structural feature based on Mn{sup 2+} indicated that Cs{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} is antiferromagnetic with a Neél temperature, T{sub N}=~3 K and a Weiss constant, θ, of −11.7(1) K. Raman and infrared spectra were also analyzed to identify the fundamental V–O vibrational modes in Cs{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2}. Mn{sub 2}(VO{sub 4})F crystalizes in the monoclinic space group of C2/c (no. 15), Z=8 with unit cell parameters of a=13.559(2) Å, b=6.8036(7) Å, c=10.1408(13) Å and β=116.16(3)°. The structure is associated with those of triplite and wagnerite. Dynamic fluorine disorder gives rise to complex alternating chains of five-and six-coordinate Mn{sup 2+}. These interpenetrating chains are additionally connected through isolated VO{sub 4} tetrahedra to form the condensed structure. - Graphical abstract: New vanadate fluorides A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} (A=Rb, Cs) and Mn{sub 2}(VO{sub 4})F have been synthesized hydrothermally. Upon cooling, the one-dimensional Mn(II) substructure results in antiferromagnetic ordering. Display Omitted - Highlights: • Single crystals of A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2}, (A=Rb, Cs) and Mn{sub 2}VO{sub 4}F were grown hydrothermally. • The use of fluoride mineralizers in the synthesis led to the formation of new compounds without OH{sup −} groups. • The structure of A{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} features zigzag chains of MnO{sub 4}F{sub 2} units. • Cs{sub 2}Mn{sub 2}V{sub 2}O{sub 7}F{sub 2} exhibits antiferromagnetic ordering with a Neel temperature of ~3 K. • Mn{sub 2}VO{sub 4}F possesses a condensed framework structure with disordered fluorine atoms.« less

Synthesis and characterization of new fluoride-containing manganese vanadates A2Mn2V2O7F2 (A=Rb, Cs) and Mn2VO4F

NASA Astrophysics Data System (ADS)

Sanjeewa, Liurukara D.; McGuire, Michael A.; Smith Pellizzeri, Tiffany M.; McMillen, Colin D.; Ovidiu Garlea, V.; Willett, Daniel; Chumanov, George; Kolis, Joseph W.

2016-09-01

Large single crystals of A2Mn2V2O7F2 (A=Rb, Cs) and Mn2VO4F were grown using a high-temperature (~600 °C) hydrothermal technique. Single crystal X-ray diffraction and powder X-ray diffraction were utilized to characterize the structures, which both possess MnO4F2 building blocks. The A2Mn2V2O7F2 series crystallizes as a new structure type in space group Pbcn (No. 60), Z=4 (Rb2Mn2V2O7F2: a=7.4389(17) Å, b=11.574(3) Å, c=10.914(2) Å; Cs2Mn2V2O7F2: a=7.5615(15) Å, b=11.745(2) Å, c=11.127(2) Å). The structure is composed of zigzag chains of edge-sharing MnO4F2 units running along the a-axis, and interconnected through V2O7 pyrovanadate groups. Temperature dependent magnetic susceptibility measurements on this interesting one-dimensional structural feature based on Mn2+ indicated that Cs2Mn2V2O7F2 is antiferromagnetic with a Neél temperature, TN=~3 K and a Weiss constant, θ, of -11.7(1) K. Raman and infrared spectra were also analyzed to identify the fundamental V-O vibrational modes in Cs2Mn2V2O7F2. Mn2(VO4)F crystalizes in the monoclinic space group of C2/c (no. 15), Z=8 with unit cell parameters of a=13.559(2) Å, b=6.8036(7) Å, c=10.1408(13) Å and β=116.16(3)°. The structure is associated with those of triplite and wagnerite. Dynamic fluorine disorder gives rise to complex alternating chains of five-and six-coordinate Mn2+. These interpenetrating chains are additionally connected through isolated VO4 tetrahedra to form the condensed structure.

Synthesis and characterization of new fluoride-containing manganese vanadates A 2Mn 2V 2O 7F 2 (A=Rb, Cs) and Mn 2VO 4F

DOE PAGES

Sanjeewa, Liurukara D.; McGuire, Michael A.; Smith Pellizzeri, Tiffany M.; ...

2016-05-10

In large single crystals of A 2Mn 2V 2O 7F 2 (A=Rb, Cs) and Mn 2VO 4F were grown using a high-temperature (~600 °C) hydrothermal technique. We utilized single crystal X-ray diffraction and powder X-ray diffraction in order to characterize the structures, which both possess MnO 4F 2 building blocks. The A 2Mn 2V 2O 7F 2 series crystallizes as a new structure type in space group Pbcn (No. 60), Z=4 (Rb 2Mn 2V 2O 7F 2: a=7.4389(17) Å, b=11.574(3) Å, c=10.914(2) Å; Cs 2Mn 2V 2O 7F 2: a=7.5615(15) Å, b=11.745(2) Å, c=11.127(2) Å). The structure is composed ofmore » zigzag chains of edge-sharing MnO 4F 2 units running along the a-axis, and interconnected through V 2O 7 pyrovanadate groups. Temperature dependent magnetic susceptibility measurements on this interesting one-dimensional structural feature based on Mn 2+ indicated that Cs 2Mn 2V 2O 7F 2 is antiferromagnetic with a Neél temperature, TN=~3 K and a Weiss constant, θ, of -11.7(1) K. Raman and infrared spectra were also analyzed to identify the fundamental V–O vibrational modes in Cs 2Mn 2V 2O 7F 2. Mn 2(VO 4)F crystalizes in the monoclinic space group of C2/c (no. 15), Z=8 with unit cell parameters of a=13.559(2) Å, b=6.8036(7) Å, c=10.1408(13) Å and β=116.16(3)°. The structure is associated with those of triplite and wagnerite. Dynamic fluorine disorder gives rise to complex alternating chains of five-and six-coordinate Mn 2+. Our interpenetrating chains are additionally connected through isolated VO 4 tetrahedra to form the condensed structure.« less

A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta.

PubMed

Zuo, Rujuan; Liu, Xiaohui; Wang, Wangsheng; Li, Wenjiao; Ying, Hao; Sun, Kang

2017-05-05

The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. Further studies revealed that, upon syncytialization, human chorionic gonadotropin reduced the phosphorylation of retinoblastoma protein (pRB) via activation of the cAMP/PKA pathway, which sequesters E2F transcription factor 1 (E2F1), the transcription factor for EZH2 expression. As a result of inactivation of the pRB-E2F1-EZH2 pathway, the repressive marker trimethylation of histone H3 lysine 27 at the 11β-HSD2 promoter is removed, which leads to the robust expression of 11β-HSD2 during syncytialization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Magnetic field-induced modification of selection rules for Rb D 2 line monitored by selective reflection from a vapor nanocell

NASA Astrophysics Data System (ADS)

Klinger, Emmanuel; Sargsyan, Armen; Tonoyan, Ara; Hakhumyan, Grant; Papoyan, Aram; Leroy, Claude; Sarkisyan, David

2017-08-01

Magnetic field-induced giant modification of the probabilities of five transitions of 5S1 / 2,Fg = 2 → 5P3 / 2,Fe = 4 of 85Rb and three transitions of 5S1 / 2,Fg = 1 → 5P3 / 2,Fe = 3 of 87Rb forbidden by selection rules for zero magnetic field has been observed experimentally and described theoretically for the first time. For the case of excitation with circularly-polarized (σ+) laser radiation, the probability of Fg = 2,mF = - 2 → Fe = 4,mF = - 1 transition becomes the largest among the seventeen transitions of 85Rb Fg = 2 → Fe = 1,2,3,4 group, and the probability of Fg = 1, mF = - 1 → Fe = 3,mF = 0 transition becomes the largest among the nine transitions of 87Rb Fg = 1 → Fe = 0,1,2,3 group, in a wide range of magnetic field 200-1000 G. Complete frequency separation of individual Zeeman components was obtained by implementation of derivative selective reflection technique with a 300 nm-thick nanocell filled with Rb, allowing formation of narrow optical resonances. Possible applications are addressed. The theoretical model is well consistent with the experimental results.

Shifting in optoelectronic properties from pure K2O and Rb2O compounds to their V- and Cr-doped alloys

NASA Astrophysics Data System (ADS)

Monir, Mohammed El Amine; Ullah, Hayat; Baltach, Hadj; Mouchaal, Younes; Merabiha, Omar; Bahnes, Aicha; Rached, Djamel

2018-04-01

First principle calculations within the density functional theory (DFT) have been used in this approach to study the electronic and optical properties of vanadium (V) and chromium (Cr) doped K2O and Rb2O compounds. Based on the structure properties reported in our previous work, the study of electronic and optoelectronic properties of V- and Cr-doped K2O and Rb2O alloys have been vastly investigated. K2O and Rb2O are found to be semiconductors while their V- and Cr-alloys are metallic in nature. The optical functions like complex dielectric constant, complex index of refraction, absorption coefficient, and reflectivity of these alloys are computed and compared with those of pure K2O and Rb2O compounds. It has been shown that due to TM-doping (TM = V and Cr transition metals), many distinguished peaks appeared in the lower energy part (infrared) of the spectrum. The negative value of 𝜀1 (ω) in this energy range confirmed the metallic behavior of these alloys. Furthermore, the frequency-dependent optical conductivity is also predicted in the entire spectrum, where it increases with increasing photon energy for all the studied alloys. The significant results of α (ω) predict that all these compounds are useful in different optoelectronic applications in a wide part of the spectrum (between 13 eV and 27 eV).

Special K: testing the potassium link between radioactive rubidium (86Rb) turnover and metabolic rate.

PubMed

Tomlinson, Sean; Mathialagan, Priya D; Maloney, Shane K

2014-04-01

The measurement of (86)Rb turnover recently has been suggested as a useful method for measuring field metabolic rate in small animals. We investigated a proposed mechanism of (86)Rb turnover, its analogy to K(+), by comparing the turnover of (86)Rb in a model insect, the rhinoceros beetle Xylotrupes gideon, fed a diet of plum jam or plum jam enriched with K(+) or Rb(+). The turnover of (86)Rb in the beetles on the K(+) and the Rb(+) diets was higher than that for beetles on the jam diet (F2,311=32.4; P=1.58×10(-13)). We also exposed the beetles to different ambient temperatures to induce differences in metabolic rate ( ) while feeding them the jam and K(+) diets. was higher at higher ambient temperature (Ta) for both jam (F1,11=14.56; P=0.003) and K(+) (F1,8=15.39; P=0.004) dietary groups, and the turnover of (86)Rb was higher at higher Ta for both jam (F1,11=10.80; P=0.007) and K(+) (F1,8=12.34; P=0.008) dietary groups. There was a significant relationship between (86)Rb turnover and for both the jam (F1,11=35.00; P=1.0×10(-3)) and the K(+) (F1,8=64.33; P=4.3×10(-5)) diets, but the relationship differed between the diets (F1,19=14.07; P=0.001), with a higher (86)Rb turnover in beetles on the K(+)-enriched than on the jam diet at all Ta. We conclude that (86)Rb turnover is related to K(+) metabolism, and that this is the mechanism of the relationship between (86)Rb turnover and . Studies relating (86)Rb turnover to should maintain dietary [K] as close as possible to that of natural diets for the most accurate calibrations for free-ranging animals.

Measurement of the Infinite Multiplication Constant of Natural Uranium--Graphite Lattices in the RB-1 Critical Assembly by Means of the Zero Reactivity Method. MISURA DELLA COSTANTE DI MOLTIPLICAZIONE INFINITA DI RETICOLI A URANIO NATURALE E GRAFITE NELL'INSIEME CRITICO RB-1 CON IL METODO DELLA REATTIVITA' NULLA (in Italian)

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

Ghillardotti, G.

1966-07-01

To reduce uncertainties to the minimum, measurements in the RB-1 were conducted on the same materials and with the same instrumentation as those used previously in MARIUS. The values measured in the RB-1, compared with the already known substitution data, are as follows: (a) the difference between the multiplication and the absorption intensity; (b) the fine structure of the flux in the cell; (c) the Pu/U index. The infinite mutiplication factor K{sub infinity} is obtained by combining measurements (a) and (b). The results of this research can be summed up as follows: 1. A consistent and complete experimental procedure hasmore » been devised for measuring the K{sub infinity} of natural uranium/graphite lattices by means of the zero reactivity method. The same applies to the procedure for analysis of the experimental data. 2. The error in (K{sub infinity} -- 1) inherent in the measurement can in our opinion be reduced to 2%. This limit was reached in the last experiment on lattices consisting of tubular elements. 3. Agreement proved to be good with the results obtained by the CEA in the critical assembly MARIUS. (auth)« less

Bibliography of Soviet Laser Developments, Number 83, May - June 1986.

DTIC Science & Technology

1987-09-01

Polymethine ..................... 8 d. Coumarin .. .o-... . .. . e. Phthalimide ................. --- f. Cyanine ....................... . - - g. Xanthene...KVEKA, no. 6, 1986, 1155-1160. 25. Kostanyan, R.B.; Sanamyan, T.V. 0. Stucy on lifetimes of erbium levels in lutecium aluminum garnet. DANAA, no. 3, 1985...60, no. 5, 1986, 937-942. d. Coumarin e. Phthalimide f. Cyanine g. Xanthene h. POPOP 2. Inorganic Liquids C. GAS LASERS 1. Theory 60. Basov, N.G

Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression

PubMed Central

Garfin, Phillip M.; Min, Dullei; Bryson, Jerrod L.; Serwold, Thomas; Edris, Badreddin; Blackburn, Clare C.; Richie, Ellen R.; Weinberg, Kenneth I.; Manley, Nancy R.; Viatour, Patrick

2013-01-01

Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients. PMID:23669396

Photoluminescence of RbCaF3:Mn2+: the influence of phase transitions

NASA Astrophysics Data System (ADS)

Marcode Lucas, M. C.; Rodriguez, F.; Moreno, M.

1993-03-01

Precise photoluminescence measurements on an RbCaF3:Mn2+ sample containing only 400 p.p.m. of Mn2+ have been carried out in the 10-300 K temperature range. The results are compared with those obtained in other fluoroperovskites doped with Mn2+. The analysis of the 6A1g(S) to 4T1g(G) excitation peak at room temperature leads to a Mn2+-F- distance R=213.3 pm which is close to that derived from the experimental isotropic superhyperfine constant, As. The plot of the first moment of the emission band, M1, against temperature reveals a slight but sensible change of slope at T=193 K which is associated with the Oh1 to D4h18 structural phase transition of the host lattice. Furthermore, at T=40 K, M1 undergoes an abrupt increase of approximately 100 cm-1. This fact supports the existence of another phase transition involving an increase Delta R/R approximately=0.2% upon cooling, and thus a situation which is similar to that detected in the structural phase transition of KMnF3 at Tc3=81.5 K. To the authors' knowledge this is the first time that clear evidence of both phase transitions in RbCaF3 has been achieved through an optical probe. Finally the variation of the 4A1g(G), 4Eg(G) peak, E3, along the fluoroperovskite series is analysed.

The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective

PubMed Central

Patrick, Ryan M.; Browning, Karen S.

2012-01-01

Translation initiation in eukaryotes requires a number of initiation factors to recruit the assembled ribosome to mRNA. The eIF4F complex plays a key role in initiation and is a common target point for regulation of protein synthesis. Most work on the translation machinery of plants to date has focused on flowering plants, which have both the eIF4F complex (eIF4E and eIF4G) as well as the plant-specific eIFiso4F complex (eIFiso4E and eIFiso4G). The increasing availability of plant genome sequence data has made it possible to trace the evolutionary history of these two complexes in plants, leading to several interesting discoveries. eIFiso4G is conserved throughout plants, while eIFiso4E only appears with the evolution of flowering plants. The eIF4G N-terminus, which has been difficult to annotate, appears to be well conserved throughout the plant lineage and contains two motifs of unknown function. Comparison of eIFiso4G and eIF4G sequence data suggests conserved features unique to eIFiso4G and eIF4G proteins. These findings have answered some questions about the evolutionary history of the two eIF4F complexes of plants, while raising new ones. PMID:22611336

On the origin of the cation templated self-assembly of uranyl-peroxide nanoclusters.

PubMed

Miró, Pere; Pierrefixe, Simon; Gicquel, Mickaël; Gil, Adrià; Bo, Carles

2010-12-22

Uranyl-peroxide nanoclusters display different topologies based on square, pentagonal and hexagonal building blocks. Computed complexation energies of different cations (Li(+), Na(+), K(+), Rb(+), and Cs(+)) with [UO(2)(O(2))(H(2)O)](n) (n = 4, 5, and 6) macrocycles suggest a strong cation templating effect. The inherent bent structure of a U-O(2)-U model dimer is demonstrated and justified through the analysis of its electronic structure, as well as of the inherent curvature of the four-, five-, and six-uranyl macrocyles. The curvature is enhaced by cation coordination, which is suggested to be the driving force for the self-assembly of the nanocapsules.

Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein.

PubMed

Gray, Steven G; Iglesias, Antonio H; Lizcano, Fernando; Villanueva, Raul; Camelo, Sandra; Jingu, Hisaka; Teh, Bin T; Koibuchi, Noriyuki; Chin, William W; Kokkotou, Efi; Dangond, Fernando

2005-08-05

To effectively direct targeted repression, the class I histone deacetylases (HDACs) associate with many important regulatory proteins. In this paper we describe the molecular characterization of a member of the Jumonji domain 2 (JMJD2) family of proteins, and demonstrate its binding to both class I HDACs and the retinoblastoma protein (pRb). JMJD2 proteins are characterized by the presence of two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers, one JmjN, one JmjC (containing an internal retinoblastoma-binding protein 2 (RBBP2)-like sequence), and two Tudor domains. The first member of this group, JMJD2A, is widely expressed in human tissues and cell lines, and high endogenous expression of JMJD2A mRNA was found in several cell types, including human T-cell lymphotropic virus 1 (HTLV-1)-infected cell lines. JMJD2A and JMJD2B exhibit cell type-specific responses to the HDAC inhibitor trichostatin A. We show that the JMJD2A protein associates in vivo with pRb and class I HDACs, and mediates repression of E2F-regulated promoters. In HTLV-1 virus-infected cells, we find that JMJD2A binds to the viral Tax protein. Antibodies to JMJD2A recognize the native protein but also a half-sized protein fragment, the latter up-regulated in THP-1 cells during the G(2)/M phase of the cell cycle. The ability of JMJD2A to associate with pRb and HDACs and potentiate pRb-mediated repression of E2F-regulated promoters implies an important role for this protein in cell proliferation and oncogenesis.

Observation of Feshbach resonances between ultracold Na and Rb atoms

NASA Astrophysics Data System (ADS)

Wang, Fudong; Xiong, Dezhi; Li, Xiaoke; Wang, Dajun

2013-03-01

Absolute ground-state 23Na87Rb molecule has a large electric dipole moment of 3.3 Debye and its two body exchange chemical reaction is energetically forbidden at ultracold temperatures. It is thus a nice candidate for studying quantum gases with dipolar interactions. We have built an experiment setup to investigate ultracold collisions between Na and Rb atoms as a first step toward the production of ground state molecular samples. Ultracold mixtures are first obtained by evaporative cooling of Rb and sympathetic cooling of Na. They are then transferred to a crossed dipole trap and prepared in different spin combinations for Feshbach resonance study. Several resonances below 1000 G are observed with both atoms prepared in either | F = 1,mF = 1 > or | F = 1,mF = - 1 > hyperfine states. Most of them are within 30 G of predicted values§ based on potentials obtained by high quality molecular spectroscopy studies. This work is supported by RGC Hong Kong. § E. Tiemann, private communications

Sign Changes in the Electric Dipole Moment of Excited States in Rubidium-Alkaline Earth Diatomic Molecules

NASA Astrophysics Data System (ADS)

Pototschnig, Johann V.; Lackner, Florian; Hauser, Andreas W.; Ernst, Wolfgang E.

2015-06-01

In a recent series of combined experimental and theoretical studies we investigated the ground state and several excited states of the Rb-alkaline earth molecules RbSr and RbCa. The group of alkali-alkaline earth (AK-AKE) molecules has drawn attention for applications in ultracold molecular physics and the measurement of fundamental constants due to their large permanent electric and magnetic dipole moments in the ground state. These properties should allow for an easy manipulation of the molecules and simulations of spin models in optical lattices. In our studies we found that the permanent electric dipole moment points in different directions for certain electronically excited states, and changes the sign in some cases as a function of bond length. We summarize our results, give possible causes for the measured trends in terms of molecular orbital theory and extrapolate the tendencies to other combinations of AK and AKE - elements. F. Lackner, G. Krois, T. Buchsteiner, J. V. Pototschnig, and W. E. Ernst, Phys. Rev. Lett., 2014, 113, 153001; G. Krois, F. Lackner, J. V. Pototschnig, T. Buchsteiner, and W. E. Ernst, Phys. Chem. Chem. Phys., 2014, 16, 22373; J. V. Pototschnig, G. Krois, F. Lackner, and W. E. Ernst, J. Chem. Phys., 2014, 141, 234309 J. V. Pototschnig, G. Krois, F. Lackner, and W. E. Ernst, J. Mol. Spectrosc., in Press (2015), doi:10.1016/j.jms.2015.01.006 M. Kajita, G. Gopakumar, M. Abe, and M. Hada, J. Mol. Spectrosc., 2014, 300, 99-107 A. Micheli, G. K. Brennen, and P. Zoller, Nature Physics, 2006, 2, 341-347

Progress with palbociclib in breast cancer: latest evidence and clinical considerations

PubMed Central

Rocca, Andrea; Schirone, Alessio; Maltoni, Roberta; Bravaccini, Sara; Cecconetto, Lorenzo; Farolfi, Alberto; Bronte, Giuseppe; Andreis, Daniele

2016-01-01

Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated. Among breast cancers, those with functioning cyclin D-CDK4/6-Rb-E2F are mainly hormone-receptor (HR) positive, with some HER2-positive and rare triple-negative cases. Deregulation results from genetic or otherwise occurring hyperactivation of molecules subtending cell cycle progression, or inactivation of cell cycle inhibitors. Based on results of randomized clinical trials, palbociclib was granted accelerated approval by the US Food and Drug Administration (FDA) for use in combination with letrozole as initial endocrine-based therapy for metastatic disease in postmenopausal women with HR-positive, HER2-negative breast cancer, and was approved for use in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. This review provides an update of the available knowledge on the cell cycle and its regulation, on the alterations in cyclin D-CDK4/6-Rb-E2F axis in breast cancer and their roles in endocrine resistance, on the preclinical activity of CDK4/6 inhibitors in breast cancer, both as monotherapy and as partners of combinatorial synergic treatments, and on the clinical development of palbociclib in breast cancer. PMID:28203301

Expansion in higher harmonics of boson stars using a generalized Ruffini-Bonazzola approach. Part 1. Bound states

NASA Astrophysics Data System (ADS)

Eby, Joshua; Suranyi, Peter; Wijewardhana, L. C. R.

2018-04-01

The method pioneered by Ruffini and Bonazzola (RB) to describe boson stars involves an expansion of the boson field which is linear in creation and annihilation operators. In the nonrelativistic limit, the equation of motion of RB is equivalent to the nonlinear Schrödinger equation. Further, the RB expansion constitutes an exact solution to a non-interacting field theory, and has been used as a reasonable ansatz for an interacting one. In this work, we show how one can go beyond the RB ansatz towards an exact solution of the interacting operator Klein-Gordon equation, which can be solved iteratively to ever higher precision. Our Generalized Ruffini-Bonazzola approach takes into account contributions from nontrivial harmonic dependence of the wavefunction, using a sum of terms with energy k E0, where k>=1 and E0 is the chemical potential of a single bound axion. The method critically depends on an expansion in a parameter Δ ≡ √1 ‑ E02/m2 < 1, where m is the mass of the boson. In the case of the axion potential, we calculate corrections which are relevant for axion stars in the transition or dense branches of solutions. We find with high precision the local minimum of the mass, Mmin≈ 463 f2/m, at Δ≈0.27, where f is the axion decay constant. This point marks the crossover from the transition branch to the dense branch of solutions, and a corresponding crossover from structural instability to stability.

On Teaching English to Speakers of Other Languages. Series I.

ERIC Educational Resources Information Center

Allen, Virginia French, Ed.

The contents of this volume, a compilation of papers read at the first conference of TESOL (Teachers of English to Speakers of Other Languages), are grouped according to general subject and authors: (1) TESOL as a Professional Field--A.H. Marckwardt, F.J. Colligan, W.F. Marquardt; (2) Reports on Special Programs--J.E. Officer, R.B. Long, M.C.…

The assembly, activation, and substrate specificity of Cyclin D1/Cdk2 complexes

PubMed Central

Jahn, Stephan C.; Law, Mary E.; Corsino, Patrick E.; Rowe, Thomas C.; Davis, Bradley J.; Law, Brian K.

2013-01-01

Previous studies have shown conflicting data regarding Cyclin D1/Cdk2 complexes and, considering the widespread overexpression of Cyclin D1 in cancer, it is important to fully understand their relevance. While many have shown Cyclin D1/Cdk2 complexes to form active complexes, others have failed to show activity or association. Here, using a novel p21-PCNA fusion protein as well as p21 mutant proteins, we show that p21 is a required scaffolding protein, with Cyclin D1 and Cdk2 failing to complex in its absence. These p21/Cyclin D1/Cdk2 complexes are active and also bind the trimeric PCNA complex, with each trimer capable of independently binding distinct Cyclin/Cdk complexes. We also show that increased p21 levels due to treatment with chemotherapeutic agents result in increased formation and kinase activity of Cyclin D1/Cdk2 complexes, and that Cyclin D1/Cdk2 complexes are able to phosphorylate a number of substrates in addition to Rb. Nucleophosmin and Cdh1, two proteins important for centrosome replication and implicated in the chromosomal instability of cancer are shown to be phosphorylated by Cyclin D1/Cdk2 complexes. Additionally, PSF is identified as a novel Cdk2 substrate, being phosphorylated by Cdk2 complexed with either Cyclin E or Cyclin D1, and given the many functions of PSF, it could have important implications on cellular activity. PMID:23627734

Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848.

PubMed

Liu, Chun-Ying; Zhou, Rui-Xin; Sun, Chang-Kai; Jin, Ying-Hua; Yu, Hong-Shan; Zhang, Tian-Yang; Xu, Long-Quan; Jin, Feng-Xie

2015-07-01

Minor ginsenosides, those having low content in ginseng, have higher pharmacological activities. To obtain minor ginsenosides, the biotransformation of American ginseng protopanaxadiol (PPD)-ginsenoside was studied using special ginsenosidase type-I from Aspergillus niger g.848. DEAE (diethylaminoethyl)-cellulose and polyacrylamide gel electrophoresis were used in enzyme purification, thin-layer chromatography and high performance liquid chromatography (HPLC) were used in enzyme hydrolysis and kinetics; crude enzyme was used in minor ginsenoside preparation from PPD-ginsenoside; the products were separated with silica-gel-column, and recognized by HPLC and NMR (Nuclear Magnetic Resonance). The enzyme molecular weight was 75 kDa; the enzyme firstly hydrolyzed the C-20 position 20-O-β-D-Glc of ginsenoside Rb1, then the C-3 position 3-O-β-D-Glc with the pathway Rb1→Rd→F2→C-K. However, the enzyme firstly hydrolyzed C-3 position 3-O-β-D-Glc of ginsenoside Rb2 and Rc, finally hydrolyzed 20-O-L-Ara with the pathway Rb2→C-O→C-Y→C-K, and Rc→C-Mc1→C-Mc→C-K. According to enzyme kinetics, K m and V max of Michaelis-Menten equation, the enzyme reaction velocities on ginsenosides were Rb1 > Rb2 > Rc > Rd. However, the pure enzyme yield was only 3.1%, so crude enzyme was used for minor ginsenoside preparation. When the crude enzyme was reacted in 3% American ginseng PPD-ginsenoside (containing Rb1, Rb2, Rc, and Rd) at 45°C and pH 5.0 for 18 h, the main products were minor ginsenosides C-Mc, C-Y, F2, and C-K; average molar yields were 43.7% for C-Mc from Rc, 42.4% for C-Y from Rb2, and 69.5% for F2 and C-K from Rb1 and Rd. Four monomer minor ginsenosides were successfully produced (at low-cost) from the PPD-ginsenosides using crude enzyme.

An Evaluation of Diagnostic Atmospheric Dispersion Models for ’Cold Spill’ Applications at Vandenberg Air Force Base, California

DTIC Science & Technology

1992-12-30

this report was 1ý.F,;,Amdauncdunc Rsearch Professor of Physics Approvei: b K. E. Woel Chairman Department of Physics Released by: P .Mar o, Dean of...R.J. Yamartino, 1987: Environmental Protection Agency complex terrain model development: final rep. EPA/600/3-88/006, U.S., 486 pp. Stull , R.B., 1988...Denmark Mr. Randall Nyman 1 ACTA Vandenberg AFB, CA 93437-5000 Prof. Gordon Schacher 1 Dean of Faculty and Graduate Studies Naval Postgraduate

Thermal, optical, and dielectric properties of fluoride Rb2TaF7

NASA Astrophysics Data System (ADS)

Pogorel'tsev, E. I.; Mel'nikova, S. V.; Kartashev, A. V.; Gorev, M. V.; Flerov, I. N.; Laptash, N. M.

2017-05-01

The thermal, optical, and dielectric properties of fluoride Rb2TaF7 were investigated. It was observed that the variation in chemical pressure in fluorides A 2 +TaF7 caused by the cation substitution of rubidium for ammonium does not affect the ferroelastic nature of structural distortions, but leads to stabilization of the high- and low-temperature phases and enhancement of birefringence. The entropy of the phase transition P4/nmm ↔ Cmma is typical of the shift transformations, which is consistent with a model of the initial and distorted phase structures. The anisotropy of chemical pressure causes the change of signs of the anomalous strain and baric coefficient dT/ dp of Rb2TaF7 as compared with the values for its ammonium analog.

The transition from granite to banded aplite-pegmatite sheet complexes: An example from Megiliggar Rocks, Tregonning topaz granite, Cornwall

NASA Astrophysics Data System (ADS)

Breiter, K.; Ďurišová, J.; Hrstka, T.; Korbelová, Z.; Vašinová Galiová, M.; Müller, A.; Simons, B.; Shail, R. K.; Williamson, B. J.; Davies, J. A.

2018-03-01

The genetic relationship between a granite pluton and adjacent complex of rare-metal pegmatite-aplite-banded sheets (Megiliggar Sheet Complex - MSC) has been studied at the border of the Tregonning topaz granite at Megiliggar Rocks, Cornwall, SW England. Similarities in whole-rock chemical and mineralogical compositions, together with a gradual change in textures away from the granite margin, provide strong evidence for a genetic link between the Tregonning Granite and MSC. The sheets are likely to represent apophyses of residual melt which escaped from the largely crystallized roof of the granite pluton. The escaping melt was peraluminous, had a composition near the F, B, Li slightly enriched granite minimum, and, in comparison with other Cornish granites, was enriched in F, Li, Rb, Cs, Sn, W, Nb, Ta, and U, and depleted in Fe, Mg, Ca, Sr, Th, Zr, and REE. With increasing distance from the Tregonning Granite, the silicate melt crystallized as homogeneous leucogranite sheets and banded complex sheets (i.e. combinations of bands with granitic, aplitic and pegmatitic textures), then layered aplite-pegmatites; this sequence becoming progressively more depleted in the fluxing and volatile elements F, Li, Rb, and Cs, but showing no change in Zr/Hf ratios. The fixed Zr/Hf ratio is interpreted as indicating a direct genetic link (parental melt) between all rock types, however the melt progressively lost fluxing and volatile elements with distance from the granite pluton, probably due to wall-rock reaction or fluid exsolution and migration via fractures. Differentiation of the primary melt into Na-Li-F-rich and separate K-B-rich domains was the dominant chemical process responsible for the textural and mineral diversity of the MSC. On a large (cliff-section) scale, the proximal Na-Li-F-rich leucogranite passes through complex sheets into K-B-rich aplite-pegmatites, whilst at a smaller (<1 m) scale, the K-B-rich bands are interspersed (largely overlain) by Na-Li-F-rich segregations. The grain size differences between the aplite and pegmatite could be related to pressure fluctuations and/or undercooling.

Determination of the Mn2+ -F- distance from the isotropic superhyperfine constant for [MnF6]4- in ionic lattices

NASA Astrophysics Data System (ADS)

Barriuso, M. T.; Moreno, M.

1984-03-01

This paper is devoted to establish a quantitative nonempirical relation between the experimental isotropic superhyperfine constant As and the metal-ligand distance R for [MnF6]4- placed in different ionic host lattices. By inspection of the theoretical molecular-orbital calculations performed on [MnF6]4-, it is proposed that λs, the 2s (F-) admixture coefficient in the antibonding e*g orbital, is just given by cSs where Ss is the corresponding group overlap integral while the value of the constant c, which is independent of R, should be close to 1.3. In a first step, we have determined R for Mn2+ in fluoroperovskite lattices from the experimental As values using a value c=1.269+/-0.017 derived from the NMR data for KMnF3 and RbMnF3. By means of this procedure, it is predicted that R=2.084+/-0.11 Å for KZnF3:Mn2+ and that R=2.124+/-0.012 Å for RbCdF3:Mn2+, which are in good agreement with recent extended x-ray-absorption fine-structure measurements on such systems. On the other hand, from the As values measured at room temperature and at 4.2 K, we have derived a thermal-expansion coefficient α=(17+/-5)×10-6 K-1 for [MnF6]4- in the KZnF3 lattice which is comparable to the value α=16.52×10-6 K-1 measured at 300 K for RbMnF3. The present method gives also reasonable results for slightly distorted [MnF6]4- clusters. In view of this, it is predicted that R=2.126+/-0.012 Å for the long Mn-F bond in K2MnF4. From this work, it is seen that if R0 (which corresponds to the metal-ligand distance of the host lattice) is less than 2.10 Å, an outward relaxation occurs, whereas the opposite happens if R0 is higher than 2.12 Å-a fact which is consistent with the mainly ionic bond between Mn2+ and F-. Along this line of reasoning it is shown that a significant inwards relaxation ΔRR0=22.1% (ΔR=R-R0) occurs for RbF:Mn2+. The foundations of the method, which is able to detect changes in R down to about 2×10-4 Å, are thoroughly examined in this work. In particular, the possible influence of 1s core orbitals of F- on the value of As is discussed: It is shown that for Mn2+-doped fluoroperovskites better results are obtained when such a contribution is neglected.

Hydrothermal crystal growth of ABe 2BO 3F 2 (A=K, Rb, Cs, Tl) NLO crystals

NASA Astrophysics Data System (ADS)

McMillen, Colin D.; Kolis, Joseph W.

2008-04-01

Crystals of a family of compounds, ABe 2BO 3F 2 (ABBF, A=K, Rb, Cs, Tl), have been grown hydrothermally. Each of these materials was studied using the powder SHG technique and exhibited promising NLO behavior. Seeded crystal growth was demonstrated and the growth conditions were optimized by modifying the temperature, thermal gradient and mineralizer concentration. RbBe 2BO 3F 2 crystals possessed a particularly good combination of SHG intensity, favorable crystal habit and fast growth rates. High quality crystals suitable for advanced deep-UV NLO studies were grown at rates of 0.11 mm/day on (0 0 1) and 0.12 mm/day perpendicular to (0 0 1).

Ratiometric detection of copper ions and alkaline phosphatase activity based on semiconducting polymer dots assembled with rhodamine B hydrazide.

PubMed

Sun, Junyong; Mei, Han; Gao, Feng

2017-05-15

The rational surface functionalization of semiconducting polymer dots (Pdots) has attracted much attention to extend their applications in fabricating chemo/biosensing platform. In this study, a novel ratiometric fluorescent sensing platform using functionalized Pdots as probes for fluorescence signal transmission has been designed for sensing Cu(Ⅱ) and activity of alkaline phosphatase (ALP) with high selectivity and enhanced sensitivity. The highly fluorescent Pdots were firstly prepared with Poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadiazole)] (PFBT) via nanoprecipitation method, and then assembled with non-fluorescent rhodamine B hydrazide (RB-hy), which shows special binding activity to Cu(Ⅱ), through adsorption process to obtain functionalized nanohybrids, Pdots@RB-hy. As thus, a FRET donors/acceptors pair, in which PFBT Pdots act as energy donors while RB-hy-Cu(II) complexes act as energy acceptors were constructed. On the basis of the varies in fluorescence intensities of donors/acceptors in the presence of different amounts of Cu(II), a ratiometric method for sensing Cu(II) has been proposed. The proposed ratiometric Cu(II) sensor shows a good linear detection range from 0.05 to 5μM with a detection limit of 15nM. Furthermore, using the Pdots@RB-hy-Cu(II) system as signal transducer, a ratiometric sensing for alkaline phosphatase (ALP) activity has also been established with pyrophosphate (PPi) as substrates. The constructed ratiometric sensor of ALP activity displays a linear detection range from 0.005 to 15UL -1 with a detection limit of 0.0018UL -1 . The sensor was further successfully used for ALP activity detection in human serum with satisfactory results. Copyright © 2016 Elsevier B.V. All rights reserved.

Adenovirus E1a prevents the retinoblastoma gene product from repressing the activity of a cellular transcription factor.

PubMed Central

Zamanian, M; La Thangue, N B

1992-01-01

The retinoblastoma (Rb) gene product forms a complex with the cellular transcription factor DRTF1, a property assumed to be important for mediating negative growth control because certain viral oncogenes, such as adenovirus E1a, prevent this interaction and mutant Rb alleles, which have lost the capacity to regulate growth, encode proteins that fail to associate with DRTF1. In this study, we show that the wild-type Rb protein can specifically repress transcription from promoters driven by DRTF1 whereas a naturally occurring mutant Rb protein cannot. Furthermore, Rb-mediated transcriptional repression can be overridden by adenovirus E1a; this requires regions in E1a necessary for cellular transformation. The Rb protein therefore acts in trans to repress the transcriptional activity of DRTF1 whereas adenovirus E1a prevents this interaction and thus maintains DRTF1 in a constitutively active state. The Rb protein and adenovirus E1a therefore have opposite effects on the activity of a common molecular target. Transcriptional repression mediated by the Rb protein and inactivation of repression by the E1a protein are likely to play an important role in mediating their biological effects. Images PMID:1385776

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

PubMed

Carcagno, Abel L; Marazita, Mariela C; Ogara, María F; Ceruti, Julieta M; Sonzogni, Silvina V; Scassa, María E; Giono, Luciana E; Cánepa, Eduardo T

2011-01-01

A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity.

E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

PubMed Central

Carcagno, Abel L.; Marazita, Mariela C.; Ogara, María F.; Ceruti, Julieta M.; Sonzogni, Silvina V.; Scassa, María E.; Giono, Luciana E.; Cánepa, Eduardo T.

2011-01-01

Background A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. Methodology/Principal Findings In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. Conclusions/Significance The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity. PMID:21765927

Organ size control is dominant over Rb family inactivation to restrict proliferation in vivo.

PubMed

Ehmer, Ursula; Zmoos, Anne-Flore; Auerbach, Raymond K; Vaka, Dedeepya; Butte, Atul J; Kay, Mark A; Sage, Julien

2014-07-24

In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, deletion of the entire Rb gene family in mature hepatocytes is not sufficient for their long-term proliferation. The cell cycle block in Rb family mutant hepatocytes is independent of the Arf/p53/p21 checkpoint but can be abrogated upon decreasing liver size. At the molecular level, we identify YAP, a transcriptional regulator involved in organ size control, as a factor required for the sustained expression of cell cycle genes in hepatocytes. These experiments identify a higher level of regulation of the cell cycle in vivo in which signals regulating organ size are dominant regulators of the core cell cycle machinery. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Transient development of Zeeman electromagnetically induced transparency during propagation of Raman-Ramsey pulses through Rb buffer gas cell

NASA Astrophysics Data System (ADS)

Nikolić, S. N.; Radonjić, M.; Lučić, N. M.; Krmpot, A. J.; Jelenković, B. M.

2015-02-01

We investigate, experimentally and theoretically, time development of Zeeman electromagnetically induced transparency (EIT) during propagation of two time separated polarization laser pulses, preparatory and probe, through Rb vapour. The pulses were produced by modifying laser intensity and degree of elliptical polarization. The frequency of the single laser beam is locked to the hyperfine {{F}g}=2\\to {{F}e}=1 transition of the D1 line in 87Rb. Transients in the intensity of {{σ }-} component of the transmitted light are measured or calculated at different values of the external magnetic field, during both preparatory and probe pulse. Zeeman EIT resonances at particular time instants of the pulse propagation are reconstructed by appropriate sampling of the transients. We observe how laser intensity, Ramsey sequence and the Rb cell temperature affect the time dependence of EIT line shapes, amplitudes and linewidths. We show that at early times of the probe pulse propagation, several Ramsey fringes are present in EIT resonances, while at later moments a single narrow peak prevails. Time development of EIT amplitudes are determined by the transmitted intensity of the {{σ }-} component during the pulse propagation.

Measurements of myocardial flow vs. extraction of rubidium under varying physiological conditions

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

Budinger, T.F.; Yano, Y.; Moyer, B.R.

1984-01-01

The relationship between myocardial rubidium extraction (E) and flow (F) are well described by the single capillary model E = (1-exp(-PS/F)) with a permeability surface product PS = 0.87 cc/min/gm. Some effects of alkalosis and acidosis have been reported. Here the authors investigate the effects of dipyridamole, norepinephrine-atropine, exsanguination, pacing, ouabain and calcium on extraction using Rb-82 PET and Rb-86 acute studies with microspheres in dogs. Thoracotomies were performed for left atrial microsphere infusion. Anesthesia was by N/sub 2/O and methoxyflurane. The degree of exsanguination, drug levels administered and pacing rates were sufficient to produce flow modifications. Extraction was calculatedmore » by dividing FE from Rb observations by F from microsphere data. These results of extraction vs. flow do not show a significant dependence on the method used for flow modification. There was less than a 20% change in FE after an infusion of 0.04 mg/kg ouabain over 5 minutes in 3 replicate studies each on 4 dogs. An important finding not previously explained in flow vs. extraction studies is the occurrence of extraction values greater than 1.0 which is possible only if the distribution opportunities of small cations are greater than that of microspheres. This is equivalent to the well known hematocrit effect in small channels.« less

Synthesis and properties of Rb2GeF6:Mn4+ red-emitting phosphors

NASA Astrophysics Data System (ADS)

Sakurai, Shono; Nakamura, Toshihiro; Adachi, Sadao

2018-02-01

Rb2GeF6:Mn4+ red-emitting phosphors were synthesized by coprecipitation and their structural and optical properties were investigated by laser microscopy observation, X-ray diffraction (XRD) analysis, photoluminescence (PL) analysis, PL excitation (PLE) spectroscopy, and PL decay measurement. Single-crystalline ingots in the form of a hexagonal pyramid were prepared with a basal plane diameter of ˜2 mm. The XRD analysis suggested that Rb2GeF6 crystallizes in the hexagonal structure (C6v4 = P63mc) with a = 0.5955 nm and c = 0.9672 nm. The phosphor exhibited the strong Mn4+-related zero-phonon line (ZPL) emission peak typically observed in host crystals with piezoelectrically active lattices such as a hexagonal lattice. The quantum efficiencies of the bulk ingot and powdered samples were 87 and 74%, respectively, with nearly the same luminescence decay time of ˜6 ms. The exact ZPL energies and related crystal-field and Racah parameters were obtained from the PL and PLE spectra by Franck-Condon analysis. Temperature-dependent PL intensities were analyzed from T = 20 to 500 K using a thermal quenching model by considering Bose-Einstein phonon statistics. A comparative discussion on the phosphor properties of Rb2GeF6:Mn4+ and Rb2MF6:Mn4+ with M = Si and Ti was also given.

Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs

PubMed Central

Huang, Mingqian; Sage, Cyrille; Tang, Yong; Lee, Sang Goo; Petrillo, Marco; Hinds, Philip W

2011-01-01

Retinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In a conditional hair cell Rb1 knockout mouse, Pou4f3-Cre-pRb™/™, pRb™/™ utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of pRb™/™ cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of pRb™/™ cochlea and utricle. The comparative analysis shows that the core pathway shared between pRb™/™ cochlea and utricle is centered on e2F, the key pathway that mediates pRb function. A majority of differentially expressed genes and enriched pathways are not shared but uniquely associated with pRb™/™ cochlea or utricle. In pRb™/™ cochlea, pathways involved in early inner ear development such as Wnt/β-catenin and Notch were enriched, whereas pathways involved in proliferation and survival are enriched in pRb™/™ utricle. Clustering analysis showed that the pRb™/™ inner ear has characteristics of a younger control inner ear, an indication of delayed differentiation. We created a transgenic mouse model (ER-Cre-pRbflox/flox) in which Rb1 can be acutely deleted postnatally. Acute Rb1 deletion in the adult mouse fails to induce proliferation or cell death in inner ear, strongly indicating that Rb1 loss in these postmitotic tissues can be effectively compensated for, or that pRb-mediated changes in the postmitotic compartment result in events that are functionally irreversible once enacted. This study thus supports the concept that pRb-regulated pathways relevant to hair cell development, encompassing proliferation, differentiation and survival, act predominantly during early development. PMID:21239885

Rubidium distribution at atomic scale in high efficient Cu(In,Ga)Se2 thin-film solar cells

NASA Astrophysics Data System (ADS)

Vilalta-Clemente, Arantxa; Raghuwanshi, Mohit; Duguay, Sébastien; Castro, Celia; Cadel, Emmanuel; Pareige, Philippe; Jackson, Philip; Wuerz, Roland; Hariskos, Dimitrios; Witte, Wolfram

2018-03-01

The introduction of a rubidium fluoride post deposition treatment (RbF-PDT) for Cu(In,Ga)Se2 (CIGS) absorber layers has led to a record efficiency up to 22.6% for thin-film solar cell technology. In the present work, high efficiency CIGS samples with RbF-PDT have been investigated by atom probe tomography (APT) to reveal the atomic distribution of all alkali elements present in CIGS layers and compared with non-treated samples. A Scanning Electron Microscopy Dual beam station (Focused Ion Beam-Gas Injection System) as well as Transmission Kikuchi diffraction is used for atom probe sample preparation and localization of the grain boundaries (GBs) in the area of interest. The analysis of the 3D atomic scale APT reconstructions of CIGS samples with RbF-PDT shows that inside grains, Rb is under the detection limit, but the Na concentration is enhanced as compared to the reference sample without Rb. At the GBs, a high concentration of Rb reaching 1.5 at. % was found, and Na and K (diffusing from the glass substrate) are also segregated at GBs but at lower concentrations as compared to Rb. The intentional introduction of Rb leads to significant changes in the chemical composition of CIGS matrix and at GBs, which might contribute to improve device efficiency.

Automatic 3D registration of dynamic stress and rest (82)Rb and flurpiridaz F 18 myocardial perfusion PET data for patient motion detection and correction.

PubMed

Woo, Jonghye; Tamarappoo, Balaji; Dey, Damini; Nakazato, Ryo; Le Meunier, Ludovic; Ramesh, Amit; Lazewatsky, Joel; Germano, Guido; Berman, Daniel S; Slomka, Piotr J

2011-11-01

The authors aimed to develop an image-based registration scheme to detect and correct patient motion in stress and rest cardiac positron emission tomography (PET)/CT images. The patient motion correction was of primary interest and the effects of patient motion with the use of flurpiridaz F 18 and (82)Rb were demonstrated. The authors evaluated stress/rest PET myocardial perfusion imaging datasets in 30 patients (60 datasets in total, 21 male and 9 female) using a new perfusion agent (flurpiridaz F 18) (n = 16) and (82)Rb (n = 14), acquired on a Siemens Biograph-64 scanner in list mode. Stress and rest images were reconstructed into 4 ((82)Rb) or 10 (flurpiridaz F 18) dynamic frames (60 s each) using standard reconstruction (2D attenuation weighted ordered subsets expectation maximization). Patient motion correction was achieved by an image-based registration scheme optimizing a cost function using modified normalized cross-correlation that combined global and local features. For comparison, visual scoring of motion was performed on the scale of 0 to 2 (no motion, moderate motion, and large motion) by two experienced observers. The proposed registration technique had a 93% success rate in removing left ventricular motion, as visually assessed. The maximum detected motion extent for stress and rest were 5.2 mm and 4.9 mm for flurpiridaz F 18 perfusion and 3.0 mm and 4.3 mm for (82)Rb perfusion studies, respectively. Motion extent (maximum frame-to-frame displacement) obtained for stress and rest were (2.2 ± 1.1, 1.4 ± 0.7, 1.9 ± 1.3) mm and (2.0 ± 1.1, 1.2 ±0 .9, 1.9 ± 0.9) mm for flurpiridaz F 18 perfusion studies and (1.9 ± 0.7, 0.7 ± 0.6, 1.3 ± 0.6) mm and (2.0 ± 0.9, 0.6 ± 0.4, 1.2 ± 1.2) mm for (82)Rb perfusion studies, respectively. A visually detectable patient motion threshold was established to be ≥2.2 mm, corresponding to visual user scores of 1 and 2. After motion correction, the average increases in contrast-to-noise ratio (CNR) from all frames for larger than the motion threshold were 16.2% in stress flurpiridaz F 18 and 12.2% in rest flurpiridaz F 18 studies. The average increases in CNR were 4.6% in stress (82)Rb studies and 4.3% in rest (82)Rb studies. Fully automatic motion correction of dynamic PET frames can be performed accurately, potentially allowing improved image quantification of cardiac PET data.

A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling

PubMed Central

Nagendraprabhu, Ponnuraj; Khatiwada, Sushil; Chaulagain, Sabal

2017-01-01

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent. ORFV119 was shown to inhibit IKK complex activation early in infection. Consistent with IKK inhibition, ORFV119 also interacted with TNF receptor associated factor 2 (TRAF2), an adaptor protein recruited to signaling complexes upstream of IKK in infected cells. ORFV119-TRAF2 interaction was enhanced in the presence of pRb, suggesting that ORFV119-pRb complex is required for efficient interaction with TRAF2. Additionally, transient expression of ORFV119 in uninfected cells was sufficient to inhibit TNFα-induced IKK activation and NF-κB signaling, indicating that no other viral proteins are required for the effect. Infection of sheep with ORFV lacking the ORFV119 gene led to attenuated disease phenotype, indicating that ORFV119 contributes to virulence in the natural host. ORFV119 represents the first poxviral protein to interfere with NF-κB signaling through interaction with pRb. PMID:29244863

Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway

PubMed Central

Viatour, Patrick; Ehmer, Ursula; Saddic, Louis A.; Dorrell, Craig; Andersen, Jesper B.; Lin, Chenwei; Zmoos, Anne-Flore; Mazur, Pawel K.; Schaffer, Bethany E.; Ostermeier, Austin; Vogel, Hannes; Sylvester, Karl G.; Thorgeirsson, Snorri S.; Grompe, Markus

2011-01-01

Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with >600,000 deaths every year. Although the major risk factors are known, therapeutic options in patients remain limited in part because of our incomplete understanding of the cellular and molecular mechanisms influencing HCC development. Evidence indicates that the retinoblastoma (RB) pathway is functionally inactivated in most cases of HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with histopathological features and gene expression profiles similar to human HCC. In this mouse model, cancer initiation is associated with the specific expansion of populations of liver stem/progenitor cells, indicating that the RB pathway may prevent HCC development by maintaining the quiescence of adult liver progenitor cells. In addition, we show that during tumor progression, activation of the Notch pathway via E2F transcription factors serves as a negative feedback mechanism to slow HCC growth. The level of Notch activity is also able to predict survival of HCC patients, suggesting novel means to diagnose and treat HCC. PMID:21875955

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography.

PubMed

Lin, Kuo-Shyan; Ding, Yu-Shin; Kim, Sung-Won; Kil, Kun-Eek

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.

GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in triple-negative breast cancer cell models

PubMed Central

Stelitano, Debora; Leticia, Yamila Peche; Dalla, Emiliano; Monte, Martin; Piazza, Silvano; Schneider, Claudio

2017-01-01

GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC). Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1. Moreover, we found that TEAD4 controls the formation of cell protrusions required for cell migration through GTSE1, unveiling a relevant effector role for this protein in the TEAD-dependent cellular functions and confirming TEAD4 role in promoting invasion and metastasis in breast cancer. Finally, we highlighted a role for the pRb-E2F1 pathway in the control of GTSE1 transcription and observed that treatment with drugs targeting the pRb-E2F1 or YAP/TAZ-TEAD pathways dramatically downregulated the expression levels of GTSE1 and of other genes involved in the formation of metastasis, suggesting their potential use in the treatment of TNBC. PMID:28978043

LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.

PubMed

Montoya-Durango, Diego E; Ramos, Kenneth A; Bojang, Pasano; Ruiz, Lorell; Ramos, Irma N; Ramos, Kenneth S

2016-01-25

Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2-β, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-β, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. RB proteins stabilize interactions of the NuRD corepressor complex within the L1 promoter to effect L1 silencing. L1 retroelements may serve as a scaffold on which RB builds heterochromatic regions that regulate chromatin function.

Albumin binds self-assembling dyes as specific polymolecular ligands.

PubMed

Stopa, Barbara; Rybarska, Janina; Drozd, Anna; Konieczny, Leszek; Król, Marcin; Lisowski, Marek; Piekarska, Barbara; Roterman, Irena; Spólnik, Paweł; Zemanek, Grzegorz

2006-12-15

Self-assembling dyes with a structure related to Congo red (e.g. Evans blue) form polymolecular complexes with albumin. The dyes, which are lacking a self-assembling property (Trypan blue, ANS) bind as single molecules. The supramolecular character of dye ligands bound to albumin was demonstrated by indicating the complexation of dye molecules outnumbering the binding sites in albumin and by measuring the hydrodynamic radius of albumin which is growing upon complexation of self-assembling dye in contrast to dyes lacking this property. The self-assembled character of Congo red was also proved using it as a carrier introducing to albumin the intercalated nonbonding foreign compounds. Supramolecular, ordered character of the dye in the complex with albumin was also revealed by finding that self-assembling dyes become chiral upon complexation. Congo red complexation makes albumin less resistant to low pH as concluded from the facilitated N-F transition, observed in studies based on the measurement of hydrodynamic radius. This particular interference with protein stability and the specific changes in digestion resulted from binding of Congo red suggest that the self-assembled dye penetrates the central crevice of albumin.

Mixing Halogens To Assemble an All-Inorganic Layered Perovskite with Warm White-Light Emission.

PubMed

Li, Xianfeng; Wang, Sasa; Zhao, Sangen; Li, Lina; Li, Yanqiang; Zhao, Bingqing; Shen, Yaoguo; Wu, Zhenyue; Shan, Pai; Luo, Junhua

2018-05-01

Most of single-component white-light-emitting materials focus on organic-inorganic hybrid perovskites, metal-organic frameworks, as well as all-inorganic semiconductors. In this work, we successfully assembled an all-inorganic layered perovskite by mixing two halogens of distinct ionic radii, namely, Rb 2 CdCl 2 I 2 , which emits "warm" white light with a high color rendering index of 88. To date, Rb 2 CdCl 2 I 2 is the first single-component white-light-emitting material with an all-inorganic layered perovskite structure. Furthermore, Rb 2 CdCl 2 I 2 is thermally highly stable up to 575 K. A series of luminescence measurements show that the white-light emission arises from the lattice deformation, which are closely related to the [CdCl 4 I 2 ] 2- octahedra with high distortion from the distinct ionic radii of Cl and I. The first-principles calculations reveal that both the Cl and I components make significant contributions to the electronic band structures of Rb 2 CdCl 2 I 2 . These findings indicate that mixing halogens is an effective route to design and synthesize new single-component white-light-emitting materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Klebsiella aerogenes UreF: Identification of the UreG Binding Site and Role in Enhancing the Fidelity of Urease Activation†

PubMed Central

Boer, Jodi L.; Hausinger, Robert P.

2012-01-01

The Ni-containing active site of Klebsiella aerogenes urease is assembled through the concerted action of the UreD, UreE, UreF, and UreG accessory proteins. UreE functions as a metallochaperone that delivers Ni to a complex of UreD—UreF—UreG bound to urease apoprotein, with UreG serving as a GTPase during enzyme activation. The present study focuses on the role of UreF, previously proposed to act as a GTPase activating protein (GAP) of UreG. Sixteen conserved UreF surface residues that may play roles in protein:protein interactions were independently changed to Ala. When produced in the context of the entire urease gene cluster, cell-free extracts of nine site-directed mutants had less than 10% of the wild-type urease activity. Enrichment of the variant forms of UreF, as the UreE-F fusion proteins, uniformly resulted in co-purification of UreD and urease apoprotein; whereas UreG bound to only a subset of the species. Notably, reduced interaction with UreG correlated with the low activity mutants. The affected residues in UreF map to a distinct surface on the crystal structure, defining the UreG binding site. In contrast to the hypothesis that UreF is a GAP, the UreD—UreF—UreG—urease apoprotein complex containing K165A UreF exhibited significantly greater levels of GTPase activity than that containing the wild-type protein. Additional studies demonstrated the UreG GTPase activity was largely uncoupled from urease activation for the complex containing this UreF variant. Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the non-cognate metal Zn. PMID:22369361

Molecular Spectra of RbSr: Helium Droplet Assisted Preparation of a Diatomic Molecule

NASA Astrophysics Data System (ADS)

Lackner, Florian; Krois, Günter; Buchsteiner, Thomas; Pototschnig, Johann V.; Ernst, Wolfgang E.

2014-06-01

We report on the first spectroscopic investigation of the ground and excited states of RbSr. The molecules are prepared in their vibronic ground state (X^2Σ^+1/2, ν" = 0) in a sequential pickup process on the surface of helium nanodroplets, confined in a cold (0.38 K) and weakly perturbing superfluid environment. Utilizing resonance-enhanced multi-photon ionization time-of-flight (REMPI-TOF) spectroscopy and laser induced fluorescence (LIF) spectroscopy our investigations cover the spectral regime of 11500 cm-1 - 23000 cm-1. The weak interaction between molecules and helium droplets causes a broadening of the observed transitions. For spectrally resolved band systems the helium droplet isolation approach facilitates the determination of molecular constants. Our assignment is assisted by theoretical calculations of potential energy curves based on a multireference configuration interaction (MRCI) approach. Several strong transitions could be identified; the most prominent spectral feature is a vibrational resolved band system at 14000 cm-1. In contrast to the excitation spectra, dispersed fluorescence (DF) spectra are not influenced by the helium environment, because the molecules leave the droplets upon photoexcitation, revealing detailed insights into the electronic structure of the free RbSr molecule. G. Krois, J.V. Pototschnig, F. Lackner and W.E. Ernst, J. Phys. Chem. A, 117 (50), 13719-13731 (2013) C. Callegari and W. E. Ernst, Helium Droplets as Nanocryostats for Molecular Spectroscopy - from the Vacuum Ultraviolet to the Microwave Regime, in: Handbook of High-Resolution Spectroscopy, eds. M. Quack and F. Merkt, John Wiley & Sons, Chichester, (2011) P.S. Żuchowski, R. Guerout, and O. Dulieu, arXiv preprint arXiv:1402.0702 (2014) B. Pasquiou, A. Bayerle, S.M. Tzanova, S. Stellmer, J. Szczepkowski, M. Parigger, R. Grimm, and F. Schreck, Phys. Rev. A, 88 (2), 023601 (2013).

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘D’, 2ND FLOOR PLAN, ARCHITECTURAL. Sheet 38 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘C’, 2ND FLOOR PLAN, ARCHITECTURAL. Sheet 15 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘B’, 2ND FLOOR PLAN, ARCHITECTURAL. Sheet 29 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Compact setup for the production of {sup 87}Rb |F = 2, m{sub F} = + 2〉 Bose-Einstein condensates in a hybrid trap

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

Nolli, Raffaele; Venturelli, Michela; Marmugi, Luca, E-mail: l.marmugi@ucl.ac.uk

We present a compact experimental apparatus for Bose-Einstein condensation of {sup 87}Rb in the |F  =  2, m{sub F} = + 2〉 state. A pre-cooled atomic beam of {sup 87}Rb is obtained by using an unbalanced magneto-optical trap, allowing controlled transfer of trapped atoms from the first vacuum chamber to the science chamber. Here, atoms are transferred to a hybrid trap, as produced by overlapping a magnetic quadrupole trap with a far-detuned optical trap with crossed beam configuration, where forced radiofrequency evaporation is realized. The final evaporation leading to Bose-Einstein condensation is then performed by exponentially lowering the optical trapmore » depth. Control and stabilization systems of the optical trap beams are discussed in detail. The setup reliably produces a pure condensate in the |F = 2, m{sub F} = + 2〉 state in 50 s, which includes 33 s loading of the science magneto-optical trap and 17 s forced evaporation.« less

G1 arrest and differentiation can occur independently of Rb family function

PubMed Central

Wirt, Stacey E.; Adler, Adam S.; Gebala, Véronique; Weimann, James M.; Schaffer, Bethany E.; Saddic, Louis A.; Viatour, Patrick; Vogel, Hannes; Chang, Howard Y.; Meissner, Alex

2010-01-01

The ability of progenitor cells to exit the cell cycle is essential for proper embryonic development and homeostasis, but the mechanisms governing cell cycle exit are still not fully understood. Here, we tested the requirement for the retinoblastoma (Rb) protein and its family members p107 and p130 in G0/G1 arrest and differentiation in mammalian cells. We found that Rb family triple knockout (TKO) mouse embryos survive until days 9–11 of gestation. Strikingly, some TKO cells, including in epithelial and neural lineages, are able to exit the cell cycle in G0/G1 and differentiate in teratomas and in culture. This ability of TKO cells to arrest in G0/G1 is associated with the repression of key E2F target genes. Thus, G1 arrest is not always dependent on Rb family members, which illustrates the robustness of cell cycle regulatory networks during differentiation and allows for the identification of candidate pathways to inhibit the expansion of cancer cells with mutations in the Rb pathway. PMID:21059851

Framework for Comparative Risk Analysis of Dredged Material Disposal Options.

DTIC Science & Technology

1986-10-01

TC3898-62 DACU67-85-D-8829 UNCLASSIFIED F/G 24/3 NL 125 ൖ ൘ ilil;1III -I uPSDDAR UTReports m ~ Puget Sound Dredged DipslAnalysis e~ od Washington State...I rB T T for Puget Sound Dredged Disposal Analysis c/o U.S. Army Corps of Engineers Seattle District 1 A" October, 1986 l-jq .__ .. _ Tetra Tech, Inc...priority pollutants C-2 E-1 Hypothetical example of total or bulk contaminant concentrations in four Puget Sound sediments E-1 E-2 ’Hypothetical example

Simultaneous observations of electromagnetically induced transparency (EIT) and absorption (EIA) in a multi-level V-type system of 87Rb and theoretical simulation of the observed spectra using a multi-mode approach

NASA Astrophysics Data System (ADS)

Das, Bankim Chandra; Bhattacharyya, Dipankar; Das, Arpita; Chakrabarti, Shrabana; De, Sankar

2016-12-01

We report here simultaneous experimental observation of Electromagnetically Induced Transparency (EIT) and Electromagnetically Induced Absorption (EIA) in a multi-level V-type system in D2 transition of 87Rb, i.e., F =2 →F' with a strong pump and a weak probe beam. We studied the probe spectrum by locking the probe beam to the transition F =2 →F'=2 while the pump is scanned from F =2 →F' . EIA is observed for the open transition (F =2 →F'=2 ) whereas EIT is observed in the closed transition (F =2 →F'=3 ). Sub natural line-width is observed for the EIA. To simulate the observed spectra theoretically, Liouville equation for the three-level V-type system is solved analytically with a multi-mode approach for the density matrix elements. We assumed both the pump and the probe beams can couple the excited states. A multi-mode approach for the coherence terms facilitates the study of all the frequency contributions due to the pump and the probe fields. Since the terms contain higher harmonics of the pump and the probe frequencies, we expressed them in Fourier transformed forms. To simulate the probe spectrum, we have solved inhomogeneous difference equations for the coherence terms using the Green's function technique and continued fraction theory. The experimental line-widths of the EIT and the EIA are compared with our theoretical model. Our system can be useful in optical switching applications as it can be precisely tuned to render the medium opaque and transparent simultaneously.

Simultaneous observations of electromagnetically induced transparency (EIT) and absorption (EIA) in a multi-level V-type system of 87Rb and theoretical simulation of the observed spectra using a multi-mode approach.

PubMed

Das, Bankim Chandra; Bhattacharyya, Dipankar; Das, Arpita; Chakrabarti, Shrabana; De, Sankar

2016-12-14

We report here simultaneous experimental observation of Electromagnetically Induced Transparency (EIT) and Electromagnetically Induced Absorption (EIA) in a multi-level V-type system in D 2 transition of Rb87, i.e., F=2→F ' with a strong pump and a weak probe beam. We studied the probe spectrum by locking the probe beam to the transition F=2→F ' =2 while the pump is scanned from F=2→F ' . EIA is observed for the open transition (F=2→F ' =2) whereas EIT is observed in the closed transition (F=2→F ' =3). Sub natural line-width is observed for the EIA. To simulate the observed spectra theoretically, Liouville equation for the three-level V-type system is solved analytically with a multi-mode approach for the density matrix elements. We assumed both the pump and the probe beams can couple the excited states. A multi-mode approach for the coherence terms facilitates the study of all the frequency contributions due to the pump and the probe fields. Since the terms contain higher harmonics of the pump and the probe frequencies, we expressed them in Fourier transformed forms. To simulate the probe spectrum, we have solved inhomogeneous difference equations for the coherence terms using the Green's function technique and continued fraction theory. The experimental line-widths of the EIT and the EIA are compared with our theoretical model. Our system can be useful in optical switching applications as it can be precisely tuned to render the medium opaque and transparent simultaneously.

Manipulation of ultracold Rb atoms using a single linearly chirped laser pulse.

PubMed

Collins, T A; Malinovskaya, S A

2012-06-15

At ultracold temperatures, atoms are free from thermal motion, which makes them ideal objects of investigations aiming to advance high-precision spectroscopy, metrology, quantum computation, producing Bose condensates, etc. The quantum state of ultracold atoms may be created and manipulated by making use of quantum control methods employing low-intensity pulses. We theoretically investigate population dynamics of ultracold Rb vapor induced by nanosecond linearly chirped pulses having kW/cm2 beam intensity and show a possibility of controllable population transfer between hyperfine (HpF) levels of 5(2)/S(1/2) state through Raman transitions. Satisfying the one-photon resonance condition with the lowest of the HpF states of 5(2)/P(1/2) or 5(2)/P(3/2) state allows us to enter the adiabatic region of population transfer at very low field intensities, such that corresponding Rabi frequencies are less than or equal to the HpF splitting. This methodology provides a robust way to create a specifically designed superposition state in Rb in the basis of HpF levels and perform state manipulation controllable on the picosecond-to-nanosecond time scale.

NASA Astrophysics Data System (ADS)

Knight, Kevin S.; Marshall, William G.; Hawkins, Philip M.

2014-06-01

The fluoroperovskite phase RbCaF3 has been investigated using high-pressure neutron powder diffraction in the pressure range ~0-7.9 GPa at room temperature. It has been found to undergo a first-order high-pressure structural phase transition at ~2.8 GPa from the cubic aristotype phase to a hettotype phase in the tetragonal space group I4/ mcm. This transition, which also occurs at ~200 K at ambient pressure, is characterised by a linear phase boundary and a Clapeyron slope of 2.96 × 10-5 GPa K-1, which is in excellent agreement with earlier, low-pressure EPR investigations. The bulk modulus of the high-pressure phase (49.1 GPa) is very close to that determined for the low-pressure phase (50.0 GPa), and both are comparable with those determined for the aristotype phases of CsCdF3, TlCdF3, RbCdF3, and KCaF3. The evolution of the order parameter with pressure is consistent with recent modifications to Landau theory and, in conjunction with polynomial approximations to the pressure dependence of the lattice parameters, permits the pressure variation of the bond lengths and angles to be predicted. On entering the high-pressure phase, the Rb-F bond lengths decrease from their extrapolated values based on a third-order Birch-Murnaghan fit to the aristotype equation of state. By contrast, the Ca-F bond lengths behave atypically by exhibiting an increase from their extrapolated magnitudes, resulting in the volume and the effective bulk modulus of the CaF6 octahedron being larger than the cubic phase. The bulk moduli for the two component polyhedra in the tetragonal phase are comparable with those determined for the constituent binary fluorides, RbF and CaF2.

A Noncanonical Role for the CKI-RB-E2F Cell Cycle Signaling Pathway in Plant Effector-Triggered Immunity

PubMed Central

Wang, Shui; Gu, Yangnan; Zebell, Sophia G.; Anderson, Lisa K.; Wang, Wei; Mohan, Rajinikanth; Dong, Xinnian

2014-01-01

SUMMARY Effector-triggered immunity (ETI), the major host defense mechanism in plants, is often associated with programmed cell death (PCD). Plants lack close homologs of caspases, the key mediators of PCD in animals. So although the NB-LRR receptors involved in ETI are well studied, how they activate PCD and confer disease resistance remains elusive. We show that the Arabidopsis nuclear envelope protein, CPR5, negatively regulates ETI and the associated PCD through a physical interaction with CYCLIN-DEPENDENT KINASE INHIBITORs (CKIs). Upon ETI induction, CKIs are released from CPR5 to cause over-activation of another core cell cycle regulator, E2F. In cki and e2f mutants, ETI responses induced by both TIR-NB-LRR and CC-NB-LRR classes of immune receptors are compromised. We further show that E2F is deregulated during ETI probably through CKI-mediated hyperphosphorylation of RETINOBLASTOMA-RELATED 1 (RBR1). This study demonstrates that canonical cell cycle regulators also play important noncanonical roles in plant immunity. PMID:25455564

New high performing scintillators: RbSr2Br5:Eu and RbSr2I5:Eu

NASA Astrophysics Data System (ADS)

Stand, L.; Zhuravleva, M.; Johnson, J.; Koschan, M.; Lukosi, E.; Melcher, C. L.

2017-11-01

We report the crystal growth and scintillation properties of two new ternary metal halide scintillators, RbSr2Br5 and RbSr2I5, activated with divalent europium. Transparent 7 mm diameter single crystals with 2.5% Eu2+ were grown in evacuated quartz ampoules via the Bridgman technique. RbSr2Br5 and RbSr2I5 have monoclinic crystal structures with densities of 4.18 g/cm3 and 4.55 g/cm3 respectively. These materials are hygroscopic and have some intrinsic radioactivity due to the presence of 87Rb. Luminescence properties typical of the 5d-4f radiative transition in Eu2+ were observed. The X-ray excited emissions consisted of singular peaks centered at 429 nm for RbSr2Br5:Eu 2.5% and 445 nm for RbSr2I4:Eu 2.5%. RbSr2Br5:Eu 2.5% had a light yield of 64,700 photons/MeV, with an energy resolution of 4.0%, and RbSr2I5:Eu 2.5% had a light yield of 90,400 ph/MeV with an energy resolution of 3.0% at 662 keV. Both crystals have an excellent proportional response over a wide range of gamma-ray energies.

Adimensional theory of shielding in ultracold collisions of dipolar rotors

NASA Astrophysics Data System (ADS)

González-Martínez, Maykel L.; Bohn, John L.; Quéméner, Goulven

2017-09-01

We investigate the electric field shielding of ultracold collisions of dipolar rotors, initially in their first rotational excited state, using an adimensional approach. We establish a map of good and bad candidates for efficient evaporative cooling based on this shielding mechanism, by presenting the ratio of elastic over quenching processes as a function of a rescaled rotational constant B ˜=B /sE3 and a rescaled electric field F ˜=d F /B . B ,d ,F ,andsE 3 are respectively the rotational constant, the full electric dipole moment of the molecules, the applied electric field, and a characteristic dipole-dipole energy. We identify two groups of bi-alkali-metal dipolar molecules. The first group, including RbCs, NaK, KCs, LiK, NaRb, LiRb, NaCs, and LiCs, is favorable with a ratio over 1000 at collision energies equal to (or even higher than) their characteristic dipolar energy. The second group, including LiNa and KRb, is not favorable. More generally, for molecules well described by Hund's case b, our adimensional study provides the conditions of efficient evaporative cooling. The range of appropriate rescaled rotational constant and rescaled field is approximately B ˜≥108 and 3.25 ≤F ˜≤3.8 , with a maximum ratio reached for F ˜≃3.4 for a given B ˜. We also discuss the importance of the electronic van der Waals interaction on the adimensional character of our study.

ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

PubMed Central

Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

2013-01-01

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

Novel calix[4]pyrrole assembly: Punctilious recognition of F- and Cu+2 ions

NASA Astrophysics Data System (ADS)

Bhatt, Keyur D.; Shah, Hemangini; Modi, Krunal M.; Kongor, Anita; Panchal, Manthan; Jain, Vinod K.

2017-12-01

A new tetra hydroxyl methoxy substituted calix[4]pyrrole (HMCP) has been synthesized and found to form stable complex with F- ions and Cu+2 ions. The red-shift in absorption band of HMCP was observed due to the presence of both cation (Cu+2) and anion (F-). These results displayed that formation of the complex is mainly attributed to the charge-transfer interactions between HMCP with electron deficient pyrrole rings and the electron-rich guest ions. Molecular dynamics simulation predicts intermolecular H-bonds and van der Waals types of interaction for the complex formation of HMCP-Cu+2 and HMCP-F-.

Trinuclear organooxotin assemblies from solvothermal synthesis reaction: Crystal structure, hydrogen bonding and π π stacking interaction

NASA Astrophysics Data System (ADS)

Ma, Chunlin; Sun, Junshan; Zhang, Rufen

2007-05-01

Two new trinuclear mono-organooxotin(IV) complexes with 2,3,4,5-tetrafluorobenzoic acid and sodium perchlorate of the types: [(SnR) 3(OH)(2,3,4,5-F 4C 6HCO 2) 4 · ClO 4] · [O 2CC 6HF 4](R = PhCH 2, 1; o- F-PhCH 2 for 2), have been solvothermally synthesized and structurally characterized by elemental, IR, 1H, 13C and 119Sn NMR and X-ray crystallography diffraction analyses. Complex 2 is also characterized by X-ray crystallography diffraction analyses. In complex 2, four carboxyl groups and a perchlorate bridged three tin atoms in a cyclohexane chair arrangement and form the basic framework. A hydroxyl group comprises the oxygen components of the stannoxane ring system. In these complexes, weak but significant intramolecular hydrogen bonding and π-π stacking interaction are also shown. These contacts lead to aggregation and supramolecular assembly of complexes 1 and 2 into 1D or 2D framework.

Constraining the 40K decay constant with 87Rb-87Sr - 40K-40Ca chronometer intercomparison

NASA Astrophysics Data System (ADS)

Naumenko-Dèzes, Maria O.; Nägler, Thomas F.; Mezger, Klaus; Villa, Igor M.

2018-01-01

A literature survey reveals that the K-Ar chronometer gives ages that are ca. 1% younger than U-Pb ages. This offset is generally attributed to an inaccurate 40K decay constant. Three geological samples selected from a shortlist of eight with known U-Pb ages were investigated using detailed petrological methods and subsequently the Rb-Sr and K-Ca chronometers in order (a) to evaluate if they meet the requirement of a geological history reflecting a ;point-like; event (i.e. isochronous formation and subsequent ideal closure of chronometers) and (b) to narrow down the systematic uncertainty on the 40K decay constant by investigating the metrologically traceable K-Ca decay branch. Lepidolite of the Rubikon pegmatite, Namibia, was dated with Rb-Sr at 504.7 ± 4.2 Ma and the phlogopite and apatite from the Phalaborwa carbonatite complex, South Africa, yielded a Rb-Sr age of 2058.9 ± 5.2 Ma. Both Rb-Sr ages agree with published U-Pb ages. The Rb-Sr age of the late Archean Siilinjärvi carbonatite, Finland, records a later regional metamorphic event at 1869 ± 10 Ma. Only the samples from the Phalaborwa complex represent a ;point-like; magmatic event and meet all the criteria to make them suitable for the 40K decay constant intercalibration. The Phalaborwa K-Ca isochron has a slope of 1.878 ± 0.012. Forcing the K-Ca isochron to coincide with the U-Pb and Rb-Sr ages gives one equation with two unknowns. Assuming that the branching ratio of the K-Ca branch, BCa, lies in the interval (k = 2) of all published references, 0.8925 < BCa < 0.8963, then the most reliable uncertainty interval (k = 2) for the total 40K decay constant, λtot, is calculated as 5.484 × 10-10 a-1 < λtot < 5.498 × 10-10 a-1. This confirms that the currently used IUGS recommendation is inaccurate.

Phytocalpain controls the proliferation and differentiation fates of cells in plant organ development.

PubMed

Ahn, Joon-Woo; Kim, Moonil; Lim, Jeong Hwa; Kim, Gyung-Tae; Pai, Hyun-Sook

2004-06-01

Calpain, a calcium-dependent cysteine protease, plays an essential role in basic cellular processes in animal cells, including cell proliferation, apoptosis, and differentiation. NbDEK encodes the calpain homolog of N. benthamiana. In this study, virus-induced gene silencing (VIGS) of NbDEK resulted in arrested organ development and hyperplasia in all the major plant organs examined. The epidermal layers of the leaves and stems were covered with hyperproliferating cell masses, and stomata and trichome development was severely inhibited. During flower development, a single dome-like structure was grown from the flower meristem to generate a large cylinder-shaped flower lacking any floral organs. At the cellular level, cell division was sustained in tissues that were otherwise already differentiated, and cell differentiation was severely hampered. NbDEK is ubiquitously expressed in all the plant tissues examined. In the abnormal organs of the NbDEK VIGS lines, protein levels of D-type cyclins (CycD)2, CycD3, and proliferating cell nuclear antigen (PCNA) were greatly elevated, and transcription of E2F (E2 promoter binding factor), E2F-regulated genes, retinoblastoma (Rb), and KNOTTED1 (KN1)-type homeobox genes was also stimulated. These results suggest that phytocalpain is a key regulator of cell proliferation and differentiation during plant organogenesis, and that it acts partly by controlling the CycD/Rb pathway.

Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.

PubMed

Findeisen, Hannes M; Pearson, Kevin J; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; de Cabo, Rafael; Bruemmer, Dennis

2011-04-14

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.

Oxidative Stress Accumulates in Adipose Tissue during Aging and Inhibits Adipogenesis

PubMed Central

Findeisen, Hannes M.; Pearson, Kevin J.; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L.; Cohn, Dianne; Heywood, Elizabeth B.; de Cabo, Rafael; Bruemmer, Dennis

2011-01-01

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G1→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction. PMID:21533223

Chemosynthesis pathway and bioactivities comparison of saponins in radix and flower of Panax notoginseng (Burk.) F.H. Chen.

PubMed

Zhou, Xin; Chen, Lin-Lin; Xie, Rui Fang; Lam, Wing; Zhang, Zi-Jia; Jiang, Zao-Li; Cheng, Yung-Chi

2017-04-06

Panax notoginseng (Burk.) F.H. Chen is a well known medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H. Chen. The liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H. Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways. The results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs another. Based on relative content of saponins, the chemosynthesis pathway of ingredients in radix and flower are proposed: for radix, both PPT (Protopanaxatriol) and PPD (Protopanaxadiol) type triterpenoids are involved, the main pathway is PPT→Rb 1 →Rg 1 →R 1 or PPD→Rh 2 20s→Rg3(20s)→R d →Rb 1 ; for flowers, only PPD is main passage with PPD→Rh 2 (20s)→Rg 3 (20s)→R d →Rb 2 →Fc. The results of signal transcription assays demonstrated that herb water extract of radix and flower had no significant influences on most of transcription activities. However, total saponins of radix and flower which have highly content of saponins were able to inhibit the inflammatory related transcriptional activities and their related mRNA expression of IFNα, TNFα, il-6 and TGFβ as well as induce anti-oxygen NrF2 activities. In summary, although chemical ingredients and chemosynthesis pathway of flower and radix for Panax notoginseng (Burk.) F.H. Chen were different, these differences might not result in their differences of pharmacological activities. Copyright © 2017. Published by Elsevier B.V.

Alkali metal and ammonium fluoro(trifluoroacetato)metallates M'[ M''3(μ3-F)(CF3COO)6(CF3COOH)3], where M' = Li, Na, K, NH4, Rb, or Cs and M'' = Ni or Co. Synthesis and crystal structures

NASA Astrophysics Data System (ADS)

Tereshchenko, D. S.; Morozov, I. V.; Boltalin, A. I.; Karpova, E. V.; Glazunova, T. Yu.; Troyanov, S. I.

2013-01-01

A series of fluoro(trifluoroacetato)metallates were synthesized by crystallization from solutions in trifluoroacetic acid containing nickel(II) or cobalt(II) nitrate hydrates and alkali metal or ammonium fluorides: Li[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)3 ( I), M'[Ni3(μ3-F)(CF3COO)6(CF3COOH)3] ( M' = Na ( II), NH4 ( IV), Rb ( V), and Cs ( VI)), NH4[Co3(μ3-F) (CF3COO)6(CF3COOH)3] ( III), and Cs[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)0.5 ( VII). The crystal structures of these compounds were determined by single-crystal X-ray diffraction. All structures contain triangular trinuclear complex anions [ M 3″(μ3-F)(CF3COO)6(CF3COOH)3]- ( M″ = Ni, Co) structurally similar to trinuclear 3d metal oxo carboxylate complexes. The three-coordinated F atom is located at the center of the triangle formed by Ni(II) or Co(II) atoms. The metal atoms are linked in pairs by six bridging trifluoroacetate groups located above and below the plane of the [ M″3 F] triangle. The oxygen atoms of the axial CF3COOH molecules complete the coordination environment of M″ atoms to an octahedron.

Detailed electrochemical studies of the tetraruthenium polyoxometalate water oxidation catalyst in acidic media: identification of an extended oxidation series using Fourier transformed alternating current voltammetry.

PubMed

Lee, Chong-Yong; Guo, Si-Xuan; Murphy, Aidan F; McCormac, Timothy; Zhang, Jie; Bond, Alan M; Zhu, Guibo; Hill, Craig L; Geletii, Yurii V

2012-11-05

The electrochemistry of the water oxidation catalyst, Rb(8)K(2)[{Ru(4)O(4)(OH)(2)(H(2)O)(4)}(γ-SiW(10)O(36))(2)] (Rb(8)K(2)-1(0)) has been studied in the presence and absence of potassium cations in both hydrochloric and sulfuric acid solutions by transient direct current (dc) cyclic voltammetry, a steady state dc method in the rotating disk configuration and the kinetically sensitive technique of Fourier transformed large-amplitude alternating current (ac) voltammetry. In acidic media, the presence of potassium ions affects the kinetics (apparent rate of electron transfer) and thermodynamics (reversible potentials) of the eight processes (A'/A to H/H') that are readily detected under dc voltammetric conditions. The six most positive processes (A'/A to F/F'), each involve a one electron ruthenium based charge transfer step (A'/A, B'/B are Ru(IV/V) oxidation and C/C' to F/F' are Ru(IV/III) reduction). The apparent rate of electron transfer of the ruthenium centers in sulfuric acid is higher than in hydrochloric acid. The addition of potassium cations increases the apparent rates and gives rise to a small shift of reversible potential. Simulations of the Fourier transformed ac voltammetry method show that the B'/B, E/E', and F/F' processes are quasi-reversible, while the others are close to reversible. A third Ru(IV/V) oxidation process is observed just prior to the positive potential limit via dc methods. Importantly, the ability of the higher harmonic components of the ac method to discriminate against the irreversible background solvent process allows this (process I) as well as an additional fourth reversible ruthenium based process (J) to be readily identified. The steady-state rotating disk electrode (RDE) method confirmed that all four Ru-centers in Rb(8)K(2)-1(0) are in oxidation state IV. The dc and ac data indicate that reversible potentials of the four ruthenium centers are evenly spaced, which may be relevant to understanding of the water oxidation electrocatalysis. A profound effect of the potassium cation is observed for the one-electron transfer process (G/G') assigned to Ru(III/II) reduction and the multiple electron transfer reduction process (H/H') that arise from the tungstate polyoxometalate framework. A significant shift of E°' to a more positive potential value for process H/H' was observed on removal of K(+) (~100 mV in H(2)SO(4) and ~50 mV in HCl).

Human T-cell leukemia virus type 1 Tax and cell cycle progression: role of cyclin D-cdk and p110Rb.

PubMed

Neuveut, C; Low, K G; Maldarelli, F; Schmitt, I; Majone, F; Grassmann, R; Jeang, K T

1998-06-01

Human T-cell leukemia virus type 1 is etiologically linked to the development of adult T-cell leukemia and various human neuropathies. The Tax protein of human T-cell leukemia virus type I has been implicated in cellular transformation. Like other oncoproteins, such as Myc, Jun, and Fos, Tax is a transcriptional activator. How it mechanistically dysregulates the cell cycle is unclear. Previously, it was suggested that Tax affects cell-phase transition by forming a direct protein-protein complex with p16(INK4a), thereby inactivating an inhibitor of G1-to-S-phase progression. Here we show that, in T cells deleted for p16(INK4a), Tax can compel an egress of cells from G0/G1 into S despite the absence of serum. We also show that in undifferentiated myocytes, expression of Tax represses cellular differentiation. In both settings, Tax expression was found to increase cyclin D-cdk activity and to enhance pRb phosphorylation. In T cells, a Tax-associated increase in steady-state E2F2 protein was also documented. In searching for a molecular explanation for these observations, we found that Tax forms a protein-protein complex with cyclin D3, whereas a point-mutated and transcriptionally inert Tax mutant failed to form such a complex. Interestingly, expression of wild-type Tax protein in cells was also correlated with the induction of a novel hyperphosphorylated cyclin D3 protein. Taken together, these findings suggest that Tax might directly influence cyclin D-cdk activity and function, perhaps by a route independent of cdk inhibitors such as p16(INK4a).

The PPARα/p16INK4a Pathway inhibits Vascular Smooth Muscle Cell Proliferation by repressing Cell Cycle-dependent Telomerase Activation

PubMed Central

Gizard, Florence; Nomiyama, Takashi; Zhao, Yue; Findeisen, Hannes M.; Heywood, Elizabeth B.; Jones, Karrie L.; Staels, Bart; Bruemmer, Dennis

2009-01-01

Peroxisome Proliferator-Activated Receptor (PPAR) α, the molecular target for fibrates used to treat dyslipidemia, exerts pleiotropic effects on vascular cells. In vascular smooth muscle cells (VSMCs), we have previously demonstrated that PPARα activation suppresses G1→S cell cycle progression by targeting the cyclin-dependent kinase inhibitor p16INK4a (p16). In the present study, we demonstrate that this inhibition of VSMC proliferation by PPARα is mediated through a p16-dependent suppression of telomerase activity, which has been implicated in key cellular functions including proliferation. PPARα activation inhibited mitogen-induced telomerase activity by repressing the catalytic subunit telomerase reverse transcriptase (TERT) through negative cross-talk with an E2F-1-dependent trans-activation of the TERT promoter. This trans-repression involved the recruitment of the retinoblastoma (RB) family proteins p107 and p130 to the TERT promoter resulting in impaired E2F-1 binding, an effect which was dependent on p16. The inhibition of cell proliferation by PPARα activation was lost in VSMC following TERT overexpression or knock-down, pointing to a key role of telomerase as a target for the antiproliferative effects of PPARα. Finally, we demonstrate that PPARα agonists suppress telomerase activation during the proliferative response following vascular injury indicating that these findings are applicable in vivo. In concert, these results demonstrate that the anti-proliferative effects of PPARα in VSMCs depend on the suppression of telomerase activity by targeting the p16/RB/E2F transcriptional cascade. PMID:18818403

Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp. causes G1 cell cycle arrest and induces apoptosis of HeLa cells.

PubMed

Lee, Chul-Hoon; Lim, Haeyoung; Moon, Sangik; Shin, Choonshik; Kim, Seunghyun; Kim, Bum-Joon; Lim, Yoongho

2007-06-01

In the course of screening for anticancer agents, a novel active compound, F3-2-5, was isolated from culture broth of Streptomyces sp., KACC91015. Its structure was identified using nuclear magnetic resonance, mass spectrometry, and molecular modeling experiments, and confirmed by total synthesis. The growth of various human cancer cell lines was inhibited in a dose-dependent manner by 0.06-0.48 mM F3-2-5 over 24 h. Its IC(50) values were estimated at 37 microM on HeLa, 72 microM on A549, and 190 microM on HT-29 cells. However, F3-2-5 had no antiproliferative effect on normal lymphocytes and normal fibroblasts used as controls. Moreover, it affected cell cycle regulation and caused apoptosis of the HeLa cells; chromatin condensation and DNA fragmentation were observed in cells exposed to 80 microM F3-2-5. Western blot analysis revealed that F3-2-5 inhibited phosphorylation of retinoblastoma protein (pRb) and reduced expression of cyclin-dependent kinase-4 and -6, and cyclin D1 and E, while levels of p53 and p21(WAF1/CIP1) increased. Taken together, these findings show that F3-2-5 inhibits proliferation of HeLa cells by inducing G(1) phase arrest as a consequence of inhibition of pRb phosphorylation following up-regulation of p21(WAF1/CIP1) and p53. Furthermore, apoptosis in HeLa cells treated with F3-2-5 was associated with an increase in Bax and p53, leading to release of cytochrome c, activation of caspase-3, and -8, and cleavage of poly (ADP-ribose) polymerase.

Parasite-specific IL-17-type cytokine responses and soluble IL-17 receptor levels in Alveolar Echinococcosis patients.

PubMed

Lechner, Christian J; Grüner, Beate; Huang, Xiangsheng; Hoffmann, Wolfgang H; Kern, Peter; Soboslay, Peter T

2012-01-01

Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.

51. Neg. No. F183E, Mar 16, 1937, EXTERIORFORD ASSEMBLY PLANT ...

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

51. Neg. No. F-183E, Mar 16, 1937, EXTERIOR-FORD ASSEMBLY PLANT EAST SIDE, SHOWING OIL WELL #6 IN THE FOREGROUND, NORTHEAST OF THE ASSEMBLY PLANT - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs.

PubMed

Lahr, Roni M; Fonseca, Bruno D; Ciotti, Gabrielle E; Al-Ashtal, Hiba A; Jia, Jian-Jun; Niklaus, Marius R; Blagden, Sarah P; Alain, Tommy; Berman, Andrea J

2017-04-07

The 5'terminal oligopyrimidine (5'TOP) motif is a cis -regulatory RNA element located immediately downstream of the 7-methylguanosine [m 7 G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (m 7 GTP), and a capped cytidine (m 7 GpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.

Structural characterization of the Yersinia pestis type III secretion system needle protein YscF in complex with its heterodimeric chaperone YscE/YscG

PubMed Central

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.; Cherry, Scott; Waugh, David S.

2008-01-01

Summary The plague-causing bacterium Yersinia pestis utilizes a Type III Secretion System (T3SS) to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as "chaperones" to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 Å resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonas aeruginosa T3SS, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat (TPR) family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal TPR motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the N-terminal 49 residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex. PMID:18281060

Structural Characterization of the Yersinia pestis Type III Secretion System Needle Protein YscF in Complex with Its Heterodimeric Chaperone YscE/YscG

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

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.

2008-05-03

The plague-causing bacterium Yersinia pestis utilizes a type III secretion system to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as 'chaperones' to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 {angstrom} resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonasmore » aeruginosa type III secretion system, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal tetratricopeptide repeat motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the 49 N-terminal residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex.« less

Emerging Therapeutics Targeting mRNA Translation

PubMed Central

Malina, Abba; Mills, John R.; Pelletier, Jerry

2012-01-01

A defining feature of many cancers is deregulated translational control. Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5′-cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein synthesis, which is controlled by the heterotrimeric eukaryotic initiation complex eIF4F. Thus, eIF4F in particular, and translation initiation in general, represent an exploitable vulnerability and unique opportunity for therapeutic intervention in many transformed cells. In this article, we discuss the development, mode of action and biological activity of a number of small-molecule inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well as compounds that more directly block eIF4F activity. PMID:22474009

Site preference for luminescent activator ions in doped fluoroperovskite RbZnF3.

PubMed

Saroj, Sanjay Kumar; Nagarajan, Rajamani

2018-08-05

With the dual objective of investigating the site preferences of larger sized activator ions and to append luminescence property to the perovskite structured RbZnF 3 , doping of manganese(II), cerium(III), europium(III) and terbium(III) ions (5 mol%) was carried out. Although cubic symmetry of RbZnF 3 was preserved for all the doped samples, site preference of rare-earth ions for the A-site Rb + leading to an inverse perovskite arrangement has been noticed from careful analysis of lattice parameters from refinement of powder X-ray diffraction data. Undoped RbZnF 3 exhibited rod-like morphology in the transmission electron microscopic image. In addition to an intense band around 230 nm assignable to the charge transfer from ZnF 3 - to Rb + , typical transitions of respective dopant ions were observed in their UV-visible spectra. The doped samples showed luminescence in blue, green and red regions and time decay experiments suggested uniform dispersion of them without any clustering effect. The lower phonon energy of RbZnF 3 matrix by virtue of the presence of heavier rubidium at the A-site together with its doping with rare-earth ions resulting in an inverse perovskite like arrangement could favour their utility in various practical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Low Work Function 2.81 eV Rb2CO3-Doped Polyethylenimine Ethoxylated for Inverted Organic Light-Emitting Diodes.

PubMed

Kim, Jeonggi; Kim, Hyo-Min; Jang, Jin

2018-06-06

We report a low work function (2.81 eV), Rb 2 CO 3 -doped polyethyleneimine ethoxylated (PEIE) which is used for highly efficient and long-lifetime, inverted organic light-emitting diodes (OLEDs). Doping Rb 2 CO 3 into PEIE decreases the work function of Li-doped ZnO (LZO) by 1.0 eV and thus significantly improves electron injection ability into the emission layer (EML). The inverted OLED with PEIE:Rb 2 CO 3 interfacial layer (IL) exhibits higher efficiency and longer operation lifetime than those of the device with a PEIE IL. It is found also that Mg-doped ZnO (MZO) can be used instead of LZO as electron transporting layer. Rb 2 CO 3 shows a low work function of 2.81 eV. The OLED with MZO/PEIE:Rb 2 CO 3 exhibits low operating voltage of 5.0 V at 1000 cd m -2 and low efficiency roll-off of 11.8% at high luminance of 10 000 cd m -2 . The results are due to the suppressed exciton quenching at the MZO/organic EML interface.

Friedreich's Ataxia Variants I154F and W155R Diminish Frataxin-Based Activation of the Iron-Sulfur Cluster Assembly Complex

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

Tsai, Chi-Lin; Bridwell-Rabb, Jennifer; Barondeau, David P

2011-11-07

Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease that has been linked to defects in the protein frataxin (Fxn). Most FRDA patients have a GAA expansion in the first intron of their Fxn gene that decreases protein expression. Some FRDA patients have a GAA expansion on one allele and a missense mutation on the other allele. Few functional details are known for the ~15 different missense mutations identified in FRDA patients. Here in vitro evidence is presented that indicates the FRDA I154F and W155R variants bind more weakly to the complex of Nfs1, Isd11, and Isu2 and thereby are defectivemore » in forming the four-component SDUF complex that constitutes the core of the Fe-S cluster assembly machine. The binding affinities follow the trend Fxn ~ I154F > W155F > W155A ~ W155R. The Fxn variants also have diminished ability to function as part of the SDUF complex to stimulate the cysteine desulfurase reaction and facilitate Fe-S cluster assembly. Four crystal structures, including the first for a FRDA variant, reveal specific rearrangements associated with the loss of function and lead to a model for Fxn-based activation of the Fe-S cluster assembly complex. Importantly, the weaker binding and lower activity for FRDA variants correlate with the severity of disease progression. Together, these results suggest that Fxn facilitates sulfur transfer from Nfs1 to Isu2 and that these in vitro assays are sensitive and appropriate for deciphering functional defects and mechanistic details for human Fe-S cluster biosynthesis.« less

Luminescence and Excitation Spectra of U 3+ doped RbY 2 Cl 7 Single Crystals

DOE PAGES

Karbowiak, M.; Murdoch, K.; Drożdżyński, J.; ...

1996-08-01

Uranium(3+) doped single crystals of RbY 2 Cl 7 with a uranium concentration of 0.05% and 0.2% were grown by the Bridgman-Stockbarger method using RbU 2 Cl 7 as the doping substance. Polished plates of ca. 5 mm in diameter were used for measurements of luminescence and excitation spectra. And since the U 3+ ions occupy two somewhat different site symmetries, a splitting of all observed f-f bands was observed. Furthermore, the analysis of the spectra enabled definitively an assignment of 22 crystal field bands for both site symmetries as well as the total crystal field splitting of the groundmore » level, equal to 473 cm -1 and 567 cm -1 for the first and second site symmetry, respectively.« less

K(86Rb) transport heterogeneity in the low-density fraction of sickle cell anemia red blood cells.

PubMed

Etzion, Z; Lew, V L; Bookchin, R M

1996-10-01

Previous studies have suggested ion transport heterogeneity among sickle cell anemia (SS) reticulocytes that could influence their dehydration susceptibility. We examined Ca2(+)-independent K transport in the lowest density (F1), reticulocyte-rich SS cells, measuring the effects of acidification, ouabain, and bumetanide on their unidirectional K(86Rb) fluxes. Unlike those of normal red blood cells and SS discocytes, the SS-F1 K(86Rb) fluxes were highly nonlinear, with large 5-min flux components (previously unobserved) and a more gradual decline over 60 min. Analysis revealed two distinct K pools: a rapid-turnover pool in a small fraction of cells, whose major ouabain-resistant K(86Rb) transport path showed distinctive properties including inhibition by high concentrations of bumetanide (> or = 1 mM) and stimulation at pH 7.0, and another heterogeneous, relatively slow-turnover pool, in most of the F1 cells, whose main ouabain-resistant K(86Rb) path was insensitive to bumetanide but was stimulated at pH 7.0, which is consistent with heterogeneous expression of the acid-sensitive K-Cl cotransport and with both rapid and slower generation of dehydrated SS cells.

Bio-Inspired Materials and Devices for Chemical and Biological Defense

DTIC Science & Technology

2010-09-01

Assembled Soft Matter for in vivo Optical Imaging. PNAS 2005, 102(8), pp 2922-2927. 37 Reiner, J.E.; Wells, J.M.; Kishore, R.B.; Pfefferkorn, C...materials ex- vivo as well as the more common standpoint of using nonbiological materials in biological environments, i.e., biocompatibility. Many...tube constitute a MWCNT . In comparison with SWCNTs, multiwalled tubes sacrifice electrical properties in favor of stability and ease of manufacture

Raman spectra and phase transitions in Rb{sub 2}KInF{sub 6} elpasolite

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

Krylov, A. S.; Krylova, S. N., E-mail: slanky@iph.krasn.ru; Vtyurin, A. N.

2011-01-15

The Raman spectra of Rb{sub 2}KInF{sub 6} elpasolite crystal have been studied in a wide temperature range, including two phase transitions: from the cubic phase to the tetragonal phase and then to the monoclinic phase. Several anomalies of internal modes of InF{sub 6} octahedra and low-frequency lattice vibrations, which are related to the structural changes at the transition points, have been found and quantitatively analyzed. The results of a quantitative analysis of the temperature dependences of the parameters of spectral lines are in good agreement with the thermodynamic data on the phase transitions.

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

Xia, Shuangluo; Konigsberg, William H.; Wang, Jimin

Results obtained using 2,4-difluorotoluene nucleobase (dF) as a nonpolar thymine isostere by Kool and colleagues challenged the Watson-Crick dogma that hydrogen bonds between complementary bases are an absolute requirement for accurate DNA replication. Here, we report crystal structure of an RB69 DNA polymerase L561A/S565G/Y567A triple mutant ternary complex with a templating dF opposite dTTP at 1.8 {angstrom}-resolution. In this structure, direct hydrogen bonds were observed between: (i) dF and the incoming dTTP, (ii) dF and residue G568 of the polymerase, and (iii) dF and ordered water molecules surrounding the nascent base pair. Therefore, this structure provides evidence that a templatingmore » dF can form novel hydrogen bonds with the incoming dTTP and with the enzyme that differ from those formed with a templating dT.« less

Structural diversities induced by cation sizes in a series of fluorogermanophosphates: A2[GeF2(HPO4)2] (A = Na, K, Rb, NH4, and Cs).

PubMed

Chen, Zhang-Gai; Huang, Xia; Zhuang, Rong-Chuan; Zhang, Yu; Liu, Xin; Shi, Tao; Wang, Shuai-Hua; Wu, Shao-Fan; Mi, Jin-Xiao; Huang, Ya-Xi

2017-09-12

Germanophosphates, in comparison with other metal phosphates, have been less studied but potentially exhibit more diverse structural chemistry with wide applications. Herein we applied a hydro-/solvo-fluorothermal route to make use of both the "tailor effect" of fluoride for the formation of low dimensional anionic clusters and the presence of alkali cations of different sizes to align the anionic clusters to control the overall crystal symmetries of germanophosphates. The synergetic effects of fluoride and alkali cations led to structural changes from chain-like structures to layered structures in a series of five novel fluorogermanophosphates: A 2 [GeF 2 (HPO 4 ) 2 ] (A = Na, K, Rb, NH 4 , and Cs, denoted as Na, K, Rb, NH4, and Cs). Although these fluorogermanophosphates have stoichiometrically equivalent formulas, they feature different anionic clusters, diverse structural dimensionalities, and contrasting crystal symmetries. Chain-like structures were observed for the compounds with the smaller sized alkali ions (Na + , K + , and Rb + ), whereas layered structures were found for those containing the larger sized cations ((NH 4 ) + and Cs + ). Specifically, monoclinic space groups were observed for the Na, K, Rb, and NH4 compounds, whereas a tetragonal space group P4/mbm was found for the Cs compound. These compounds provide new insights into the effects of cation sizes on the anionic clusters built from GeO 4 F 2 octahedra and HPO 4 tetrahedra as well as their influences on the overall structural symmetries in germanophosphates. Further characterization including IR spectroscopy and thermal analyses for all five compounds is also presented.

Nonequivalence of chemical and hydrostatic pressures: A1g and Eg frequencies and Stokes shift of Mn2+-doped perovskites

NASA Astrophysics Data System (ADS)

Barriuso, M. T.; Moreno, M.; Aramburu, J. A.

2002-02-01

The frequency of A1g and Eg modes of MnF4-6 in cubic ABF3 (A: K; B: Mg, Zn and A: Rb, Cs; B: Cd, Ca) perovskites has been derived through density functional calculations on MnF6A8B16+6 clusters which reproduce the experimental impurity-ligand distance Re. Both frequencies are found to experience a drastic decrement on passing from KMgF3:Mn2+ (ħωA=556 cm-1, ħωE=456 cm-1) to CsCdF3:Mn2+ (ħωA=317 cm-1, ħωE=239 cm-1) despite the fact that Re increases only by 5%, leading to effective Grüneisen constants (called γcA and γcE) around 3.0 along the series. This figure is 60% higher than the usual Grüneisen constant γA calculated for a given system like KMgF3:Mn2+ or KZnF3:Mn2+ when hydrostatic pressure is applied. For supporting this relevant result the value of γA for CrF3-6 in a fluoroelpasolite has been calculated as well. The obtained value γA=2.1 is close to the experimental one (γA=1.9) derived in K2NaGaF6:Cr3+ by combined optical and Raman measurements. As a salient feature, the increase of the Stokes shift when Re increases observed along the ABF3:Mn2+ series is now well explained through the bigger variations of A1g and Eg frequencies induced by the chemical pressure in comparison to those coming from an hydrostatic pressure on a given system. The difference between γcA and γA is discussed through a simple model that emphasizes the role played by the coupling of the MnF4-6 complex to the lattice. The influence of chemical and hydrostatic pressures upon the luminescence efficiency is also briefly discussed. Attention is addressed to the method of calculating impurity-associated Grüneisen constants using clusters. Recent results on Cr3+ in several cubic chloroelpasolites that support the present conclusions are briefly discussed as well.

La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs

PubMed Central

Lahr, Roni M; Fonseca, Bruno D; Ciotti, Gabrielle E; Al-Ashtal, Hiba A; Jia, Jian-Jun; Niklaus, Marius R; Blagden, Sarah P; Alain, Tommy; Berman, Andrea J

2017-01-01

The 5’terminal oligopyrimidine (5’TOP) motif is a cis-regulatory RNA element located immediately downstream of the 7-methylguanosine [m7G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5’TOP motif, a cap analog (m7GTP), and a capped cytidine (m7GpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5’TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5’TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis. DOI: http://dx.doi.org/10.7554/eLife.24146.001 PMID:28379136

Photocopy of drawing. LAUNCH COMPLEX 39. NASA John F. Kennedy ...

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

Photocopy of drawing. LAUNCH COMPLEX 39. NASA John F. Kennedy Space Center, Florida. File Number 203-100, Urbahn-Roberts-Seelye-Moran, October 1963. VERTICAL ASSEMBLY BUILDING, LOW BAY, SECTIONS J-J, K-K, & L-L. Sheet 33-32 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

The RB-related gene Rb2/p130 in neuroblastoma differentiation and in B-myb promoter down-regulation.

PubMed

Raschellà, G; Tanno, B; Bonetto, F; Negroni, A; Claudio, P P; Baldi, A; Amendola, R; Calabretta, B; Giordano, A; Paggi, M G

1998-05-01

The retinoblastoma family of nuclear factors is composed of RB, the prototype of the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130. The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and are involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RB family gene products during the DMSO-induced differentiation of the N1E-115 murine neuroblastoma cells. In this system, pRb2/p130 was strongly up-regulated during mid-late differentiation stages, while, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RB family genes in these cells was able, at different degrees, to induce neuronal differentiation, to inhibit [3H]thymidine incorporation and to down-regulate the activity of the B-myb promoter.

A2TiF 5· nH 2O ( A=K, Rb, or Cs; n=0 or 1): Synthesis, structure, characterization, and calculations of three new uni-dimensional titanium fluorides

NASA Astrophysics Data System (ADS)

Jo, Vinna; Woo Lee, Dong; Koo, Hyun-Joo; Ok, Kang Min

2011-04-01

Three new uni-dimensional alkali metal titanium fluoride materials, A2TiF 5· nH 2O ( A=K, Rb, or Cs; n=0 or 1) have been synthesized by hydrothermal reactions. The structures of A2TiF 5· nH 2O have been determined by single-crystal X-ray diffraction. The Ti 4+ cations have been reduced to Ti 3+ during the synthesis reactions. All three A2TiF 5· nH 2O materials contain novel 1-D chain structures that are composed of the slightly distorted Ti 3+F 6 corner-sharing octahedra attributable to the Jahn-Teller distortion. The coordination environment of the alkali metal cations plays an important role to determine the degree of turning in the chain structures. Complete structural analyses, Infrared and UV-vis diffuse reflectance spectra, and thermal analyses are presented, as are electronic structure calculations.

miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

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

Park, Jong-Kook; Henry, Jon C.; Jiang, Jinmai

2011-03-25

Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target themore » retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.« less

Determination of the electric field gradient in RbCaF3 near the phase transition

NASA Astrophysics Data System (ADS)

Hepp, M. A.; Man, P. P.; Trokiner, A.; Zanni, H.; Fraissard, J.

1992-12-01

The fluoroperovskite, RbCaF 3 undergoes a phase transition at 195.5K from a cubic to a tetragonal phase. The order parameter for this transition is directly related to the electric field gradient which arises in the tetragonal phase. In this work, we have used three NMR methods to measure the electric field gradient at the 87Rb site in a single crystal of RbCaF 3, very near this transition. These experiments are based on recent theoretical developments which allow the measurement of quadrupole parameters even for nuclei in a weak electric field gradient.

MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis.

PubMed

Ali, Aamir; Veeranki, Sailaja Naga; Chinchole, Akash; Tyagi, Shweta

2017-06-19

Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Expansion in higher harmonics of boson stars using a generalized Ruffini-Bonazzola approach. Part 1. Bound states

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

Eby, Joshua; Suranyi, Peter; Wijewardhana, L. C. R.

The method pioneered by Ruffini and Bonazzola (RB) to describe boson stars involves an expansion of the boson field which is linear in creation and annihilation operators. This expansion constitutes an exact solution to a non-interacting field theory, and has been used as a reasonable ansatz for an interacting one. In this work, we show how one can go beyond the RB ansatz towards an exact solution of the interacting operator Klein-Gordon equation, which can be solved iteratively to ever higher precision. Our Generalized Ruffini-Bonazzola approach takes into account contributions from nontrivial harmonic dependence of the wavefunction, using a sum of terms with energymore » $$k\\,E_0$$, where $$k\\geq1$$ and $$E_0$$ is the chemical potential of a single bound axion. The method critically depends on an expansion in a parameter $$\\Delta \\equiv \\sqrt{1-E_0{}^2/m^2}<1$$, where $m$ is the mass of the boson. In the case of the axion potential, we calculate corrections which are relevant for axion stars in the transition or dense branches. We find with high precision the local minimum of the mass, $$M_{min}\\approx 463\\,f^2/m$$, at $$\\Delta\\approx0.27$$, where $f$ is the axion decay constant. This point marks the crossover from transition to dense branches of solutions, and a corresponding crossover from structural instability to stability.« less

Expansion in higher harmonics of boson stars using a generalized Ruffini-Bonazzola approach. Part 1. Bound states

DOE PAGES

Eby, Joshua; Suranyi, Peter; Wijewardhana, L. C. R.

2018-04-10

The method pioneered by Ruffini and Bonazzola (RB) to describe boson stars involves an expansion of the boson field which is linear in creation and annihilation operators. This expansion constitutes an exact solution to a non-interacting field theory, and has been used as a reasonable ansatz for an interacting one. In this work, we show how one can go beyond the RB ansatz towards an exact solution of the interacting operator Klein-Gordon equation, which can be solved iteratively to ever higher precision. Our Generalized Ruffini-Bonazzola approach takes into account contributions from nontrivial harmonic dependence of the wavefunction, using a sum of terms with energymore » $$k\\,E_0$$, where $$k\\geq1$$ and $$E_0$$ is the chemical potential of a single bound axion. The method critically depends on an expansion in a parameter $$\\Delta \\equiv \\sqrt{1-E_0{}^2/m^2}<1$$, where $m$ is the mass of the boson. In the case of the axion potential, we calculate corrections which are relevant for axion stars in the transition or dense branches. We find with high precision the local minimum of the mass, $$M_{min}\\approx 463\\,f^2/m$$, at $$\\Delta\\approx0.27$$, where $f$ is the axion decay constant. This point marks the crossover from transition to dense branches of solutions, and a corresponding crossover from structural instability to stability.« less

WAVE binds Ena/VASP for enhanced Arp2/3 complex–based actin assembly

PubMed Central

Havrylenko, Svitlana; Noguera, Philippe; Abou-Ghali, Majdouline; Manzi, John; Faqir, Fahima; Lamora, Audrey; Guérin, Christophe; Blanchoin, Laurent; Plastino, Julie

2015-01-01

The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells. Other important players in lamellipodial protrusion are Ena/VASP proteins, which enhance actin filament elongation. Here we examine the molecular coordination between the nucleating activity of the Arp2/3 complex and the elongating activity of Ena/VASP proteins for the formation of actin networks. Using an in vitro bead motility assay, we show that WAVE directly binds VASP, resulting in an increase in Arp2/3 complex–based actin assembly. We show that this interaction is important in vivo as well, for the formation of lamellipodia during the ventral enclosure event of Caenorhabditis elegans embryogenesis. Ena/VASP's ability to bind F-actin and profilin-complexed G-actin are important for its effect, whereas Ena/VASP tetramerization is not necessary. Our data are consistent with the idea that binding of Ena/VASP to WAVE potentiates Arp2/3 complex activity and lamellipodial actin assembly. PMID:25355952

HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A.

PubMed

Tommasino, M; Adamczewski, J P; Carlotti, F; Barth, C F; Manetti, R; Contorni, M; Cavalieri, F; Hunt, T; Crawford, L

1993-01-01

E7 is the major transforming protein of human papillomavirus type 16 (HPV16). It has been found to associate with the retinoblastoma protein Rb1. We investigated whether HPV16 E7 protein was associated with other cellular proteins, in particular with those involved in cell cycle control. Immunoprecipitates from CaSki cell extracts with an anti E7 monoclonal antibody contained a histone H1 kinase. Recombinant E7, synthesized in yeast, when mixed with protein extracts from epithelial cells bound histone H1 kinase activity in vitro. The in vivo and the in vitro-formed E7-kinase complex had the same periodicity of activity during the cell cycle, being most active in S and G2/M. Immunoblotting of E7 immunoprecipitates with an antibody raised against the p33CDK2, revealed a 33 kDa protein band not detected by an anti-p34cdc2 antibody, suggesting that the E7-associated kinase activity is due to the p33CDK2. The interaction appears to be via cyclin A, since probing of similar immunoblots showed a 50 kDa band corresponding to cyclin A. The association of E7 with cyclin A appeared to be direct, not involving Rb 1 or other proteins.

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

PubMed Central

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

2002-01-01

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

Light-Shifts of an Integrated Filter-Cell Rubidium Atomic Clock

DTIC Science & Technology

2015-05-25

the light-shift coefficient for two different rf- discharge lamps (i.e., a pure 87Rb lamp and a lamp filled with the natural Rb isotope abundance...for the Galileo Rb clock under the assumption of a natural (or 85Rb isotopically enriched) rf- discharge lamp for the Galileo clock. I...satellites [14]. 6.8347… GHz 85Rb Filter Cell Cell Resonance Photodiode Microwave Cavity 87Rb Discharge Lamp 87Rb & N2 Rb & Xe, Kr Optical Pumping 87Rb

Charging Properties of Cassiterite (alpha-SnO2) surfaces in NaCl and RbCl Ionic Media.

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

Rosenqvist, Jorgen K; Machesky, Michael L.; Vlcek, Lukas

2009-01-01

The acid-base properties of cassiterite (alpha-SnO2) surfaces at 10-50 degrees C were studied using potentiometric titrations of powder suspensions in aqueous NaCl and RbCl media. The proton sorption isotherms exhibited common intersection points in the pH range of 4.0-4.5 under all conditions, and the magnitude of charging was similar but not identical in NaCl and RbCl. The hydrogen bonding configuration at the oxide-water interface, obtained from classical molecular dynamics (MD) simulations, was analyzed in detail, and the results were explicitly incorporated in calculations of protonation constants for the reactive surface sites using the revised MUSIC model. The calculations indicated thatmore » the terminal SnOH2 group is more acidic than the bridging Sn2OH group, with protonation constants (log KH) of 3.60 and 5.13 at 25 degrees C, respectively. This is contrary to the situation on the isostructural alpha-TiO2 (rutile), apparently because of the difference in electronegativity between Ti and Sn. MD simulations and speciation calculations indicated considerable differences in the speciation of Na+ and Rb+, despite the similarities in overall charging. Adsorbed sodium ions are almost exclusively found in bidentate surface complexes, whereas adsorbed rubidium ions form comparable numbers of bidentate and tetradentate complexes. Also, the distribution of adsorbed Na+ between the different complexes shows a considerable dependence on the surface charge density (pH), whereas the distribution of adsorbed Rb+ is almost independent of pH. A surface complexation model (SCM) capable of accurately describing both the measured surface charge and the MD-predicted speciation of adsorbed Na+/Rb+ was formulated. According to the SCM, the deprotonated terminal group (SnOH(-0.40)) and the protonated bridging group (Sn2OH+0.36) dominate the surface speciation over the entire pH range of this study (2.7-10). The complexation of medium cations increases significantly with increasing negative surface charge, and at pH 10, roughly 40% of the terminal sites are predicted to form cation complexes, whereas anion complexation is minor throughout the studied pH range.« less

Electron affinities of the alkali dimers - Na2, K2, and Rb2

NASA Technical Reports Server (NTRS)

Partridge, H.; Dixon, D. A.; Walch, S. P.; Bauschlicher, C. W., Jr.; Gole, J. L.

1983-01-01

Ab initio calculations on the ground states of the alkali dimers, Na2, K2, and Rb2, and their anions are reported. The calculations employ large Gaussian basis sets and account for nearly all of the valence correlation energy. The calculated atomic electron affinities are within 0.02 eV of experiment and the calculated adiabatic electron affinities for Na2, K2, and Rb2 are, respectively, 0.470, 0.512, and 0.513 eV.

Comparison of 18F SPECT with PET in myocardial imaging: a realistic thorax-cardiac phantom study.

PubMed

Knešaurek, Karin; Machac, Josef

2006-10-31

Positron emission tomography (PET) imaging with fluorine-18 (18F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 (82Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive 18F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to 18F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of 18F and 22.2 MBq of Technetium-99m (99mTc) in the SPECT study and with 7.4 MBq of 18F and 370 MBq of 82Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. The contrast for 3 cm, 2 cm and 1 cm inserts were for 18F PET data, 1.0 +/- 0.01, 0.67 +/- 0.02 and 0.25 +/- 0.01, respectively. For 82Rb PET data, the corresponding contrast values were 0.61 +/- 0.02, 0.37 +/- 0.02 and 0.19 +/- 0.01, respectively. For 18F SPECT the contrast values were, 0.31 +/- 0.03 and 0.20 +/- 0.05 for 3 cm and 2 cm inserts, respectively. For 99mTc SPECT the contrast values were, 0.63 +/- 0.04 and 0.24 +/- 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". For smaller defects the 99mTc/18F SPECT imaging cannot entirely replace the more expensive 82Rb/18F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast.

Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging.

PubMed

Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai

2007-11-01

Administration of an orally active agonist (MK-0677) of the growth hormone secretagogue receptor (GHS-R1a) to elderly subjects restored the amplitude of endogenous episodic growth hormone (GH) release to that of young adults. Functional benefits include increased lean mass and bone density and modest improvements in strength. In old mice, a similar agonist partially restored function to the thymus and reduced tumor cell growth and metastasis. Treatment of old mice with the endogenous GHS-R1a agonist ghrelin restored a young liver phenotype. The mechanism involves inhibition of cyclin D3:cdk4/cdk6 activity and increased protein phosphatase-2A (PP2A) activity in liver nuclei, which stabilizes the dephosphorylated form of the transcription factor C/EBPalpha preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear complex. By inhibiting formation of this complex, repression of E2F target genes is de-repressed and C/EBPalpha regulated expression of Pepck, a regulator of gluconeogenesis, is normalized, thereby restoring a young liver phenotype. In the brain, aging is associated with decline in dopamine function. We investigated the potential neuromodulatory role of GHS-R1a on dopamine action. Neurons were identified in the hippocampus, cortex, substantia nigra, and ventral tegmental areas that coexpressed GHS-R1a and dopamine receptor subtype-1 (D1R). Cell culture studies showed that, in the presence of ghrelin and dopamine, GHS-R and D1R form heterodimers, which modified G-protein signal transduction resulting in amplification of dopamine signaling. We speculate that aging is associated with deficient endogenous ghrelin signaling that can be rescued by intervention with GHS-R1a agonists to improve quality of life and maintain independence.

Reference quality assembly of the 3.5-Gb genome of Capsicum annuum from a single linked-read library.

PubMed

Hulse-Kemp, Amanda M; Maheshwari, Shamoni; Stoffel, Kevin; Hill, Theresa A; Jaffe, David; Williams, Stephen R; Weisenfeld, Neil; Ramakrishnan, Srividya; Kumar, Vijay; Shah, Preyas; Schatz, Michael C; Church, Deanna M; Van Deynze, Allen

2018-01-01

Linked-Read sequencing technology has recently been employed successfully for de novo assembly of human genomes, however, the utility of this technology for complex plant genomes is unproven. We evaluated the technology for this purpose by sequencing the 3.5-gigabase (Gb) diploid pepper ( Capsicum annuum ) genome with a single Linked-Read library. Plant genomes, including pepper, are characterized by long, highly similar repetitive sequences. Accordingly, significant effort is used to ensure that the sequenced plant is highly homozygous and the resulting assembly is a haploid consensus. With a phased assembly approach, we targeted a heterozygous F 1 derived from a wide cross to assess the ability to derive both haplotypes and characterize a pungency gene with a large insertion/deletion. The Supernova software generated a highly ordered, more contiguous sequence assembly than all currently available C. annuum reference genomes. Over 83% of the final assembly was anchored and oriented using four publicly available  de novo linkage maps. A comparison of the annotation of conserved eukaryotic genes indicated the completeness of assembly. The validity of the phased assembly is further demonstrated with the complete recovery of both 2.5-Kb insertion/deletion haplotypes of the PUN1 locus in the F 1 sample that represents pungent and nonpungent peppers, as well as nearly full recovery of the BUSCO2 gene set within each of the two haplotypes. The most contiguous pepper genome assembly to date has been generated which demonstrates that Linked-Read library technology provides a tool to de novo assemble complex highly repetitive heterozygous plant genomes. This technology can provide an opportunity to cost-effectively develop high-quality genome assemblies for other complex plants and compare structural and gene differences through accurate haplotype reconstruction.

RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development.

PubMed

Elchuri, Sailaja V; Rajasekaran, Swetha; Miles, Wayne O

2018-01-01

Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1). Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area's to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

Self-assembly of graphene oxide with a silyl-appended spiropyran dye for rapid and sensitive colorimetric detection of fluoride ions.

PubMed

Li, Yinhui; Duan, Yu; Zheng, Jing; Li, Jishan; Zhao, Wenjie; Yang, Sheng; Yang, Ronghua

2013-12-03

Fluoride ion (F(-)), the smallest anion, exhibits considerable significance in a wide range of environmental and biochemical processes. To address the two fundamental and unsolved issues of current F(-) sensors based on the specific chemical reaction (i.e., the long response time and low sensitivity) and as a part of our ongoing interest in the spiropyran sensor design, we reported here a new F(-) sensing approach that, via assembly of a F(-)-specific silyl-appended spiropyran dye with graphene oxide (GO), allows rapid and sensitive detection of F(-) in aqueous solution. 6-(tert-Butyldimethylsilyloxy)-1',3',3'-trimethylspiro [chromene- 2,2'-indoline] (SPS), a spiropyran-based silylated dye with a unique reaction activity for F(-), was designed and synthesized. The nucleophilic substitution reaction between SPS and F(-) triggers cleavage of the Si-O bond to promote the closed spiropyran to convert to its opened merocyanine form, leading to the color changing from colorless to orange-yellow with good selectivity over other anions. With the aid of GO, the response time of SPS for F(-) was shortened from 180 to 30 min, and the detection limit was lowered more than 1 order of magnitude compared to the free SPS. Furthermore, due to the protective effect of nanomaterials, the SPS/GO nanocomposite can function in a complex biological environment. The SPS/GO nanocomposite was characterized by XPS and AFM, etc., and the mechanism for sensing F(-) was studied by (1)H NMR and ESI-MS. Finally, this SPS/GO nanocomposite was successfully applied to monitoring F(-) in the serum.

The Role of Skp2 in the Prostate Tumorigenesis Following Rb and p53 Loss

DTIC Science & Technology

2015-12-01

Developmental and Molecular Biology Room 521 Ullmann 1300 Morris Park Avenue Bronx, NY 10461-1975 AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER rt...t f l t l Molecular Biology Room 521 Ullmann 1300 Morris Park Avenue Bronx, NY 10461-1975 9. SPONSORING / MONITORING AGENCY NAME(S) AND...1300 Morris Park Ave., Room U-521, Bronx, NY 10461. Tel.: 718-430-3320; Fax: 718-430- 8975; E-mail: liang.zhu@einstein.yu.edu. 2 The abbreviations used

A theoretical study of the structure and thermochemical properties of alkali metal fluoroplumbates MPbF3.

PubMed

Boltalin, A I; Korenev, Yu M; Sipachev, V A

2007-07-19

Molecular constants of MPbF3 (M=Li, Na, K, Rb, and Cs) were calculated theoretically at the MP2(full) and B3LYP levels with the SDD (Pb, K, Rb, and Cs) and cc-aug-pVQZ (F, Li, and Na) basis sets to determine the thermochemical characteristics of the substances. Satisfactory agreement with experiment was obtained, including the unexpected nonmonotonic dependence of substance dissociation energies on the alkali metal atomic number. The bond lengths of the theoretical CsPbF3 model were substantially elongated compared with experimental estimates, likely because of errors in both theoretical calculations and electron diffraction data processing.

Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice.

PubMed

Miyake, Masato; Kuroda, Masashi; Kiyonari, Hiroshi; Takehana, Kenji; Hisanaga, Satoshi; Morimoto, Masatoshi; Zhang, Jun; Oyadomari, Miho; Sakaue, Hiroshi; Oyadomari, Seiichi

2017-01-01

Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly. The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly. A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly. Thus, muscle atrophic phenotypes, intracellular signaling pathways, and intracellular free amino acid profiles were investigated in human skeletal muscle α-actin (HSA) promoter-driven Fv2E-PERK transgenic (Tg) mice. HSA-Fv2E-PERK Tg mice treated with the artificial dimerizer AP20187 phosphorylates eIF2α in skeletal muscles and leads to severe muscle atrophy within a few days of ligand injection. Muscle atrophy was accompanied by a counter regulatory activation of mTORC1 signaling. Moreover, intracellular free amino acid levels were distinctively altered in the skeletal muscles of HSA-Fv2E-PERK Tg mice. As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics.

78 FR 61168 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (RR) RB211-535E4-37, RB211-535E4-B-37, RB211-535E4-C- 37, and RB211-535E4-B-75 turbofan engines. This...-37, RB211-535E4-B-37, RB211-535E4-C-37, and RB211-535E4-B-75 turbofan engines. (d) Unsafe Condition...

Kinetic recognition of the retinoblastoma tumor suppressor by a specific protein target.

PubMed

Chemes, Lucía B; Sánchez, Ignacio E; de Prat-Gay, Gonzalo

2011-09-16

The retinoblastoma tumor suppressor (Rb) plays a key role in cell cycle control and is linked to various types of human cancer. Rb binds to the LxCxE motif, present in a number of cellular and viral proteins such as AdE1A, SV40 large T-antigen and human papillomavirus (HPV) E7, all instrumental in revealing fundamental mechanisms of tumor suppression, cell cycle control and gene expression. A detailed kinetic study of RbAB binding to the HPV E7 oncoprotein shows that an LxCxE-containing E7 fragment binds through a fast two-state reaction strongly favored by electrostatic interactions. Conversely, full-length E7 binds through a multistep process involving a pre-equilibrium between E7 conformers, a fast electrostatically driven association step guided by the LxCxE motif and a slow conformational rearrangement. This kinetic complexity arises from the conformational plasticity and intrinsically disordered nature of E7 and from multiple interaction surfaces present in both proteins. Affinity differences between E7N domains from high- and low-risk types are explained by their dissociation rates. In fact, since Rb is at the center of a large protein interaction network, fast and tight recognition provides an advantage for disruption by the viral proteins, where the balance of physiological and pathological interactions is dictated by kinetic ligand competition. The localization of the LxCxE motif within an intrinsically disordered domain provides the fast, diffusion-controlled interaction that allows viral proteins to outcompete physiological targets. We describe the interaction mechanism of Rb with a protein ligand, at the same time an LxCxE-containing model target, and a paradigmatic intrinsically disordered viral oncoprotein. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of early indicators of altered metabolism in normal development using a rodent model system.

PubMed

Prabakaran, Ashok Daniel; Karakkat, Jimsheena Valiyakath; Vijayan, Ranjit; Chalissery, Jisha; Ibrahim, Marwa F; Kaimala, Suneesh; Adeghate, Ernest A; Al-Marzouqi, Ahmed Hassan; Ansari, Suraiya Anjum; Mensah-Brown, Eric; Emerald, Bright Starling

2018-03-01

Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups - lower birth weight (LBW, 5th to 25th percentile) and average birth weight (ABW, 50th to 75th percentile) - using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII ( Ins2 ) gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1) and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life. © 2018. Published by The Company of Biologists Ltd.

Identification of early indicators of altered metabolism in normal development using a rodent model system

PubMed Central

Prabakaran, Ashok Daniel; Karakkat, Jimsheena Valiyakath; Chalissery, Jisha; Ibrahim, Marwa F.; Kaimala, Suneesh; Adeghate, Ernest A.; Al-Marzouqi, Ahmed Hassan; Ansari, Suraiya Anjum

2018-01-01

ABSTRACT Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile) and average birth weight (ABW, 50th to 75th percentile) – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2) gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1) and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life. PMID:29434026

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

PubMed Central

Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

2018-01-01

Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the anti-diabetic effects of ginsenosides. PMID:29765322

Complexes of monocationic Group 13 elements with pentaphospha- and pentaarsaferrocene.

PubMed

Fleischmann, Martin; Welsch, Stefan; Krauss, Hannes; Schmidt, Monika; Bodensteiner, Michael; Peresypkina, Eugenia V; Sierka, Marek; Gröger, Christian; Scheer, Manfred

2014-03-24

Reactions of the sandwich complexes [Cp*Fe(η(5)-E5)] (Cp*=η(5)-C5Me5; E=P (1), As (2)) with the monovalent Group 13 metals Tl(+), In(+), and Ga(+) containing the weakly coordinating anion [TEF] ([TEF]=[Al{OC(CF3)3}4](-)) are described. Here, the one-dimensional coordination polymers [M(μ,η(5):η(1 -E5 FeCp*)3]n [TEF]n (E=P, M=Tl (3 a), In (3 b), Ga (3 c); E=As, M=Tl (4 a), In (4 b)) are obtained as sole products in good yields. All products were analyzed by single-crystal X-ray diffraction, revealing a similar assembly of the products with η(5)-bound E5 ligands and very weak σ-interactions between one P or As atom of the ring to the neighbored Group 13 metal cation. By exchanging the [TEF] anion of 4 a for the larger [FAl] anion ([FAl]=[FAl{OC6F10(C6F5)}3](-)), the coordination compound [Tl{(η(5)-As5)FeCp*}3][FAl] (5) without any σ-interactions of the As5-ring is obtained. All products are readily soluble in CH2 Cl2 and exhibit a dynamic coordination behavior in solution, which is supported by NMR spectroscopy and ESI-MS spectrometry as well as by osmometric molecular-weight determination. For a better understanding of the proceeding equilibrium DFT calculations of the cationic complexes were performed for the gas phase and in solution. Furthermore, the (31)P{(1)H} magic-angle spinning (MAS) NMR spectra of 3 a-c are presented and the first crystal structure of the starting material 2 was determined. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Deregulation of RB1 expression by loss of imprinting in human hepatocellular carcinoma.

PubMed

Anwar, Sumadi Lukman; Krech, Till; Hasemeier, Britta; Schipper, Elisa; Schweitzer, Nora; Vogel, Arndt; Kreipe, Hans; Lehmann, Ulrich

2014-08-01

The tumour suppressor gene RB1 is frequently silenced in many different types of human cancer, including hepatocellular carcinoma (HCC). However, mutations of the RB1 gene are relatively rare in HCC. A systematic screen for the identification of imprinted genes deregulated in human HCC revealed that RB1 shows imprint abnormalities in a high proportion of primary patient samples. Altogether, 40% of the HCC specimens (16/40) showed hyper- or hypomethylation at the CpG island in intron 2 of the RB1 gene. Re-analysis of publicly available genome-wide DNA methylation data confirmed these findings in two independent HCC cohorts. Loss of correct DNA methylation patterns at the RB1 locus leads to the aberrant expression of an alternative RB1-E2B transcript, as measured by quantitative real-time PCR. Demethylation at the intron 2 CpG island by DNMT1 knock-down or aza-deoxycytidine (DAC) treatment stimulated expression of the RB1-E2B transcript, accompanied by diminished RB1 main transcript expression. No aberrant DNA methylation was found at the RB1 locus in hepatocellular adenoma (HCA, n = 10), focal nodular hyperplasia (FNH, n = 5) and their corresponding adjacent liver tissue specimens. Deregulated RB1 expression due to hyper- or hypomethylation in intron 2 of the RB1 gene is found in tumours without loss of heterozygosity and is associated with a decrease in overall survival (p = 0.032) if caused by hypermethylation of CpG85. This unequivocally demonstrates that loss of imprinting represents an important additional mechanism for RB1 pathway inactivation in human HCC, complementing well-described molecular defects. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

E2 Ubiquitin-conjugating Enzyme, UBE2C Gene, Is Reciprocally Regulated by Wild-type and Gain-of-Function Mutant p53.

PubMed

Bajaj, Swati; Alam, Sk Kayum; Roy, Kumar Singha; Datta, Arindam; Nath, Somsubhra; Roychoudhury, Susanta

2016-07-01

Spindle assembly checkpoint governs proper chromosomal segregation during mitosis to ensure genomic stability. At the cellular level, this event is tightly regulated by UBE2C, an E2 ubiquitin-conjugating enzyme that donates ubiquitin to the anaphase-promoting complex/cyclosome. This, in turn, facilitates anaphase-onset by ubiquitin-mediated degradation of mitotic substrates. UBE2C is an important marker of chromosomal instability and has been associated with malignant growth. However, the mechanism of its regulation is largely unexplored. In this study, we report that UBE2C is transcriptionally activated by the gain-of-function (GOF) mutant p53, although it is transcriptionally repressed by wild-type p53. We showed that wild-type p53-mediated inhibition of UBE2C is p21-E2F4-dependent and GOF mutant p53-mediated transactivation of UBE2C is NF-Y-dependent. We further explored that DNA damage-induced wild-type p53 leads to spindle assembly checkpoint arrest by repressing UBE2C, whereas mutant p53 causes premature anaphase exit by increasing UBE2C expression in the presence of 5-fluorouracil. Identification of UBE2C as a target of wild-type and GOF mutant p53 further highlights the contribution of p53 in regulation of spindle assembly checkpoint. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Single Cell Analysis to locate the Restriction Point with respect to E2F Expression

NASA Astrophysics Data System (ADS)

Pimienta, R.; Johnson, A.

2011-12-01

The restriction point is a G1-phase checkpoint that regulates passage through the cell cycle and is misregulated in all known types of cancer. The Rb-E2F switch is thought to be one of the most relevant molecular mechanisms which regulate the restriction point in mammalian cells. However, recent experiments have brought the timing of the restriction point into question. In previous studies, cells were analyzed as populations and this prevented an accurate determination of the restriction point. By creating and analyzing an E2F-GFP reporter in single cells, we can pinpoint the timing of E2F activation and determine whether it coincides with the restriction point. Using calcium phosphate and Fugene,we transfected human embryonic kidney (293T) cells with a CMV-GFP plasmid and an E2F-GFP reporter. Based on our results, it appears that calcium phosphate is more effective than Fugene at transfecting mammalian cells. The calcium phosphate transfection had 9.59% more fluorescent cells than Fugene. However, this result only occurred with the CMV-GFP plasmid and not the E2F-GFP reporter, which was not properly expressed in human embryonic kidney (293T) cells. We will continue troubleshooting to fix this reporter as we proceed with our research. Once the reporter is properly cloned, we will transfect it into retinal pigmented epithelial (RPE1-hTERT) cells using the calcium phosphate method. RPE1-hTERT cells are an immortalized with telomerase and are more close to normal cells than tumor-derived cell lines. Through this research we will better comprehend commitment to the mammalian cell cycle.

Integrative Analysis Reveals an Outcome-associated and Targetable Pattern of p53 and Cell Cycle Deregulation in Diffuse Large B-cell Lymphoma

PubMed Central

Monti, Stefano; Chapuy, Bjoern; Takeyama, Kunihiko; Rodig, Scott J; Hao, Yangsheng; Yeda, Kelly T.; Inguilizian, Haig; Mermel, Craig; Curie, Treeve; Dogan, Ahmed; Kutok, Jeffery L; Beroukim, Rameen; Neuberg, Donna; Habermann, Thomas; Getz, Gad; Kung, Andrew L; Golub, Todd R; Shipp, Margaret A

2013-01-01

Summary Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease with a high proliferation rate. By integrating copy number data with transcriptional profiles and performing pathway analysis in primary DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that decreased p53 activity and perturbed cell cycle regulation. Primary tumors either had multiple complementary alterations of p53 and cell cycle components or largely lacked these lesions. DLBCLs with p53 and cell cycle pathway CNAs had decreased abundance of p53 target transcripts and increased expression of E2F target genes and the Ki67 proliferation marker. CNAs of the CDKN2A-TP53-RB-E2F axis provide a structural basis for increased proliferation in DLBCL, predict outcome with current therapy and suggest targeted treatment approaches. PMID:22975378

Revised RB 100-9: A Guide to the Formulation and Selection of Feasible Tactical Courses of Action.

DTIC Science & Technology

1981-04-23

Department of Defense ATTN: M. Minnemam U.S. Army Armament Rsch Dev & Cmd ATTN: K . Hinman ATTN: DRDAR-LCN-E ATTN: Strategic & Space Sys (OS) ATTN: F...B2590D. Is. K EY WORDS (Cmnthme an rever. side it aaeceety OWd IdentIfy by Week munst) Tactical Course of Action Defensive Operations Integrated... 12 CHAPTER 2. STEPS LOADING TO FORMULATION OF COURSES OF ACTION ..........13 Section I. Introduction

Transformation of EIA to EIT by incoherent pumping of the 85Rb D1 line

NASA Astrophysics Data System (ADS)

Yu, Hoon; Kim, Jung Dong; Jung, Tae Young; Kim, Jung Bog

2012-10-01

We have observed a transformation from electromagnetically-induced absorption (EIA) to electromagnetically induced transparency (EIT) in open systems of the 85Rb D1 line by adding an incoherent optical pumping laser. This result raises a new question about recent theoretical work which does not address the degree of open. The pump beam only plays a role in transferring atoms by a spontaneous transition into the interacting system for EIT observation, which is an incoherent process. The dependence of the absorption spectra on the intensity and the polarization of each laser beam were observed. We have found the same tendencies in all transitions except the F = 2 ↔ F' = 3 transition of the 85Rb D1 line, which is the system that almost satisfies conventional EIA conditions.

Observation of coherent backscattering of light in ultracold ^85Rb

NASA Astrophysics Data System (ADS)

Kulatunga, P.; Sukenik, C. I.; Havey, M. D.; Kupriyanov, D. V.; Sokolov, I. M.

2002-05-01

We report investigation of multiple coherent light scattering from ^85Rb atoms confined in a magneto-optic trap. In experimental studies, measurements are made of coherent backscattering of a low-intensity probe beam tuned near the F = 3 - F' = 4 transition in ^85Rb atoms. Polarization of backscattered light is determined by a backscattering polarimeter; the spatial distribution of light intensity is measured by a liquid-nitrogen cooled CCD camera set in the focal plane of the analyzing optics. The instrument has angular resolution of about 100 micro-radians, and a polarization analyzing power of roughly 1000. In this paper we describe the instrument details, including calibration procedures, and our measurements of atomic coherent backscattering. In a theoretical study of intensity enhancement of near-resonant backscattered light from cold ^85,87Rb atoms, we consider scattering orders up to 8 and a Gaussian atom distribution in the MOT. Enhancement factors are calculated for all D1 and D2 hyperfine components and for both isotopes.

Spirolactone and spirothiolactone rhodamine-pyrene probes for detection of Hg2 + with different sensing properties and its application in living cells

NASA Astrophysics Data System (ADS)

Rui, Qing-Qing; Zhou, Yi; Fang, Yuan; Yao, Cheng

2016-04-01

Two new rhodamine B-based fluorescent probes PyRbS and PyRbO containing pyrene moiety were designed and synthesized. Both of the probes showed colorimetric and fluorometric sensing abilities for Hg2 + with high selectivity over other metal ions. The binding analysis using Job's plot suggested 1:1 stoichiometry for the complexes formed for Hg2 +. Compared with PyRbO, the PyRbS showed higher selectivity and sensitivity due to the thiophilic property of Hg2 + ion. The PyRbS exhibited the linear fluorescence quenching to Hg2 + in the range of 0.3 to 4.8 μM (λex = 365 nm) and 0.3 to 5.4 μM (λex = 515 nm), and the detection limit was 0.72 μM. Moreover, ratiometric changes of PyRbS with Hg2 + in absorption spectrum were observed, which could not be obtained in the combination of PyRbO with Hg2 +. In addition, the methyl thiazolyl tetrazolium (MTT) assay demonstrated that RbPyS had low cytotoxicity and was successfully used to monitor intracellular Hg2 + levels in living cells.

Adsorption with biodegradation for decolorization of reactive black 5 by Funalia trogii 200800 on a fly ash-chitosan medium in a fluidized bed bioreactor-kinetic model and reactor performance.

PubMed

Lin, Yen-Hui; Lin, Wen-Fan; Jhang, Kai-Ning; Lin, Pei-Yu; Lee, Mong-Chuan

2013-02-01

A non-steady-state mathematical model system for the kinetics of adsorption and biodegradation of reactive black 5 (RB5) by Funalia trogii (F. trogii) ATCC 200800 biofilm on fly ash-chitosan bead in the fluidized bed process was derived. The mechanisms in the model system included adsorption by fly ash-chitosan beads, biodegradation by F. trogii cells and mass transport diffusion. Batch kinetic tests were independently performed to determine surface diffusivity of RB5, adsorption parameters for RB5 and biokinetic parameters of F. trogii ATCC 200800. A column test was conducted using a continuous-flow fluidized bed reactor with a recycling pump to approximate a completely-mixed flow reactor for model verification. The experimental results indicated that F. trogii biofilm bioregenerated the fly ash-chitosan beads after attached F. trogii has grown significantly. The removal efficiency of RB5 was about 95 % when RB5 concentration in the effluent was approximately 0.34 mg/L at a steady-state condition. The concentration of suspended F. trogii cells reached up to about 1.74 mg/L while the thickness of attached F. trogii cells was estimated to be 80 μm at a steady-state condition by model prediction. The comparisons of experimental data and model prediction show that the model system for adsorption and biodegradation of RB5 can predict the experimental results well. The approaches of experiments and mathematical modeling in this study can be applied to design a full-scale fluidized bed process to treat reactive dye in textile wastewater.

Process for the production of .sup.18 F-2-deoxy-2-fluoro-D-glucose

DOEpatents

Elmaleh, David R.; Levy, Shlomo; Shiue, Chyng-Yann; Wolf, Alfred P.

1986-01-01

Process for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding .sup.18 F-compound in which methyl 4,6-O-benzylidine-3-O-methyl-2-O-trifluoromethanesulfonyl-.beta.-D-mannopy ranoside is reacted with a triflating reagent, the resulting compound reacted with CsHF.sub.2, RbF or the corresponding .sup.18 F-compounds, and thereafter the alkyl groups removed by hydrolysis.

Charging Properties of Cassiterite (alpha-SnO2) Surfaces in NaCl and RbCl Ionic Media.

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

Rosenqvist, Jorgen K; Machesky, Michael L.; Vlcek, Lukas

2009-01-01

The acid-base properties of cassiterite ({alpha}-SnO{sub 2}) surfaces at 10-50 C were studied using potentiometric titrations of powder suspensions in aqueous NaCl and RbCl media. The proton sorption isotherms exhibited common intersection points in the pH range of 4.0-4.5 under all conditions, and the magnitude of charging was similar but not identical in NaCl and RbCl. The hydrogen bonding configuration at the oxide-water interface, obtained from classical molecular dynamics (MD) simulations, was analyzed in detail, and the results were explicitly incorporated in calculations of protonation constants for the reactive surface sites using the revised MUSIC model. The calculations indicated thatmore » the terminal SnOH{sub 2} group is more acidic than the bridging Sn{sub 2}OH group, with protonation constants (log K{sub H}) of 3.60 and 5.13 at 25 C, respectively. This is contrary to the situation on the isostructural {alpha}-TiO{sub 2} (rutile), apparently because of the difference in electronegativity between Ti and Sn. MD simulations and speciation calculations indicated considerable differences in the speciation of Na{sup +} and Rb{sup +}, despite the similarities in overall charging. Adsorbed sodium ions are almost exclusively found in bidentate surface complexes, whereas adsorbed rubidium ions form comparable numbers of bidentate and tetradentate complexes. Also, the distribution of adsorbed Na{sup +} between the different complexes shows a considerable dependence on the surface charge density (pH), whereas the distribution of adsorbed Rb{sup +} is almost independent of pH. A surface complexation model (SCM) capable of accurately describing both the measured surface charge and the MD-predicted speciation of adsorbed Na{sup +}/Rb{sup +} was formulated. According to the SCM, the deprotonated terminal group (SnOH{sup -0.40}) and the protonated bridging group (Sn{sub 2}OH{sup +0.36}) dominate the surface speciation over the entire pH range of this study (2.7-10). The complexation of medium cations increases significantly with increasing negative surface charge, and at pH 10, roughly 40% of the terminal sites are predicted to form cation complexes, whereas anion complexation is minor throughout the studied pH range.« less

Photoluminescence, optically stimulated luminescence, and thermoluminescence study of RbMgF3:Eu2+

NASA Astrophysics Data System (ADS)

Dotzler, C.; Williams, G. V. M.; Rieser, U.; Robinson, J.

2009-01-01

Optically stimulated luminescence (OSL) and thermoluminescence are observed in polycrystalline RbMgF3:Eu2+ after x-ray, γ-ray, or β irradiation. The main electron traps are F-centers but there are other unidentified traps. The main hole traps at room temperature are probably Eu3+ and thermal or optical stimulation leads to electron-hole recombination at the Eu3+ site and Eu2+ emissions arising from P6J to S87/2 and 4f5d(Eg) to S87/2 transitions. We find that some of the electron traps can be emptied by infrared stimulation and all of the electron traps can be emptied by white light stimulation. The OSL dark decay is long and exceeds 5 days for traps that are emptied by white light stimulation after initial infrared bleaching. Our results show that this compound can be used as a radiation dosimeter for intermediate dose levels where the R87b self-dose does not significantly affect the dose reading.

Ion mobility and conductivity in the M{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} (M=K, Rb) solid solutions with fluorite structure

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

Kavun, V. Ya., E-mail: kavun@ich.dvo.ru; Uvarov, N.F.; Slobodyuk, A.B.

Ionic mobility and conductivity in the K{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} and Rb{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} (x=0.05, 0.09) solid solutions with the fluorite structure have been investigated using the methods of {sup 19}F NMR, X-ray diffraction and impedance spectroscopy. Types of ionic motions in the fluoride sublattice of solid solutions have been established and temperature ranges of their realization have been determined (150–450 K). Diffusion of fluoride ions is a dominating type of ionic motions in the fluoride sublattice of solid solutions under study above 350 K. Due to high ionic conductivity, above 10{sup –3} S/cm at 450 K,more » these solid solutions can be used as solid electrolytes in various electrochemical devices and systems. - Graphical abstract: Temperature dependence of the concentration of mobile (2, 4) and immobile (1, 3) F ions in the K{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} solid solutions. - Highlights: • Studied the ion mobility, conductivity in M{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} solid solutions (M=K, Rb). • An analysis of {sup 19}F NMR spectra made it possible to identify types of ion mobility. • The main type of ion motion above 300 K in solid solutions is a diffusion of ions F{sup –}. • The ionic conductivity of the solid solutions studied more than 10{sup –3} S/cm at 450 K.« less

Tellurite‐Squarate Driven Assembly of a New Family of Nanoscale Clusters Based on (Mo2O2S2)2+

PubMed Central

Purcell, Jamie W.; Miras, Haralampos N.; Long, De‐Liang; Markopoulou, Panagiota

2017-01-01

Abstract The preparation and characterization of a new family of four polyoxothiometalate (POTM) clusters are reported, with varying size and complexity, based upon the dimeric [Mo2O2S2(H2O)6]2+ cation with the general formula (NMe4)aKb[(Mo2O2S2)c(TeO4)d(C4O4)e(OH)f] where a,b,c,d,e,f={1,7,14,2,4,10}=1, {Mo28Te2}; {2,26,36,12,10,48}=2, {Mo72Te12}; {0,11,15,3,3,21}=3, {Mo30Te3}; {2,6,12,2,4,16}=4, {Mo24Te2}. The incorporation of tellurite anions allowed the fine tuning of the templating and bridging of the available building blocks, leading to new topologies of increased complexity. The structural diversity of this family of compounds ranges from the highly symmetrical cross‐shaped {Mo24Te2} to the stacked ring structure of {Mo72Te12}, which is the largest tellurium‐containing POTM cluster reported so far. Also a detailed experimental analysis revealed that the pH isolation window extends from acidic to basic values. ESI‐MS analyses not only confirmed the stability of this family in solution but also revealed the stability of the observed virtual building blocks. PMID:28548217

Cardiac PET perfusion tracers: current status and future directions.

PubMed

Maddahi, Jamshid; Packard, René R S

2014-09-01

PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of (18)F would result in better image resolution. Flurpiridaz F 18 is by far the most thoroughly studied in animal models and is the only (18)F-based PET MPI radiotracer currently undergoing clinical evaluation. Preclinical and clinical experience with Flurpiridaz F 18 demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast that was stable over time-important properties of an ideal PET MPI radiotracer. Preclinical data from other (18)F-labeled myocardial perfusion tracers are encouraging. Copyright © 2014. Published by Elsevier Inc.

Anion binding in the C3v-symmetric cavity of a protonated tripodal amine receptor: potentiometric and single crystal X-ray studies.

PubMed

Bose, Purnandhu; Ravikumar, I; Ghosh, Pradyut

2011-11-07

Tris(2-aminoethyl)amine (tren) based pentafluorophenyl-substituted tripodal L, tris[[(2,3,4,5,6-pentafluorobenzyl)amino]ethyl]amine receptor is synthesized in good yield and characterized by single crystal X-ray diffraction analysis. Detailed structural aspects of binding of different anionic guests toward L in its triprotonated form are examined thoroughly. Crystallographic results show binding of fluoride in the C(3v)-symmetric cavity of [H(3)L](3+) where spherical anion fluoride is in tricoordinated geometry via (N-H)(+)···F interaction in the complex [H(3)L(F)]·[F](2)·2H(2)O, (3). In the case of complexes [H(3)L(OTs)]·[OTs](2), (4) and [H(3)L(OTs)]·[NO(3)]·[OTs], (5), tetrahedral p-toluenesulphonate ion is engulfed in the cavity of [H(3)L](3+) via (N-H)(+)···O interactions. Interestingly, complex [(H(3)L)(2)(SiF(6))]·[BF(4)](4)·CH(3)OH·H(2)O, (6) shows encapsulation of octahedral hexafluorosilicate in the dimeric capsular assembly of two [H(3)L](3+) units, via a number of (N-H)(+)···F interactions. The kinetic parameters of L upon binding with different anions are evaluated using a potentiometric study in solution state. The potentiometric titration experiments in a polar protic methanol/water (1:1 v/v) binary solvent system show high affinity of the receptor toward more basic fluoride and acetate anions, with a lesser affinity for other inorganic anions (e.g., chloride, bromide, nitrate, sulfate, dihydrogenphosphate, and p-toluenesulphonate). © 2011 American Chemical Society

STM study of C60F18 high dipole moment molecules on Au(111)

NASA Astrophysics Data System (ADS)

Bairagi, K.; Bellec, A.; Chumakov, R. G.; Menshikov, K. A.; Lagoute, J.; Chacon, C.; Girard, Y.; Rousset, S.; Repain, V.; Lebedev, A. M.; Sukhanov, L. P.; Svechnikov, N. Yu.; Stankevich, V. G.

2015-11-01

Scanning tunneling microscopy and spectroscopy studies of C60F18 molecules deposited on Au(111) are reported and compared to C60 molecules both at liquid helium temperature and room temperature (RT). Whereas adsorption and electronic properties of C60F18 single molecules were studied at low temperature (LT), self-assemblies were investigated at RT. In both cases, the fluorine atoms of the C60F18 molecules are pointed towards the surface. Individual C60F18 molecules on Au(111) have a HOMO-LUMO gap of 2.9 eV. The self-assembled islands exhibit a close-packed hexagonal lattice with amorphous borders. The comparison with C60 molecules clearly demonstrates the influence of the C60F18 electric dipole moment (EDM) on the electronic properties of single molecules and on the thermodynamics of self-assembled islands. Besides, the apparent height value of a separate molecule increases in a self-assembly environment as a result of a depolarization phenomenon.

Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F.

PubMed

Oliveira, Amanda; Beyer, Georg; Chugh, Rohit; Skube, Steven J; Majumder, Kaustav; Banerjee, Sulagna; Sangwan, Veena; Li, Lihua; Dawra, Rajinder; Subramanian, Subbaya; Saluja, Ashok; Dudeja, Vikas

2015-06-01

Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude that Triptolide and Minnelide are effective against colon cancer in multiple pre-clinical models.

Cubic-to-tetragonal structural phase transition in Rb1-xCsxCaF3 solid solutions: Thermal expansion and EPR studies

NASA Astrophysics Data System (ADS)

Lahoz, F.; Villacampa, B.; Alcalá, R.; Marquina, C.; Ibarra, M. R.

1997-04-01

The influence of crystal mixing on the structural phase transitions in Rb1-xCsxCaF3 (0=0.44. This transition shows a weak first-order component in the x=0 and 0.1 samples, which is progressively smeared out for x>0.1, indicating a spatial distribution of the critical temperature in those crystals with high ionic substitution rate. In RbCaF3 , another structural phase transition was observed at 20 K with a thermal hysteresis between 20 and 40 K. This transition has not been found in any of the mixed crystals.

HBV core promoter mutations promote cellular proliferation through E2F1-mediated upregulation of S-phase kinase-associated protein 2 transcription.

PubMed

Huang, Yuehua; Tai, Andrew W; Tong, Shuping; Lok, Anna S F

2013-06-01

Hepatitis B virus (HBV) core promoter (CP) mutations have been associated with an increased risk of hepatocellular carcinoma (HCC) in clinical studies. We previously reported that a combination of CP mutations seen in HCC patients, expressed in HBx gene, increased SKP2 (S-phase kinase-associated protein 2) expression, thereby promoting cellular proliferation. Here, we investigate the possible mechanisms by which CP mutations upregulate SKP2. We used immunoblotting and ATPlite assay to validate the effect of CP mutations in full-length HBV genome on cell cycle regulator levels and cell proliferation. Activation of SKP2 mRNA was assessed by quantitative real-time PCR in primary human hepatocytes (PHH) and HCC cell lines. Effect of CP mutations on SKP2 promoter activity was determined by luciferase assay. Target regulation of E2F1 on SKP2 was analyzed by siRNAs. CP mutations in full-length HBV genome upregulated SKP2 expression, thereby downregulating cell cycle inhibitors and accelerating cellular proliferation. CP mutations enhanced SKP2 promoter activity but had no effect on SKP2 protein stability. Mapping of the SKP2 promoter identified a region necessary for activation by CP mutations that contains an E2F1 response element. Knocking down E2F1 reduced the effects of CP mutations on SKP2 and cellular proliferation. The effect of CP mutations on E2F1 might be mediated through hyperphosphorylation of RB. HBV CP mutations enhance SKP2 transcription by activating the E2F1 transcription factor and in turn downregulate cell cycle inhibitors, thus providing a potential mechanism for an association between CP mutations and HCC. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA, John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA, John F. Kennedy Space Center, Florida. Drawing 79K05424, Seelye Stevenson Value & Knecht, March, 1975. SITE WORK, GENERAL AREA PLAN. Sheet 8 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING. NASA John F. Kennedy ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING. NASA John F. Kennedy Space Center, Florida. File Number 79K06740, NASA, November 1975. SPACE & WEIGHT ALLOCATION, ORBITER PATH IN TRANSFER AISLE. Sheet 6 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Ionic conductivity of β-cyclodextrin-polyethylene-oxide/alkali-metal-salt complex.

PubMed

Yang, Ling-Yun; Fu, Xiao-Bin; Chen, Tai-Qiang; Pan, Li-Kun; Ji, Peng; Yao, Ye-Feng; Chen, Qun

2015-04-20

Highly conductive, crystalline, polymer electrolytes, β-cyclodextrin (β-CD)-polyethylene oxide (PEO)/LiAsF6 and β-CD-PEO/NaAsF6 , were prepared through supramolecular self-assembly of PEO, β-CD, and LiAsF6 /NaAsF6 . The assembled β-CDs form nanochannels in which the PEO/X(+) (X=Li, Na) complexes are confined. The nanochannels provide a pathway for directional motion of the alkali metal ions and, at the same time, separate the cations and the anions by size exclusion. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The electronic structure of RbTiOPO4 and the effects of the A-site cation substitution in KTiOPO4-family crystals

NASA Astrophysics Data System (ADS)

Atuchin, V. V.; Kesler, V. G.; Meng, Guangsi; Lin, Z. S.

2012-10-01

The electronic structure of RbTiOPO4 has been investigated with x-ray photoemission spectroscopy. Detailed photoemission spectra of the element core levels have been recorded under excitation by nonmonochromatic Al Kα radiation (1486.6 eV). The chemical bonding parameters are compared to those reported for complex titanates and phosphates. The band structures of KTiOPO4, RbTiOPO4, K0.535R0.465TiOPO4 and TlTiOPO4 have been calculated by ab initio methods and compared to available experimental results. It is found that the band structure of KTP-type phosphate crystals is weakly dependent on the nature of the A-site (A=K, Rb, Tl) element.

Study of a structural phase transition by two dimensional Fourier transform NMR method

NASA Astrophysics Data System (ADS)

Trokiner, A.; Man, P. P.; Théveneau, H.; Papon, P.

1985-09-01

The fluoroperovskite RbCaF 3 undergoes a structural phase transition at 195.5 K, from a cubic phase where the 87Rb nuclei have no quadrupolar interaction ( ωQ= 0) to a tetragonal phase where ω Q ≠ O. The transition is weakly first-order. A two-dimensional FT NMR experiment has been performed on 87Rb ( I = {3}/{2}) in a single crystal in both phases and in the vicinity of the phase transition. Our results show the coexistence of the two phases at the phase transition.

The relationship between the electronic structure and thermoelectric properties of Zintl compounds M2Zn5As4 (M = K, Rb).

PubMed

Yang, Gui; Yang, Jueming; Yan, Yuli; Wang, Yuanxu

2014-03-28

The electronic structure and the thermoelectric properties of M2Zn5As4 (M = K, Rb) are studied by the first principles and the semiclassical BoltzTraP theory. It is determined that they are semiconductors with an indirect band gap of about 1 eV, which is much larger than that of Ca5Al2Sb6 (0.50 eV). The calculated electronic localization function indicates that they are typical Zintl bonding compounds. The combination of heavy and light bands near the valence band maximum may improve their thermoelectric performance. Rb2Zn5As4 exhibits relatively large Seebeck coefficients, high electrical conductivities, and the large "maximum" thermoelectric figures of merit (ZeT). Compared with Ca5Al2Sb6, the highest ZeT of Rb2Zn5As4 appears at relatively low carrier concentration. For Rb2Zn4As5, the p-type doping may achieve a higher thermoelectric performance than n-type doping. The thermoelectric properties of Rb2Zn5As4 are possibly superior to those of Ca5Al2Sb6.

Assembly of silver Trigons into a buckyball-like Ag180 nanocage

PubMed Central

Wang, Zhi; Su, Hai-Feng; Tan, Yuan-Zhi; Schein, Stan; Lin, Shui-Chao; Liu, Wei; Wang, Shu-Ao; Wang, Wen-Guang; Tung, Chen-Ho; Zheng, Lan-Sun

2017-01-01

Buckminsterfullerene (C60) represents a perfect combination of geometry and molecular structural chemistry. It has inspired many creative ideas for building fullerene-like nanopolyhedra. These include other fullerenes, virus capsids, polyhedra based on DNA, and synthetic polynuclear metal clusters and cages. Indeed, the regular organization of large numbers of metal atoms into one highly complex structure remains one of the foremost challenges in supramolecular chemistry. Here we describe the design, synthesis, and characterization of a Ag180 nanocage with 180 Ag atoms as 4-valent vertices (V), 360 edges (E), and 182 faces (F)––sixty 3-gons, ninety 4-gons, twelve 5-gons, and twenty 6-gons––in agreement with Euler’s rule V − E + F = 2. If each 3-gon (or silver Trigon) were replaced with a carbon atom linked by edges along the 4-gons, the result would be like C60, topologically a truncated icosahedron, an Archimedean solid with icosahedral (Ih) point-group symmetry. If C60 can be described mathematically as a curling up of a 6.6.6 Platonic tiling, the Ag180 cage can be described as a curling up of a 3.4.6.4 Archimedean tiling. High-resolution electrospray ionization mass spectrometry reveals that {Ag3}n subunits coexist with the Ag180 species in the assembly system before the final crystallization of Ag180, suggesting that the silver Trigon is the smallest building block in assembly of the final cage. Thus, we assign the underlying growth mechanism of Ag180 to the Silver-Trigon Assembly Road (STAR), an assembly path that might be further employed to fabricate larger, elegant silver cages. PMID:29087328

The molecular origins of specificity in the assembly of a multienzyme complex.

PubMed

Frank, René A W; Pratap, J Venkatesh; Pei, Xue Y; Perham, Richard N; Luisi, Ben F

2005-08-01

The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative metabolism. We present the first crystal structure of a complex between pyruvate decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of the PDH assembly. The PSBD achieves this dual recognition largely through the addition of a network of interfacial water molecules unique to the E1-PSBD complex. These structural comparisons illuminate our observations that the formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas that of the E3-PSBD complex (from which water is excluded) is entropy driven. Interfacial water molecules thus diversify surface complementarity and contribute to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight into the organization and active site coupling within the approximately 9 MDa PDH complex.

The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1

PubMed Central

Osada, Shigehiro; Sutton, Ann; Muster, Nemone; Brown, Christine E.; Yates, John R.; Sternglanz, Rolf; Workman, Jerry L.

2001-01-01

It is well established that acetylation of histone and nonhistone proteins is intimately linked to transcriptional activation. However, loss of acetyltransferase activity has also been shown to cause silencing defects, implicating acetylation in gene silencing. The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ∼450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein. Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing. Furthermore, the SAS complex is found to interact with chromatin assembly factor Asf1p, and asf1 mutants show silencing defects similar to mutants in the SAS complex. Thus, ASF1-dependent chromatin assembly may mediate the role of the SAS complex in silencing. PMID:11731479

Charging properties of cassiterite (alfa-SnO2) surfaces

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

Rosenqvist, Jorgen K; Machesky, Michael L.; Vlcek, L.

The acid-base properties of cassiterite (alfa-SnO2) surfaces at 10 50 C were studied using potentiometric titrations of powder suspensions in aqueous NaCl and RbCl media. The proton sorption isotherms exhibited common intersection points in the pH-range 4.0 to 4.5 at all conditions and the magnitude of charging was similar but not identical in NaCl and RbCl. The hydrogen bonding configuration at the oxide-water interface, obtained from classical Molecular Dynamics (MD) simulations, was analyzed in detail and the results were explicitly incorporated in calculations of protonation constants for the reactive surface sites using the revised MUSIC model. The calculations indicated thatmore » the terminal SnOH2 group is more acidic than the bridging Sn2OH group, with protonation constants (log KH) of 3.60 and 5.13 at 25 C, respectively. This is contrary to the situation on the isostructural alfa-TiO2 (rutile), apparently due to the difference in electronegativity between Ti and Sn. MD simulations and speciation calculations indicated considerable differences in the speciation of Na+ and Rb+, despite the similarities in overall charging. Adsorbed sodium ions are almost exclusively found in bidentate surface complexes, while adsorbed rubidium ions form comparable amounts of bidentate and tetradentate complexes. Also, the distribution of adsorbed Na+ between the different complexes shows a considerable dependence on surface charge density (pH), while the distribution of adsorbed Rb+ is almost independent of pH. A Surface Complexation Model (SCM) capable of accurately describing both the measured surface charge and the MD predicted speciation of adsorbed Na+/Rb+ was formulated. According to the SCM, the deprotonated terminal group (SnOH-0.40) and the protonated bridging group (Sn2OH+0.36) dominate the surface speciation over the entire pH-range (2.7 10), illustrating the ability of positively and negatively charged surface groups to coexist. Complexation of the medium cations increases significantly with increasing negative surface charge and at pH 10 roughly 40 percent of the terminal sites are predicted to form cation complexes, while anion complexation is minor throughout the studied pH-range.« less

Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.

PubMed

Park, Su-Jung; Ciccone, Samantha L M; Beck, Brian D; Hwang, Byounghoon; Freie, Brian; Clapp, D Wade; Lee, Suk-Hee

2004-07-16

Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Eight FANC genes have been identified so far, and five of them (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at least in part in a complex to activate FANCD2 by monoubiquitination. Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or form a nuclear complex in response to oxidative stress/damage. Both FANCA and FANCG proteins exist as monomers under non-oxidizing conditions, whereas they become multimers following H2O2 treatment. Treatment of cells with oxidizing agent not only triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken together, our results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming complex(es) via intermolecular disulfide linkage(s), which may be crucial in forming such complexes and in determining their function.

PP2A: more than a reset switch to activate pRB proteins during the cell cycle and in response to signaling cues

PubMed Central

Kurimchak, Alison; Graña, Xavier

2015-01-01

In their active hypophosphorylated state, members of the retinoblastoma family of pocket proteins negatively regulate cell cycle progression at least in part by repressing expression of E2F-dependent genes. Mitogen-dependent activation of G1 and G1/S Cyclin Dependent Kinases (CDKs) results in coordinated hyperphosphorylation and inactivation of these proteins, which no longer bind and repress E2Fs. S and G2/M CDKs maintain pocket protein hyperphosphorylated through the end of mitosis. The inactivating action of inducible CDKs is opposed by the Ser/Thr protein phosphatases PP2A and PP1. Various trimeric PP2A holoenzymes have been implicated in dephosphorylation of pocket proteins in response to specific cellular signals and stresses or as part of an equilibrium with CDKs throughout the cell cycle. PP1 has specifically been implicated in dephosphorylation of pRB in late mitosis and early G1. This review is particularly focused on the emerging role of PP2A as a major hub for integration of growth suppressor signals that require rapid inactivation of pocket proteins. Of note, activation of particular PP2A holoenzymes triggers differential activation of pocket proteins in the presence of active CDKs.

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. ALL PLATFORMS-ARCHITECTURAL, GENERAL ARRANGEMENT, EAST-WEST ELEVATIONS. Sheet 12 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Pigmented rice bran and plant sterol combination reduces serum lipids in overweight and obese adults.

PubMed

Hongu, Nobuko; Kitts, David D; Zawistowski, Jerzy; Dossett, Cynthia M; Kopeć, Aneta; Pope, Benjamin T; Buchowski, Maciej S

2014-01-01

This study investigated the dietary effect of including pigmented rice bran with or without plant sterols on lipid profiles during energy restriction-induced weight loss in overweight and obese adults not taking cholesterol-lowering medication. In addition, the study examined the effect of intervention on biomarkers of oxidative stress and inflammation. A group of 24 overweight and obese adults (age: 43 ± 6 years, body mass index 32 ± 1 kg/m(2), 18 females) were randomized to a 25% calorie-restricted diet containing either pigmented rice bran (RB) or the RB with addition of plant sterols (RB+PS) snack bars for 8 weeks. The individualized nutrient-balanced diet contained ∼70% of daily energy needs assessed from indirect calorimetry measured resting energy expenditure (EE) and physical activity-related EE assessed using accelerometry. Anthropometrics, blood pressure, blood lipids, glucose, urinary F2-isoprostanes, C-reactive protein, insulin, and leptin were measured at baseline and after 8 weeks of intervention. Participants lost approximately 4.7 ± 2.2 kg (p < 0.001). Weight loss was not significant between the RB+PS and RB group (p = 0.056). Changes in body fat corresponded to changes in body weight. Average decrease in total cholesterol was significantly higher in the RB+PS group than in the RB group (difference 36 ± 25 g/dL vs 7 ± 16 g/dL; p = 0.044). A similar pattern was observed for the decrease in low-density lipoprotein (LDL) cholesterol (difference 22.3 ± 25.2 g/dL vs 4.4 ± 18.9 g/dL; p = 0.062). Changes in systolic blood pressure, serum levels of leptin, and F2-isoprostanes were significant between baseline values and after 8 weeks on the diet in both groups (p < 0.05) but did not differ between the 2 groups. A nutrient-balanced and energy-restricted diet supplemented with rice bran and plant sterols resulted in a significant decrease in total and LDL cholesterol in overweight and obese adults.

Novel Binding Motif and New Flexibility Revealed by Structural Analyses of a Pyruvate Dehydrogenase-Dihydrolipoyl Acetyltransferase Subcomplex from the Escherichia coli Pyruvate Dehydrogenase Multienzyme Complex*

PubMed Central

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S.; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-01-01

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. PMID:25210042

Novel binding motif and new flexibility revealed by structural analyses of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase subcomplex from the Escherichia coli pyruvate dehydrogenase multienzyme complex.

PubMed

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-10-24

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Electronic structure and fundamental absorption edges of KPb2Br5, K0.5Rb0.5Pb2Br5, and RbPb2Br5 single crystals

NASA Astrophysics Data System (ADS)

Tarasova, A. Yu.; Isaenko, L. I.; Kesler, V. G.; Pashkov, V. M.; Yelisseyev, A. P.; Denysyuk, N. M.; Khyzhun, O. Yu.

2012-05-01

X-ray photoelectron core-level and valence-band spectra for pristine and Ar+-ion irradiated (001) surfaces of KPb2Br5, K0.5Rb0.5Pb2Br5, and RbPb2Br5 single crystals grown by the Bridgman method have been measured and fundamental absorption edges of the ternary bromides have been recorded in the polarized light at 300 K and 80 K. The present X-ray photoelectron spectroscopy (XPS) results reveal high chemical stability of (001) surfaces of KxRb1-xPb2Br5 (x=0, 0.5, and 1.0) single crystals. Substitution of potassium for rubidium in KxRb1-xPb2Br5 does not cause any changes of binding energy values and shapes of the XPS constituent element core-level spectra. Measurements of the fundamental absorption edges indicate that band gap energy, Eg, increases by about 0.14 and 0.19 eV when temperature decreases from 300 K to 80 K in KPb2Br5 and RbPb2Br5, respectively. Furthermore, there is no dependence of the Eg value for KPb2Br5 upon the light polarization, whilst the band gap energy value for RbPb2Br5 is bigger by 0.03-0.05 eV in the case of E‖c compared to those in the cases of E‖a and E‖b.

Hyperfine structure of 2Σ molecules containing alkaline-earth-metal atoms

NASA Astrophysics Data System (ADS)

Aldegunde, Jesus; Hutson, Jeremy M.

2018-04-01

Ultracold molecules with both electron spin and an electric dipole moment offer new possibilities in quantum science. We use density-functional theory to calculate hyperfine coupling constants for a selection of molecules important in this area, including RbSr, LiYb, RbYb, CaF, and SrF. We find substantial hyperfine coupling constants for the fermionic isotopes of the alkaline-earth-metal and Yb atoms. We discuss the hyperfine level patterns and Zeeman splittings expected for these molecules. The results will be important both to experiments aimed at forming ultracold open-shell molecules and to their applications.

DOSIMETRY MODELING OF INHALED FORMALDEHYDE: BINNING NASAL FLUX PREDICTIONS FOR QUANTITATIVE RISK ASSESSMENT

EPA Science Inventory

Dosimetry Modeling of Inhaled Formaldehyde: Binning Nasal Flux Predictions for Quantitative Risk Assessment. Kimbell, J.S., Overton, J.H., Subramaniam, R.P., Schlosser, P.M., Morgan, K.T., Conolly, R.B., and Miller, F.J. (2001). Toxicol. Sci. 000, 000:000.

Interspecies e...

Spirolactone and spirothiolactone rhodamine-pyrene probes for detection of Hg²⁺ with different sensing properties and its application in living cells.

PubMed

Rui, Qing-Qing; Zhou, Yi; Fang, Yuan; Yao, Cheng

2016-04-15

Two new rhodamine B-based fluorescent probes PyRbS and PyRbO containing pyrene moiety were designed and synthesized. Both of the probes showed colorimetric and fluorometric sensing abilities for Hg(2+) with high selectivity over other metal ions. The binding analysis using Job's plot suggested 1:1 stoichiometry for the complexes formed for Hg(2+). Compared with PyRbO, the PyRbS showed higher selectivity and sensitivity due to the thiophilic property of Hg(2+) ion. The PyRbS exhibited the linear fluorescence quenching to Hg(2+) in the range of 0.3 to 4.8 μM (λ(ex)=365 nm) and 0.3 to 5.4 μM (λ(ex)=515 nm), and the detection limit was 0.72 μM. Moreover, ratiometric changes of PyRbS with Hg(2+) in absorption spectrum were observed, which could not be obtained in the combination of PyRbO with Hg(2+). In addition, the methyl thiazolyl tetrazolium (MTT) assay demonstrated that RbPyS had low cytotoxicity and was successfully used to monitor intracellular Hg(2+) levels in living cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Faraday effect on the Rb D{sub 1} line in a cell with a thickness of half the wavelength of light

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

Sargsyan, A., E-mail: sarmeno@mail.ru, E-mail: sargsyanarmen85@gmail.com; Pashayan-Leroy, Y.; Leroy, C.

2016-09-15

The rotation of the radiation polarization plane in a longitudinal magnetic field (Faraday effect) on the D{sub 1} line in atomic Rb vapor has been studied with the use of a nanocell with the thickness L varying in the range of 100–900 nm. It has been shown that an important parameter is the ratio L/λ, where λ = 795 nm is the wavelength of laser radiation resonant with the D{sub 1} line. The best parameters of the signal of rotation of the radiation polarization plane have been obtained at the thickness L = λ/2 = 397.5 nm. The fabricated nanocellmore » had a large region with such a thickness. The spectral width of the signal reached at the thickness L = 397.5 nm is approximately 30 MHz, which is much smaller than the spectral width (≈ 500 MHz) reached with ordinary cells with a thickness in the range of 1–100 mm. The parameters of the Faraday rotation signal have been studied as functions of the temperature of the nanocell, the laser power, and the magnetic field strength. The signal has been reliably detected at the laser power P{sub L} ≥ 1 μW, magnetic field strength B ≥ 0.5 G, and the temperature of the nanocell T ≥ 100°C. It has been shown that the maximum rotation angle of the polarization plane in the longitudinal magnetic field is reached on the F{sub g} = 3 → F{sub e} = 2 transition of the {sup 85}Rb atom. The spectral profile of the Faraday rotation signal has a specific shape with a sharp peak, which promotes its applications. In particular, Rb atomic transitions in high magnetic fields about 1000 G are split into a large number of components, which are completely spectrally resolved and allow the study of the behavior of an individual transition.« less

Determining pre-eruptive compositions of late Paleozoic magma from kaolinized volcanic ashes: Analysis of glass inclusions in quartz microphenocrysts from tonsteins

NASA Astrophysics Data System (ADS)

Webster, James D.; Congdon, Roger D.; Lyons, Paul C.

1995-02-01

Glass inclusions in quartz microphenocrysts were analyzed for major and minor elements by electron microprobe and H, Li, Be, B, Rb, Sr, Y, Nb, Mo, Sn, Cs, Ce, Th, and U by ion microprobe. The phenocrysts and inclusions occur as fresh relicts in about eleven strongly kaolinized, air-fall volcanic ash units (tonsteins) that outcrop in five states located in the central Appalachian basin; the ashes were erupted during the Pennsylvanian. Even though the whole-rock tonstein samples are extremely altered, the glass trapped in quartz microphenocrysts preserves pre-eruptive melt compositions, and, consequently, the inclusions are useful for determining compositions of source magmas and identifying geochemical trends indicative of magmatic evolution. Interpretation of inclusion compositions indicates the strongly altered tonsteins were derived from potassium-enriched, metaluminous to mildly peraluminous magma(s). The tonsteins can be divided into two groups on the basis of trapped melt compositions: older tonsteins that have inclusions with high Sr and normative quartz contents and comparatively low concentrations of U, Th, Rb, Y, Cs, Nb, F, and Cl (±Be) and younger tonsteins whose inclusions contain low Sr and normative quartz and high concentrations of U, Th, Rb, Y, Cs, Nb, F, and Cl (±Be). In general, as concentrations of Sr decreased, the magmatic abundances of Rb, Y, Cs, Nb, U, Th, Cl, and F (±Be) increased. The associated magma or magmas were highly evolved, volatile enriched, and contained Rb, Nb, and Y abundances characteristic of continental within-plate granites; compositions ranged from high-silica rhyolite to topaz rhyolite. Pre-eruptive volatile abundances in the source magma(s) were generally high but also highly variable. Chlorine contents of melt(s) ranged from 0.02-0.23 wt%, and F ranged from 0.01-0.7 wt%. Concentrations of H 2O in melt(s) ranged from 1.6-6.5 wt%. The high pre-eruptive H 2O contents are consistent with large eruptive volumes indicating the precursor rhyolites, which weathered to tonsteins, were a result of plinian eruptions. Even though pre-eruptive water concentrations exhibit no recognizable trends with any elements studied, magmatic evolution appears to have been a strong function of F and H 2O in melt(s); the thermal stabilities of quartz and feldspar were controlled by F and H 2O activities at pressures of approximately 0.5-1 kbar.

Characterization of glial cell K-Cl cotransport.

PubMed

Gagnon, Kenneth B E; Adragna, Norma C; Fyffe, Robert E W; Lauf, Peter K

2007-01-01

The molecular mechanism of K-Cl cotransport (KCC) consists of at least 4 isoforms, KCC 1, 2, 3, and 4 which, in multiple combinations, exist in most cells, including erythrocytes and neuronal cells. We utilized reverse-transcriptase-polymerase chain reaction (RT-PCR) and ion flux studies to characterize KCC activity in an immortalized in vitro cell model for fibrous astrocytes, the rat C6 glioblastoma cell. Isoform-specific sets of oligonucleotide primers were synthesized for NKCC1, KCC1, KCC2, KCC3, KCC4, and also for NKCC1 and actin. K-Cl cotransport activity was determined by measuring either the furosemide-sensitive, or the Cl(-)-dependent bumetanide-insensitive Rb(+) (a K(+) congener) influx in the presence of the Na/K pump inhibitor ouabain. Rb(+) influx was measured at a fixed external Cl concentrations, [Cl(-)](e), as a function of varying external Rb concentrations, [Rb(+)](e), and at a fixed [Rb(+)](e) as a function of varying [Cl(-)](e), and with equimolar Cl replacement by anions of the chaotropic series. RT-PCR of C6 glioblastoma (C6) cells identified mRNA for three KCC isoforms (1, 3, and 4). NKCC1 mRNA was also detected. The apparent K(m) for KCC-mediated Rb(+) influx was 15 mM [Rb(+)](e), and V(max) 12.5 nmol Rb(+) * mg protein(-1) * minute(-1). The calculated apparent K(m) for external Cl(-) was 13 mM and V(max) 14.4 nmol Rb(+) * mg protein(-1) * minute(-1). The anion selectivity sequence of the furosemide-sensitive Rb(+) influx was Cl(-)>Br-=NO(3)(-)>I(-)=SCN(-)>Sfm(-) (sulfamate). Established activators of K-Cl cotransport, hyposmotic shock and N-ethylmaleimide (NEM) pretreatment, stimulated furosemide-sensitive Rb(+) influx. A ñ50% NEM-induced loss of intracellular K(+) was prevented by furosemide. We have identified by RT-PCR the presence of three distinct KCC isoforms (1, 3, and 4) in rat C6 glioblastoma cells, and functionally characterized the anion selectivity and kinetics of their collective sodium-independent cation-chloride cotransport activity.

Syntheses, crystal structure, and electronic properties of the five ABaMQ{sub 4} compounds RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4}

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

Mesbah, Adel; ICSM, UMR 5257 CEA / CNRS / UM / ENSCM, Site de Marcoule-Bâtiment 426, BP 17171, 30207 Bagnols-sur-Cèze Cedex; Prakash, Jai

Five new compounds belonging to the ABaMQ{sub 4} family were synthesized by solid-state chemistry at 1123 K. The compounds RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4} are isostructural and have the TlEuPS{sub 4} structure type. They crystallize in space group D{sup 16}{sub 2h} – Pnma of the orthorhombic system. Their structure consists isolated MQ{sub 4} tetrahedra separated by A and Ba atoms to form a salt-like structure. Density Functional Theory (DFT) calculations of the electronic structures with the use of the HSE functional suggest that the compounds are semiconductors with calculated band gaps of 3.3 eVmore » (RbBaPS{sub 4}), 3.4 eV (CsBaPS{sub 4}), 2.3 eV (CsBaVS{sub 4}), and 1.6 eV (RbBaVSe{sub 4}). - Graphical abstract: General view of the ABaMQ{sub 4} structure down the a axis. - Highlights: • Five new ABaMQ{sub 4} compounds were synthesized by solid-state chemistry at 1123 K. • RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4} have the TlEuPS{sub 4} structure type. • The compounds are semiconductors with calculated band gaps ranging from 1.6 to 3.4 eV.« less

New Rh 2 (II,II) Complexes for Solar Energy Applications: Panchromatic Absorption and Excited-State Reactivity

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

Whittemore, Tyler J.; Sayre, Hannah J.; Xue, Congcong

In this work, the new heteroleptic paddlewheel complexes cis-[Rh 2(μ-form) 2(μ-np) 2][BF 4] 2, where form = p-ditolylformamidinate (DTolF) or p-difluorobenzylformamidinate (F-form) and np = 1,8-napthyridyine, and cis-Rh 2(μ-form) 2(μ-npCOO) 2 (npCOO – = 1,8-naphthyridine-2-carboxylate), were synthesized and characterized. The complexes absorb strongly throughout the ultraviolet (λ max = 300 nm, ε = 20 300 M –1 cm –1) and visible regions (λ max = 640 nm ε = 3500 M –1 cm –1), making them potentially useful new dyes with panchromatic light absorption for solar energy conversion applications. Ultrafast and nanosecond transient absorption and time-resolved infrared spectroscopies were usedmore » to characterize the identity and dynamics of the excited states, where singlet and triplet Rh 2/form-to-naphthyridine, metal/ligand-to-ligand charge-transfer (ML-LCT) excited states were observed in all four complexes. The npCOO – complexes exhibit red-shifted absorption profiles extending into the near-IR and undergo photoinitiated electron transfer to generate reduced methyl viologen, a species that persists in the presence of a sacrificial donor. The energy of the triplet excited state of each complex was estimated from energy-transfer quenching experiments using a series of organic triplet donors (E( 3ππ*) from 1.83 to 0.78 eV). The singlet reduction (+0.6 V vs Ag/AgCl) potentials, and singlet and triplet oxidation potentials (-1.1 and -0.5 V vs Ag/AgCl, respectively) were determined. Finally, based on the excited-state lifetimes and redox properties, these complexes represent a new class of light absorbers with potential application as dyes for charge injection into semiconductor solar cells and in sensitizer-catalyst assemblies for photocatalysis that operate with irradiation from the ultraviolet to ~800 nm.« less

New Rh 2 (II,II) Complexes for Solar Energy Applications: Panchromatic Absorption and Excited-State Reactivity

DOE PAGES

Whittemore, Tyler J.; Sayre, Hannah J.; Xue, Congcong; ...

2017-10-04

In this work, the new heteroleptic paddlewheel complexes cis-[Rh 2(μ-form) 2(μ-np) 2][BF 4] 2, where form = p-ditolylformamidinate (DTolF) or p-difluorobenzylformamidinate (F-form) and np = 1,8-napthyridyine, and cis-Rh 2(μ-form) 2(μ-npCOO) 2 (npCOO – = 1,8-naphthyridine-2-carboxylate), were synthesized and characterized. The complexes absorb strongly throughout the ultraviolet (λ max = 300 nm, ε = 20 300 M –1 cm –1) and visible regions (λ max = 640 nm ε = 3500 M –1 cm –1), making them potentially useful new dyes with panchromatic light absorption for solar energy conversion applications. Ultrafast and nanosecond transient absorption and time-resolved infrared spectroscopies were usedmore » to characterize the identity and dynamics of the excited states, where singlet and triplet Rh 2/form-to-naphthyridine, metal/ligand-to-ligand charge-transfer (ML-LCT) excited states were observed in all four complexes. The npCOO – complexes exhibit red-shifted absorption profiles extending into the near-IR and undergo photoinitiated electron transfer to generate reduced methyl viologen, a species that persists in the presence of a sacrificial donor. The energy of the triplet excited state of each complex was estimated from energy-transfer quenching experiments using a series of organic triplet donors (E( 3ππ*) from 1.83 to 0.78 eV). The singlet reduction (+0.6 V vs Ag/AgCl) potentials, and singlet and triplet oxidation potentials (-1.1 and -0.5 V vs Ag/AgCl, respectively) were determined. Finally, based on the excited-state lifetimes and redox properties, these complexes represent a new class of light absorbers with potential application as dyes for charge injection into semiconductor solar cells and in sensitizer-catalyst assemblies for photocatalysis that operate with irradiation from the ultraviolet to ~800 nm.« less

Disruption of the G1/S Transition in Human Papillomavirus Type 16 E7-Expressing Human Cells Is Associated with Altered Regulation of Cyclin E

PubMed Central

Martin, Larry G.; Demers, G. William; Galloway, Denise A.

1998-01-01

The development of neoplasia frequently involves inactivation of the p53 and retinoblastoma (Rb) tumor suppressor pathways and disruption of cell cycle checkpoints that monitor the integrity of replication and cell division. The human papillomavirus type 16 (HPV-16) oncoproteins, E6 and E7, have been shown to bind p53 and Rb, respectively. To further delineate the mechanisms by which E6 and E7 affect cell cycle control, we examined various aspects of the cell cycle machinery. The low-risk HPV-6 E6 and E7 proteins did not cause any significant change in the levels of cell cycle proteins analyzed. HPV-16 E6 resulted in very low levels of p53 and p21 and globally elevated cyclin-dependent kinase (CDK) activity. In contrast, HPV-16 E7 had a profound effect on several aspects of the cell cycle machinery. A number of cyclins and CDKs were elevated, and despite the elevation of the levels of at least two CDK inhibitors, p21 and p16, CDK activity was globally increased. Most strikingly, cyclin E expression was deregulated both transcriptionally and posttranscriptionally and persisted at high levels in S and G2/M. Transit through G1 was shortened by the premature activation of cyclin E-associated kinase activity. Elevation of cyclin E levels required both the CR1 and CR2 domains of E7. These data suggest that cyclin E may be a critical target of HPV-16 E7 in the disruption of G1/S cell cycle progression and that the ability of E7 to regulate cyclin E involves activities in addition to the release of E2F. PMID:9444990

Protactinium and the intersection of actinide and transition metal chemistry

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

Wilson, Richard E.; De Sio, Stephanie; Vallet, Valérie

The role of the 5f and 6d orbitals in the chemistry of the actinide elements has been of considerable interest since their discovery and synthesis. Relativistic effects cause the energetics of the 5f and 6d orbitals to change as the actinide series is traversed left to right imparting a rich and complex chemistry. The 5f and 6d atomic states cross in energy at protactinium (Pa), making it a potential intersection between transition metal and actinide chemistries. Herein, we report the synthesis of a Pa-peroxo cluster, A(6)(Pa4O(O-2)(6)F-12) [A = Rb, Cs, (CH3)(4)N], formed in pursuit of an actinide polyoxometalate. Quantum chemicalmore » calculations at the density functional theory level demonstrate equal 5f and 6d orbital participation in the chemistry of Pa and increasing 5f orbital participation for the heavier actinides. Periodic changes in orbital character to the bonding in the early actinides highlights the influence of the 5f orbitals in their reactivity and chemical structure.« less

Topological formation of a multiply charged vortex in the Rb Bose-Einstein condensate: Effectiveness of the gravity compensation

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

Kumakura, M.; PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama 332-0012; CREST, JST, 4-1-8 Honcho Kawaguchi, Saitama 332-0012

2006-06-15

In a Bose-Einstein condensate of {sup 87}Rb (F=2,m{sub F}=2) atoms we have topologically created a quantized vortex with a charge of 4 by reversing the magnetic field of the trap. Experimental conditions of reversal time and initial magnetic field strength for the successful vortex creation were restricted within narrower ranges, compared to those in the case of the {sup 23}Na condensate. The experimental difficulty was explained in terms of a non-negligible gravitational sag arising from its large atomic mass. We have successfully stabilized the vortex formation by compensating gravity with a blue-detuned laser beam.

Production of complex rubidium and cesium hydrogen sulfate‒phosphates

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

Komornikov, V. A., E-mail: v.a.kom@mail.ru; Grebenev, V. V.; Makarova, I. P.

2016-07-15

The solubility in the CsH{sub 2}PO{sub 4}‒CsHSO{sub 4}‒H{sub 2}O system at different temperatures (25, 50, and 75°C) is studied and the phase equilibria in the Rb{sub 3}H(SO{sub 4}){sub 2}‒RbH{sub 2}PO{sub 4}‒H{sub 2}O system under isothermal conditions (at 25°C) are analyzed. The temperature and concentration conditions for forming Rb{sub 2}(HSO{sub 4})(H{sub 2}PO{sub 4}), Rb{sub 4}(HSO{sub 4}){sub 3}(H{sub 2}PO{sub 4}), Cs{sub 4}(HSO{sub 4}){sub 3}(H{sub 2}PO{sub 4}), Cs{sub 3}(HSO{sub 4}){sub 2}(H{sub 2}PO{sub 4}), Cs{sub 2}(HSO{sub 4})(H{sub 2}PO{sub 4}), and Cs{sub 6}H(HSO{sub 4}){sub 3}(H{sub 2}PO{sub 4}){sub 4} compounds (the latter has been obtained for the first time) are determined. The conditions for growing largemore » single crystals of complex acid rubidium and cesium salts are found.« less

78 FR 20507 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking...) RB211-535E4-37, RB211-535E4-B-37, RB211-535E4-C- 37, and RB211-535E4-B-75 turbofan engines. This...-535E4-C-37, and RB211-535E4-B-75 turbofan engines. (d) Reason This AD was prompted by RR updating the...

Rb + adsorption at the quartz(101)-aqueous interface: comparison of resonant anomalous x-ray reflectivity with ab initio calculations

DOE PAGES

Bellucci, Francesco; Lee, Sang Soo; Kubicki, James D.; ...

2015-01-29

We study adsorption of Rb + to the quartz(101)–aqueous interface at room temperature with specular X-ray reflectivity, resonant anomalous X-ray reflectivity, and density functional theory. The interfacial water structures observed in deionized water and 10 mM RbCl solution at pH 9.8 were similar, having a first water layer at height of 1.7 ± 0.1 Å above the quartz surface and a second layer at 4.8 ± 0.1 Å and 3.9 ± 0.8 Å for the water and RbCl solutions, respectively. The adsorbed Rb + distribution is broad and consists of presumed inner-sphere (IS) and outer-sphere (OS) complexes at heights ofmore » 1.8 ± 0.1 and 6.4 ± 1.0 Å, respectively. Projector-augmented planewave density functional theory (DFT) calculations of potential configurations for neutral and negatively charged quartz(101) surfaces at pH 7 and 12, respectively, reveal a water structure in agreement with experimental results. These DFT calculations also show differences in adsorbed speciation of Rb + between these two conditions. At pH 7, the lowest energy structure shows that Rb + adsorbs dominantly as an IS complex, whereas at pH 12 IS and OS complexes have equivalent energies. The DFT results at pH 12 are generally consistent with the two site Rb distribution observed from the X-ray data at pH 9.8, albeit with some differences that are discussed. In conclusion, surface charge estimated on the basis of the measured total Rb + coverage was -0.11 C/m 2, in good agreement with the range of the surface charge magnitudes reported in the literature.« less

A luminescence-optical spectroscopy study of Rb2KTiOF5 single crystals

NASA Astrophysics Data System (ADS)

Pustovarov, V. A.; Ogorodnikov, I. N.; Kozlov, A. V.; Isaenko, L. I.

2018-06-01

Large single crystals of Rb2KTiOF5 (RKTF), grown by slow solidification method, were studied (7-400 K) for various types of optical and radiation effects. The optical absorption spectra, the parameters of the Urbach rule at 293 K (σ = 0.24 and EU = 105 meV), the low-temperature reflection spectra (T = 7 K, E = 3.7-22 eV) were determined. The luminescence spectra (1.2-6.2 eV) and luminescence decay kinetics are studied upon excitation by a nanosecond electron beam (PCL), ultraviolet and vacuum ultraviolet light (PL), or X-rays radiation (XRL). PL excitation spectra under selective photoexcitation by synchrotron radiation (E = 3.7-22 eV, T = 7 K), temperature dependences of the intensity of steady-state XRL in different emission bands, as well as thermoluminescence (7-400 K) are studied. In the visible spectral region, we detected three luminescence bands that were attributed to radiative annihilation of intrinsic excitons (2.25 eV), recombination-type luminescence (2.1 eV) and luminescence of higher TiOF5 complexes (1.9 eV). The exponential component with lifetime of about 19 μs was revealed in the PCL decay kinetics at 2.25 eV. The low-energy onset of the intrinsic host absorption Ec = 3.55 eV was determined on the basis of the experimental data obtained. Spectra of optical constants were calculated by the Kramers-Krönig method, the energy of the onset of the interband transitions Eg = 4.2 eV was determined, and the main peaks of the optical spectra were identified.

Dia-Interacting Protein (DIP) Imposes Migratory Plasticity in mDia2-Dependent Tumor Cells in Three-Dimensional Matrices

PubMed Central

Wyse, Meghan M.; Lei, Jun; Nestor-Kalinoski, Andrea L.; Eisenmann, Kathryn M.

2012-01-01

Tumor cells rely upon membrane pliancy to escape primary lesions and invade secondary metastatic sites. This process relies upon localized assembly and disassembly cycles of F-actin that support and underlie the plasma membrane. Dynamic actin generates both spear-like and bleb structures respectively characterizing mesenchymal and amoeboid motility programs utilized by metastatic cells in three-dimensional matrices. The molecular mechanism and physiological trigger(s) driving membrane plasticity are poorly understood. mDia formins are F-actin assembly factors directing membrane pliancy in motile cells. mDia2 is functionally coupled with its binding partner DIP, regulating cortical actin and inducing membrane blebbing in amoeboid cells. Here we show that mDia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. DIP controls mesenchymal/amoeboid cell interconvertability, while CXCL12 induces assembly of mDia2:DIP complexes to bleb cortices in 3D matrices. These results demonstrate how DIP-directed mDia2-dependent F-actin dynamics regulate morphological plasticity in motile cancer cells. PMID:23024796

Analysis of C/E results of fission rate ratio measurements in several fast lead VENUS-F cores

NASA Astrophysics Data System (ADS)

Kochetkov, Anatoly; Krása, Antonín; Baeten, Peter; Vittiglio, Guido; Wagemans, Jan; Bécares, Vicente; Bianchini, Giancarlo; Fabrizio, Valentina; Carta, Mario; Firpo, Gabriele; Fridman, Emil; Sarotto, Massimo

2017-09-01

During the GUINEVERE FP6 European project (2006-2011), the zero-power VENUS water-moderated reactor was modified into VENUS-F, a mock-up of a lead cooled fast spectrum system with solid components that can be operated in both critical and subcritical mode. The Fast Reactor Experiments for hybrid Applications (FREYA) FP7 project was launched in 2011 to support the designs of the MYRRHA Accelerator Driven System (ADS) and the ALFRED Lead Fast Reactor (LFR). Three VENUS-F critical core configurations, simulating the complex MYRRHA core design and one configuration devoted to the LFR ALFRED core conditions were investigated in 2015. The MYRRHA related cores simulated step by step design peculiarities like the BeO reflector and in pile sections. For all of these cores the fuel assemblies were of a simple design consisting of 30% enriched metallic uranium, lead rodlets to simulate the coolant and Al2O3 rodlets to simulate the oxide fuel. Fission rate ratios of minor actinides such as Np-237, Am-241 as well as Pu-239, Pu-240, Pu-242 and U-238 to U-235 were measured in these VENUS-F critical assemblies with small fission chambers in specially designed locations, to determine the spectral indices in the different neutron spectrum conditions. The measurements have been analyzed using advanced computational tools including deterministic and stochastic codes and different nuclear data sets like JEFF-3.1, JEFF-3.2, ENDF/B7.1 and JENDL-4.0. The analysis of the C/E discrepancies will help to improve the nuclear data in the specific energy region of fast neutron reactor spectra.

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘E’, ROOF PLAN, ARCHITECTURAL. Sheet 22 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘D’, MAIN FLOOR PLAN, ARCHITECTURAL. Sheet 39 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘E’, MAIN FLOOR PLAN, ARCHITECTURAL. Sheet 23 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘D’, ROOF PLAN, ARCHITECTURAL. Sheet 36 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘D’, 3RD FLOOR PLAN, ARCHITECTURAL. Sheet 37 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘B’, MAIN FLOOR PLAN, ARCHITECTURAL. Sheet 30 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘C’, ROOF PLAN, ARCHITECTURAL. Sheet 14 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘B’, ROOF PLAN, ARCHITECTURAL. Sheet 28 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. HIGH BAY 3, EXTENSIBLE WORK PLATFORM ‘C’, MAIN FLOOR PLAN, ARCHITECTURAL. Sheet 16 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Construction of near-infrared light-triggered reactive oxygen species-sensitive (UCN/SiO2-RB + DOX)@PPADT nanoparticles for simultaneous chemotherapy and photodynamic therapy

NASA Astrophysics Data System (ADS)

Zhou, Fang; Zheng, Bin; Zhang, Ying; Wu, Yudong; Wang, Hanjie; Chang, Jin

2016-06-01

Combined therapy now plays a major role in cancer therapy due to the outcome of huge amounts of scientific experiments in recent years. However, all systems designed previously have been unable to simultaneously deliver therapy effects using several methods to produce a greater overall therapeutic effect. To solve the problem, we constructed a delivery system of near-infrared light (NIR)-triggered reactive oxygen species (ROS)-sensitive nanoparticles (NPs) for simultaneous chemotherapy and photodynamic therapy (PDT). The inner NP was assembled from a hydrophobic upconverting nanoparticle (UCN) core, with a thin silica shell linked with rose bengal (RB). Finally, a type of ROS-induced biodegradable polymer named poly-(1, 4-phenyleneacetone dimethylenethioketal) (PPADT) was self-assembled to form the NP as an outer shell to load the inner NP and doxorubicin (DOX). As the results show, the UCN core works as a transducer to convert deeply penetrating NIR to visible light for activating the photosensitizer RB for PDT under NIR excitation. In the meantime, the redundant ROS caused PPADT to biodegrade to release the loaded DOX, realizing simultaneous chemotherapy and PDT. Properties such as structure, size distribution, morphology, Fourier transform infrared spectroscopy, ROS production test, cell uptake test and combined therapy treatment effect in vitro were evaluated to prove NIR triggered ROS-sensitive (UCN/SiO2-RB + DOX)@PPADT NPs. Based on our data, this delivery system could provide an effective means to realize simultaneous chemotherapy and PDT through external NIR-triggered ROS sensitivity.

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

PubMed Central

Dürr, Katharina L.; Tavraz, Neslihan N.; Friedrich, Thomas

2012-01-01

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50∶50, by −100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P→E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ∼90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P→E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P→E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ∼0.5 and ∼0.2, respectively. PMID:22448261

A strategy for optical properties investigation in ABe2BO3F2 (A=K, Rb, Cs) using finite field methods

NASA Astrophysics Data System (ADS)

Mushahali, Hahaer; Mu, Baoxia; Wang, Qian; Mamat, Mamatrishat; Cao, Haibin; Yang, Guang; Jing, Qun

2018-07-01

The finite-field methods can be used to intuitively learn about the optical response and find out the atomic contributions to the birefringence and SHG tensors. In this paper, the linear and second-order nonlinear optical properties of ABe2BO3F2 family (A = K, Rb, Cs) compounds are investigated using the finite-field methods within different exchange-correlation functionals. The results show that the obtained birefringence and SHG tensors are in good agreement with the experimental values. The atomic contribution to the total birefringence was further investigated using the variation of the atomic charges, and the Born effective charges. The results show that the boron-oxygen groups give main contribution to the anisotropic birefringence.

Structural analysis and characterization of layer perovskite oxynitrides made from Dion Jacobson oxide precursors

NASA Astrophysics Data System (ADS)

Schottenfeld, Joshua A.; Benesi, Alan J.; Stephens, Peter W.; Chen, Gugang; Eklund, Peter C.; Mallouk, Thomas E.

2005-07-01

A three-layer oxynitride Ruddlesden-Popper phase Rb 1+xCa 2Nb 3O 10-xN x· yH 2O ( x=0.7-0.8, y=0.4-0.6) was synthesized by ammonialysis at 800 °C from the Dion-Jacobson phase RbCa 2Nb 3O 10 in the presence of Rb 2CO 3. Incorporation of nitrogen into the layer perovskite structure was confirmed by XPS, combustion analysis, and MAS NMR. The water content was determined by thermal gravimetric analysis and the rubidium content by ICP-MS. A similar layered perovskite interconversion occurred in the two-layer Dion-Jacobson oxide RbLaNb 2O 7 to yield Rb 1+xLaNb 2O 7-xN x· yH 2O ( x=0.7-0.8, y=0.5-1.0). Both compounds were air- and moisture-sensitive, with rapid loss of nitrogen by oxidation and hydrolysis reactions. The structure of the three-layer oxynitride Rb 1.7Ca 2Nb 3O 9.3N 0.7·0.5H 2O was solved in space group P4 /mmm with a=3.887(3) and c=18.65(1) Å, by Rietveld refinement of X-ray powder diffraction data. The two-layer oxynitride structure Rb 1.8LaNb 2O 6.3N 0.7·1.0H 2O was also determined in space group P4 /mmm with a=3.934(2) and c=14.697(2) Å. GSAS refinement of synchrotron X-ray powder diffraction data showed that the water molecules were intercalated between a double layer of Rb+ ions in both the two- and three-layer Ruddlesden-Popper structures. Optical band gaps were measured by diffuse reflectance UV-vis for both materials. An indirect band gap of 2.51 eV and a direct band gap of 2.99 eV were found for the three-layer compound, while an indirect band gap of 2.29 eV and a direct band gap of 2.84 eV were measured for the two-layer compound. Photocatalytic activity tests of the three-layer compound under 380 nm pass filtered light with AgNO 3 as a sacrificial electron acceptor gave a quantum yield of 0.025% for oxygen evolution.

Multiple coherent light scattering in ultracold rubidium

NASA Astrophysics Data System (ADS)

Kulatunga, P.; Sukenik, C. I.; Havey, M. D.; Kupriyanov, D. V.; Sokolov, I. M.

2001-11-01

We report investigation of multiple coherent light scattering from ^85Rb atoms confined in a magneto-optic trap. In a theoretical study of intensity enhancement of near-resonant backscattered light from cold ^85,87Rb atoms, we consider the dominant mode of double scattering only. Enhancement factors are calculated for all D1 and D2 hyperfine components and for both isotopes. In experimental studies, measurements are made of coherent backscattering of a low-intensity probe beam tuned near the F = 3 - F' = 4 transition in ^85Rb atoms. Polarization of backscattered light is determined by a backscattering polarimeter; the spatial distribution of light intensity is measured by a liquid-nitrogen cooled CCD camera set in the focal plane of the analyzing optics. The instrument has angular resolution of about 100 micro-radians, and a polarization analyzing power of roughly 1000. In this paper we describe the instrument details, including calibration procedures, and progress towards observation of atomic coherent backscattering.

Multiple coherent light scattering in ultracold rubidium

NASA Astrophysics Data System (ADS)

Havey, M. D.; Sukenik, C. I.; Kulatunga, P.; Kupriyanov, D. V.; Sokolov, I. M.

2001-05-01

We report investigation of multiple coherent light scattering from ^85Rb atoms confined in a magneto-optic trap. In a theoretical study of intensity enhancement of near-resonant backscattered light from cold ^85,87Rb atoms, we consider the dominant mode of double scattering only. Enhancement factors are calculated for all D1 and D2 hyperfine components and for both isotopes. In experimental studies, measurements are made of coherent backscattering of a low-intensity probe beam tuned near the F = 3 - F' = 4 transition in ^85Rb atoms. Polarization of backscattered light is determined by a backscattering polarimeter; the spatial distribution of light intensity is measured by a liquid-nitrogen cooled CCD camera set in the focal plane of the analyzing optics. The instrument has angular resolution of about 100 micro-radians, and a polarization analyzing power of roughly 1000. In this paper we describe the instrument details, including calibration procedures, and progress towards observation of atomic coherent backscattering.

A versatile tripodal amide receptor for the encapsulation of anions or hydrated anions via formation of dimeric capsules.

PubMed

Arunachalam, M; Ghosh, Pradyut

2010-02-01

A bowl-shaped tripodal receptor with an appropriately positioned amide functionality on the benzene platform and electron-withdrawing p-nitrophenyl terminals (L(1)) has been designed, synthesized, and studied for the anion binding properties. The single-crystal X-ray crystallographic analysis on crystals of L(1) with tetrabutylammonium salts of nitrate (1), acetate (2), fluoride (3), and chloride (4) obtained in moist dioxane medium showed encapsulation of two NO(3)(-), [(AcO)(2)(H(2)O)(4)](2-), [F(2)(H(2)O)(6)](2-), and [Cl(2)(H(2)O)(4)](2-) respectively as the anionic guests inside the staggered dimeric capsular assembly of L(1). The p-nitro substitution in the aryl terminals assisted the formation of dimeric capsular assembly of L(1) exclusively upon binding/encapsulating above different guests. Though L(1) demonstrates capsule formation upon anion or hydrated anion complexation for all of the anions studied here, its positional isomer with the o-nitro-substituted tripodal triamide receptor L(2) selectively formed the dimeric capsular assembly upon encapsulation of [F(2)(H(2)O)(6)](2-) and noncapsular aggregates in the cases of other anions such as Cl(-), NO(3)(-), and AcO(-). Interestingly, structural investigations upon anion exchange of the complexes revealed that both isomers have selectivity toward the formation of a [F(2)(H(2)O)(6)](2-) encapsulated dimeric capsule. In contrast, solution-state (1)H NMR titration studies of L(1) and L(2) in DMSO-d(6) with AcO(-) indicated 1:3 (host:guest) binding.

A Morphological Analysis of Gamma-Ray Burst Early-optical Afterglows

NASA Astrophysics Data System (ADS)

Gao, He; Wang, Xiang-Gao; Mészáros, Peter; Zhang, Bing

2015-09-01

Within the framework of the external shock model of gamma-ray burst (GRB) afterglows, we perform a morphological analysis of the early-optical light curves to directly constrain model parameters. We define four morphological types, i.e., the reverse shock-dominated cases with/without the emergence of the forward shock peak (Type I/Type II), and the forward shock-dominated cases without/with νm crossing the band (Type III/IV). We systematically investigate all of the Swift GRBs that have optical detection earlier than 500 s and find 3/63 Type I bursts (4.8%), 12/63 Type II bursts (19.0%), 30/63 Type III bursts (47.6%), 8/63 Type IV bursts (12.7%), and 10/63 Type III/IV bursts (15.9%). We perform Monte Carlo simulations to constrain model parameters in order to reproduce the observations. We find that the favored value of the magnetic equipartition parameter in the forward shock ({ɛ }B{{f}}) ranges from 10-6 to 10-2, and the reverse-to-forward ratio of ɛB ({{R}}B) is about 100. The preferred electron equipartition parameter {ɛ }{{e}}{{r},{{f}}} value is 0.01, which is smaller than the commonly assumed value, e.g., 0.1. This could mitigate the so-called “efficiency problem” for the internal shock model, if ɛe during the prompt emission phase (in the internal shocks) is large (say, ˜0.1). The preferred {{R}}B value is in agreement with the results in previous works that indicate a moderately magnetized baryonic jet for GRBs.

Crown Ether Complexes of Alkali-Metal Chlorides from SO2.

PubMed

Reuter, Kirsten; Rudel, Stefan S; Buchner, Magnus R; Kraus, Florian; von Hänisch, Carsten

2017-07-18

The structures of alkali-metal chloride SO 2 solvates (Li-Cs) in conjunction with 12-crown-4 or 1,2-disila-12-crown-4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2-disila-12-crown-4)(SO 2 Cl)] (1) and [Li(12-crown-4)Cl]⋅4 SO 2 (2). However, 1,2-disila-12-crown-4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich-type complexes. As a result, 12-crown-4 reacts exclusively with the heavier alkali-metal chlorides NaCl, KCl and RbCl. Compounds [Na(12-crown-4) 2 ]Cl⋅4 SO 2 (3) and [M(12-crown-4) 2 (SO 2 )]Cl⋅4 SO 2 (4: M=K; 5: M=Rb) all showed S-coordination to the chloride ions through four SO 2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non-bridging O,O'-coordination mode of SO 2 . Unexpectedly, the disila-crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO 2 -solvated alkali-metal chlorides [MCl⋅3 SO 2 ] (6: M=Rb; 7: M=Cs), which incorporate bridging μ-O,O'-coordinating moieties and the unprecedented side-on O,O'-coordination mode. All compounds were characterised by single-crystal X-ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO 2 at ambient temperature was revealed by IR spectroscopy of the neat compounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Asai, Hirohide; Hirano, Makito; Kiriyama, Takao

Intranuclear events due to mutations in the Parkin gene remain elusive in autosomal recessive juvenile parkinsonism (ARJP). We identified a mutant PARKIN protein in fibroblast cultures from a pair of siblings with ARJP who were homozygous for the exon 4-deleted Parkin gene. Disease was mild in one patient and debilitating in the other. The detected mutant, encoded by a transcript lacking exon 3 as well as exon 4, is an in-frame deletion that removes 121 aa, resulting in a 344-aa protein (PaDel3,4). Cell culture and transfection studies revealed negative correlations between expression levels of PaDel3,4 and those of cell cyclemore » proteins, including cyclin E, CDK2, ppRb, and E2F-1, and demonstrated that GFP-PaDel3,4 entered nucleus and ubiquitinated cyclin E as a part of SCF{sup hSel-10} ligase complex in the patient cells. In addition, nuclear localization signal-tagged PaDel3,4 expressed in the transfected patient cells most effectively ubiquitinated cyclin E and reduced DNA damage, protecting cells from oxidative stress. Antisense-oligonucleotide treatment promoted skipping of exon 3 and thus generated PaDel3,4, increasing cell survival. Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping.« less

Simple Atomic Quantum Memory Suitable for Semiconductor Quantum Dot Single Photons.

PubMed

Wolters, Janik; Buser, Gianni; Horsley, Andrew; Béguin, Lucas; Jöckel, Andreas; Jahn, Jan-Philipp; Warburton, Richard J; Treutlein, Philipp

2017-08-11

Quantum memories matched to single photon sources will form an important cornerstone of future quantum network technology. We demonstrate such a memory in warm Rb vapor with on-demand storage and retrieval, based on electromagnetically induced transparency. With an acceptance bandwidth of δf=0.66  GHz, the memory is suitable for single photons emitted by semiconductor quantum dots. In this regime, vapor cell memories offer an excellent compromise between storage efficiency, storage time, noise level, and experimental complexity, and atomic collisions have negligible influence on the optical coherences. Operation of the memory is demonstrated using attenuated laser pulses on the single photon level. For a 50 ns storage time, we measure η_{e2e}^{50  ns}=3.4(3)% end-to-end efficiency of the fiber-coupled memory, with a total intrinsic efficiency η_{int}=17(3)%. Straightforward technological improvements can boost the end-to-end-efficiency to η_{e2e}≈35%; beyond that, increasing the optical depth and exploiting the Zeeman substructure of the atoms will allow such a memory to approach near unity efficiency. In the present memory, the unconditional read-out noise level of 9×10^{-3} photons is dominated by atomic fluorescence, and for input pulses containing on average μ_{1}=0.27(4) photons, the signal to noise level would be unity.

Micaschist and Impure Marble - two Examples for Lithology Related Constraints to Rb-Sr Microsampling Analysis

NASA Astrophysics Data System (ADS)

Wegmann, M. I.; Hammerschmidt, K.

2003-12-01

Retrograde overprinted calcite-bearing micaschists and mica-containing marbles from the northern part of the Cycladic blueschist belt on South-Evia, Greece, have been investigated to understand the interplay between bulk rock chemistry, mineral assemblage and resetting of the Rb-Sr isotope system during deformation. White mica represents two optical distinguishable microstructures, isoclinal folds (S1) and axial plain cleavage (S2) induced by flattening and elongation episode of isothermal exhumation. The varying Si content of phengites is not related to microstructures. Due to microstructural complexity and grain size variation the application of Rb-Sr microsampling method was expected effective investigation of Rb and Sr rich mineral phases to elucidate constraints for geochronological and isotope geochemical imprint in microstructures. Drilling out calcite, albite and mica samples with weights down to 200æg each out of 30æm thick sections realized textural controlled separation. Calculated Rb-Sr mica ages show lithology-related scattering but totally not microstructural induced variation. Particulary, S1 and S2 phengites in micaschist yield similar age values around 31 Ma. In contrast, impure marble mica within similar S1 and S2 have Rb-Sr mica ages widely scattering between 34 and 50 Ma. Therefore, structural elements formed by these phengites are not distinguishable in terms of geochronolgy. Explaining the scatter of age values, principally, two possibilities were taken into account, (i) the fluid flux neccessary to homogenize Sr isotope composition in mica and calcite (albite) might have been less effective in impure marble than in micaschist due to the generation of CO2. In constrast to this possibility, calcite 87Sr/86Sr in both specimen are quite homogeneous at least on cm-scale, e.g. values of 0.712125 ñ 66 (2s) for impure marble and of 0.721419 ñ 42 for micaschist were meassured. Albite 87Sr/86Sr corroborate Sr homogenisation on scale this study was focussed on. So far, (ii) we would assume calculated age values date moments of growth of single mica crystals. However, the image of microstructure by crystals may be realized by new growth, recrystallization or just reorientation, e.g. by passive rotation of pre-existing grains. To interpret the mineral age values, it must be scrutinized, which process is responsible for current mineral position in the structure. Additionally, duration of (prograde) exumation induced contineous deformation and the contribution of fluid influx can be prospected by further investigation of south-Evian blueschist facies units on other mineral phases by Rb-Sr microsampling technique.

Nuclear assortment of eIF4E coincides with shut-off of host protein synthesis upon poliovirus infection.

PubMed

Sukarieh, R; Sonenberg, N; Pelletier, J

2010-05-01

Eukaryotic initiation factor (eIF) 4E is a subunit of the cap-binding protein complex, eIF4F, which recognizes the cap structure of cellular mRNAs to facilitate translation initiation. eIF4E is assembled into the eIF4F complex via its interaction with eIF4G, an event that is under Akt/mTOR regulation. The eIF4E-eIF4G interaction is regulated by the eIF4E binding partners, eIF4E-binding proteins and eIF4E-transporter. Cleavage of eIF4G occurs upon poliovirus infection and is responsible for the shut-off of host-cell protein synthesis observed early in infection. Here, we document that relocalization of eIF4E to the nucleus occurs concomitantly with cleavage of eIF4G upon poliovirus infection. This event is not dependent upon virus replication, but is dependent on eIF4G cleavage. We postulate that eIF4E nuclear relocalization may contribute to the shut-off of host protein synthesis that is a hallmark of poliovirus infection by perturbing the circular status of actively translating mRNAs.

Pan-African alkali granites and syenites of Kerala as imprints of taphrogenic magmatism in the South Indian shield

NASA Technical Reports Server (NTRS)

Santosh, M.; Drury, S. A.; Iyer, S. S.

1988-01-01

Granite and syenite plutons with alkaline affinities ranging in age from 550 to 750 Ma sporadically puncture the Precambrian granulites of the Kerala region. All the bodies are small (20 to 60 sq km), E-W to NW-SE elongated elliptical intrusives with sharp contacts and lie on or close to major late Proterozoic lineaments. Geochemical plots of A-F-M and An-Ab-Or relations show an apparent alkali enrichment trend on the former, but the plutons define relatively distinct fields on the latter. Most of the plutons are adamellitic to granitic by chemistry. The variations of SiO2 with log sub 10 K2O/MgO (1) brings out the distinct alkaline nature of the plutons. Some of the granites are extremely potassic, like the Peralimala pluton, which shows up to 11.8 percent K2O. On a SiO2-Al2O3-Na2O+K2O (mol percent) plot, the plutons vary from peraluminous to peralkaline, but none are nepheline normative. Low MgO, low to moderate CaO and high Fe2O3/FeO values are other common characteristics. Among trace elements, depletion of Ba, Sr and Rb with high K/Ba and K/Rb values are typical. Overall, the plutons show a trend of decreasing K/Rb ratio with increasing K content. Individual plutons show more clearly defined trends similar to those from granitic masses characterized by plagioclase fractionation.

Fluid/rock Interaction History of a Faulted Rhyolite-Granite Contact Determined by Sr- Pb-Isotopes, Th/U-Disequilibria and Elemental Distributions (Eastern Rhine Graben Shoulder, SW-Germany)

NASA Astrophysics Data System (ADS)

Marbach, T.; Mangini, A.; Kober, B.; Schleicher, A.; Warr, L. N.

2003-04-01

Major and trace element analyses allow to obtain information concerning the chemical changes induced by alteration. Differences are partly petrographic because the profile crosses the granite-rhyolite contact, but they are also due to different alteration levels induced by fluid circulation along the fault system which has drained the alteration processes. The granite-rhyolite contact constitutes the primary structure. Only the most incompatible elements (Si, Al, Zr, Hf) retain their original signatures and reflect a mixing between typical granite and rhyolite lithologies across the altered zones (cataclasite). The more mobile elements show a different composition within the altered zones (cataclasite) notably a high leaching of cations. The geochemical tracers also suggest at least one strong hydrothermal event with reducing conditions in the altered zones. The isotopic analyses delivered qualitative and temporal information. The use of several isotopic systems, Rb/Sr-, U/Pb-isotopes and Th/U disequilibria, reveals a complex history of polyphase fluid/rock interaction following the Permian volcanic extrusion, showing notable disturbances during the late Jurassic hydrothermal activities, the Tertiary rifting of the Rhine Graben and more recent Quaternary alteration. The granite zone of the sampling profile has underwent an event which set up a new Rb-Sr isotopic composition and reset the Rb/Sr system which originatly corresponded to the Carboniferous intrusion ages. The Rb-Sr data of the granite samples produce a whole rock isochron of 152 ± 5,7 Ma (2σ error) in good agreement with the well-known late Jurassic hydrothermal event (135--160 Ma). The rocks evolution lines for Pb support a Tertiary hydrothermal event (54 Ma ± 16; 1σ error), potentially connected with the development of the Rhine Graben. The profile samples have undergone uranium and thorium redistribution processes which have occurred within the last ˜10^6 years. The samples of the altered zones record a more complex history of uranium exchange with the aqueous phase. This uranium exchange is proportional to the porosity. The best approximation is reached for an exchange coefficient (λ_E) for uranium ranging from 2,5 E-06 [a-1] in the middle of the altered zones to 2,5 E-05 [a-1] on the sides of the altered zones.

Up-regulation of Survivin during Immortalization of Human Myofibroblasts Is Linked to Repression of Tumor Suppressor p16INK4a Protein and Confers Resistance to Oxidative Stress*

PubMed Central

Kan, Chin-Yi; Petti, Carlotta; Bracken, Lauryn; Maritz, Michelle; Xu, Ning; O'Brien, Rosemary; Yang, Chen; Liu, Tao; Yuan, Jun; Lock, Richard B.; MacKenzie, Karen L.

2013-01-01

Survivin is an essential component of the chromosomal passenger complex and a member of the inhibitor of apoptosis family. It is expressed at high levels in a large variety of malignancies, where it has been implicated in drug resistance. It was also shown previously that survivin is up-regulated during telomerase-mediated immortalization, which occurs at a relatively early stage during carcinogenesis. This study shows that up-regulation of survivin during immortalization of human myofibroblasts is an indirect consequence of the repression of p16INK4a. Survivin and p16INK4a were functionally linked by assays that showed that either the up-regulation of survivin or repression of p16INK4a rendered telomerase-transduced MRC-5 myofibroblasts resistant to oxidative stress. Conversely, siRNA-mediated down-regulation of survivin activated caspases and enhanced the sensitivity of immortal MRC-5 cells to oxidative stress. The E2F1 transcription factor, which is negatively regulated by the pRB/p16INK4a tumor suppressor pathway, was implicated in the up-regulation of survivin. Using the ChIP assay, it was shown that E2F1 directly interacted with the survivin gene (BIRC5) promoter in cells that spontaneously silenced p16INK4a during telomerase-mediated immortalization. E2F1 binding to the BIRC5 was also enhanced in telomerase-transduced cells subjected to shRNA-mediated repression of p16INK4a. Together, these data show that repression of p16INK4a contributes to the up-regulation of survivin and thereby provides a survival advantage to cells exposed to oxidative stress during immortalization. The up-regulation of survivin during immortalization likely contributes to the vulnerability of immortal cells to transformation by oncogenes that alter intracellular redox state. PMID:23449974

Dynamics of energy transfer from lycopene to bacteriochlorophyll in genetically-modified LH2 complexes of Rhodobacter sphaeroides.

PubMed

Hörvin Billsten, H; Herek, J L; Garcia-Asua, G; Hashøj, L; Polívka, T; Hunter, C N; Sundström, V

2002-03-26

LH2 complexes from Rb. sphaeroides were modified genetically so that lycopene, with 11 saturated double bonds, replaced the native carotenoids which contain 10 saturated double bonds. Tuning the S1 level of the carotenoid in LH2 in this way affected the dynamics of energy transfer within LH2, which were investigated using both steady-state and time-resolved techniques. The S1 energy of lycopene in n-hexane was determined to be approximately 12 500 +/- 150 cm(-1), by direct measurement of the S1-S2 transient absorption spectrum using a femtosecond IR-probing technique, thus placing an upper limit on the S1 energy of lycopene in the LH2 complex. Fluorescence emission and excitation spectra demonstrated that energy can be transferred from lycopene to the bacteriochlorophyll molecules within this LH2 complex. The energy-transfer dynamics within the mutant complex were compared to wild-type LH2 from Rb. sphaeroides containing the carotenoid spheroidene and from Rs. molischianum, in which lycopene is the native carotenoid. The results show that the overall efficiency for Crt --> B850 energy transfer is approximately 80% in lyco-LH2 and approximately 95% in WT-LH2 of Rb. sphaeroides. The difference in overall Crt --> BChl transfer efficiency of lyco-LH2 and WT-LH2 mainly relates to the low efficiency of the Crt S(1) --> BChl pathway for complexes containing lycopene, which was 20% in lyco-LH2. These results show that in an LH2 complex where the Crt S1 energy is sufficiently high to provide efficient spectral overlap with both B800 and B850 Q(y) states, energy transfer via the Crt S1 state occurs to both pigments. However, the introduction of lycopene into the Rb. sphaeroides LH2 complex lowers the S1 level of the carotenoid sufficiently to prevent efficient transfer of energy to the B800 Q(y) state, leaving only the Crt S1 --> B850 channel, strongly suggesting that Crt S1 --> BChl energy transfer is controlled by the relative Crt S1 and BChl Q(y) energies.

Coregulation of FANCA and BRCA1 in human cells.

PubMed

Haitjema, Anneke; Mol, Berber M; Kooi, Irsan E; Massink, Maarten Pg; Jørgensen, Jens Al; Rockx, Davy Ap; Rooimans, Martin A; de Winter, Johan P; Meijers-Heijboer, Hanne; Joenje, Hans; Dorsman, Josephine C

2014-01-01

Fanconi anemia (FA) is a genetically heterogeneous syndrome associated with increased cancer predisposition. The underlying genes govern the FA pathway which functions to protect the genome during the S-phase of the cell cycle. While upregulation of FA genes has been linked to chemotherapy resistance, little is known about their regulation in response to proliferative stimuli. The purpose of this study was to examine how FA genes are regulated, especially in relation to the cell cycle, in order to reveal their possible participation in biochemical networks. Expression of 14 FA genes was monitored in two human cell-cycle models and in two RB1/E2F pathway-associated primary cancers, retinoblastoma and basal breast cancer. In silico studies were performed to further evaluate coregulation and identify connected networks and diseases. Only FANCA was consistently induced over 2-fold; FANCF failed to exhibit any regulatory fluctuations. Two tools exploiting public data sets indicated coregulation of FANCA with BRCA1. Upregulation of FANCA and BRCA1 correlated with upregulation of E2F3. Genes coregulated with both FANCA and BRCA1 were enriched for MeSH-Term id(s) genomic instability, microcephaly, and Bloom syndrome, and enriched for the cellular component centrosome. The regulation of FA genes appears highly divergent. In RB1-linked tumors, upregulation of FA network genes was associated with reduced expression of FANCF. FANCA and BRCA1 may jointly act in a subnetwork - supporting vital function(s) at the subcellular level (centrosome) as well as at the level of embryonic development (mechanisms controlling head circumference).

Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

PubMed

Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

2017-06-27

CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

Efficient Optical Logic, Interconnections and Processing Using Quantum Confined Structures

DTIC Science & Technology

1993-05-20

mnounced D ELECTE j LL.,iicEtion ......... -..................- JUN 14 1993 B y .. . ........ . . . . . .. Di~t ibution l Availability Codes Avail...coefficient of rt( b ) and power reflectivity of RT( B )=lrt( b )12 , viewed from the cavity. RB>RT is used in the design. Written in terms of the power...reflectivities, the total power reflectivity from the Fabry-Perot is given by: p lf-RT. R-f-• B exp(-.al)1 2 I ~ ~l .•RTRBeXp(._C.)j2 Assuming RB=0.97, Figure

Micromachined Radio Frequency (RF) Switches and Tunable Capacitors for Higher Performance Secure Communications Systems

DTIC Science & Technology

2003-04-01

range filters implemented with traditional semiconductor varactor diodes can require complex series-parallel circuit constructions to achieve sufficient...filter slice of the AIU and the varactor array modules are shown in Fig. 6.2. The complexity of the varactor array is clearly apparent. Further, it is...38 Fig. 6.2: Schematic of F-22 AIU UHF tracking filter, 2-pole filter, and varactor diode assembly

Kinin receptor classification.

PubMed

Regoli, D; Jukic, D; Tousignant, C; Rhaleb, N E

1992-01-01

Apparent affinities of kinin agonists and antagonists were determined in terms of pD2 and pA2 respectively, on three isolated smooth muscles: rabbit jugular vein (Rb.J.V.), rabbit aorta (Rb.A.) and guinea pig ileum (G.P.I.). Both kinin agonists and antagonists were evaluated for their ability to induce the release of histamine from rat mastocytes. Our results indicate that the kininase I metabolites (desArg9-BK and desArg10-KD) were inactive on Rb.J.V. and G.P.I. (B2 preparations) and were full agonists on Rb.A. (B1) while [Tyr(Me)8]-BK and [Hyp3,Tyr(Me)8]-BK were inactive on Rb.A. and maintain a high affinity on Rb.J.V. and G.P.I. In addition, [Hyp3]-BK was a potent agonist on Rb.J.V. (pD2 = 8.88) and was of a moderate affinity on G.P.I. (pD2 = 7.27). On the other hand, the affinity of [Aib7]-BK was identical to that of BK on G.P.I. (pD2 = 7.90) but drastically reduced in Rb.J.V. (pD2 = 6.28). Conctractile effects of kinins in the Rb.J.V. and G.P.I. were reduced or eliminated by B2 receptor antagonists but at different concentration levels (e.g. DArg[Hyp3,DPhe7,Leu8]-BK showed pA2 values of 8.86 on Rb.J.V., but only 6.77 on G.P.I. DArg[Hyp3,Gly6,Leu8]BK showed high affinity on Rb.J.V. (pA2 = 7.60) but was a full agonist on G.P.I. Conversely, DArg[Tyr3,DPhe7,Leu8,BK] showed high agonistic activity on Rb.J.V. (pD2 = 8.30, alpha E = 1.0) and showed a pA2 value of 6.80 on G.P.I. All compounds (agonists and antagonists) were quite potent on histamine release induced in rat mastocytes. [Arg1(Tos),Hyp3,Thi5,DTic7,Oic8]-BK and DArg[Hyp3,Thi5,DTic7,Oic8]-BK showed almost similar pA2 values on both Rb.J.V. and G.P.I., but were inactive on Rb.A. (B1). These results suggest that kinins act on at least four functional sites: B1 (Rb.A.), B2A (Rb.J.V.), B2B (G.P.I.) and BH. However, there is no clear evidence of a kinin receptor on rat mast cells and the release of histamine may simply be a non-receptor phenomenon. Our data also show that B2A and B2B receptor subtypes might simply be variations of the B2 receptor in different species.

Quantitation of ten 30S ribosomal assembly intermediates using fluorescence triple correlation spectroscopy

PubMed Central

Ridgeway, William K.; Millar, David P.; Williamson, James R.

2012-01-01

The self-assembly of bacterial 30S ribosomes involves a large number of RNA folding and RNA-protein binding steps. The sequence of steps determines the overall assembly mechanism and the structure of the mechanism has ramifications for the robustness of biogenesis and resilience against kinetic traps. Thermodynamic interdependencies of protein binding inferred from omission-reconstitution experiments are thought to preclude certain assembly pathways and thus enforce ordered assembly, but this concept is at odds with kinetic data suggesting a more parallel assembly landscape. A major challenge is deconvolution of the statistical distribution of intermediates that are populated during assembly at high concentrations approaching in vivo assembly conditions. To specifically resolve the intermediates formed by binding of three ribosomal proteins to the full length 16S rRNA, we introduce Fluorescence Triple-Correlation Spectroscopy (F3CS). F3CS identifies specific ternary complexes by detecting coincident fluctuations in three-color fluorescence data. Triple correlation integrals quantify concentrations and diffusion kinetics of triply labeled species, and F3CS data can be fit alongside auto-correlation and cross-correlation data to quantify the populations of 10 specific ribosome assembly intermediates. The distribution of intermediates generated by binding three ribosomal proteins to the entire native 16S rRNA included significant populations of species that were not previously thought to be thermodynamically accessible, questioning the current interpretation of the classic omission-reconstitution experiments. F3CS is a general approach for analyzing assembly and function of macromolecular complexes, especially those too large for traditional biophysical methods. PMID:22869699

Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography

PubMed Central

Park, Hee-Won; In, Gyo; Han, Sung-Tai; Lee, Myoung-Woo; Kim, So-Young; Kim, Kyung-Tack; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo

2013-01-01

A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides. PMID:24235860

All 17 S-locus F-box proteins of the S2 - and S3 -haplotypes of Petunia inflata are assembled into similar SCF complexes with a specific function in self-incompatibility.

PubMed

Li, Shu; Williams, Justin S; Sun, Penglin; Kao, Teh-Hui

2016-09-01

The collaborative non-self-recognition model for S-RNase-based self-incompatibility predicts that multiple S-locus F-box proteins (SLFs) produced by pollen of a given S-haplotype collectively mediate ubiquitination and degradation of all non-self S-RNases, but not self S-RNases, in the pollen tube, thereby resulting in cross-compatible pollination but self-incompatible pollination. We had previously used pollen extracts containing GFP-fused S2 -SLF1 (SLF1 with an S2 -haplotype) of Petunia inflata for co-immunoprecipitation (Co-IP) and mass spectrometry (MS), and identified PiCUL1-P (a pollen-specific Cullin1), PiSSK1 (a pollen-specific Skp1-like protein) and PiRBX1 (a conventional Rbx1) as components of the SCF(S) (2-) (SLF) (1) complex. Using pollen extracts containing PiSSK1:FLAG:GFP for Co-IP/MS, we identified two additional SLFs (SLF4 and SLF13) that were assembled into SCF(SLF) complexes. As 17 SLF genes (SLF1 to SLF17) have been identified in S2 and S3 pollen, here we examined whether all 17 SLFs are assembled into similar complexes and, if so, whether these complexes are unique to SLFs. We modified the previous Co-IP/MS procedure, including the addition of style extracts from four different S-genotypes to pollen extracts containing PiSSK1:FLAG:GFP, to perform four separate experiments. The results taken together show that all 17 SLFs and an SLF-like protein, SLFLike1 (encoded by an S-locus-linked gene), co-immunoprecipitated with PiSSK1:FLAG:GFP. Moreover, of the 179 other F-box proteins predicted by S2 and S3 pollen transcriptomes, only a pair with 94.9% identity and another pair with 99.7% identity co-immunoprecipitated with PiSSK1:FLAG:GFP. These results suggest that SCF(SLF) complexes have evolved specifically to function in self-incompatibility. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Limits of transforming competence of SV40 nuclear and cytoplasmic large T mutants with altered Rb binding sequences.

PubMed

Tedesco, D; Fischer-Fantuzzi, L; Vesco, C

1993-03-01

Multiple amino acid substitutions were introduced into the SV40 large T region that harbors the retinoblastoma protein (Rb) binding site and the nuclear transport signal, changing either one or both of these determinants. Mutant activities were examined in a set of assays allowing different levels of transforming potential to be distinguished; phenotypic changes in established and pre-crisis rat embryo fibroblasts (REFs) were detected under isogenic cell conditions, and comparisons made with other established rodent cells. The limit of the transforming ability of mutants with important substitutions in the Rb binding site fell between two transformation levels of the same established rat cells. Such cells could be induced to form dense foci but not agar colonies (their parental pre-crises REFs, as expected, were untransformed either way). Nonetheless, agar colony induction was possible in other cell lines, such as mouse NIH3T3 and (for one of the mutants) rat F2408. All these mutants efficiently immortalized pre-crisis REFs. The transforming ability of cytoplasmic mutants appeared to depend on the integrity of the Rb-binding sequence to approximately the same extent as that of the wild-type large T, although evidence of in vivo Rb-cytoplasmic large T complexes was not found. The presence or absence of small t was critical when the transforming task of mutants was near the limit of their abilities.

Synthesis and SMM behaviour of trinuclear versus dinuclear 3d-5f uranyl(v)-cobalt(ii) cation-cation complexes.

PubMed

Chatelain, Lucile; Tuna, Floriana; Pécaut, Jacques; Mazzanti, Marinella

2017-05-02

Trinuclear versus dinuclear heterodimetallic U V O 2 + Co 2+ complexes were selectively assembled via a cation-cation interaction by tuning the ligand. The trimeric complex 2, with a linear [Co-O[double bond, length as m-dash]U[double bond, length as m-dash]O-Co] core, exhibits magnetic exchange and slow relaxation with a reversal barrier of 30.5 ± 0.9 K providing the first example of a U-Co exchange-coupled SMM.

Crystallographic site swapping of La3+ ion in BaA'LaTeO6 (A' = Na, K, Rb) double perovskite type compounds: diffraction and photoluminescence evidence for the site swapping.

PubMed

Phatak, R; Gupta, S K; Krishnan, K; Sali, S K; Godbole, S V; Das, A

2014-02-28

Double perovskite type compounds of the formula BaA'LaTeO6 (A' = Na, K, Rb) were synthesized by solid state route and their crystal structures were determined by Rietveld analysis using powder X-ray diffraction and neutron diffraction data. Na compound crystallizes in the monoclinic system with P2₁/n space group whereas, K and Rb compounds crystallize in Fm3m space group. All the three compounds show rock salt type ordering at B site. Crystal structure analysis shows that La ion occupies A site in Na compound whereas, it occupies B site in K and Rb compounds according to the general formula of AA'BB'O6 for a double perovskite type compound. Effect of this crystallographic site swapping of the La ion was also observed in the photoluminescence study by doping Eu(3+) in La(3+) site. The large decrease in the intensity of the electric dipole ((5)D0-(7)F2) transition in the Rb compound compared to the Na compound indicates that Eu(3+) ion resides in the centrosymmetric octahedral environment in the Rb compound.

Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes.

PubMed

Izard, T; Aevarsson, A; Allen, M D; Westphal, A H; Perham, R N; de Kok, A; Hol, W G

1999-02-16

The pyruvate dehydrogenase multienzyme complex (Mr of 5-10 million) is assembled around a structural core formed of multiple copies of dihydrolipoyl acetyltransferase (E2p), which exhibits the shape of either a cube or a dodecahedron, depending on the source. The crystal structures of the 60-meric dihydrolipoyl acyltransferase cores of Bacillus stearothermophilus and Enterococcus faecalis pyruvate dehydrogenase complexes were determined and revealed a remarkably hollow dodecahedron with an outer diameter of approximately 237 A, 12 large openings of approximately 52 A diameter across the fivefold axes, and an inner cavity with a diameter of approximately 118 A. Comparison of cubic and dodecahedral E2p assemblies shows that combining the principles of quasi-equivalence formulated by Caspar and Klug [Caspar, D. L. & Klug, A. (1962) Cold Spring Harbor Symp. Quant. Biol. 27, 1-4] with strict Euclidean geometric considerations results in predictions of the major features of the E2p dodecahedron matching the observed features almost exactly.

Tuning of the ionization potential of paddlewheel diruthenium(II, II) complexes with fluorine atoms on the benzoate ligands.

PubMed

Miyasaka, Hitoshi; Motokawa, Natsuko; Atsuumi, Ryo; Kamo, Hiromichi; Asai, Yuichiro; Yamashita, Masahiro

2011-01-21

A series of paddlewheel diruthenium(ii, ii) complexes with various fluorine-substituted benzoate ligands were isolated as THF adducts and structurally characterized: [Ru(2)(F(x)PhCO(2))(4)(THF)(2)] (F(x)PhCO(2)(-) = o-fluorobenzoate, o-F; m-fluorobenzoate, m-F; p-fluorobenzoate, p-F; 2,6-difluorobenzoate, 2,6-F(2); 3,4-difluorobenzoate, 3,4-F(2); 3,5-difluorobenzoate, 3,5-F(2); 2,3,4-trifluorobenzoate, 2,3,4-F(3); 2,3,6-trifluorobenzoate, 2,3,6-F(3); 2,4,5-trifluorobenzoate, 2,4,5-F(3); 2,4,6-trifluorobenzoate, 2,4,6-F(3); 3,4,5-trifluorobenzoate, 3,4,5-F(3); 2,3,4,5-tetrafluorobenzoate, 2,3,4,5-F(4); 2,3,5,6-tetrafluorobenzoate, 2,3,5,6-F(4); pentafluorobenzoate, F(5)). By adding fluorine atoms on the benzoate ligands, it was possible to tune the redox potential (E(1/2)) for [Ru(2)(II,II)]/[Ru(2)(II,III)](+) over a wide range of potentials from -40 mV to 350 mV (vs. Ag/Ag(+) in THF). 2,3,6-F(3), 2,3,4,5-F(4), 2,3,5,6-F(4) and F(5) were relatively air-stable compounds even though they are [Ru(2)(II,II)] species. The redox potential in THF was dependent on an electronic effect rather than on a structural (steric) effect of the o-F atoms, although more than one substituent in the m- and p-positions shifted E(1/2) to higher potentials in relation to the general Hammett equation. A quasi-Hammett parameter for an o-F atom (σ(o)) was estimated to be ∼0.2, and a plot of E(1/2)vs. a sum of Hammett parameters including σ(o) was linear. In addition, the HOMO energy levels, which was calculated based on atomic coordinates of solid-state structures, as well as the redox potential were affected by adding F atoms. Nevertheless, a steric contribution stabilizing their static structures in the solid state was present in addition to the electronic effect. On the basis of the electronic effect, the redox potential of these complexes is correlated to the HOMO energy level, and the electronic effect of F atoms is the main factor controlling the ionization potential of the complexes with ligands free from the rotational constraint, i.e. complexes in solution.

[Promoting effect of cyclin D1 overexpression on proliferation and epithelial mesenchymal transition of cervical squamous cell carcinoma SiHa cells].

PubMed

Wang, P; Liu, S; Cheng, B; Wu, X Z; Ding, S S; Xu, L; Liu, Y; Duan, L; Sun, S Z

2017-03-08

Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively. Cell growth curve was documented by MTT assay. CK7, E-cadherin, vimentin, Snail gene and protein expression in transfected cells were detected by RT-PCR and Western blot. RT-PCR was used to detect the mRNA expression of proliferation and differentiation-related genes like CDK4, CDK2, p21, p27, cyclin E, Rb, E2F, E6/E7 and Ki-67. After synchronization of cells, RT-PCR was used to detect of cyclin D1 and p21 mRNA expression at different time points of the cell cycle. Results: The G-3 cells with cyclin D1 overexpression were successfully established. The growth curve and Ki-67 mRNA expression accelerated in G-3 cells.Vimentin and Snail expression significantly increased at both gene and protein levels, while E-cadherin, CK7 gene and protein expression significantly decreased, indicating epithelial mesenchymal transitionoccurred in G-3 cells.Meanwhile, mRNA expression of cyclin D1, CDK4, CDK2, p21, p27, cyclin E, E2F and Rb increased, while E6/E7 and p16 showed no significant change. The expression trends of p21 and cyclin D1 were almost identical with fluctuation at different time points in the cell cycle. Conclusions: Overexpression of cyclin D1 induced by gene transfection promotes proliferation and epithelial mesenchymal transition in SiHa cells.The process is accompanied by up-regulation of CDK4, CDK2, p21, p27 and cyclin E genes.p21 expression increases synchronously with cyclin D1, suggesting a regulatory role in epithelial mesenchymal transition by affecting expression of vimentin in G-3 cells.

Metal Nanoparticles Embedded in Cellulose Nanocrystal Based Films: Material Properties and Post-use Analysis.

PubMed

Lizundia, Erlantz; Goikuria, Uribarri; Vilas, José Luis; Cristofaro, Francesco; Bruni, Giovanna; Fortunati, Elena; Armentano, Ilaria; Visai, Livia; Torre, Luigi

2018-04-25

The dispersion of nanoparticles having different size-, shape-, and composition-dependent properties is an exciting approach to design and synthesize multifunctional materials and devices. This work shows a detailed investigation of the preparation and properties of free-standing nanocomposite films based on cellulose nanocrystals (CNC) loaded with three different types of metal nanoparticles. CNC-based nanocomposites having zinc oxide (ZnO), titanium dioxide (TiO 2 ), and silver oxide (Ag 2 O) have been obtained through evaporation-induced self-assembly (EISA) in acqueous solution. Morphological and optical characteristics, chemical properties, wettability, and antimicrobial assays of the produced films were conducted. Furthermore, disintegrability in composting condition of CNC based nanocomposites was here investigated for the first time. The morphological observations revealed the formation of a chiral nematic structure with uniformly distributed nanoparticles. The bionanocomposite films based on the metal nanoparticles had effective antimicrobial activity, killing both Escherichia coli RB ( E. coli RB) and Staphylococcus aureus 8325-4 ( S. aureus 8325-4). The simplicity method of film preparation, the large quantity of cellulose in the world, and the free-standing nature of the nanocomposite films offer highly advantageous characteristics that can for the new development of multifunctional materials.

Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency

PubMed Central

Yang, Yul W; Flynn, Ryan A; Chen, Yong; Qu, Kun; Wan, Bingbing; Wang, Kevin C; Lei, Ming; Chang, Howard Y

2014-01-01

The WDR5 subunit of the MLL complex enforces active chromatin and can bind RNA; the relationship between these two activities is unclear. Here we identify a RNA binding pocket on WDR5, and discover a WDR5 mutant (F266A) that selectively abrogates RNA binding without affecting MLL complex assembly or catalytic activity. Complementation in ESCs shows that WDR5 F266A mutant is unable to accumulate on chromatin, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and ESC self renewal. We identify a family of ESC messenger and lncRNAs that interact with wild type WDR5 but not F266A mutant, including several lncRNAs known to be important for ESC gene expression. These results suggest that specific RNAs are integral inputs into the WDR5-MLL complex for maintenance of the active chromatin state and embryonic stem cell fates. DOI: http://dx.doi.org/10.7554/eLife.02046.001 PMID:24521543

76 FR 23298 - Bottom Mount Combination Refrigerator-Freezers From the Republic of Korea: Initiation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

.... Changwon City Provision of Waste Heat Electricity For further information explaining why the Department is..., (e) wiring, and (f) insulation; (2) any assembled external doors designed for use in bottom mount... plastic liner, and (c) insulation; and (3) any assembled external drawers designed for use in bottom mount...

76 FR 72440 - Bottom Mount Combination Refrigerator-Freezers From Korea and Mexico; Scheduling of the Final...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... refrigeration using compression technology, with all of the following characteristics: (1) The cabinet contains... interior plastic liner, (e) wiring, and (f) insulation; (2) any assembled external doors designed for use... metal shell, (b) an interior plastic liner, and (c) insulation; and (3) any assembled external drawers...

Ionic ASi{sub 2}N{sub 3} (A=Li, Na, K and Rb) stabilized by the covalent Si–N bonding: First-principles calculations

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

Zhang, Huijun; Ren, Jiadong, E-mail: jdren@ysu.edu.cn; Wu, Lailei

The structural, elastic and electronic properties of LiSi{sub 2}N{sub 3} and its substitutions by Na, K and Rb were investigated through first-principles computations. The expansion of lattice parameters of ASi{sub 2}N{sub 3} from Li, Na, K to Rb is found to be determined by the bond angle of Si–N1–Si, which suggests a possible way to improve the lithium ionic conductivity by substitutions. ASi{sub 2}N{sub 3} (A=Li, Na, K and Rb) shows the similar elastic behaviors, while the electronic band gap gradually decreases from 5.1 to 3.4 eV from LiSi{sub 2}N{sub 3} to RbSi{sub 2}N{sub 3}. Interestingly, the analysis of electronicmore » structure, crystal orbital Hamiltonian populations and Bader charges shows that the covalence of Si–N bonding is critical for the stability of ASi{sub 2}N{sub 3} phase. Among ASi{sub 2}N{sub 3} phases, there is a relatively high ionicity in NaSi{sub 2}N{sub 3}; the Si–N bond strength in [Si{sub 2}N{sub 3}]{sup −} net for KSi{sub 2}N{sub 3} and RbSi{sub 2}N{sub 3} is comparable to LiSi{sub 2}N{sub 3}, but stronger than NaSi{sub 2}N{sub 3}. - Graphic abstract: Universal trend of structural and electronic properties in alkaline metal silicon nitrides, ASi{sub 2}N{sub 3}, A=Li, Na, K and Rb. - Highlights: • Trend in structure, electronic and mechanical properties of ASi{sub 2}N{sub 3} (A=Li-Rb) were predicted. • Lattice expansion of ASi{sub 2}N{sub 3} induced by the bond angle of Si–N1–Si was found. • Calculated band gap decreases from 5.1 to 3.4 eV from LiSi{sub 2}N{sub 3} to RbSi{sub 2}N{sub 3}. • Covalent Si–N bonding is critical for the stability of ASi{sub 2}N{sub 3}.« less

Initial Isotopic Heterogeneities in ZAGAMI: Evidence of a Complex Magmatic History

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C.-Y.; Reese, Y. D.

2006-01-01

Interpretations of Zagami s magmatic history range from complex [1,2] to relatively simple [3]. Discordant radiometric ages led to a suggestion that the ages had been reset [4]. In an attempt to identify the mechanism, Rb-Sr isochrons were individually determined for both fine-grained and coarse-grained Zagami [5]. Ages of approx.180 Ma were obtained from both lithologies, but the initial Sr-87/Sr-86 (ISr) of the fine-grained lithology was higher by 8.6+/-0.4 e-units. Recently, a much older age of approx.4 Ga has been advocated [6]. Here, we extend our earlier investigation [5]. Rb-Sr Data: In [5] we applied identical, simplified, procedures to both lithologies to test whether a grain-size dependent process such as thermally-driven subsolidus isotopic reequilibration had caused age-resetting. Minerals were separated only by density. In the present experiment, purer mineral separates were analysed with improved techniques. Combined Rb-Sr results give ages (T) = 166+/-12 Ma and 177+/-9 Ma and I(subSr) = 0.72174+/-9 and 0.72227+/-7 for the coarse-grained and fine-grained lithologies, respectively. ISr in the fine-grained sample is thus higher than in the coarse-grained sample by 7.3+/-1.6 e-units. The results for the coarse-grained lithology are in close agreement with T = 166+/-6 Ma, ISr = 0.72157+/-8 for an adjacent sample [7] and T = 178+/-4 Ma, ISr = 0.72151+/-5 [4, adjusted] for a separate sample. Thus, fine-grained Zagami appears on average to be less typical of the bulk than coarse-grained Zagami.

Neutronics Investigations for the Lower Part of a Westinghouse SVEA-96+ Assembly

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

Murphy, M.F.; Luethi, A.; Seiler, R.

2002-05-15

Accurate critical experiments have been performed for the validation of total fission (F{sub tot}) and {sup 238}U-capture (C{sub 8}) reaction rate distributions obtained with CASMO-4, HELIOS, BOXER, and MCNP4B for the lower axial region of a real Westinghouse SVEA-96+ fuel assembly. The assembly comprised fresh fuel with an average {sup 235}U enrichment of 4.02 wt%, a maximum enrichment of 4.74 wt%, 14 burnable-absorber fuel pins, and full-density water moderation. The experimental configuration investigated was core 1A of the LWR-PROTEUS Phase I project, where 61 different fuel pins, representing {approx}64% of the assembly, were gamma-scanned individually. Calculated (C) and measured (E)more » values have been compared in terms of C/E distributions. For F{sub tot}, the standard deviations are 1.2% for HELIOS, 0.9% for CASMO-4, 0.8% for MCNP4B, and 1.7% for BOXER. Standard deviations of 1.1% for HELIOS, CASMO-4, and MCNP4B and 1.2% for BOXER were obtained in the case of C{sub 8}. Despite the high degree of accuracy observed on the average, it was found that the five burnable-absorber fuel pins investigated showed a noticeable underprediction of F{sub tot}, quite systematically, for the deterministic codes evaluated (average C/E for the burnable-absorber fuel pins in the range 0.974 to 0.988, depending on the code)« less

Human 2-Oxoglutarate Dehydrogenase Complex E1 Component Forms a Thiamin-derived Radical by Aerobic Oxidation of the Enamine Intermediate*

PubMed Central

Nemeria, Natalia S.; Ambrus, Attila; Patel, Hetalben; Gerfen, Gary; Adam-Vizi, Vera; Tretter, Laszlo; Zhou, Jieyu; Wang, Junjie; Jordan, Frank

2014-01-01

Herein are reported unique properties of the human 2-oxoglutarate dehydrogenase multienzyme complex (OGDHc), a rate-limiting enzyme in the Krebs (citric acid) cycle. (a) Functionally competent 2-oxoglutarate dehydrogenase (E1o-h) and dihydrolipoyl succinyltransferase components have been expressed according to kinetic and spectroscopic evidence. (b) A stable free radical, consistent with the C2-(C2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (ThDP) cation radical was detected by electron spin resonance upon reaction of the E1o-h with 2-oxoglutarate (OG) by itself or when assembled from individual components into OGDHc. (c) An unusual stability of the E1o-h-bound C2-(2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (the “ThDP-enamine”/C2α-carbanion, the first postdecarboxylation intermediate) was observed, probably stabilized by the 5-carboxyl group of OG, not reported before. (d) The reaction of OG with the E1o-h gave rise to superoxide anion and hydrogen peroxide (reactive oxygen species (ROS)). (e) The relatively stable enzyme-bound enamine is the likely substrate for oxidation by O2, leading to the superoxide anion radical (in d) and the radical (in b). (f) The specific activity assessed for ROS formation compared with the NADH (overall complex) activity, as well as the fraction of radical intermediate occupying active centers of E1o-h are consistent with each other and indicate that radical/ROS formation is an “off-pathway” side reaction comprising less than 1% of the “on-pathway” reactivity. However, the nearly ubiquitous presence of OGDHc in human tissues, including the brain, makes these findings of considerable importance in human metabolism and perhaps disease. PMID:25210035

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis.

PubMed

Fu, Junjiang; Qin, Li; He, Tao; Qin, Jun; Hong, Jun; Wong, Jiemin; Liao, Lan; Xu, Jianming

2011-02-01

The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis.

THE INTERSECTION OF STABLE AND NON-EQUILIBRIUM TETRAHEDRA IN A MUTUAL 7- COMPONENT SYSTEM OF Li, Na, Rb, T1/Br, C1, NO$sub 3$, SO$sub 4$ (in Russian)

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

Dombrovskaya, N.S.; Khakhlova, N.V.; Alekseeva, E.A.

1961-04-21

The most stable configuration of the mixture of the 16 salts formed from Li, Na, Rb, Tl/Br, Cl, NO/sub 3/, and S0/sub 4/ con ture which however interact, resulting in a stable mixture. On the basis of exchange reactions the following equation has been derived: LiBr + NaNO/sub 3/ + RbCl + 1/2Tl/sub 2/SO/sub 4/ = 1/ 2LiSO/sub 4/ + NaCl + RbNO/sub 3/ + TlBr. In addition, several binary complexes are also formed, such as Li/sub 2/SO/sub 4/ - Rb/sub 2/SO/sub 4/, 4Li/sub 2/SO/ sub 4/ - RbSO /sub 4/, RbCl - 2Li/sub 2/SO/sub 4/ and possible others. Inmore » view of the great interest, the intersection of stable and non-equilibrium tetrahedra consisting of components of both, was experimentally studied by thermai analysis. On the basis of cooling curves the following deflection points have been observed: 453 deg C, precipitation of the first Li/sub 2/SO/sub 4/ crystals; 409 deg , coprecipitation of Li/sub 2/SO/sub 4/ and NaCl; 391 deg , coprecipitation of Li/sub 2/SO/sub 4/, NaCl snd TlBr; and finally at 107 deg , formation of the quaternary eutectic with the previously mentioned salts + RbNO/sub 3/. The microstructures of the stable and non-equilibrium phases are quite similar. (TTT)« less

Simultaneous Determination of Multiple Ginsenosides in Panax ginseng Herbal Medicines with One Single Reference Standard.

PubMed

Wu, Chunwei; Guan, Qingxiao; Wang, Shumei; Rong, Yueying

2017-01-01

Root of Panax ginseng C. A. Mey (Renseng in Chinese) is a famous Traditional Chinese Medicine. Ginsenosides are the major bioactive components. However, the shortage and high cost of some ginsenoside reference standards make it is difficult for quality control of P. ginseng . A method, single standard for determination of multicomponents (SSDMC), was developed for the simultaneous determination of nine ginsenosides in P. ginseng (ginsenoside Rg 1 , Re, Rf, Rg 2 , Rb 1 , Rc, Rb 2 , Rb 3 , Rd). The analytes were separated on Inertsil ODS-3 C18 (250 mm × 4.6 mm, 5 μm) with gradient elution of acetonitrile and water. The flow rate was 1 mL/min and detection wavelength was set at 203 nm. The feasibility and accuracy of SSDMC were checked by the external standard method, and various high-performance liquid chromatographic (HPLC) instruments and chromatographic conditions were investigated to verify its applicability. Using ginsenoside Rg 1 as the internal reference substance, the contents of other eight ginsenosides were calculated according to conversion factors (F) by HPLC. The method was validated with linearity ( r 2 ≥ 0.9990), precision (relative standard deviation [RSD] ≤2.9%), accuracy (97.5%-100.8%, RSD ≤ 1.6%), repeatability, and stability. There was no significant difference between the SSDMC method and the external standard method. New SSDMC method could be considered as an ideal mean to analyze the components for which reference standards are not readily available. A method, single standard for determination of multicomponents (SSDMC), was established by high-performance liquid chromatography for the simultaneous determination of nine ginsenosides in Panax ginseng (ginsenoside Rg1, Re, Rf, Rg2, Rb1, Rc, Rb2, Rb3, Rd)Various chromatographic conditions were investigated to verify applicability of FsThe feasibility and accuracy of SSDMC were checked by the external standard method. Abbreviations used: DRT: Different value of retention time; F: Conversion factor; HPLC: High-performance Liquid Chromatography; LOD: Limit of detection; LOQ: Limit of quantitation; PD: Percent difference; PPD: 20(S)-protopanaxadiol; PPT: 20(S)-protopanaxatriol; RSD: Relative standard deviation; SSDMC: Single Standard for Determination of Multicomponents; TCM: Traditional Chinese Medicine.

.sup.82 Sr-.sup.82 Rb Radioisotope generator

DOEpatents

Grant, Patrick M.; Erdal, Bruce R.; O'Brien, Harold A.

1976-01-01

An improved .sup.82 Sr-.sup.82 Rb radioisotope generator system, based upon the complexing ion exchange resin Chelex-100, has been developed. Columns of this material can be easily and rapidly milked, and the Rb-Sr separation factor for a fresh generator was found to be > 10.sup.7. Approximately 80 percent of the .sup.82 Rb present was delivered in a 15-ml volume of aqueous 0.2 M NH.sub.4 Cl solution. After more than 6 liters of eluant had been put through the generator, the Rb-Sr separation factor was still observed to be > 10.sup.5, and no unusual strontium breakthrough behavior was seen in the system over nearly three .sup.82 Sr half lives.

Competitive cesium-133 NMR spectroscopic study of complexation of different metal ions with dibenzo-21-crown-7 in acetonitrile-dimethylsulfoxide and nitromethane-dimethylsulfoxide mixtures.

PubMed

Sahmsipur, Mojtaba; Dastjerdi, Leila Shafiee; Alizadeh, Nader; Bijanzadeh, Hamid Reza

2008-04-01

(133)Cs NMR spectroscopy was used to determine the stoichiometry and stability of the Cs(+) ion complex with dibenzo-21-crown-7 (DB21C7) in acetonitrile-dimethylsulfoxide (96.5:3.5, w/w) and nitromethane-dimethylsulfoxide (96.5:3.5, w/w) mixtures. A competitive (133)Cs NMR technique was also employed to probe the complexation of Na(+), K(+), Rb(+), Ag(+), Tl(+), NH(4)(+), Mg(2+), Ba(2+), Hg(2+), Pb(2+) and UO(2)(2+) ions with DB21C7 in the same solvent systems. All the resulting 1:1 complexes in nitromethane-dimethylsulfoxide were more stable than those in acetonitrile-dimethylsulfoxide solution. In both solvent systems, the stability of the resulting complexes was found to vary in the order Rb(+)>K(+) approximately Ba(2+)>Tl(+)>Cs(+)>NH(4)(+) approximately Pb(2+)>Ag(+)>UO(2)(2+)>Hg(2+)>Mg(2+)>Na(+).

A novel mechanism for Bcr-Abl action: Bcr-Abl-mediated induction of the eIF4F translation initiation complex and mRNA translation.

PubMed

Prabhu, S; Saadat, D; Zhang, M; Halbur, L; Fruehauf, J P; Ong, S T

2007-02-22

The oncogenic kinase Bcr-Abl is thought to cause chronic myelogenous leukemia (CML) by altering the transcription of specific genes with growth- and survival-promoting functions. Recently, Bcr-Abl has also been shown to activate an important regulator of protein synthesis, the mammalian target of rapamycin (mTOR), which suggests that dysregulated translation may also contribute to CML pathogenesis. In this study, we found that both Bcr-Abl and the rapamycin-sensitive mTORC1 complex contribute to the phosphorylation (inactivation) of 4E-BP1, an inhibitor of the eIF4E translation initiation factor. Experiments with rapamycin and the Bcr-Abl inhibitor, imatinib mesylate, in Bcr-Abl-expressing cell lines and primary CML cells indicated that Bcr-Abl and mTORC1 induced formation of the translation initiation complex, eIF4F. This was characterized by reduced 4E-BP1 binding and increased eIF4G binding to eIF4E, two events that lead to the assembly of eIF4F. One target transcript is cyclin D3, which is regulated in Bcr-Abl-expressing cells by both Bcr-Abl and mTORC1 in a translational manner. In addition, the combination of imatinib and rapamycin was found to act synergistically against committed CML progenitors from chronic and blast phase patients. These experiments establish a novel mechanism of action for Bcr-Abl, and they provide insights into the modes of action of imatinib mesylate and rapamycin in treatment of CML. They also suggest that aberrant cap-dependent mRNA translation may be a therapeutic target in Bcr-Abl-driven malignancies.

Constrained Surface Complexation Modeling: Rutile in RbCl, NaCl, and NaCF 3SO 3 Media to 250 °C

DOE PAGES

Machesky, Michael L.; Předota, Milan; Ridley, Moira K.; ...

2015-06-01

In this paper, a comprehensive set of molecular-level results, primarily from classical molecular dynamics (CMD) simulations, are used to constrain CD-MUSIC surface complexation model (SCM) parameters describing rutile powder titrations conducted in RbCl, NaCl, and NaTr (Tr = triflate, CF 3SO 3 –) electrolyte media from 25 to 250 °C. Rb + primarily occupies the innermost tetradentate binding site on the rutile (110) surface at all temperatures (25, 150, 250 °C) and negative charge conditions (-0.1 and -0.2 C/m 2) probed via CMD simulations, reflecting the small hydration energy of this large, monovalent cation. Consequently, variable SCM parameters (Stern-layer capacitancemore » values and intrinsic Rb + binding constants) were adjusted relatively easily to satisfactorily match the CMD and titration data. The larger hydration energy of Na + results in a more complex inner-sphere distribution, which shifts from bidentate to tetradentate binding with increasing negative charge and temperature, and this distribution was not matched well for both negative charge conditions, which may reflect limitations in the CMD and/or SCM approaches. Finally, in particular, the CMD axial density profiles for Rb + and Na + reveal that peak binding distances shift toward the surface with increasing negative charge, suggesting that the CD-MUSIC framework may be improved by incorporating CD or Stern-layer capacitance values that vary with charge.« less

Constrained Surface Complexation Modeling: Rutile in RbCl, NaCl, and NaCF 3SO 3 Media to 250 °C

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

Machesky, Michael L.; Předota, Milan; Ridley, Moira K.

In this paper, a comprehensive set of molecular-level results, primarily from classical molecular dynamics (CMD) simulations, are used to constrain CD-MUSIC surface complexation model (SCM) parameters describing rutile powder titrations conducted in RbCl, NaCl, and NaTr (Tr = triflate, CF 3SO 3 –) electrolyte media from 25 to 250 °C. Rb + primarily occupies the innermost tetradentate binding site on the rutile (110) surface at all temperatures (25, 150, 250 °C) and negative charge conditions (-0.1 and -0.2 C/m 2) probed via CMD simulations, reflecting the small hydration energy of this large, monovalent cation. Consequently, variable SCM parameters (Stern-layer capacitancemore » values and intrinsic Rb + binding constants) were adjusted relatively easily to satisfactorily match the CMD and titration data. The larger hydration energy of Na + results in a more complex inner-sphere distribution, which shifts from bidentate to tetradentate binding with increasing negative charge and temperature, and this distribution was not matched well for both negative charge conditions, which may reflect limitations in the CMD and/or SCM approaches. Finally, in particular, the CMD axial density profiles for Rb + and Na + reveal that peak binding distances shift toward the surface with increasing negative charge, suggesting that the CD-MUSIC framework may be improved by incorporating CD or Stern-layer capacitance values that vary with charge.« less

AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

PubMed

Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

2016-10-01

Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Simple Atomic Quantum Memory Suitable for Semiconductor Quantum Dot Single Photons

NASA Astrophysics Data System (ADS)

Wolters, Janik; Buser, Gianni; Horsley, Andrew; Béguin, Lucas; Jöckel, Andreas; Jahn, Jan-Philipp; Warburton, Richard J.; Treutlein, Philipp

2017-08-01

Quantum memories matched to single photon sources will form an important cornerstone of future quantum network technology. We demonstrate such a memory in warm Rb vapor with on-demand storage and retrieval, based on electromagnetically induced transparency. With an acceptance bandwidth of δ f =0.66 GHz , the memory is suitable for single photons emitted by semiconductor quantum dots. In this regime, vapor cell memories offer an excellent compromise between storage efficiency, storage time, noise level, and experimental complexity, and atomic collisions have negligible influence on the optical coherences. Operation of the memory is demonstrated using attenuated laser pulses on the single photon level. For a 50 ns storage time, we measure ηe2 e 50 ns=3.4 (3 )% end-to-end efficiency of the fiber-coupled memory, with a total intrinsic efficiency ηint=17 (3 )%. Straightforward technological improvements can boost the end-to-end-efficiency to ηe 2 e≈35 %; beyond that, increasing the optical depth and exploiting the Zeeman substructure of the atoms will allow such a memory to approach near unity efficiency. In the present memory, the unconditional read-out noise level of 9 ×10-3 photons is dominated by atomic fluorescence, and for input pulses containing on average μ1=0.27 (4 ) photons, the signal to noise level would be unity.

Spectroscopy of LiCa and RbSr Molecules on Helium Nanodroplets

NASA Astrophysics Data System (ADS)

Lackner, Florian; Krois, Gunter; Ernst, Wolfgang E.

2013-06-01

We report on the investigation of mixed alkali metal (Ak) - alkaline earth metal (Ake) molecules on the surface of helium nanodroplets (He_{N}). These molecules have recently attracted considerable attention as candidates for the formation of ultracold molecules with a magnetic and an electronic dipole moment. In our experiments, LiCa and RbSr molecules are formed in a sequential pick-up process in their X^{2}Σ^{+} ground state and cool down rapidly to the droplet temperature of 0.38 K. Excitation spectra of LiCa and RbSr were recorded by using resonance enhanced multi-photon ionization time-of-flight (REMPI-TOF) spectroscopy and laser induced fluorescence (LIF) spectroscopy. On the helium droplet, vibronic transitions in Ak-Ake molecules are broadened and show a characteristic asymmetric peak form, which is caused by the interaction between the molecule and the superfluid He_{N} environment. For the lower electronic transitions in LiCa and RbSr progressions of vibrational bands excited from the X^{2}Σ^{+} (ν'' = 0) state are observed. The LiCa spectra can be compared to molecular beam experiments, which enables the assignment of three band systems near 15260 cm^{-1}, 19300 cm^{-1} and 22120 cm^{-1} as ^{2}Σ^{+}, ^{2}Π_{Ω} and ^{2}Π band, respectively. In the RbSr excitation spectrum we observe a vibrationally resolved band system near 14020 cm^{-1}. Upon electronic excitation, a fraction of the molecules desorb from the droplet surface and dispersed fluorescence spectra allow to study the X^{2}Σ^{+} ground state and excited states of free Ak-Ake molecules. H. Hara, Y. Takasu, Y. Yamaoka, J.M. Doyle, Y. Takahashi, Phys. Rev. Lett. 106, 205304 (2011) C. Callegari and W. E. Ernst, Helium Droplets as Nanocryostats for Molecular Spectroscopy - from the Vacuum Ultraviolet to the Microwave Regime, in: Handbook of High-Resolution Spectroscopy, eds. M. Quack and F. Merkt, John Wiley & Sons, Chichester, (2011) L. M. Russon, G. K. Rothschopf, M. D. Morse, A. I. Boldyrev, J. Simons, J. Chem. Phys. 109, 6655-6665 (1998)

Electromagnetically induced transparency in a Zeeman-sublevels Λ-system of cold 87Rb atoms in free space

NASA Astrophysics Data System (ADS)

Xiaojun, Jiang; Haichao, Zhang; Yuzhu, Wang

2016-03-01

We report the experimental investigation of electromagnetically induced transparency (EIT) in a Zeeman-sublevels Λ-type system of cold 87Rb atoms in free space. We use the Zeeman substates of the hyperfine energy states 52S1/2, F = 2 and 52P3/2, F‧ = 2 of 87Rb D2 line to form a Λ-type EIT scheme. The EIT signal is obtained by scanning the probe light over 1 MHz in 4 ms with an 80 MHz arbitrary waveform generator. More than 97% transparency and 100 kHz EIT window are observed. This EIT scheme is suited for an application of pulsed coherent storage atom clock (Yan B, et al. 2009 Phys. Rev. A 79 063820). Project supported by the National Basic Research Program of China (Grant No. 2011CB921504) and the National Natural Science Foundation of China (Grant No. 91536107).

Cubic-to-tetragonal structural phase transition in Rb{sub 1{minus}x}Cs{sub x}CaF{sub 3} solid solutions: Thermal expansion and EPR studies

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

Lahoz, F.; Villacampa, B.; Alcala, R.

1997-04-01

The influence of crystal mixing on the structural phase transitions in Rb{sub 1{minus}x}Cs{sub x}CaF{sub 3} (0{lt}x{lt}1) fluoroperovskite crystals has been studied by thermal expansion and EPR measurements of Ni{sup 2+} and Ni{sup 3+} paramagnetic probes. A cubic-to-tetragonal phase transition has been detected in crystals with x=0, 0.1, 0.21, 0.27, and 0.35. The critical temperature and the tetragonal distortion decrease as x increases. No transition was observed for x{ge}0.44. This transition shows a weak first-order component in the x=0 and 0.1 samples, which is progressively smeared out for x{gt}0.1, indicating a spatial distribution of the critical temperature in those crystals withmore » high ionic substitution rate. In RbCaF{sub 3}, another structural phase transition was observed at 20 K with a thermal hysteresis between 20 and 40 K. This transition has not been found in any of the mixed crystals.« less

First results from TN273 studies of the SE Mariana Forearc rift

NASA Astrophysics Data System (ADS)

Ribeiro, J. M.; Stern, R. J.; Kelley, K. A.; Shaw, A. M.; Shimizu, N.; Martinez, F.; Ishii, T.; Ishizuka, O.; Manton, W. I.

2012-12-01

TN 273 aboard R/V Thomas Thompson (Dec. 22 2011- Jan. 22 2012) studied an unusual region of rifting affecting the southern Mariana forearc S.W. of Guam. The S.E. Mariana Forearc Rift (SEMFR) formed by diffuse tectonic and volcanic deformation (Martinez and Sleeper, this meeting) ~2.7-3.7 Ma ago to accommodate opening of the southernmost Mariana Trough backarc basin. A total of 730 km linear-track of SEMFR seafloor was surveyed with deep-towed side-scan sonar IMI-30. 14 dredges provided samples of SEMFR igneous rocks, analyzed for whole rock (WR) and glass compositions. These new results coupled with results of earlier investigations confirm that SEMFR is dominated by Miocene lavas along with minor gabbro and diabase. SEMFR lavas range in major element composition from primitive basalt to fractionated andesite (Mg# = 0.36-0.73; SiO2 = 50-57 wt%), mainly controlled by crystal fractionation. Rare Earth Element (REE) patterns range from LREE-depleted, N-MORB-like to flat patterns, reflecting different mantle processes (i.e. different sources, degree of melting …). Glassy rinds and olivine-hosted melt inclusions in these lavas contain variable volatile compositions (F = 75-358 ppm, S = 35-1126 ppm, Cl= 74-1400 ppm, CO2 = 15-520 ppm, 0.36-2.36 wt% H2O). SEMFR lavas show spider diagrams with positive anomalies in LILE and negative anomalies in HSFE. SEMFR lavas have backarc basin-like (BAB-like) chemical composition (H2O < 2.5wt%, Ba/Yb~20, Nb/Yb~1 and ɛNd~9) along with stronger enrichment in Rb and Cs than arc and BAB lavas, as demonstrated by their higher Rb/Th and Cs/Ba ratios in WR and glasses, which may reflect the role of the ultra-shallow fluids. Ultra-shallow fluids are derived from the top of the subducting slab, beneath the forearc, where most of the water and the fluid-mobile elements (Rb, Cs, Ba,) are thought to be released (Schmidt and Poli, 1998, EPSL, Savov et al., 2005, G-3). Our results suggest that i) SEMFR lavas formed by metasomatism of a BAB mantle source by ultra-shallow fluids, likely released from subducted sediments and the altered oceanic crust; and ii) the ultra-shallow fluid is aqueous and is characterized by enrichment in Cs and Rb, suggesting that Cs and Rb are decoupled from Ba in ultra-shallow subduction processes.

WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

DTIC Science & Technology

2016-10-01

661, that disrupt the assembly of assembly of a specific signaling complex consisting of G, PI3K and AKT2, and blocked GPCR-stimulated PI3K/AKT...AKT2 with a higher efficacy than AKT1, and WDR26 also directly binds PI3K (Fig. 2). Second, we generated stable MDA-MB231 cell lines expressing...promotes Gβf signaling. Here, we demonstrate that WDR26 is overexpressed in highly malignant breast tumor cell lines and human breast cancer samples, and

A Computer Code to Calculate Emission and Transmission of Infrared Radiation through Non-Equilibrium Atmospheres.

DTIC Science & Technology

1983-07-08

A(xPCQNWL SEARCI THE. LINE FILE rbN,5, C’ 129 lIE,’ CM-I FOR LINES OF *,A&’,/,5X, III 2-- - ’IS C CFE =’,14,/95xs 131 T’e;NO =,IX .5,’ - ,x5/5, 1 32...15407wE’C8 131 -7e.3(5 221.141 .11Z230"J7 .1462zGE*1e 132 487.34C 22?.w53 .10S47C1-,7 .1.84E01.18 133 %9( Zfl375 22 -,E su 11M -0 7 klu 136 523.410 22M...144 589.530 23C.441 SME0043E-08 .2294301.07 145 59?.fi1C 23r.420 GsC?jlnF- .;cc.2iFtc7 146 604.490 iO35 .5345431-08 E271?53E*C7 14? R1lf LAIC t. 131

Laser cooling of nuclear spin 0 alkali 78Rb

NASA Astrophysics Data System (ADS)

Behr, J. A.; Gorelov, A.; Anholm, M.

2015-05-01

The textbook example for sub-Doppler cooling is a J = 1/2 I = 0 alkali atom in lin ⊥ lin molasses. In the σ+ σ- configuration of a standard MOT, the main sub-Doppler cooling mechanism relies on changing alignment (MF2 population) with the summed linear polarization orientation, but there is no such variation in AC Stark shift for F = 1/2. We have nevertheless looked for signs of sub-Doppler cooling by trapping I = 0 78Rb in a standard MOT and measuring the cloud size as a function of laser detuning and intensity. The 78Rb cloud size does not change significantly with lowered intensity, and expands slightly with detuning, consistent with minimal to no sub-Doppler cooling. Our geometry does show the well-known substantially smaller cloud size with detuning and intensity for I = 3/2 87Rb. Maintaining an I = 0 alkali cloud size with lowered intensity will help our planned β- ν correlation experiments in 38mK decay by suppressing possible production of photoassisted dimers. Supported by NSERC and NRC Canada through TRIUMF.

Production of rare ginsenosides (compound Mc, compound Y and aglycon protopanaxadiol) by β-glucosidase from Dictyoglomus turgidum that hydrolyzes β-linked, but not α-linked, sugars in ginsenosides.

PubMed

Lee, Gi-Woong; Kim, Kyoung-Rok; Oh, Deok-Kun

2012-09-01

Optimal hydrolytic activity of β-glucosidase from Dictyoglomus turgidum for the ginsenoside Rd was at pH 5.5 and 80 °C, with a half-life of ~11 h. The enzyme hydrolysed β-linked, but not α-linked, sugar moieties of ginsenosides. It produced the rare ginsenosides, aglycon protopanaxadiol (APPD), compounds Y, and Mc, via three unique transformation pathways: Rb(1) → Rd → F(2) → compound K → APPD, Rb(2) → compound Y, and Rc → compound Mc. The enzyme converted 0.5 mM Rb(2) and 0.5 mM Rc to 0.5 mM compound Y and 0.5 mM compound Mc after 3 h, respectively, with molar conversion yields of 100 %.

Scaling of an Optically Pumped Mid-Infrared Rubidium Laser

DTIC Science & Technology

2015-03-26

v AFIT-ENP-MS-15-M-104 Abstract An optically pumped mid-infrared rubidium (Rb) pulsed laser has been demonstrated in a heat pipe ... Heat Pipe Assembly ........................................................................................12 Figure 3.3. Rb Number Density vs. Heat ...the first experiments that used a heat pipe as the gain cell. This experiment would influence the work of Sharma (Sharma, 1981:210). 9 Krupke

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

McCall, Kyle M.; Stoumpos, Constantinos C.; Kostina, Svetlana S.

The optical and electronic properties of Bridgman grown single crystals of the wide-bandgap semiconducting defect halide perovskites A3M2I9 (A = Cs, Rb; M = Bi, Sb) have been investigated. Intense Raman scattering was observed at room temperature for each compound, indicating high polarizability and strong electron–phonon coupling. Both low-temperature and room-temperature photoluminescence (PL) were measured for each compound. Cs3Sb2I9 and Rb3Sb2I9 have broad PL emission bands between 1.75 and 2.05 eV with peaks at 1.96 and 1.92 eV, respectively. The Cs3Bi2I9 PL spectra showed broad emission consisting of several overlapping bands in the 1.65–2.2 eV range. Evidence of strong electron–phononmore » coupling comparable to that of the alkali halides was observed in phonon broadening of the PL emission. Effective phonon energies obtained from temperature-dependent PL measurements were in agreement with the Raman peak energies. A model is proposed whereby electron–phonon interactions in Cs3Sb2I9, Rb3Sb2I9, and Cs3Bi2I9 induce small polarons, resulting in trapping of excitons by the lattice. The recombination of these self-trapped excitons is responsible for the broad PL emission. Rb3Bi2I9, Rb3Sb2I9, and Cs3Bi2I9 exhibit high resistivity and photoconductivity response under laser photoexcitation, indicating that these compounds possess potential as semiconductor hard radiation detector materials.« less

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking

PubMed Central

Wei, Yu; Li, Jinlong; Qing, Jie; Huang, Mingjie; Wu, Ming; Gao, Fenghua; Li, Dongmei; Hong, Zhangyong; Kong, Lingbao; Huang, Weiqiang; Lin, Jianping

2016-01-01

The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01–23.84 μM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development. PMID:26845440

A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53

PubMed Central

Bechill, John; Zhong, Rong; Zhang, Chen; Solomaha, Elena

2016-01-01

p53 function is frequently inhibited in cancer either through mutations or by increased degradation via MDM2 and/or E6AP E3-ubiquitin ligases. Most agents that restore p53 expression act by binding MDM2 or E6AP to prevent p53 degradation. However, fewer compounds directly bind to and activate p53. Here, we identified compounds that shared a core structure that bound p53, caused nuclear localization of p53 and caused cell death. To identify these compounds, we developed a novel cell-based screen to redirect p53 degradation to the Skip-Cullin-F-box (SCF) ubiquitin ligase complex in cells expressing high levels of p53. In a multiplexed assay, we coupled p53 targeted degradation with Rb1 targeted degradation in order to identify compounds that prevented p53 degradation while not inhibiting degradation through the SCF complex or other proteolytic machinery. High-throughput screening identified several leads that shared a common 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that stabilized p53. Surface plasmon resonance analysis indicated that these compounds bound p53 with a KD of 200 ± 52 nM. Furthermore, these compounds increased p53 nuclear localization and transcription of the p53 target genes PUMA, BAX, p21 and FAS in cancer cells. Although p53-null cells had a 2.5±0.5-fold greater viability compared to p53 wild type cells after treatment with core compounds, loss of p53 did not completely rescue cell viability suggesting that compounds may target both p53-dependent and p53-independent pathways to inhibit cell proliferation. Thus, we present a novel, cell-based high-throughput screen to identify a 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that bound to p53 and increased p53 activity in cancer cells. These compounds may serve as anti-neoplastic agents in part by targeting p53 as well as other potential pathways. PMID:27124407

Fluorine-Labeling as a Diagnostic for Thiol-Ligand and Gold Nanocluster Self-Assembly

DTIC Science & Technology

2009-01-01

A . Chandekar, S. K. Sengupta, C . M. F . Barry, J. L . Mead and J. E. Whitten...of O ( a factor up to 2.4) relative to its C:O:S:F composition remained although the relative compositions of C , S and F were consistent with the 6:2:1...and 2-prop- anol followed by a UV-ozone treatment (Samco International, Inc., Model UV-1 UV-Ozone stripper/cleaner) of 12 min at 150 C with a 0.50 L

Syntheses, Raman spectroscopy and crystal structures of alkali hexa­fluorido­rhenates(IV) revisited

PubMed Central

Louis-Jean, James; Salamat, Ashkan; Pham, Chien Thang; Poineau, Frederic

2018-01-01

The A 2[ReF6] (A = K, Rb and Cs) salts are isotypic and crystallize in the trigonal space group type P m1, adopting the K2[GeF6] structure type. Common to all A 2[ReF6] structures are slightly distorted octa­hedral [ReF6]2− anions with an average Re—F bond length of 1.951 (8) Å. In those salts, symmetry lowering on the local [ReF6]2− anions from Oh (free anion) to D 3d (solid-state structure) occur. The distortions of the [ReF6]2− anions, as observed in their Raman spectra, are correlated to the size of the counter-cations.

Syntheses, Raman spectroscopy and crystal structures of alkali hexafluoridorhenates(IV) revisited

DOE PAGES

Louis-Jean, James; Mariappan Balasekaran, Samundeeswari; Smith, Dean; ...

2018-04-06

The A 2[ReF 6] (A = K, Rb and Cs) salts are isotypic and crystallize in the trigonal space group type Pmore » $$\\bar{3}$$m1, adopting the K 2[GeF 6] structure type. Common to all A 2[ReF 6] structures are slightly distorted octa­hedral [ReF 6] 2- anions with an average Re—F bond length of 1.951 (8) Å. In these salts, symmetry lowering on the local [ReF 6] 2- anions from O h (free anion) to D 3d (solid-state structure) occur. The distortions of the [ReF 6] 2- anions, as observed in their Raman spectra, are correlated to the size of the counter-cations.« less

Unusual Nonemissive Behavior of Rubrene J-Aggregates: A Rare Violation.

PubMed

Aggarwal, Nikhil; Patnaik, Archita

2017-04-13

Structure-property correlations in rubrene (RB) colloidal J-aggregates were unravelled by steady state and time-resolved spectroscopy in conjunction with excited state density functional calculations. The RB J-aggregate with a slippage angle θ = 30.4°, estimated from the monomeric transition dipole moment directions, exhibited a broad fwhm of 1073 cm -1 and a 5 nm red-shifted absorption band carrying a transition dipole moment (M⃗ λ agg = 1.80 D) almost equivalent to the monomeric dye (M⃗ λ mon = 1.89 D). A significantly low magnitude of exciton coupling energy, ΔE exc = -358 cm -1 for the rhombic-RB colloidal J-aggregates resulted owing to the weaker electronic communication between the largely separated RB subunits (r = 7.2 Å) and a restricted exciton delocalization over the RB J-dimer (N = 2). The RB J-dimer exhibited a perfect balance between the computed singlet (2.53 eV) and the triplet (1.29 eV) exciton energies for singlet fission (SF). Supporting this, the PL decay profile of the J-aggregates revealed a delayed fluorescence, substantiating triplet pair formation via SF. The experimental evidence for the long-lived triplet formation was furthermore confirmed by its transient absorption (T 1 → T N ) at 530 nm. Consequently, a high probability for SF and a low probability for triplet-triplet recombination, leading to a dramatic lowering in photoluminescence quantum yield from 0.172 down to 0.035 was noted. The electronic structure calculations for the RB J-dimer followed TD-DFT-M062X/6-31G+(d,p) level of theory following integral equation formalism polarizable continuum model (IEFPCM) in water. S 1 excited state for RB J-dimer was carefully analyzed using integral overlap of electron and hole density distribution (ϕ) and the defined t-indexes along all three spatial directions, and was found to be of locally excited in character.

Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements.

PubMed

Liu, Shu; Bolger, Joshua K; Kirkland, Lindsay O; Premnath, Padmavathy N; McInnes, Campbell

2010-12-17

An alternative strategy for inhibition of the cyclin dependent kinases (CDKs) in antitumor drug discovery is afforded through the substrate recruitment site on the cyclin positive regulatory subunit. Critical CDK substrates such as the Rb and E2F families must undergo cyclin groove binding before phosphorylation, and hence inhibitors of this interaction also block substrate specific kinase activity. This approach offers the potential to generate highly selective and cell cycle specific CDK inhibitors and to reduce the inhibition of transcription mediated through CDK7 and 9, commonly observed with ATP competitive compounds. While highly potent peptide and small molecule inhibitors of CDK2/cyclin A, E substrate recruitment have been reported, little information has been generated on the determinants of inhibitor binding to the cyclin groove of the CDK4/cyclin D1 complex. CDK4/cyclin D is a validated anticancer drug target and continues to be widely pursued in the development of new therapeutics based on cell cycle blockade. We have therefore investigated the structural basis for peptide binding to its cyclin groove and have examined the features contributing to potency and selectivity of inhibitors. Peptidic inhibitors of CDK4/cyclin D of pRb phosphorylation have been synthesized, and their complexes with CDK4/cyclin D1 crystal structures have been generated. Based on available structural information, comparisons of the cyclin grooves of cyclin A2 and D1 are presented and provide insights into the determinants for peptide binding and the basis for differential binding and inhibition. In addition, a complex structure has been generated in order to model the interactions of the CDKI, p27(KIP)¹, with cyclin D1. This information has been used to shed light onto the endogenous inhibition of CDK4 and also to identify unique aspects of cyclin D1 that can be exploited in the design of cyclin groove based CDK inhibitors. Peptidic and nonpeptidic compounds have been synthesized in order to explore structure-activity relationship for binding to the cyclin D1 groove, which to date has not been carried out in a systematic fashion. Collectively, the data presented provide new insights into how compounds can be developed that function as chemical biology probes to determine the cellular and antitumor effects of CDK inhibition. Furthermore, such compounds will serve as templates for structure-guided efforts to develop potential therapeutics based on selective inhibition of CDK4/cyclin D activity.

Self-assembly of five 8-hydroxyquinolinate-based complexes: tunable core, supramolecular structure, and photoluminescence properties.

PubMed

Yuan, Guozan; Shan, Weilong; Qiao, Xuelong; Ma, Li; Huo, Yanping

2014-07-01

Five new Zn(II) complexes, namely [Zn(3)(L)(6)] (1), [Zn(2)(Cl)(2)(L)(2) (py)(2)] (2), [Zn(2)(Br)(2) (L)(2)(py)(2)] (3), [Zn(L)(2)(py)] (4), and [Zn(2)(OAc)(2)(L)(2)(py)(2)] (5), were prepared by the solvothermal reaction of ZnX(2) (X(-) =Cl(-), Br(-), F(-), and OAc(-)) salts with a 8-hydroxyquinolinate ligand (HL) that contained a trifluorophenyl group. All of the complexes were characterized by elemental analysis, IR spectroscopy, and powder and single-crystal X-ray crystallography. The building blocks exhibited unprecedented structural diversification and their self-assembly afforded one mononuclear, three binuclear, and one trinuclear Zn(II) structures in response to different anions and solvent systems. Complexes 1-5 featured four types of supramolecular network controlled by non-covalent interactions, such as π⋅⋅⋅π-stacking, C-H⋅⋅⋅π, hydrogen-bonding, and halogen-related interactions. Investigation of their photoluminescence properties exhibited disparate emission wavelengths, lifetimes, and quantum yields in the solid state. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tetragonal distortions of some tetragonal Cr 3+ centers in fluoroperovskite ABF 3 crystals

NASA Astrophysics Data System (ADS)

Zhou, Qing; Wu, Hong-Ye; Wu, Xiao-Xuan; Zheng, Wen-Chen

2006-07-01

The tetragonal distortions [characterized by the displacement Δ R of the F - ion intervening in Cr 3+ and V B (B 2+ vacancy) or M + ion in B 2+ site] for Cr 3+-V B and Cr 3+-Li + centers in Cr 3+-doped fluoroperovskites KBF 3 (B = Mg, Zn) and ACdF 3 (A = K, Rb, Cs) and also for Cr 3+-Na + center in KZnF 3 have been studied by calculating the EPR parameters D, g|| and g⊥ from the crystal-field theory. From the studies, an interesting trend is suggested, i.e., when the size of the co-doped monovalent impurity M + in the nearest neighbor B 2+ site is comparable to that of the replaced B 2+ ion, the displacement Δ R of the intervening F - ion in Cr 3+-M + center is smaller than that in Cr 3+-V B center and if the M + iron is much smaller or much larger than that of the replaced B 2+ ion, the displacement Δ R in Cr 3+-M + center is greater than that in Cr 3+-V B center. The causes of the trend are discussed.

Tetragonal distortions of some tetragonal Cr3+ centers in fluoroperovskite ABF3 crystals.

PubMed

Zhou, Qing; Wu, Hong-Ye; Wu, Xiao-Xuan; Zheng, Wen-Chen

2006-07-01

The tetragonal distortions [characterized by the displacement DeltaR of the F(-) ion intervening in Cr(3+) and V(B) (B(2+) vacancy) or M(+) ion in B(2+) site] for Cr(3+)-V(B) and Cr(3+)-Li(+) centers in Cr(3+)-doped fluoroperovskites KBF(3) (B=Mg, Zn) and ACdF(3) (A=K, Rb, Cs) and also for Cr(3+)-Na(+) center in KZnF(3) have been studied by calculating the EPR parameters D, g(parallel) and g(perpendicular) from the crystal-field theory. From the studies, an interesting trend is suggested, i.e., when the size of the co-doped monovalent impurity M(+) in the nearest neighbor B(2+) site is comparable to that of the replaced B(2+) ion, the displacement DeltaR of the intervening F(-) ion in Cr(3+)-M(+) center is smaller than that in Cr(3+)-V(B) center and if the M(+) iron is much smaller or much larger than that of the replaced B(2+) ion, the displacement DeltaR in Cr(3+)-M(+) center is greater than that in Cr(3+)-V(B) center. The causes of the trend are discussed.

Origin of selenium–gold interaction in F{sub 2}CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH{sub 3}): Synergistic effects

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

Guo, Xin; Yang, Yu-Ping; Li, Qing-Zhong, E-mail: liqingzhong1990@sina.com, E-mail: lihaibei@sdu.edu.cn

Selenium–gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium–gold interaction by studying complexes F{sub 2}CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH{sub 3}). The results showed that the formation of selenium–gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au—Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium–gold interaction. Interestingly, the chalcogen–gold interaction becomes stronger with the increasemore » of chalcogen atomic mass in F{sub 2}CX⋯AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH{sub 3} into F{sub 2}CSe⋯AuY, in which selenium–gold interaction is weakened and selenium–nitrogen interaction is strengthened due to the synergistic effects.« less

Identification and Characterization of Citrus tristeza virus Isolates Breaking Resistance in Trifoliate Orange in California.

PubMed

Yokomi, Raymond K; Selvaraj, Vijayanandraj; Maheshwari, Yogita; Saponari, Maria; Giampetruzzi, Annalisa; Chiumenti, Michela; Hajeri, Subhas

2017-07-01

Most Citrus tristeza virus (CTV) isolates in California are biologically mild and symptomless in commercial cultivars on CTV tolerant rootstocks. However, to better define California CTV isolates showing divergent serological and genetic profiles, selected isolates were subjected to deep sequencing of small RNAs. Full-length sequences were assembled, annotated and trifoliate orange resistance-breaking (RB) isolates of CTV were identified. Phylogenetic relationships based on their full genomes placed three isolates in the RB clade: CA-RB-115, CA-RB-AT25, and CA-RB-AT35. The latter two isolates were obtained by aphid transmission from Murcott and Dekopon trees, respectively, containing CTV mixtures. The California RB isolates were further distinguished into two subclades. Group I included CA-RB-115 and CA-RB-AT25 with 99% nucleotide sequence identity with RB type strain NZRB-G90; and group II included CA-RB-AT35 with 99 and 96% sequence identity with Taiwan Pumelo/SP/T1 and HA18-9, respectively. The RB phenotype was confirmed by detecting CTV replication in graft-inoculated Poncirus trifoliata and transmission from P. trifoliata to sweet orange. The California RB isolates induced mild symptoms compared with severe isolates in greenhouse indexing tests. Further examination of 570 CTV accessions, acquired from approximately 1960 and maintained in planta at the Central California Tristeza Eradication Agency, revealed 16 RB positive isolates based on partial p65 sequences. Six isolates collected from 1992 to 2011 from Tulare and Kern counties were CA-RB-115-like; and 10 isolates collected from 1968 to 2010 from Riverside, Fresno, and Kern counties were CA-RB-AT35-like. The presence of the RB genotype is relevant because P. trifoliata and its hybrids are the most popular rootstocks in California.

Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus.

PubMed

Tan, Joanne Sh; Yeo, Chia-Rou; Popovich, David G

2017-07-01

Ginsenosides are believed to be the principal components behind the pharmacological actions of ginseng, and their bioactive properties are closely related to the type, position, and number of sugar moieties attached to the aglycone; thus, modification of the sugar chains may markedly change their biological activities. In this study, major protopanaxadiol type ginsenosides (PD) Rb1, Rc, and Rb2 were isolated from Panax ginseng and were transformed using two probiotic strains namely Bifidobacterium lactis Bi-07 and Lactobacillus rhamnosus HN001 to obtain specific deglycosylated ginsenosides. It was demonstrated that B. lactis transformed ginsenosides Rb1, Rc, and Rb2 to Rd within 1 h of fermentation and rare ginsenoside F2 by the conversion of Rd after 12-h fermentation. The maximum Rd concentration was 147.52 ± 1.45 μg/mL after 48-h fermentation as compared to 45.85 ± 0.71 μg/mL before fermentation. In contrast, L. rhamnosus transformed Rb1, Rc, and Rb2 into Rd as the final metabolite after 72-h fermentation. B. lactis displayed significantly (p < 0.05) higher β-glucosidase activity against p-nitrophenyl-β-glucopyranoside than L. rhamnosus and higher bioconversion efficiency during fermentation. The present study suggests that the fermentation of major PD type ginsenosides with B. lactis Bi-07 may serve as an effective means to afford bioactive deglycosylated ginsenosides and to create novel ginsenoside extracts.

Paramagnetic 19F NMR and Electrospray Ionization Mass Spectrometric Studies of Substituted Pyridine Complexes of Chromium(III): Models for Potential Use of 19F NMR to Probe Cr(III)-Nucleotide Interaction1

PubMed Central

Rhodes, Nicholas R.; Belmore, Ken; Cassady, Carolyn J.; Vincent, John B.

2013-01-01

The synthesis and characterization of chromium basic carboxylate complexes, [Cr3(O2CR)6L3]+, containing trifluoroacetate, 3-fluoropyridine, 3-trifluoromethylpyridine, and 4-trifluoromethylpyridine are described. The substituted pyridine ligands are used as models of DNA bases to determine whether 19F NMR would be a potentially useful probe of the binding of Cr3+ to DNA. The 19F NMR resonances of the coordinated ligands, while broadened by delocalization of unpaired electron density from the S=3/2 chromic centers, are readily discernable, and the contact shifts are of sufficient magnitude that the signals from coordinated and free ligands can easily be differentiated. Thus, 19F NMR appears to be a potentially useful probe of the binding of Cr3+ to DNA containing F-labeled bases. Additionally, electrospray MS is shown to be a convenient method to establish the identity of chromium basic carboxylate assemblies. PMID:24222929

Assessing Chronology and Mantle Evolution In-Situ with CODEX

NASA Astrophysics Data System (ADS)

Anderson, F. S.; Levine, J.; Whitaker, T.

2017-12-01

Understanding lunar bombardment history is crucial to understanding the dynamic evolution of the Moon. Using an instrument called CODEX (Chemistry, Organics, and Dating Experiment) intended for in-situ dating [1-5], we have obtained Pb-Pb dates for Martian meteorites Zagami and Northwest Africa (NWA) 7034, and lunar meteorites Miller Range 05035, LaPaz Icefield 02205, and NWA 032. In conjunction with our previous Rb-Sr success, these measurments demonstrate the potential for in-situ measurements of the Moon. Some of these Pb dates are consistent with young age estimates, however, many are consistent with previous anomalously old Pb measurements for lunar and SNC meteorites. Proposed explanations for this paradox include terrestrial Pb contamination, that the SNC's are actually ancient and reset in Rb/Sr, that there are multiple isotopic reservoirs sampled by the impact process, or that multiple reservoirs are sampled during the volcanic emplacement. In the future, we plan to use CODEX to test these hypotheses by making measurements on outcrops in-situ on Mars or the Moon, avoiding terrestrial or impact mixing. If in-situ Rb-Sr and Pb-Pb measurements are not concordant, then we are likely constraining the common Pb signature, and hence mantle evolution, of the Moon or Mars. Alternatively, we are likely obtaining a robust age estimate. References: [1] F. S. Anderson et al. LPSC 1246, 2 (2017); [2] F. S. Anderson et al. LPSC 2957, 2 (2017); [3] S. Beck et al., LPSC, 3001, 2 (2017); [4] T. J. Whitaker et al. LPSC 2328, 2 (2017); [5] F. S. Anderson et al. RCMS 29, 191 (2015);

Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

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

Altamura, Gennaro, E-mail: gennaro.altamura@unina.it; Corteggio, Annunziata, E-mail: ancorteg@unina.it; Pacini, Laura, E-mail: PaciniL@students.iarc.fr

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting inmore » upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.« less

Controlling Self-Assembly in Al(110) Homoepitaxy

NASA Astrophysics Data System (ADS)

Tiwary, Yogesh; Fichthorn, Kristen

2010-03-01

Homoepitaxial growth on Al(110) exhibits nanoscale self-assembly into huts with well-defined (100) and (111) facets [1]. Although some of the diffusion mechanisms underlying this kinetic self-assembly were identified and incorporated into a two-dimensional model [2], we used density-functional theory (DFT) to identify many other mechanisms that are needed to describe the three-dimensional assembly seen experimentally [3]. We developed a three-dimensional kinetic Monte Carlo (KMC) model of Al(110) homoepitaxy. The inputs to the model were obtained from DFT [3,4]. Our model is in agreement with experimentally observed trends for this system. We used KMC to predict self-assembly under various growth conditions. To achieve precise placement of Al nanohuts, we simulated thermal-field-directed assembly [5]. Our results indicate that this technique can be used to create uniform arrays of nanostructures. [1] F. Buatier de Mongeot, W. Zhu, A. Molle, R. Buzio, C. Boragno, U. Valbusa, E. Wang, and Z. Zhang, Phys. Rev. Lett. 91, 016102 (2003). [2] W. Zhu, F. Buatier de Mongeot, U. Valbusa, E. G. Wang, and Z. Y. Zhang, Phys. Rev. Lett. 92, 106102 (2004). [3] Y. Tiwary and K. A. Fichthorn, submitted to Phys. Rev. B. [4] Y. Tiwary and K. A. Fichthorn, Phys. Rev. B 78, 205418 (2008). [5] C. Zhang and R. Kalyanaraman, Appl. Phys. Lett. 83, 4827 (2003).

Self-assembled coordination nanoparticles from nucleotides and lanthanide ions with doped-boronic acid-fluorescein for detection of cyanide in the presence of Cu2+ in water.

PubMed

Kulchat, Sirinan; Chaicham, Anusak; Ekgasit, Sanong; Tumcharern, Gamolwan; Tuntulani, Thawatchai; Tomapatanaget, Boosayarat

2012-01-30

The sensor molecule, F-oBOH, containing boronic acid-linked hydrazide and fluorescein moieties was synthesized. For anion sensing applications, F-oBOH was studied in aqueous media. Unfortunately, F-oBOH was found to be hydrolyzed in water. Therefore, a new strategy was developed to prevent the hydrolysis of F-oBOH by applying self-assembly coordination nanoparticles network (F-oBOH-AMP/Gd(3+) CNPs). Interestingly, the nanoparticles network displayed the enhancement of fluorescent signal after adding Cu(2+) following by CN(-). The network, therefore, possessed a high selectivity for detection of CN(-) compared to other competitive anions in the presence of Cu(2+). Cyanide ion could promote the Cu(2+) binding to F-oBOH incorporated in AMP/Gd(3+) CNPs to give the opened-ring form of spirolactam resulting in the fourfold of fluorescence enhancement compared to Cu(2+) complexation without CN(-). Additionally, the log K value of F-oBOH-AMP/Gd(3+) CNPs⊂Cu(2+) toward CN(-) was 3.97 and the detection limits obtained from naked-eye and spectrofluorometry detections were 20μM and 4.03μM, respectively. The proposed method was demonstrated to detect CN(-) in drinking water with high accuracy. Copyright © 2011 Elsevier B.V. All rights reserved.

Event-by-Event Continuous Respiratory Motion Correction for Dynamic PET Imaging.

PubMed

Yu, Yunhan; Chan, Chung; Ma, Tianyu; Liu, Yaqiang; Gallezot, Jean-Dominique; Naganawa, Mika; Kelada, Olivia J; Germino, Mary; Sinusas, Albert J; Carson, Richard E; Liu, Chi

2016-07-01

Existing respiratory motion-correction methods are applied only to static PET imaging. We have previously developed an event-by-event respiratory motion-correction method with correlations between internal organ motion and external respiratory signals (INTEX). This method is uniquely appropriate for dynamic imaging because it corrects motion for each time point. In this study, we applied INTEX to human dynamic PET studies with various tracers and investigated the impact on kinetic parameter estimation. The use of 3 tracers-a myocardial perfusion tracer, (82)Rb (n = 7); a pancreatic β-cell tracer, (18)F-FP(+)DTBZ (n = 4); and a tumor hypoxia tracer, (18)F-fluoromisonidazole ((18)F-FMISO) (n = 1)-was investigated in a study of 12 human subjects. Both rest and stress studies were performed for (82)Rb. The Anzai belt system was used to record respiratory motion. Three-dimensional internal organ motion in high temporal resolution was calculated by INTEX to guide event-by-event respiratory motion correction of target organs in each dynamic frame. Time-activity curves of regions of interest drawn based on end-expiration PET images were obtained. For (82)Rb studies, K1 was obtained with a 1-tissue model using a left-ventricle input function. Rest-stress myocardial blood flow (MBF) and coronary flow reserve (CFR) were determined. For (18)F-FP(+)DTBZ studies, the total volume of distribution was estimated with arterial input functions using the multilinear analysis 1 method. For the (18)F-FMISO study, the net uptake rate Ki was obtained with a 2-tissue irreversible model using a left-ventricle input function. All parameters were compared with the values derived without motion correction. With INTEX, K1 and MBF increased by 10% ± 12% and 15% ± 19%, respectively, for (82)Rb stress studies. CFR increased by 19% ± 21%. For studies with motion amplitudes greater than 8 mm (n = 3), K1, MBF, and CFR increased by 20% ± 12%, 30% ± 20%, and 34% ± 23%, respectively. For (82)Rb rest studies, INTEX had minimal effect on parameter estimation. The total volume of distribution of (18)F-FP(+)DTBZ and Ki of (18)F-FMISO increased by 17% ± 6% and 20%, respectively. Respiratory motion can have a substantial impact on dynamic PET in the thorax and abdomen. The INTEX method using continuous external motion data substantially changed parameters in kinetic modeling. More accurate estimation is expected with INTEX. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ion Diffusion Within Water Films in Unsaturated Porous Media.

PubMed

Tokunaga, Tetsu K; Finsterle, Stefan; Kim, Yongman; Wan, Jiamin; Lanzirotti, Antonio; Newville, Matthew

2017-04-18

Diffusion is important in controlling local solute transport and reactions in unsaturated soils and geologic formations. Although it is commonly assumed that thinning of water films controls solute diffusion at low water contents, transport under these conditions is not well understood. We conducted experiments in quartz sands at low volumetric water contents (θ) to quantify ion diffusion within adsorbed films. At the lowest water contents, we employed fixed relative humidities to control water films at nm thicknesses. Diffusion profiles for Rb + and Br - in unsaturated sand packs were measured with a synchrotron X-ray microprobe, and inverse modeling was used to determine effective diffusion coefficients, D e, as low as ∼9 × 10 -15 m 2 s -1 at θ = 1.0 × 10 -4 m 3 m -3 , where the film thickness = 0.9 nm. Given that the diffusion coefficients (D o ) of Rb + and Br - in bulk water (30 °C) are both ∼2.4 × 10 -9 m 2 s -1 , we found the impedance factor f = D e /(θD o ) is equal to 0.03 ± 0.02 at this very low saturation, in agreement with the predicted influence of interface tortuosity (τ a ) for diffusion along grain surfaces. Thus, reduced cross-sectional area (θ) and tortuosity largely accounted for the more than 5 orders of magnitude decrease in D e relative to D o as desaturation progressed down to nanoscale films.

CRISPR/Cas9-mediated knockout of PiSSK1 reveals essential role of S-locus F-box protein-containing SCF complexes in recognition of non-self S-RNases during cross-compatible pollination in self-incompatible Petunia inflata.

PubMed

Sun, Linhan; Kao, Teh-Hui

2018-06-01

Function of Petunia PiSSK1. Self-incompatibility (SI), an inbreeding-preventing mechanism, is regulated in Petunia inflata by the polymorphic S-locus, which houses multiple pollen-specific S-locus F-box (SLF) genes and a single pistil-specific S-RNase gene. S 2 -haplotype and S 3 -haplotype possess the same 17 polymorphic SLF genes (named SLF1 to SLF17), and each SLF protein produced in pollen is assembled into an SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligase complex. A complete suite of SLF proteins is thought to collectively interact with all non-self S-RNases to mediate their ubiquitination and degradation by the 26S proteasome, allowing cross-compatible pollination. For each SCF SLF complex, the Cullin1 subunit (named PiCUL1-P) and Skp1 subunit (named PiSSK1), like the F-box protein subunits (SLFs), are pollen-specific, raising the possibility that they also evolved specifically to function in SI. Here we used CRISPR/Cas9-meditated genome editing to generate frame-shift indel mutations in PiSSK1 and examined the SI behavior of a T 0 plant (S 2 S 3 ) with biallelic mutations in the pollen genome and two progeny plants (S 2 S 2 ) each homozygous for one of the indel alleles and not carrying the Cas9-containing T-DNA. Their pollen was completely incompatible with pistils of seven otherwise-compatible S-genotypes, but fully compatible with pistils of an S 3 S 3 transgenic plant in which production of S 3 -RNase was completely suppressed by an antisense S 3 -RNase gene, and with pistils of immature flower buds, which produce little S-RNase. These results suggest that PiSSK1 specifically functions in SI and support the hypothesis that SLF-containing SCF complexes are essential for compatible pollination.

Synthesis, characterization and cytotoxic activity of substituted benzyl iminoether Pt(II) complexes of the type cis- and trans-[PtCl2{E-N(H)=C(OMe)CH2-C6H4-p-R}2] (R=Me, OMe, F). X-ray structure of trans-[PtCl2{E-N(H)=C(OMe)CH2-C6H4-p-F}2].

PubMed

Mazzega Sbovata, Silvia; Bettio, Frazia; Marzano, Christine; Tassan, Augusto; Mozzon, Mirto; Bertani, Roberta; Benetollo, Franco; Michelin, Rino A

2008-04-01

New substituted benzyl iminoether derivatives of the type cis- and trans-[PtCl(2){E-N(H)C(OMe)CH(2)-C(6)H(4)-p-R}(2)] (R=Me (1a, 2a), OMe (3a, 4a), F (5a, 6a)) have been synthesized and characterized by elemental analyses, FT-IR spectroscopy and NMR techniques. The iminoether ligands are in the E configuration, which is stable in solution and in the solid state, as confirmed by the (1)H NMR data. Complex trans-[PtCl(2){E-N(H)C(OMe)CH(2)-C(6)H(4)-p-F}(2)] (6a) was also characterized by an X-ray diffraction study. Complexes 1a-6a have been tested against a panel of human tumor cell lines in order to evaluate their cytotoxic activity. cis-Isomers were significant more potent than the corresponding trans-isomers against all tumor cell lines tested; moreover, complexes 1a and 5a showed IC(50) values from about 2-fold to 6-fold lower than those exhibited by cisplatin, used as reference platinum anticancer drug.

Specific subpopulations of hypothalamic leptin receptor-expressing neurons mediate the effects of early developmental leptin receptor deletion on energy balance.

PubMed

Rupp, Alan C; Allison, Margaret B; Jones, Justin C; Patterson, Christa M; Faber, Chelsea L; Bozadjieva, Nadejda; Heisler, Lora K; Seeley, Randy J; Olson, David P; Myers, Martin G

2018-06-06

To date, early developmental ablation of leptin receptor (LepRb) expression from circumscribed populations of hypothalamic neurons (e.g., arcuate nucleus (ARC) Pomc- or Agrp-expressing cells) has only minimally affected energy balance. In contrast, removal of LepRb from at least two large populations (expressing vGat or Nos1) spanning multiple hypothalamic regions produced profound obesity and metabolic dysfunction. Thus, we tested the notion that the total number of leptin-responsive hypothalamic neurons (rather than specific subsets of cells with a particular molecular or anatomical signature) subjected to early LepRb deletion might determine energy balance. We generated new mouse lines deleted for LepRb in ARC Ghrh Cre neurons or in Htr2c Cre neurons (representing roughly half of all hypothalamic LepRb neurons, distributed across many nuclei). We compared the phenotypes of these mice to previously-reported models lacking LepRb in Pomc, Agrp, vGat or Nos1 cells. The early developmental deletion of LepRb from vGat or Nos1 neurons produced dramatic obesity, but deletion of LepRb from Pomc, Agrp, Ghrh, or Htr2c neurons minimally altered energy balance. Although early developmental deletion of LepRb from known populations of ARC neurons fails to substantially alter body weight, the minimal phenotype of mice lacking LepRb in Htr2c cells suggests that the phenotype that results from early developmental LepRb deficiency depends not simply upon the total number of leptin-responsive hypothalamic LepRb cells. Rather, specific populations of LepRb neurons must play particularly important roles in body energy homeostasis; these as yet unidentified LepRb cells likely reside in the DMH. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Light-Induced Conversion of Chemical Permeability to Enhance Electron and Molecular Transfer in Nanoscale Assemblies

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

Balgley, Renata; de Ruiter, Graham; Evmenenko, Guennadi

In this paper, we demonstrate how photochemically enhancing the permeability of metal–organic assemblies results in a significant enhancement of the electrochemical activity of metal complexes located within the assembly. The molecular assemblies consist of different layers of redox-active metal complexes ([M(mbpy-py)3][PF6]2; M = Ru or Os) that are separated by redox-inactive spacers consisting of 1,4-bis[2-(4-pyridyl)ethenyl]benzene (BPEB) and PdCl2 of variable thicknesses (0–13.4 nm). UV-irradiation (λ = 254 nm) of our assemblies induces a photochemical reaction in the redox-inactive spacer increasing the permeability of the assembly. The observed increase was evident by trapping organic (nBu4NBF4) and inorganic (NiCl2) salts inside themore » assemblies, and by evaluating the electrochemical response of quinones absorbed inside the molecular assemblies before and after UV irradiation. The increase in permeability is reflected by higher currents and a change in the directionality of electron transfer, i.e., from mono- to bidirectional, between the redox-active metal complexes and the electrode surface. The supramolecular structure of the assemblies dominates the overall electron transfer properties and overrules possible electron transfer mediated by the extensive π-conjugation of its individual organic components.« less

Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation

PubMed Central

Zhang, Yi; Ng, Huck-Hui; Erdjument-Bromage, Hediye; Tempst, Paul; Bird, Adrian; Reinberg, Danny

1999-01-01

ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation. PMID:10444591

The G Protein-Coupled Estrogen Receptor-1, GPER-1, Promotes Fibrillogenesis via a Shc-Dependent Pathway Resulting in Anchorage-Independent Growth

PubMed Central

Magruder, Hilary T.; Quinn, Jeffrey A.; Schwartzbauer, Jean E.; Reichner, Jonathan; Huang, Allan

2016-01-01

The G protein-coupled estrogen receptor-1, GPER-1, coordinates fibronectin (FN) matrix assembly and release of heparan-bound epidermal growth factor (HB-EGF). This mechanism of action results in the recruitment of FN-engaged integrin α5β1 to fibrillar adhesions and the formation of integrin α5β1-Shc adaptor protein complexes. Here, we show that GPER-1 stimulation of murine 4 T1 or human SKBR3 breast cancer cells with 17β-estradiol (E2β) promotes the formation of focal adhesions and actin stress fibers and results in increased cellular adhesion and haptotaxis on FN, but not collagen. These actions are also induced by the xenoestrogen, bisphenol A, and the estrogen receptor (ER) antagonist, ICI 182, 780, but not the inactive stereoisomer, 17α-estradiol (E2α). In addition, we show that GPER-1 stimulation of breast cancer cells allows for FN-dependent, anchorage-independent growth and FN fibril formation in “hanging drop” assays, indicating that these GPER-1-mediated actions occur independently of adhesion to solid substrata. Stable expression of Shc mutant Y317F lacking its primary tyrosyl phosphorylation site disrupts E2β-induced focal adhesion and actin stress fiber formation and abolishes E2β-enhanced haptotaxis on FN and anchorage-dependent growth. Collectively, these data demonstrate that E2β action via GPER-1 enhances cellular adhesivity and FN matrix assembly and allows for anchorage-independent growth, cellular events that may allow for cellular survival, and tumor progression. PMID:25096985

Materials Data on Rb2Be3Cd2F12 (SG:198) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Computer-Based Methods for Thermodynamic Analysis of Materials Processing.

DTIC Science & Technology

1983-11-30

metallic alloys (12,13), silicides (14),and oxynitride * . systems (15). - . 2. Thermochemical System Employed to Characterize Binary Ill-V Phase Diagrams The...reference to Figure I shows that the stable form of RbF is the sodium chloride S form. Table I shows that OGH -oS -RFRFLS-RFRFLM-12866-.381T J/g.at. (5...KF, BF=(I/3)8aF LF-(I/4)LaF3V PF-(113)PbF 2 S- Sodium Chloride Structures Stable form of NF, KE, RE and (;F L-Liquid, M-Stable form of ZF, KeStable form

Growth and Structure of Strontium Doped LaGaO3

DTIC Science & Technology

2001-01-01

Sandstrom, E.A. Giess, W.J. Gallagher, A. Segmifler, E.I. Cooper, M.F. Chisholm, A. Gupta, S. Shinole, R.B. Laibowitz," Lanthanum gallate substrates...that a structural phase transition occurs at -150 °C 5. The phase transition is the most serious drawback of many lanthanide gallates and aluminates5 for...and C.D. Brandle, "Thermal analysis of rare earth gallates and aluminates", J Mater. Res. 5, p. 183, 1990. 6. S. Miyazawa," Surface roughening

Materials by Design - Computational Alloy Design for Corrosion

DTIC Science & Technology

2011-02-01

Es = + 0.33 eV Cs Rb K · ~·Ba Sr ::~ \\ H ~ YCd ./ G B FS A~ Zn " Be• ’f_ Ni?.Au SeA. ’\\ . At-v Rh Ru • Zr Ja Mo Tc _,. • • • pt • lr Nb w...Windows Air Conditioning Autoflight Electrical Power Navigation Engine Exhaust Stabilizer Doors Fuel system Nacelles/Pylons Power Plant Equip...p. 14 ASETSDefense 2011: Sustainable Surface Engineering for Aerospace and Defense Workshop Quantum Mechanics Insights into SCC resistance 3.5 -E 0

(Ag{sub 2}TeS{sub 3}){sub 2} {small_bullet} A{sub 2}S{sub 6} (A = Rb, Cs) : layers of silver thiotellurite intergrown with alkali-metal polysulfides.

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

Nguyen, S. L.; Jang, J. I.; Ketterson, J. B.

2010-09-22

The layered compounds RbAg{sub 2}TeS{sub 6} and CsAg{sub 2}TeS{sub 6} crystallize in the noncentrosymmetric space group P6{sub 3}cm, with a = 19.15 {angstrom}, c = 14.64 {angstrom}, and V = 4648 {angstrom}{sup 3} and a = 19.41 {angstrom}, c = 14.84 {angstrom}, and V = 4839 {angstrom}{sup 3}, respectively. The structures are composed of neutral [Ag{sub 2}TeS{sub 3}] layers alternating with charge-balanced salt layers containing polysulfide chains of [S{sub 6}]{sup 2-} and alkali-metal ions. RbAg{sub 2}TeS{sub 6} and CsAg{sub 2}TeS{sub 6} are air- and water-stable, wide-band-gap semiconductors (E{sub g} {approx} 2.0 eV) exhibiting nonlinear-optical second-harmonic generation.

Microbial transformation of ginsenoside Rb1 to compound K by Lactobacillus paralimentarius.

PubMed

Quan, Lin-Hu; Kim, Yeon-Ju; Li, Guan Hao; Choi, Kwang-Tea; Yang, Deok-Chun

2013-06-01

In this study, the major ginsenoside Rb1 was transformed into the more pharmacologically active minor compound K by food grade Lactobacillus paralimentarius LH4, which was isolated from kimchi, a traditional Korean fermented food. The enzymatic reaction was analyzed by TLC, HPLC, and NMR. Using the cell-free enzyme of Lactobacillus paralimentarius LH4 at optimal conditions for 30 °C at pH 6.0, 1.0 mg ml(-1) ginsenoside Rb1 was transformed into 0.52 mg ml(-1) compound K within 72 h, with a corresponding molar conversion yield of 88 %. The cell-free enzyme hydrolyzed the two glucose moieties attached to the C-3 position and the outer glucose moiety attached to the C-20 position of the ginsenoside Rb1. The cell-free enzyme hydrolyzed the ginsenoside Rb1 along the following pathway: ginsenoside Rb1 → gypenoside XVII and ginsenoside Rd → ginsenoside F2 → compound K. Our results indicate that Lactobacillus paralimentarius LH4 has the potential to be applied for the preparation of compound K in the food industry.

Three-color FRET expands the ability to quantify the interactions of several proteins involved in actin filament nucleation

NASA Astrophysics Data System (ADS)

Wallrabe, Horst; Sun, Yuansheng; Fang, Xiaolan; Periasamy, Ammasi; Bloom, George

2012-03-01

With traditional 2-color Förster Resonance Energy Transfer (FRET) microscopy, valuable quantitative analyses can be conducted. Correlations of donor (D), acceptor (A) and their ratios (D:A) with energy transfer efficiency (E%) or distance (r) allows measurement of changes between control and experimental samples; also, clustered vs. random assembly of cellular components can be differentiated. Essentially, only the above three parameters D, A and D:A vs. E% are the basis for these deductions. 3-color FRET uses the same basic parameters, but exponentially expands the opportunities to quantify interrelationships among 3 cellular components. We investigated a number of questions based on the results of a triple combination (F1-F2-F3) of TFPNWASP/ Venus-IQGAP1/mCherry-Actin - all involved in the nucleation of actin - to apply the extensive analysis assay possible with 3-color FRET. How do changing N-WASP or IQGAP1 fluorescence levels affect actin fluorescence? What is the effect on E% of NWASP-actin by IQGAP1 or E% of IQGAP1-actin by N-WASP? These and other questions are explored in the context of all proteins of interest being in FRET distance vs. any two in the absence of the third. 4 cases are compared based on bleed-through corrected FRET: (1) all 3 interact, (2) only F1- F3 and F2-F3 [not F1-F2], (3) only F1-F2 and F2-F3 interact [not F1-F3], (4) only F1-F2 and F1-F3 interact [not F2-F3]. Other than describing the methodology in detail, several biologically relevant results are presented showing how E% (i.e. distance), fluorescence levels and ratios are affected in each of the cases. These correlations can only be observed in a 3-fluorophore combination. 3-color FRET will greatly expand the investigative range of quantitative analysis for the life-science researcher.

The mineralogy and geochemistry of quartz-tourmaline schlieren in the granites of the Primorsky Complex, Western Baikal Region

NASA Astrophysics Data System (ADS)

Savel'eva, V. B.; Bazarova, E. P.; Kanakin, S. V.

2014-12-01

Quartz-tourmaline schlieren have been found within rapakivi-like granites of the Early Proterozoic Primorsky Complex in the Western Baikal Region. These rocks are biotite leucogranites with normal alkalinity (A/CNK = 1.00-1.04); a high iron mole fraction (92-95%); a K2O/Na2O value of about 2.0; relatively high F, Li, Rb, Cs, Sn, Pb, Th, and U contents; and low Ba, Sr, Eu, Zn, Sc, and V contents. The schlieren composed of quartz and tourmaline with relics of feldspar also contain fluorite, rare muscovite, chlorite, and accessory rutile, ilmenite, zircon, monazite, xenotime, and bastnäsite. B2O3 and F contents in the schlieren are 2.29-2.63 and 0.30-0.47 wt %, respectively. Fe2O3 (4.8-5.4 wt %), F, and H2O contents are higher in these schlieren than in the host granite, while SiO2, CaO, Na2O, K2O, and P2O5 contents are lower than in host rocks. K2O/Na2O values decrease in the schlieren down to 0.4. Enrichment of the schlieren in Fe and other ore elements (Zn, Co, Cu, Sn, etc.), together with B, F, H2O, and Na, suggests that they crystallized from fluid-saturated melt segregated from aluminosilicate melt in the apical part of a shallow-seated intrusion. The formation of tourmaline may be related to the interaction of the fluid with feldspars in the crystallizing granites; it was accompanied by a separation of fluid F-CO2. Quartz precipitated at the next stage, due to the acidic character of the aqueous fluid. In general, the relationships of minerals in the schlieren indicate distinct fractionation of LREE, HREE, and Y in the fluid-saturated melt.

Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

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

Hong, Wei, E-mail: hongwei@tijmu.edu.cn; College of Basic Medicine, Tianjin Medical University, 300070 Tianjin; Li, Jinru

Highlights: Black-Right-Pointing-Pointer Corepressor Alien interacts with histone methyltransferase ESET in vivo. Black-Right-Pointing-Pointer Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TR{beta}1. Black-Right-Pointing-Pointer ESET-mediated H3K9 methylation is required for liganded TR{beta}1-repressed transcription. Black-Right-Pointing-Pointer ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by whichmore » Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TR{beta}1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TR{beta}1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TR{beta}1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TR{beta}1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.« less

Compact mode-locked diode laser system for high precision frequency comparisons in microgravity

NASA Astrophysics Data System (ADS)

Christopher, H.; Kovalchuk, E. V.; Wicht, A.; Erbert, G.; Tränkle, G.; Peters, A.

2017-11-01

Nowadays cold atom-based quantum sensors such as atom interferometers start leaving optical labs to put e.g. fundamental physics under test in space. One of such intriguing applications is the test of the Weak Equivalence Principle, the Universality of Free Fall (UFF), using different quantum objects such as rubidium (Rb) and potassium (K) ultra-cold quantum gases. The corresponding atom interferometers are implemented with light pulses from narrow linewidth lasers emitting near 767 nm (K) and 780 nm (Rb). To determine any relative acceleration of the K and Rb quantum ensembles during free fall, the frequency difference between the K and Rb lasers has to be measured very accurately by means of an optical frequency comb. Micro-gravity applications not only require good electro-optical characteristics but are also stringent in their demand for compactness, robustness and efficiency. For frequency comparison experiments the rather complex fiber laser-based frequency comb system may be replaced by one semiconductor laser chip and some passive components. Here we present an important step towards this direction, i.e. we report on the development of a compact mode-locked diode laser system designed to generate a highly stable frequency comb in the wavelength range of 780 nm.

In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic

PubMed Central

Huang, Hsiao-Yun

2015-01-01

Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1–RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. PMID:25838545

Molecular single-bond covalent radii for elements 1-118.

PubMed

Pyykkö, Pekka; Atsumi, Michiko

2009-01-01

A self-consistent system of additive covalent radii, R(AB)=r(A) + r(B), is set up for the entire periodic table, Groups 1-18, Z=1-118. The primary bond lengths, R, are taken from experimental or theoretical data corresponding to chosen group valencies. All r(E) values are obtained from the same fit. Both E-E, E-H, and E-CH(3) data are incorporated for most elements, E. Many E-E' data inside the same group are included. For the late main groups, the system is close to that of Pauling. For other elements it is close to the methyl-based one of Suresh and Koga [J. Phys. Chem. A 2001, 105, 5940] and its predecessors. For the diatomic alkalis MM' and halides XX', separate fits give a very high accuracy. These primary data are then absorbed with the rest. The most notable exclusion are the transition-metal halides and chalcogenides which are regarded as partial multiple bonds. Other anomalies include H(2) and F(2). The standard deviation for the 410 included data points is 2.8 pm.

The Flagellar Hook Protein, FlgE, of Salmonella enterica Serovar Typhimurium Is Posttranscriptionally Regulated in Response to the Stage of Flagellar Assembly

PubMed Central

Bonifield, Heather R.; Yamaguchi, Shigeru; Hughes, Kelly T.

2000-01-01

We investigated the posttranscriptional regulation of flgE, a class 2 gene that encodes the hook subunit protein of the flagella. RNase protection assays demonstrated that the flgE gene was transcribed at comparable levels in numerous strains defective in known steps of flagellar assembly. However, Western analyses of these strains demonstrated substantial differences in FlgE protein levels. Although wild-type FlgE levels were observed in strains with deletions of genes encoding components of the switch complex and the flagellum-specific secretion apparatus, no protein was detected in a strain with deletions of the rod, ring, and hook-associated proteins. To determine whether FlgE levels were affected by the stage of hook–basal-body assembly, Western analysis was performed on strains with mutations at individual loci encompassed by the deletion. FlgE protein was undetectable in rod mutants, intermediate in ring mutants, and wild type in hook-associated protein mutants. The lack of negative regulation in switch complex and flagellum-specific secretion apparatus deletion mutants blocked for flagellar construction prior to rod assembly suggests that these structures play a role in the negative regulation of FlgE. Quantitative Western analyses of numerous flagellar mutants indicate that FlgE levels reflect the stage at which flagellar assembly is blocked. These data provide evidence for negative posttranscriptional regulation of FlgE in response to the stage of flagellar assembly. PMID:10869084

Tunable multicolor and enhanced red emission of monodisperse CaF2:Yb3+/Ho3+ microspheres via Mn2+ doping

NASA Astrophysics Data System (ADS)

Wang, Rui; Yuan, Maohui; Zhang, Chaofan; Wang, Hongyan; Xu, Xiaojun

2018-05-01

Transition metal ions (e.g. Mn2+) and lanthanide co-doped upconversion (UC) materials have attracted wide attention in recent years due to their promising application in multicolor display. Here, we report the hydrothermal synthesis and characterization of Mn2+ doped monodisperse CaF2:Yb3+/Ho3+ microspheres. The results of X-ray diffraction (XRD) revealed that Mn2+ doping does not change the cubic phase of CaF2 material but will lead to diffraction peaks shifting slightly towards higher angle due to the substitution of larger Ca2+ by the relatively smaller Mn2+. Under the excitation of 980 nm continuous wave (CW) laser, these microspheres exhibit green-yellow-red tuning colors and remarkable enhancement of both red to green ratio (R/G) and red to blue ratio (R/B) when increasing Mn2+ concentration from 0 to 30 mol%. The energy migration process between Ho3+ and Mn2+ was proposed and supported by time-decay and power dependence measurements of Ho3+ UC emission. These upconversion materials may have potential applications in optical devices, color display, nanoscale lasers and biomedical imaging.

Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly

DOE PAGES

Brown, Nicholas G.; Watson, Edmond R.; Weissmann, Florian; ...

2014-10-09

Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here in this paper we show that human APC’s RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms.more » During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation.« less

Impact of a systolic parameter, defined as the ratio of right brachial pre-ejection period to ejection time, on the relationship between brachial-ankle pulse wave velocity and left ventricular diastolic function.

PubMed

Hsu, Po-Chao; Lin, Tsung-Hsien; Lee, Chee-Siong; Chu, Chun-Yuan; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2011-04-01

Arterial stiffness is correlated with left ventricular (LV) diastolic function as well as susceptibility to LV systolic function. Therefore, if LV systolic function is not known, the relationship between arterial stiffness and LV diastolic function is difficult to determine. A total of 260 patients were included in the study. The brachial-ankle pulse wave velocity (baPWV) and the ratio of right brachial pre-ejection period to ejection time (rbPEP/rbET) were measured using an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3 and 4 were patients with rbPEP/rbET and baPWV below the median, rbPEP/rbET above but baPWV below the median, rbPET/rbET below but baPWV above the median, and rbPET/rbET and baPWV above the median, respectively. The LV ejection fractions in groups 1 and 3 were higher than those in groups 2 and 4 (P<0.001 for all). Patients in group 1 had a lower left atrial volume index (LAVI) and higher early diastolic mitral annular velocity (Ea) than patients in the other groups (P≤0.002). Patients in group 2 had a LAVI and ratio of transmitral E wave velocity to Ea that were comparable to those in groups 3 and 4. In conclusion, rbPEP/rbET had an impact on the relationship between baPWV and LV diastolic function. In patients with high rbPEP/rbET but low baPWV, low baPWV may not indicate good LV diastolic function but implies that cardiac dysfunction may precede vascular dysfunction in such patients. When interpreting the relationship between baPWV and LV diastolic function, the rbPEP/rbET value obtained from the same examination should be considered.

Age and petrogenesis of the Diana Complex, Adirondack Mountains, New York

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

Grant, N.; Yang, Yingping; Cliff, R.

1992-01-01

U-Pb zircon data show that the Diana Complex was emplaced 1152[plus minus]12 Ma ago along the Carthage-Colton Mylonite Zone (CCMZ), that marks the boundary between the Adirondack Highlands and the Lowlands. The tectonic setting of the Complex is uncertain because granitoid plutons of the same age were emplaced under syntectonic conditions in the Lowlands, while in the Highlands the same plutons have been viewed as anorogenic. Deformation focused on the CCMZ is reflected in whole-rock Rb-Sr isochron age of 1038[plus minus]97 Ma for the Complex. This resetting is typical of granitoid plutons within a 10 km-wide zone across the CCMZ,more » but is absent outside this zone elsewhere in the Lowlands. Although the chemical continuity of the Complex with Adirondack mafic rocks of the same presumed age demonstrates that crystal fractionation from a basic parent was a likely origin for the Complex, it is probable the magmas were modified by crustal assimilation. For example, the initial [sup 87]Sr/[sup 86]Sr[sub 1152] values for the Complex (0.7042[plus minus]3) are higher than the same ratios for Adirondack mafic rocks (0.7033[plus minus]6), and one zircon fraction lies to the right of the discordia defined by the other four analyzed fractions. The nature and age of the assimilant may be constrained by a metasedimentary xenolith with a whole-rock Rb-Sr isochron age of 1318[plus minus]15 Ma. Changes in TiO[sub 2] and P[sub 2]O[sub 5] abundances and La/Yb values indicate that the crystallization of both accessory (e.g., Fe-Ti oxides, apatite and zircon) and silicate phases were important in the fractionation of the Diana Complex syenites.« less

Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.

PubMed

Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

2008-11-28

FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression.

Spin Polarization of Rb and Cs n p P2 3/2 (n =5 , 6) Atoms by Circularly Polarized Photoexcitation of a Transient Diatomic Molecule

NASA Astrophysics Data System (ADS)

Mironov, A. E.; Hewitt, J. D.; Eden, J. G.

2017-03-01

We report the selective population of Rb or Cs n p P2 3/2 (n =5 , 6; F =4 , 5) hyperfine states by the photodissociation of a transient, alkali-rare gas diatomic molecule. Circularly polarized (σ-), amplified spontaneous emission (ASE) on the D2 line of Rb or Cs (780.0 and 852.1 nm, respectively) is generated when Rb-Xe or Cs-Xe ground state collision pairs are photoexcited by a σ+-polarized optical field having a wavelength within the D2 blue satellite continuum, associated with the B Σ2 1/2 +←X Σ2 1/2 + (free←free ) transition of the diatomic molecule. The degree of spin polarization of Cs (6 p P3/2 2 ), specifically, is found to be dependent on the interatomic distance (R ) at which the excited complex is born, a result attributed to the structure of the B Σ2 1/2 + state. For Cs-Xe atomic pairs, tuning the wavelength of the optical field from 843 to 848 nm varies the degree of circular polarization of the ASE from 63% to almost unity because of the perturbation, in the 5 ≤R ≤6 Å interval, of the Σ2 1/2 + potential by a d σ molecular orbital associated with a higher Λ 2 electronic state. Monitoring only the Cs 6 p P3/2 2 spin polarization reveals a previously unobserved interaction of CsXe (B Σ2 1/2 + ) with the lowest vibrational levels of a Λ 2 state derived from Cs (5 d )+Xe . By inserting a molecular intermediate into the alkali atom excitation mechanism, these experiments realize electronic spin polarization through populating no more than two n p P2 3/2 hyperfine states, and demonstrate a sensitive spectroscopic probe of R -dependent state-state interactions and their impact on interatomic potentials.

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

PubMed Central

Fu, Junjiang; Qin, Li; He, Tao; Qin, Jun; Hong, Jun; Wong, Jiemin; Liao, Lan; Xu, Jianming

2011-01-01

The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis. PMID:20714342

The geochemical nature of the Archean Ancient Gneiss Complex and Granodiorite Suite, Swaziland: a preliminary study

USGS Publications Warehouse

Hunter, D.R.; Barker, F.; Millard, H.T.

1978-01-01

The Ancient Gneiss Complex (AGC) of Swaziland, an Archean gray gneiss complex, lies southeast and south of the Barberton greenstone belt and includes the most structurally complex and highly metamorphosed portions of the eastern Kaapvaal craton. The AGC is not precisely dated but apparently is older than 3.4 Ga. The AGC consists of three major units: (a) a bimodal suite of closely interlayered siliceous, low-K gneisses and metabasalt; (b) homogeneous tonalite gneiss; and (c) interlayered siliceous microcline gneiss, metabasalt, and minor metasedimentary rocks - termed the metamorphite suite. A geologically younger gabbro-diorite-tonalite-trondhjemite suite, the Granodiorite Suite, is spatially associated with the AGC and intrusive into it. The bimodal suite consists largely of two types of low-K siliceous gneiss: one has SiO2 14%, low Rb/Sr ratios, and depleted heavy rare earth elements (REE's); the other has SiO2 > 75%, Al2O3 < 13%, high Rb/Sr ratios, and relatively abundant REE's except for negative Eu anomalies. The interlayered metabasalt ranges from komatiitic to tholeiitic compositions. Lenses of quartz monzonitic gneiss of K2O/Na2O close to 1 form a minor part of the bimodal suite. Tonalitic to trondhjemitic migmatite locally is abundant and has major-element abundances similar to those of non-migmatitic varieties. The siliceous gneisses of the metamorphic suite show low Al2O, K2O/Na2O ratios of about 1, high Rb/Sr ratios, moderate REE abundances and negative Eu anomalies. K/Rb ratios of siliceous gneisses of the bimodal suite are very low (???130); of the tonalitic gneiss, low (???225); of the siliceous gneiss of the metamorphite suite, moderate (???300); and of the Granodiorite Suite, high (???400). Rocks of the AGC differ geochemically in several ways from the siliceous volcanic and hypabyssal rocks of the Upper Onverwacht Group and from the diapirs of tonalite and trondhjemite that intrude the Swaziland Group. ?? 1978.

Dynamics of Energy Transfer and Soft-Landing in Collisions of Protonated Dialanine with Perfluorinated Self-Assembled Monolayer Surfaces

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

Pratihar, Subha; Kohale, Swapnil C.; Bhakta, Dhruv G.

2014-11-21

Chemical dynamics simulations are reported which provide atomistic details of collisions of protonated dialanine, ala2-H+, with a perfluorinateted octanethiolate self-assembled monolayer (F-SAM ) surface. The simulations are performed at collisions energy Ei of 5.0, 13.5, 22.5, 30.00, and 70 eV, and incident angles 0o 0 (normal) and grazing 45o. Excellent agreement with experiment (J. Am. Chem. Soc. 2000, 122, 9703-9714) is found for both the average fraction and distribution of the collision energy transferred to the ala2-H+ internal degrees of freedom. The dominant pathway for this energy transfer is to ala2-H+ vibration, but for Ei = 5.0 eV ~20% ofmore » the energy transfer is to ala2-H+ rotation. Energy transfer to ala2-H+ rotation decreases with increase in Ei and becomes negligible at high Ei. Three types of collisions are observed in the simulations: i.e. those for which ala2-H+ (1) directly scatters off the F-SAM surface; (2) sticks/physisorbs on//in the surface, but desorbs within the 10 ps numerical integration of the simulations; and (3) remains trapped (i.e. soft-landed) on/in the surface when the simulations are terminated. Penetration of the F-SAM by ala2-H+ is important for the latter two types of events. The trapped trajectories are expected to have relatively long residence times on the surface, since a previous molecular dynamics simulation (J. Phys. Chem. B 2014, 118, 5577-5588) shows that thermally accommodated ala2-H+ ions have an binding energy with the F-SAM surface of at least ~15 kcal/mol.« less

First principles study of structural, electronic and optical properties of polymorphic forms of Rb 2Te

NASA Astrophysics Data System (ADS)

Alay-e-Abbas, S. M.; Shaukat, A.

2011-05-01

First-principles density functional theory calculations have been performed for structural, electronic and optical properties of three polymorphic forms of rubidium telluride. Our calculations show that the sequence of pressure induced phase transitions for Rb 2Te is Fm3¯m → Pnma → P6 3/mmc which is governed by the coordination numbers of the anions. From our calculated low transition pressure value for the Fm3¯m phase to the Pnma phase transition of Rb 2Te, the experimentally observed meta-stability of Fm3¯m phase at ambient conditions seems reasonable. The electronic band structure has been calculated for all the three phases and the change in the energy band gap is discussed for the transitioning phases. The energy band gaps obtained for the three phases of Rb 2Te decrease on going from the meta-stable phase to the high-pressure phases. Total and partial density of states for the polymorphs of Rb 2Te has been computed to elucidate the contribution of various atomic states on the electronic band structure. Furthermore, optical properties for all the polymorphic forms have been presented in form of the complex dielectric function.

Structural Determination of Biomolecules in Microfluidic Systems

NASA Astrophysics Data System (ADS)

Butler, John C.; Menard, Etienne; Rogers, John A.; Wong, Gerard C. L.

2004-03-01

Supramolecular biological complexes are often too large to be crystallized for structural studies. Here, we explore the use of microfluidic arrays to order a model self-assembled cytoskeletal system. Filamentous actin (F-actin) is a negatively charged protein rod and is a key structural component in the eukaryotic cytoskeleton. In this context, F-actin can self-assemble with actin binding proteins (ABP) in a highly regulated manner to dynamically form structures for a wide range of biomechanical functions. In this work, we will systematically study the action of 3 types of actin binding proteins (a-actinin, fimbrin, cofilin) on the self-assembled structures of F-actin that have been aligned in microfluidic arrays.

Adhesive F-actin Waves: A Novel Integrin-Mediated Adhesion Complex Coupled to Ventral Actin Polymerization

PubMed Central

Case, Lindsay B.; Waterman, Clare M.

2011-01-01

At the leading lamellipodium of migrating cells, protrusion of an Arp2/3-nucleated actin network is coupled to formation of integrin-based adhesions, suggesting that Arp2/3-mediated actin polymerization and integrin-dependent adhesion may be mechanistically linked. Arp2/3 also mediates actin polymerization in structures distinct from the lamellipodium, in “ventral F-actin waves” that propagate as spots and wavefronts along the ventral plasma membrane. Here we show that integrins engage the extracellular matrix downstream of ventral F-actin waves in several mammalian cell lines as well as in primary mouse embryonic fibroblasts. These “adhesive F-actin waves” require a cycle of integrin engagement and disengagement to the extracellular matrix for their formation and propagation, and exhibit morphometry and a hierarchical assembly and disassembly mechanism distinct from other integrin-containing structures. After Arp2/3-mediated actin polymerization, zyxin and VASP are co-recruited to adhesive F-actin waves, followed by paxillin and vinculin, and finally talin and integrin. Adhesive F-actin waves thus represent a previously uncharacterized integrin-based adhesion complex associated with Arp2/3-mediated actin polymerization. PMID:22069459

Analysis of a Soluble (UreD:UreF:UreG)2 Accessory Protein Complex and Its Interactions with Klebsiella aerogenes Urease by Mass Spectrometry

NASA Astrophysics Data System (ADS)

Farrugia, Mark A.; Han, Linjie; Zhong, Yueyang; Boer, Jodi L.; Ruotolo, Brandon T.; Hausinger, Robert P.

2013-09-01

Maturation of the nickel-containing urease of Klebsiella aerogenes is facilitated by the UreD, UreF, and UreG accessory proteins along with the UreE metallo-chaperone. A fusion of the maltose binding protein and UreD (MBP-UreD) was co-isolated with UreF and UreG in a soluble complex possessing a (MBP-UreD:UreF:UreG)2 quaternary structure. Within this complex a UreF:UreF interaction was identified by chemical cross-linking of the amino termini of its two UreF protomers, as shown by mass spectrometry of tryptic peptides. A pre-activation complex was formed by the interaction of (MBP-UreD:UreF:UreG)2 and urease. Mass spectrometry of intact protein species revealed a pathway for synthesis of the urease pre-activation complex in which individual hetero-trimer units of the (MBP-UreD:UreF:UreG)2 complex bind to urease. Together, these data provide important new insights into the structures of protein complexes associated with urease activation.

Repetitive Behaviours in Patients with Gilles de la Tourette Syndrome: Tics, Compulsions, or Both?

PubMed Central

Worbe, Yulia; Mallet, Luc; Golmard, Jean-Louis; Béhar, Cécile; Durif, Franck; Jalenques, Isabelle; Damier, Philippe; Derkinderen, Pascal; Pollak, Pierre; Anheim, Mathieu; Broussolle, Emannuel; Xie, Jing; Mesnage, Valérie; Mondon, Karl; Viallet, François; Jedynak, Pierre; Djebara, Mouna Ben; Schüpbach, Michael; Pelissolo, Antoine; Vidailhet, Marie; Agid, Yves; Houeto, Jean-Luc; Hartmann, Andreas

2010-01-01

Background Repetitive behaviours (RB) in patients with Gilles de la Tourette syndrome (GTS) are frequent. However, a controversy persists whether they are manifestations of obssessive-compulsive disorder (OCD) or correspond to complex tics. Methods 166 consecutive patients with GTS aged 15–68 years were recruited and submitted to extensive neurological, psychiatric and psychological evaluations. RB were evaluated by the YBOCS symptom checklist and Mini International Neuropsychiatric Interview (M.I.N.I), and classified on the basis of a semi-directive psychiatric interview as compulsions or tics. Results RB were present in 64.4% of patients with GTS (107/166) and categorised into 3 major groups: a ‘tic-like’ group (24.3%–40/166) characterised by RB such as touching, counting, ‘just right’ and symmetry searching; an ‘OCD-like’ group (20.5%–34/166) with washing and checking rituals; and a ‘mixed’ group (13.2%–22/166) with both ‘tics-like’ and ‘OCD-like’ types of RB present in the same patient. In 6.3% of patients, RB could not be classified into any of these groups and were thus considered ‘undetermined’. Conclusions The results confirm the phenomenological heterogeneity of RB in GTS patients and allows to distinguish two types: tic-like behaviours which are very likely an integral part of GTS; and OCD-like behaviours, which can be considered as a comorbid condition of GTS and were correlated with higher score of complex tics, neuroleptic and SSRIs treatment frequency and less successful socio-professional adaptation. We suggest that a meticulous semiological analysis of RB in GTS patients will help to tailor treatment and allow to better classify patients for future pathophysiologic studies. Trial Registration ClinicalTrials.gov NCT00169351 PMID:20885982

Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?

PubMed

Worbe, Yulia; Mallet, Luc; Golmard, Jean-Louis; Béhar, Cécile; Durif, Franck; Jalenques, Isabelle; Damier, Philippe; Derkinderen, Pascal; Pollak, Pierre; Anheim, Mathieu; Broussolle, Emannuel; Xie, Jing; Mesnage, Valérie; Mondon, Karl; Viallet, François; Jedynak, Pierre; Ben Djebara, Mouna; Schüpbach, Michael; Pelissolo, Antoine; Vidailhet, Marie; Agid, Yves; Houeto, Jean-Luc; Hartmann, Andreas

2010-09-24

Repetitive behaviours (RB) in patients with Gilles de la Tourette syndrome (GTS) are frequent. However, a controversy persists whether they are manifestations of obsessive-compulsive disorder (OCD) or correspond to complex tics. 166 consecutive patients with GTS aged 15-68 years were recruited and submitted to extensive neurological, psychiatric and psychological evaluations. RB were evaluated by the YBOCS symptom checklist and Mini International Neuropsychiatric Interview (M.I.N.I), and classified on the basis of a semi-directive psychiatric interview as compulsions or tics. RB were present in 64.4% of patients with GTS (107/166) and categorised into 3 major groups: a 'tic-like' group (24.3%-40/166) characterised by RB such as touching, counting, 'just right' and symmetry searching; an 'OCD-like' group (20.5%-34/166) with washing and checking rituals; and a 'mixed' group (13.2%-22/166) with both 'tics-like' and 'OCD-like' types of RB present in the same patient. In 6.3% of patients, RB could not be classified into any of these groups and were thus considered 'undetermined'. The results confirm the phenomenological heterogeneity of RB in GTS patients and allows to distinguish two types: tic-like behaviours which are very likely an integral part of GTS; and OCD-like behaviours, which can be considered as a comorbid condition of GTS and were correlated with higher score of complex tics, neuroleptic and SSRIs treatment frequency and less successful socio-professional adaptation. We suggest that a meticulous semiological analysis of RB in GTS patients will help to tailor treatment and allow to better classify patients for future pathophysiologic studies. ClinicalTrials.gov NCT00169351.

Thin film assembly of nano-sized Zn(II)-8-hydroxy-5,7-dinitroquinolate by using successive ion layer adsorption and reaction (SILAR) technique: characterization and optical-electrical-photovoltaic properties.

PubMed

Farag, A A M; Haggag, Sawsan M S; Mahmoud, Mohamed E

2012-07-01

A method is described for thin film assembly of nano-sized Zn(II)-8-hydroxy-5,7-dinitroquinolate complex, Zn[((NO(2))(2)-8HQ)(2)] by using successive ion layer adsorption and reaction (SILAR) technique. Highly homogeneous assembled nano-sized metal complex thin films with particle size distribution in the range 27-47nm was identified by using scanning electron microscopy (SEM). Zn[((NO(2))(2)-8HQ)(2)] and [(NO(2))(2)-8HQ] ligand were studied by thermal gravimetric analysis (TGA). Graphical representation of temperature dependence of the dark electrical conductivity produced two distinct linear parts for two activation energies at 0.377eV and 1.11eV. The analysis of the spectral behavior of the absorption coefficient in the intrinsic absorption region reveals a direct allowed transition with a fundamental band gap of 2.74eV. The dark current density-voltage (J-V) characteristics showed the rectification effect due to the formation of junction barrier of Zn[((NO(2))(2)-8HQ)(2)] complex film/n-Si interface. The photocurrent in the reverse direction is strongly increased by photo-illumination and the photovoltaic characteristics were also determined and evaluated. Copyright © 2012 Elsevier B.V. All rights reserved.

Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

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

Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 1,2,&3. Sheet 6 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Horizontal transmission of Marek's disease virus requires US2, the UL13 protein kinase, and gC.

PubMed

Jarosinski, Keith W; Margulis, Neil G; Kamil, Jeremy P; Spatz, Stephen J; Nair, Venugopal K; Osterrieder, Nikolaus

2007-10-01

Marek's disease virus (MDV) causes a general malaise in chickens that is mostly characterized by the development of lymphoblastoid tumors in multiple organs. The use of bacterial artificial chromosomes (BACs) for cloning and manipulation of the MDV genome has facilitated characterization of specific genes and genomic regions. The development of most MDV BACs, including pRB-1B-5, derived from a very virulent MDV strain, involved replacement of the US2 gene with mini-F vector sequences. However, when reconstituted viruses based on pRB-1B were used in pathogenicity studies, it was discovered that contact chickens housed together with experimentally infected chickens did not contract Marek's disease (MD), indicating a lack of horizontal transmission. Staining of feather follicle epithelial cells in the skins of infected chickens showed that virus was present but was unable to be released and/or infect susceptible chickens. Restoration of US2 and removal of mini-F sequences within viral RB-1B did not alter this characteristic, although in vivo viremia levels were increased significantly. Sequence analyses of pRB-1B revealed that the UL13, UL44, and US6 genes encoding the UL13 serine/threonine protein kinase, glycoprotein C (gC), and gD, respectively, harbored frameshift mutations. These mutations were repaired individually, or in combination, using two-step Red mutagenesis. Reconstituted viruses were tested for replication, MD incidence, and their abilities to horizontally spread to contact chickens. The experiments clearly showed that US2, UL13, and gC in combination are essential for horizontal transmission of MDV and that none of the genes alone is able to restore this phenotype.

Genetic Networks Activated by Blast Injury to the Eye

DTIC Science & Technology

2018-03-01

em be r 7 C hr 4: 1 4. 42 95 77 7. 98 0. 89 C ar 12 ca rb on...12 .2 8 -0 .8 6 Tm em 16 1b tr an sm em br an e pr ot ei n 16 1B C hr 13 : 8 4. 36 19 01 10 .9 1 0. 86 Pd cd 5 pr og ra m m ed c el l d ea th 5...sy nt he ta se fa m ily m em be r 3 C hr 8: 1 25 .2 99 40 5 9. 51 -0 .8 6 Sl c1 7a 7 so lu te c ar rie r f am

Function of multiple Lis-Homology domain/WD-40 repeat-containing proteins in feed-forward transcriptional repression by silencing mediator for retinoic and thyroid receptor/nuclear receptor corepressor complexes.

PubMed

Choi, Hyo-Kyoung; Choi, Kyung-Chul; Kang, Hee-Bum; Kim, Han-Cheon; Lee, Yoo-Hyun; Haam, Seungjoo; Park, Hyoung-Gi; Yoon, Ho-Geun

2008-05-01

Lis-homology (LisH) motifs are involved in protein dimerization, and the discovery of the conserved N-terminal LisH domain in transducin beta-like protein 1 and its receptor (TBL1 and TBLR1) led us to examine the role of this domain in transcriptional repression. Here we show that multiple beta-transducin (WD-40) repeat-containing proteins interact to form oligomers in solution and that oligomerization depends on the presence of the LisH domain in each protein. Repression of transcription, as assayed using Gal4 fusion proteins, also depended on the presence of the LisH domain, suggesting that oligomerization is a prerequisite for efficient transcriptional repression. Furthermore, we show that the LisH domain is responsible for the binding to the hypoacetylated histone H4 tail and for stable chromatin targeting by the nuclear receptor corepressor complex. Mutations in conserved residues in the LisH motif of TBL1 and TBLR1 block histone binding, oligomerization, and transcriptional repression, supporting the functional importance of the LisH motif in transcriptional repression. Our results indicate that another WD-40 protein, TBL3, also preferentially binds to the N-terminal domain of TBL1 and TBLR1, and forms oligomers with other WD-40 proteins. Finally, we observed that the WD-40 proteins RbAp46 and RbAp48 of the sin3A corepressor complex failed to dimerize. We also found the specific interaction UbcH/E2 with TBL1, but not RbAp46/48. Altogether, our results thus indicate that the presence of multiple LisH/WD-40 repeat containing proteins is exclusive to nuclear receptor corepressor/ silencing mediator for retinoic and thyroid receptor complexes compared with other class 1 histone deacetylase-containing corepessor complexes.

Mass spectrometric characterization of membrane integral low molecular weight proteins from photosystem II in barley etioplasts.

PubMed

Plöscher, Matthias; Granvogl, Bernhard; Zoryan, Mikael; Reisinger, Veronika; Eichacker, Lutz Andreas

2009-02-01

In Photosystem II (PSII), a high number of plastid encoded and membrane integral low molecular weight proteins smaller than 10 kDa, the proteins PsbE, F, H, I, J, K, L, M, N, Tc, Z and the nuclear encoded PsbW, X, Y1, Y2 proteins have been described. Here we show that all low molecular weight proteins of PSII already accumulate in the etioplast membrane fraction in darkness, whereas PsaI and PsaJ of photosystem I (PSI) represent the only low molecular weight proteins that do not accumulate in darkness. We found by BN-PAGE separation of membrane protein complexes and selective MS that the accumulation of one-helix proteins from PSII is light independent and occurs in etioplasts. In contrast, in chloroplasts isolated from light-grown plants, low molecular weight proteins were found to specifically accumulate in PSI and II complexes. Our results demonstrate how plants grown in darkness prepare for the induction of chlorophyll dependent photosystem assembly upon light perception. We anticipate that our investigation will provide the essential means for the analysis of protein assembly in any membrane utilizing low molecular weight protein subunits.

Highly efficient red-emitting BaMgBO3F:Eu3+,R+ (R: Li, Na, K, Rb) phosphor for near-UV excitation synthesized via glass precursor solid-state reaction

NASA Astrophysics Data System (ADS)

Shinozaki, Kenji; Akai, Tomoko

2017-09-01

Eu3+-doped fluoroborate crystals of BaMgBO3F were synthesized by a solid-state reaction using a glassy precursor material, and their photoluminescence (PL) was investigated. To compensate for the incorporation of Eu3+ into Ba2+ sites, samples codoped with alkali ions (Li+, Na+, K+, Rb+) were also prepared. The Eu3+-doped sample showed red PL with a quantum yield (QY) of 65% caused by near-UV excitation (λ = 393 nm), and PL intensity and QY increased with the codoping of Eu3+ and alkali ions. It was found that the Eu3+,Li+-codoped sample showed the highest PL intensity and a QY of 83%.

A Manual for the Prediction of Blast and Fragment Loadings on Structures

DTIC Science & Technology

1981-08-15

ives , assembles exp los ives components i n t o assemblies , does more i n s p e c t i o n s , and f i n a l l y packages and s h i p s t h...4100, Los Alamos S c i e n t i f i c Laboratory, Un ive r s i ty of C a l i f o r n i a , Los Alamos , New Mexico, February 1970. 4.29 " I n t e...Massachusetts I n s t i t u t e of Technology, 1976. B- 7 Bdzi l , J. B. and Davis, W. C., "Time-Dependent Detonat ions," J.A-5926-MS, Los Alamos S c i

A turn-on coordination nanoparticle-based fluorescent probe for phosphate in human serum

NASA Astrophysics Data System (ADS)

Lin, Na; Li, Jian; Lu, Zhixiang; Bian, Longchun; Zheng, Liyan; Cao, Qiue; Ding, Zhongtao

2015-03-01

Coordination nanoparticles (CNPs) are becoming attractive platforms for chemical sensing applications because their unique adjustable properties offer the opportunity to design various luminescent nanoprobes. Here, we present a CNP-based fluorescent nanoprobe, in which fluorophores (rhodamine B, RB) and quenchers (methylene blue, MB) were spontaneously enfolded by coordination networks self-assembled of adenine, biphenyl-4,4'-dicarboxylic acid (BDA) and zinc ions. The aggregation of fluorophores and quenchers in CNPs resulted in a quenched state fluorescence of RB. RB and MB could be released from CNPs in the presence of phosphate, which triggered the fluorescence of RB. On the basis of recognition-driven disassembly principle, a novel turn-on fluorescent probe for the determination of PO43- with a wide response range (0.5-50 μM) has been successfully applied in the detection of phosphate in human serum samples. This work not only develops a probe for phosphate but also provides a general strategy for designing nanoprobes or nanocarriers towards various targets by altering organic linkers or metal ions.Coordination nanoparticles (CNPs) are becoming attractive platforms for chemical sensing applications because their unique adjustable properties offer the opportunity to design various luminescent nanoprobes. Here, we present a CNP-based fluorescent nanoprobe, in which fluorophores (rhodamine B, RB) and quenchers (methylene blue, MB) were spontaneously enfolded by coordination networks self-assembled of adenine, biphenyl-4,4'-dicarboxylic acid (BDA) and zinc ions. The aggregation of fluorophores and quenchers in CNPs resulted in a quenched state fluorescence of RB. RB and MB could be released from CNPs in the presence of phosphate, which triggered the fluorescence of RB. On the basis of recognition-driven disassembly principle, a novel turn-on fluorescent probe for the determination of PO43- with a wide response range (0.5-50 μM) has been successfully applied in the detection of phosphate in human serum samples. This work not only develops a probe for phosphate but also provides a general strategy for designing nanoprobes or nanocarriers towards various targets by altering organic linkers or metal ions. Electronic supplementary information (ESI) available: Supplementary figures. See DOI: 10.1039/c5nr00515a

An Assembly Funnel Makes Biomolecular Complex Assembly Efficient

PubMed Central

Zenk, John; Schulman, Rebecca

2014-01-01

Like protein folding and crystallization, the self-assembly of complexes is a fundamental form of biomolecular organization. While the number of methods for creating synthetic complexes is growing rapidly, most require empirical tuning of assembly conditions and/or produce low yields. We use coarse-grained simulations of the assembly kinetics of complexes to identify generic limitations on yields that arise because of the many simultaneous interactions allowed between the components and intermediates of a complex. Efficient assembly occurs when nucleation is fast and growth pathways are few, i.e. when there is an assembly “funnel”. For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific. However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions. The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis. PMID:25360818

Forming Rb(+) snowballs in the center of He nanodroplets.

PubMed

Theisen, Moritz; Lackner, Florian; Ernst, Wolfgang E

2010-12-07

Helium nanodroplets doped with rubidium atoms are ionized by applying a resonant two-step ionization scheme. Subsequent immersion of rubidium ions is observed in time-of-flight mass spectra. While alkali-metal atoms usually desorb from the surface of a helium nanodroplet upon electronic excitation, rubidium in its excited 5(2)P(1/2) state provides an exception from this rule (Auböck et al., Phys. Rev. Lett., 2008, 101, 35301). In our new experiment, Rb atoms are selectively excited either to the 5(2)P(1/2) or to the 5(2)P(3/2) state. From there they are ionized by a laser pulse. Time-of-flight mass spectra of the ionization products reveal that the intermediate population of the 5(2)P(1/2) state does not only make the ionization process Rb-monomer selective, but also gives rise to a very high yield of Rb(+)-He(N) complexes. Ions with masses of up to several thousand amu have been monitored, which can be explained by an immersion of the single Rb ion into the He nanodroplet, where most likely a snowball is formed in the center of the He nanodroplet. As the most stable position for an ion is in the center of a He nanodroplet, our results agree well with theory.

Fluid fractionation of tungsten during granite-pegmatite differentiation and the metal source of peribatholitic W quartz veins: Evidence from the Karagwe-Ankole Belt (Rwanda)

NASA Astrophysics Data System (ADS)

Hulsbosch, Niels; Boiron, Marie-Christine; Dewaele, Stijn; Muchez, Philippe

2016-02-01

The identification of a magmatic source for granite-associated rare metal (W, Nb, Ta and Sn) mineralisation in metasediment-hosted quartz veins is often obscured by intense fluid-rock interactions which metamorphically overprinted most source signatures in the vein system. In order to address this recurrent metal sourcing problem, we have studied the metasediment-hosted tungsten-bearing quartz veins of the Nyakabingo deposit of the Karagwe-Ankole belt in Central Rwanda. The vein system (992 ± 2 Ma) is spatiotemporal related to the well-characterised B-rich, F-poor G4 leucogranite-pegmatite suite (986 ± 10 Ma to 975 ± 8 Ma) of the Gatumba-Gitarama area which culminated in Nb-Ta-Sn mineralisation. Muscovite in the Nyakabingo veins is significantly enriched in granitophile elements (Rb, Cs, W and Sn) and show alkali metal signatures equivalent to muscovite of less-differentiated pegmatite zones of the Gatumba-Gitarama area. Pegmatitic muscovite records a decrease in W content with increasing differentiation proxies (Rb and Cs), in contrast to the continuous enrichment of other high field strength elements (Nb and Ta) and Sn. This is an indication of a selective redistribution for W by fluid exsolution and fluid fractionation. Primary fluid inclusions in tourmaline of these less-differentiated pegmatites demonstrate the presence of medium to low saline, H2O-NaCl-KCl-MgCl2-complex salt (e.g. Rb, Cs) fluids which started to exsolve at the G4 granite-pegmatite transition stage. Laser ablation inductively coupled plasma mass-spectrometry shows significant tungsten enrichment in these fluid phases (∼5-500 ppm). Fractional crystallisation has been identified previously as the driving mechanism for the transition from G4 granites, less-differentiated biotite, biotite-muscovite towards muscovite pegmatites and eventually columbite-tantalite mineralised pegmatites. The general absence of tungsten mineralisation in this magmatic suite, including the most differentiated columbite-tantalite mineralised pegmatites of the Gatumba-Gitarama area, emphasises the efficiency of fluid saturation to extract crystal-melt incompatible tungsten from the differentiating melt phase. Fluid-melt-crystal partitioning calculations support the concept of a magmatic-hydrothermal fluid source for tungsten and constrain the range of permissible crystal-melt and fluid-melt partition coefficients together with realistic values for water solubility in the parental G4 granitic melt. Consequently, we propose that for highly-differentiated B-rich, F-poor granite systems fluid saturation started prior to or at the granite-pegmatite transition stage resulting in apical to peribatholitic tungsten veins systems that are paragenetically older than the final pegmatite stage.

Insights into the Functional Architecture of the Catalytic Center of a Maize β-Glucosidase Zm-p60.11

PubMed Central

Zouhar, Jan; Vévodová, Jitka; Marek, Jaromír; Damborský, Jir̆í; Su, Xiao-Dong; Brzobohatý, Br̆etislav

2001-01-01

The maize (Zea mays) β-glucosidase Zm-p60.1 has been implicated in regulation of plant development by the targeted release of free cytokinins from cytokinin-O-glucosides, their inactive storage forms. The crystal structure of the wild-type enzyme was solved at 2.05-Å resolution, allowing molecular docking analysis to be conducted. This indicated that the enzyme specificity toward substrates with aryl aglycones is determined by aglycone aromatic system stacking with W373, and interactions with edges of F193, F200, and F461 located opposite W373 in a slot-like aglycone-binding site. These aglycone-active site interactions recently were hypothesized to determine substrate specificity in inactive enzyme substrate complexes of ZM-Glu1, an allozyme of Zm-p60.1. Here, we test this hypothesis by kinetic analysis of F193I/Y/W mutants. The decreased Km of all mutants confirmed the involvement of F193 in determining enzyme affinity toward substrates with an aromatic aglycone. It was unexpected that a 30-fold decrease in kcat was found in F193I mutant compared with the wild type. Kinetic analysis and computer modeling demonstrated that the F193-aglycone-W373 interaction not only contributes to aglycone recognition as hypothesized previously but also codetermines catalytic rate by fixing the glucosidic bond in an orientation favorable for attack by the catalytic pair, E186 and E401. The catalytic pair, assigned initially by their location in the structure, was confirmed by kinetic analysis of E186D/Q and E401D/Q mutants. It was unexpected that the E401D as well as C205S and C211S mutations dramatically impaired the assembly of a catalysis-competent homodimer, suggesting novel links between the active site structure and dimer formation. PMID:11706179

Superconductivity in the Narrow Gap Semiconductor RbBi 11/3Te 6

DOE PAGES

Malliakas, Christos D.; Chung, Duck Young; Claus, Helmut; ...

2016-10-16

Superconductivity was discovered in the layered compound RbBi 11/3Te 6, featuring Bi vacancies and a narrow band gap of 0.25(2) eV at room temperature. In addition, a sharp superconducting transition at similar to 3.2 K was observed in polycrystalline ingots. The superconducting volume fraction of oriented single crystals is almost 100%, confirming bulk superconductivity. Systematic Se and Sb substitutions in RbBi 11/3-ySb ySe xTe 6-x, revealed a dependence of the superconducting transition on composition that can increase the T c up to similar to 10%. The RbBi 11/3Te 6 system is the first member of the new homologous series Rb[Bimore » 2n+11/3Te 3n+6] with infinite Bi 2Te 3-like layers. Lastly, the large degree of chemical tunability of the electronic structure of the homology via doping and/or substitution gives rise to a new family of superconductors.« less

Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

PubMed Central

Wongpalee, Somsakul Pop; Vashisht, Ajay; Sharma, Shalini; Chui, Darryl; Wohlschlegel, James A; Black, Douglas L

2016-01-01

Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest. DOI: http://dx.doi.org/10.7554/eLife.19743.001 PMID:27882870

Self-Assembly through Noncovalent Preorganization of Reactants: Explaining the Formation of a Polyfluoroxometalate.

PubMed

Schreiber, Roy E; Avram, Liat; Neumann, Ronny

2018-01-09

High-order elementary reactions in homogeneous solutions involving more than two molecules are statistically improbable and very slow to proceed. They are not generally considered in classical transition-state or collision theories. Yet, rather selective, high-yield product formation is common in self-assembly processes that require many reaction steps. On the basis of recent observations of crystallization as well as reactions in dense phases, it is shown that self-assembly can occur by preorganization of reactants in a noncovalent supramolecular assembly, whereby directing forces can lead to an apparent one-step transformation of multiple reactants. A simple and general kinetic model for multiple reactant transformation in a dense phase that can account for many-bodied transformations was developed. Furthermore, the self-assembly of polyfluoroxometalate anion [H 2 F 6 NaW 18 O 56 ] 7- from simple tungstate Na 2 WO 2 F 4 was demonstrated by using 2D 19 F- 19 F NOESY, 2D 19 F- 19 F COSY NMR spectroscopy, a new 2D 19 F{ 183 W} NMR technique, as well as ESI-MS and diffusion NMR spectroscopy, and the crucial involvement of a supramolecular assembly was found. The deterministic kinetic reaction model explains the reaction in a dense phase and supports the suggested self-assembly mechanism. Reactions in dense phases may be of general importance in understanding other self-assembly reactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

αE-catenin regulates actin dynamics independently of cadherin-mediated cell–cell adhesion

PubMed Central

Benjamin, Jacqueline M.; Kwiatkowski, Adam V.; Yang, Changsong; Korobova, Farida; Pokutta, Sabine; Svitkina, Tatyana

2010-01-01

αE-catenin binds the cell–cell adhesion complex of E-cadherin and β-catenin (β-cat) and regulates filamentous actin (F-actin) dynamics. In vitro, binding of αE-catenin to the E-cadherin–β-cat complex lowers αE-catenin affinity for F-actin, and αE-catenin alone can bind F-actin and inhibit Arp2/3 complex–mediated actin polymerization. In cells, to test whether αE-catenin regulates actin dynamics independently of the cadherin complex, the cytosolic αE-catenin pool was sequestered to mitochondria without affecting overall levels of αE-catenin or the cadherin–catenin complex. Sequestering cytosolic αE-catenin to mitochondria alters lamellipodia architecture and increases membrane dynamics and cell migration without affecting cell–cell adhesion. In contrast, sequestration of cytosolic αE-catenin to the plasma membrane reduces membrane dynamics. These results demonstrate that the cytosolic pool of αE-catenin regulates actin dynamics independently of cell–cell adhesion. PMID:20404114

Total reflection X-ray Fluorescence determination of interfering elements rubidium and uranium by profile fitting

NASA Astrophysics Data System (ADS)

Dhara, Sangita; Khooha, Ajay; Singh, Ajit Kumar; Tiwari, M. K.; Misra, N. L.

2018-06-01

Systematic studies to assess the analytical parameters obtained in the total reflection X-ray fluorescence (TXRF) determinations of interfering elements Rb and U using profile fitting are reported in the present manuscript. The X-ray lines Rb Kα and U Lα having serious spectral interference (ΔE = 218 eV), have been used as analytical lines. The intensities of these X-ray lines have been assessed using profile fitting. In order to compare the analytical results of Rb determinations in presence of U, with and without U excitation, synchrotron radiation was tuned to energy just above and below the U Labs edge. This approach shall excite both Rb Kα and U Lα simultaneously and Rb Kα selectively. Finally, the samples were also analyzed with a laboratory based TXRF spectrometer. The analytical results obtained in all these conditions were comparable. The authenticity of the results was assessed by analyzing U with respect to Rb in Rb2U(SO4)3, a standard reference material for U. The average precision obtained for TXRF determinations was below 3% (RSD, n = 3, 1σ) and the percent deviation of TXRF values from the expected values calculated on the basis of sample preparation was within 3%.

The Salmonella type III secretion system virulence effector forms a new hexameric chaperone assembly for export of effector/chaperone complexes

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

Tsai, Chi -Lin; Burkinshaw, Brianne J.; Strynadka, Natalie C. J.

Bacteria hijack eukaryotic cells by injecting virulence effectors into host cytosol with a type III secretion system (T3SS). Effectors are targeted with their cognate chaperones to hexameric T3SS ATPase at the bacterial membrane's cytosolic face. In this issue of the Journal of Bacteriology, Roblin et al. (P. Roblin, F. Dewitte, V. Villeret, E. G. Biondi, and C. Bompard, J Bacteriol 197:688–698, 2015, http://dx.doi.org/10.1128/JB.02294-14) show that the T3SS chaperone SigE of Salmonella can form hexameric rings rather than dimers when bound to its cognate effector, SopB, implying a novel multimeric association for chaperone/effector complexes with their ATPase.

The Salmonella type III secretion system virulence effector forms a new hexameric chaperone assembly for export of effector/chaperone complexes

DOE PAGES

Tsai, Chi -Lin; Burkinshaw, Brianne J.; Strynadka, Natalie C. J.; ...

2014-12-08

Bacteria hijack eukaryotic cells by injecting virulence effectors into host cytosol with a type III secretion system (T3SS). Effectors are targeted with their cognate chaperones to hexameric T3SS ATPase at the bacterial membrane's cytosolic face. In this issue of the Journal of Bacteriology, Roblin et al. (P. Roblin, F. Dewitte, V. Villeret, E. G. Biondi, and C. Bompard, J Bacteriol 197:688–698, 2015, http://dx.doi.org/10.1128/JB.02294-14) show that the T3SS chaperone SigE of Salmonella can form hexameric rings rather than dimers when bound to its cognate effector, SopB, implying a novel multimeric association for chaperone/effector complexes with their ATPase.

Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha

PubMed Central

Senior, Alan E.; Muharemagi, Alma; Wilke-Mounts, Susan

2008-01-01

Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6-His tag and purified. Pure alpha was monomeric, competent in nucleotide binding, and had normal N-terminal sequence. In F1-subunit dissociation/reassociation experiments it supported full reconstitution of ATPase, and reassociated complexes were able to bind to F1-depleted membranes with restoration of ATP-driven proton pumping. Therefore interaction between the stator delta subunit and the N-terminal residue 1-22 region of alpha occurred normally when pure alpha was complexed with other F1 subunits. On the other hand, three different types of experiment showed that no interaction occurred between pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of isolated alpha was not susceptible to trypsin cleavage. Therefore, during assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha. We suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated alpha until released by binding of beta to alpha subunit. This prevents 1/1 delta/alpha complexes from forming, and provides a satisfactory explanation of the stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase, assuming that steric hindrance prevents binding of more than one delta to the alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector. PMID:17176112

Potential antidiabetic activity of extracellular polysaccharides in submerged fermentation culture of Coriolus versicolor LH1.

PubMed

Yang, John Powen; Hsu, Taihao; Lin, Fangyi; Hsu, Wenkuang; Chen, Yucheng

2012-09-01

The separation and purification of extracellular polysaccharides from Coriolus versicolor LH1 were investigated along with their α-glucosidase inhibition properties. Three polysaccharide fractions (ePS-F2-1, ePS-F3-1, and ePS-F4-1) were separated from the culture medium of LH1 using a DEAE anion-exchange column and a Sephadex™ G-50 gel filtration column. Their chemical compositions was determined. On the basis of an α-glucosidase inhibition assay, the enzyme inhibition activities of ePS-F2-1, ePS-F3-1, and ePS-F4-1 were investigated. Among these, ePS-F4-1 had the highest enzyme inhibition effects on α-glucosidase. According to the results of the chemical component analysis, ePS-F3-1 and ePS-F4-1 are the polysaccharides which are combined with triterpenoides, and ePS-F2-1 is complexed with proteins and triterpenoides. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preparation and Analysis of Cyclodextrin-Based Metal-Organic Frameworks: Laboratory Experiments Adaptable for High School through Advanced Undergraduate Students

ERIC Educational Resources Information Center

Smith, Merry K.; Angle, Samantha R.; Northrop, Brian H.

2015-01-01

?-Cyclodextrin can assemble in the presence of KOH or RbOH into metal-organic frameworks (CD-MOFs) with applications in gas adsorption and environmental remediation. Crystalline CD-MOFs are grown by vapor diffusion and their reversible adsorption of CO[subscript 2](g) is analyzed both qualitatively and quantitatively. The experiment can be…

[General anesthesia vs. retrobulbar anesthesia in cataract surgery. A randomized comparison of patients at risk].

PubMed

Heinze, J; Rohrbach, M

1992-08-01

Several studies comparing retrobulbar block (RB) and general anaesthesia (GA) for cataract surgery in the elderly have been published. Most of them were retrospective. Our prospective study was designed in order to determine the benefits or disadvantages using RB or GA. Arterial blood gases (ABG) and cardiovascular stability were explored in high-risk patients undergoing elective unilateral cataract extraction. METHODS. Forty patients over 65 years of age and with other co-existing diseases (ASA III-IV) were allocated randomly to receive either GA or RB. No premedication was given to either group of patients. On arrival in the anaesthetic room, a radial artery was cannulated for collection of blood samples and direct monitoring of the blood pressure. Pulse oximetry and ECG were continuously monitored in all patients, the end-expiratory CO2 (F(eexCO2)) only in the GA group. GA was induced with vecuronium 0.1 mg/kg and thiopentone 5 mg/kg; the lungs were ventilated with 100% oxygen. After intubation of the trachea controlled mechanical ventilation was continued with N2O/O2 (55:45) and enflurane 1%-2%. Only enflurane concentrations were varied to correct changes in mean arterial pressure (MAP) if these exceeded +/- 20%. Respiratory frequency and tidal volume were kept constant until completion of surgery. The patients were extubated when they were able to ventilate more than 5 1/min (pressure support 10 cmH2O; PEEP 5 cmH2O). After extubation no O2 was given. In the RB group neural block was undertaken with prilocaine 2% (3 ml) as a retrobulbar injection and prilocaine 1% (5 ml) to block the facial innervation of the orbicularis muscle (Van Lint, O'Brien). Oxygen 3 1/min was administered by nasal tube during the operation. Nine arterial samples for blood gas analysis were collected: (1) control; (2) before operation; (3) 5 min after beginning the operation; (4) 15 min after beginning the operation and before i.v. administration of 500 mg acetazolamide over 5 min; (5) after acetazolamide; (6 and 7) 10 and 20 min after acetazolamide; and (8 and 9) 15 and 30 min after operation (RB) or extubation (GA). RESULTS. The patient demography, including duration of anaesthesia and operation, was similar in both groups (Table 1). Four patients in the GA group (2 needed O2 after extubation because of hypoxaemia) and 2 in the RB group were excluded. No significant differences were seen in base excess (BE) and standard bicarbonate (SHCO3). Arterial O2 tension, arterial O2 saturation, and pulse-oximetric O2 saturation were higher in the RB group intra- and postoperatively (Figs. 1, 3, 4). Arterial CO2 tension (PaCO2) was significantly higher in the GA group during the pre- and postoperative period (Fig. 2), but not during the operation. The PaCO2- F(eexCO2) gradient ranged between 5 and 9 mmHg. Administration of acetazolamide did not influence this gradient by regressive analysis. The postoperative outcome of the patients was comparable in both groups. Nausea or vomiting did not occur. MAP was significantly higher in the RB group during the operation. No significant differences were seen in the pre- and postoperative period. Heart rate in the GA group was higher only after extubation, but was within physiological limits. DISCUSSION. Despite the differing results between the two groups, our study showed no important advantage related to either RB or GA. Changes in ABG, MAP, and heart rate during the investigation period were within physiological limits in elderly patients. Intravenous acetazolamide did not influence ABG in a significant manner. With regard to the preference of each patient, we recommend both RB and GA for cataract surgery in high-risk patients on the assumption of sufficient preoperative treatment of co-existing diseases. In conclusion, cardiovascular and ABG stability were maintained during both anaesthetic techniques.

Materials Data on Rb2SiF6 (SG:225) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

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

Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 4,5,&6. Sheet 7 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

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

Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 7,8,&9. Sheet 8 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

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

Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. GENERAL ARRANGEMENT, PLAN & ELEVATIONS. Sheet 4 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

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

Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. HINGED PANEL EQUIPMENT SCHEDULE. Sheet 28 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in the presence of virus RNA

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

Ibrahim, Amr; Present address: Genomics Facility, Agricultural Genetic Engineering Research Institute, Agricultural Research Center, Giza 12619; Hutchens, Heather M.

2012-11-25

To identify the virus components important for assembly of the Alfalfa mosaic virus replicase complex, we used live cell imaging of Arabidopsis thaliana protoplasts that expressed various virus cDNAs encoding native and GFP-fusion proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1-mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies (MVBs), which are also called prevacuolar compartments, that mediate traffic to the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed withmore » P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which surrounds the vacuole, in the presence of infectious virus RNA, replication competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that a functional replication complex containing P1, P2, and a full-length AMV RNA assembles on MVBs to traffic to the tonoplast.« less

A photo-cross-linking approach to monitor folding and assembly of newly synthesized proteins in a living cell.

PubMed

Miyazaki, Ryoji; Myougo, Naomi; Mori, Hiroyuki; Akiyama, Yoshinori

2018-01-12

Many proteins form multimeric complexes that play crucial roles in various cellular processes. Studying how proteins are correctly folded and assembled into such complexes in a living cell is important for understanding the physiological roles and the qualitative and quantitative regulation of the complex. However, few methods are suitable for analyzing these rapidly occurring processes. Site-directed in vivo photo-cross-linking is an elegant technique that enables analysis of protein-protein interactions in living cells with high spatial resolution. However, the conventional site-directed in vivo photo-cross-linking method is unsuitable for analyzing dynamic processes. Here, by combining an improved site-directed in vivo photo-cross-linking technique with a pulse-chase approach, we developed a new method that can analyze the folding and assembly of a newly synthesized protein with high spatiotemporal resolution. We demonstrate that this method, named the pulse-chase and in vivo photo-cross-linking experiment (PiXie), enables the kinetic analysis of the formation of an Escherichia coli periplasmic (soluble) protein complex (PhoA). We also used our new technique to investigate assembly/folding processes of two membrane complexes (SecD-SecF in the inner membrane and LptD-LptE in the outer membrane), which provided new insights into the biogenesis of these complexes. Our PiXie method permits analysis of the dynamic behavior of various proteins and enables examination of protein-protein interactions at the level of individual amino acid residues. We anticipate that our new technique will have valuable utility for studies of protein dynamics in many organisms. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Cyclin A recruits p33cdk2 to the cellular transcription factor DRTF1.

PubMed

Bandara, L R; Adamczewski, J P; Zamanian, M; Poon, R Y; Hunt, T; Thangue, N B

1992-01-01

Cyclins are regulatory molecules that undergo periodic accumulation and destruction during each cell cycle. By activating p34cdc2 and related kinase subunits they control important events required for normal cell cycle progression. Cyclin A, for example, regulates at least two distinct kinase subunits, the mitotic kinase subunit p34cdc2 and related subunit p33cdk2, and is widely believed to be necessary for progression through S phase. However, cyclin A also forms a stable complex with the cellular transcription factor DRTF1 and thus may perform other functions during S phase. DRTF1, in addition, associates with the tumour suppressor retinoblastoma (Rb) gene product and the Rb-related protein p107. We now show, using biologically active fusion proteins, that cyclin A can direct the binding of the cdc2-like kinase subunit, p33cdk2, to complexed DRTF1, containing either Rb or p107, as well as activate its histone H1 kinase activity. Cyclin A cannot, however, direct p34cdc2 to the DRTF1 complex and we present evidence suggesting that the stability of the cyclin A-p33cdk2 complex is influenced by DRTF1 or an associated protein. Cyclin A, therefore, serves as an activating and targeting subunit of p33cdk2. The ability of cyclin A to activate and recruit p33cdk2 to DRTF1 may play an important role in regulating cell cycle progression and moreover defines a mechanism for coupling cell-cycle events to transcriptional initiation.

Electron {sup 83}Rb/{sup 83m}Kr Source for the Energy Scale Monitoring in the KATRIN Experiment

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

Zboril, Miroslav; Nuclear Physics Institute of the ASCR, p. r. i., CZ-25068 Rez; Collaboration: KATRIN Collaboration

The KATRIN (KArlsruhe TRItium Neutrino) experiment investigates the endpoint region of the tritium {beta}-spectrum aiming for the sensitivity on the neutrino mass of 0.2 eV (90% C.L.). A spectrometer of the MAC-E filter (Magnetic Adiabatic Collimation with an Electrostatic filter) type will be used for a total time of at least 5 years. An unrecognized shift of the filtering potential would directly influence the resulting neutrino mass. To continuously monitor the filtering potential the high voltage (HV) will be simultaneously applied to an additional MAC-E filter spectrometer. In this monitor spectrometer suitable electron sources based on atomic/nuclear standards will bemore » utilized. As one of such monitoring tools the solid {sup 83}Rb/{sup 83m}Kr source is intended. It provides conversion electrons from {sup 83m}Kr(t{sub 1/2} = 1.83 h) which is continuously generated by {sup 83}Rb(t{sub 1/2}{approx_equal}86 d). The Calibration and Monitoring task of the KATRIN project demands the long-term energy stability {Delta}E/E of the K-32 conversion electron line (E = 17.8 keV, {Gamma} = 2.7 eV) of {+-}1.6 ppm/month.« less

Proto-oncogene FBI-1 (Pokemon/ZBTB7A) Represses Transcription of the Tumor Suppressor Rb Gene via Binding Competition with Sp1 and Recruitment of Co-repressors*S⃞

PubMed Central

Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

2008-01-01

FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp –308 to –188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp –65 to –56) and GC-box 2 (bp –18 to –9), the latter of which is also bound by FBI-1. We found that FRE3 (bp –244 to –236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression. PMID:18801742

In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic.

PubMed

Huang, Hsiao-Yun; Hopper, Anita K

2015-04-01

Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1-RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. © 2015 Huang and Hopper; Published by Cold Spring Harbor Laboratory Press.

Levels of control exerted by the Isc iron-sulfur cluster system on biosynthesis of the formate hydrogenlyase complex.

PubMed

Pinske, Constanze; Jaroschinsky, Monique; Sawers, R Gary

2013-06-01

The membrane-associated formate hydrogenlyase (FHL) complex of bacteria like Escherichia coli is responsible for the disproportionation of formic acid into the gaseous products carbon dioxide and dihydrogen. It comprises minimally seven proteins including FdhF and HycE, the catalytic subunits of formate dehydrogenase H and hydrogenase 3, respectively. Four proteins of the FHL complex have iron-sulphur cluster ([Fe-S]) cofactors. Biosynthesis of [Fe-S] is principally catalysed by the Isc or Suf systems and each comprises proteins for assembly and for delivery of [Fe-S]. This study demonstrates that the Isc system is essential for biosynthesis of an active FHL complex. In the absence of the IscU assembly protein no hydrogen production or activity of FHL subcomponents was detected. A deletion of the iscU gene also resulted in reduced intracellular formate levels partially due to impaired synthesis of pyruvate formate-lyase, which is dependent on the [Fe-S]-containing regulator FNR. This caused reduced expression of the formate-inducible fdhF gene. The A-type carrier (ATC) proteins IscA and ErpA probably deliver [Fe-S] to specific apoprotein components of the FHL complex because mutants lacking either protein exhibited strongly reduced hydrogen production. Neither ATC protein could compensate for the lack of the other, suggesting that they had independent roles in [Fe-S] delivery to complex components. Together, the data indicate that the Isc system modulates FHL complex biosynthesis directly by provision of [Fe-S] as well as indirectly by influencing gene expression through the delivery of [Fe-S] to key regulators and enzymes that ultimately control the generation and oxidation of formate.

Biotransformation of ginsenoside Rb1 to ginsenoside C-K by endophytic fungus Arthrinium sp. GE 17-18 isolated from Panax ginseng.

PubMed

Fu, Y; Yin, Z-H; Wu, L-P; Yin, C-R

2016-09-01

This research aimed to isolate β-glycosidase-producing endophytic fungus in Panax ginseng to achieve biotransformation of ginsenoside Rb1 to ginsenoside C-K. Of these 15 β-glucosidase-producing endophytic fungus isolated from ginseng roots, a β-glucosidase-producing endophytic fungi GE 17-18 could hydrolyse major ginsenosides Rb1 to minor ginsenoside C-K with metabolic pathways: ginsenoside Rb1→ginsenoside Rd→ginsenoside F2→ginsenoside C-K. Phylogenetic analysis of ITS gene sequences indicated that the strain GE 17-18 belongs to the genus Arthrinium and is most closely related to Arthrinium sp. HQ832803.1. This is the first study to provide information of cultivable β-glycosidase-producing Endophytic fungus in Panax ginseng. The strain GE 17-18 has potential to be applied on the preparation for minor ginsenoside C-K in pharmaceutical industry. © 2016 The Society for Applied Microbiology.

Lone pair effect, structural distortions, and potential for superconductivity in Tl perovskites.

PubMed

Schoop, Leslie M; Müchler, Lukas; Felser, Claudia; Cava, R J

2013-05-06

Drawing the analogy to BaBiO3, we investigate via ab initio electronic structure calculations potential new superconductors of the type ATlX3 with A = Rb and Cs and X = F, Cl, and Br, with a particular emphasis on RbTlCl3. On the basis of chemical reasoning, supported by the calculations, we show that Tl-based perovskites have structural and charge instabilities driven by the lone pair effect, similar to the case of BaBiO3, effectively becoming A2Tl(+)Tl(3+)X6. We find that upon hole doping of RbTlCl3, structures without Tl(+) and Tl(3+) charge disproportionation become more stable, although the ideal cubic perovskite, often viewed as the best host for superconductivity, should not be the most stable phase in the system. The known superconductor (Sr,K)BiO3 and hole doped RbTlCl3, predicted to be most stable in the same tetragonal structure, display highly analogous calculated electronic band structures.

Functional expression of the Na-K-2Cl cotransporter NKCC2 in mammalian cells fails to confirm the dominant-negative effect of the AF splice variant.

PubMed

Hannemann, Anke; Christie, Jenny K; Flatman, Peter W

2009-12-18

The renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is the major salt transport pathway in the apical membrane of the mammalian thick ascending limb. It is differentially spliced and the three major variants (A, B, and F) differ in their localization and transport characteristics. Most knowledge about its regulation comes from experiments in Xenopus oocytes as NKCC2 proved difficult to functionally express in a mammalian system. Here we report the cloning and functional expression of untagged and unmodified versions of the major splice variants from ferret kidney (fNKCC2A, -B, and -F) in human embryonic kidney (HEK) 293 cells. Many NKCC2 antibodies used in this study detected high molecular weight forms of the transfected proteins, probably NKCC2 dimers, but not the monomers. Interestingly, monomers were strongly detected by phosphospecific antibodies directed against phosphopeptides in the regulatory N terminus. Bumetanide-sensitive (86)Rb uptake was significantly higher in transfected HEK-293 cells and could be stimulated by incubating cells in a medium containing a low chloride concentration prior the uptake measurements. fNKCC2 was less sensitive to the reduction in chloride concentration than NKCC1. Using HEK-293 cells stably expressing fNKCC2A we also show that co-expression of variant NKCC2AF does not have the dominant-negative effect on NKCC2A activity that was seen in Xenopus oocytes, nor is it trafficked to the cell surface. In addition, fNKCC2AF is neither complex glycosylated nor phosphorylated in its N terminus regulatory region like other variants.

TOM9.2 Is a Calmodulin-Binding Protein Critical for TOM Complex Assembly but Not for Mitochondrial Protein Import in Arabidopsis thaliana.

PubMed

Parvin, Nargis; Carrie, Chris; Pabst, Isabelle; Läßer, Antonia; Laha, Debabrata; Paul, Melanie V; Geigenberger, Peter; Heermann, Ralf; Jung, Kirsten; Vothknecht, Ute C; Chigri, Fatima

2017-04-03

The translocon on the outer membrane of mitochondria (TOM) facilitates the import of nuclear-encoded proteins. The principal machinery of mitochondrial protein transport seems conserved in eukaryotes; however, divergence in the composition and structure of TOM components has been observed between mammals, yeast, and plants. TOM9, the plant homolog of yeast Tom22, is significantly smaller due to a truncation in the cytosolic receptor domain, and its precise function is not understood. Here we provide evidence showing that TOM9.2 from Arabidopsis thaliana is involved in the formation of mature TOM complex, most likely by influencing the assembly of the pore-forming subunit TOM40. Dexamethasone-induced RNAi gene silencing of TOM9.2 results in a severe reduction in the mature TOM complex, and the assembly of newly imported TOM40 into the complex is impaired. Nevertheless, mutant plants are fully viable and no obvious downstream effects of the loss of TOM complex, i.e., on mitochondrial import capacity, were observed. Furthermore, we found that TOM9.2 can bind calmodulin (CaM) in vitro and that CaM impairs the assembly of TOM complex in the isolated wild-type mitochondria, suggesting a regulatory role of TOM9.2 and a possible integration of TOM assembly into the cellular calcium signaling network. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Tunable High Q Superconducting Microwave Resonator for Hybrid System with ^87Rb atoms

NASA Astrophysics Data System (ADS)

Kim, Zaeill; Voigt, K. D.; Lee, Jongmin; Hoffman, J. E.; Grover, J. A.; Ravets, S.; Zaretskey, V.; Palmer, B. S.; Hafezi, M.; Taylor, J. M.; Anderson, J. R.; Dragt, A. J.; Lobb, C. J.; Orozco, L. A.; Rolston, S. L.; Wellstood, F. C.

2012-02-01

We have developed a frequency tuning system for a ``lumped-element'' thin-film superconducting Al microwave resonator [1] on sapphire intended for coupling to hyperfine ground states of cold trapped ^87Rb atoms, which are separated by about fRb=6.83 GHz. At T=12 mK and on resonance at 6.81 GHz, the loaded quality factor was 120,000. By moving a carefully machined Al pin towards the inductor of the resonator using a piezo stage, we were able to tune the resonance frequency over a range of 35 MHz and within a few kHz of fRb. While measuring the power dependent response of the resonator at each tuned frequency, we observed anomalous decreases in the quality factor at several frequencies. These drops were more pronounced at lower power. We discuss our results, which suggest these resonances are attributable to discrete two-level systems.[4pt] [1] Z. Kim et al., AIP ADVANCES 1, 042107 (2011).

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

PubMed Central

Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary; Kota, Krishna P.; Whitehouse, Chris A.; Bavari, Sina

2016-01-01

Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection. PMID:26837067

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase.

PubMed

Mudhasani, Rajini; Tran, Julie P; Retterer, Cary; Kota, Krishna P; Whitehouse, Chris A; Bavari, Sina

2016-02-01

Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

DOE PAGES

Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary; ...

2016-02-02

Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through anmore » alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.« less

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

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

Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary

Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through anmore » alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.« less

PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

PubMed

Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin; Adelmant, Guillaume; Huang, Jialiang; Joyce, Cailin E; Vazquez, Francisca; Weir, Barbara A; Montgomery, Philip; Tsherniak, Aviad; Giacomelli, Andrew O; Perry, Jennifer A; Trowbridge, Jennifer; Fujiwara, Yuko; Cowley, Glenn S; Xie, Huafeng; Kim, Woojin; Novina, Carl D; Hahn, William C; Marto, Jarrod A; Orkin, Stuart H

2017-09-01

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR . ©2017 American Association for Cancer Research.

p-halo N4-phenyl substituted thiosemicarbazones: Crystal structure, supramolecular architecture, characterization and bio-assay of their Co(III) and Ni(II) complexes

NASA Astrophysics Data System (ADS)

Kotian, Avinash; Kumara, Karthik; Kamat, Vinayak; Naik, Krishna; Kokare, Dhoolesh G.; Nevrekar, Anupama; Lokanath, Neratur Krishnappagowda; Revankar, Vidyanand K.

2018-03-01

In the present work, three potential metal ion chelating ligands, p-halo N4-phenyl substituted thiosemicarbazones are synthesized and characterized. The molecular structure of all (E)-4-(4-halophenyl)-1-(3-hydroxyiminobutan-2-ylidene) thiosemicarbazones (halo = F/Cl/Br) are determined by single crystal X-ray diffraction method. All the molecules have crystallized in monoclinic crystal system with P21/n space group. The ligands show Csbnd H⋯S and Nsbnd H⋯S intermolecular interactions, which are responsible to form the supramolecular self-assemblies through R22(8), R22(12) and R22(14) ring motifs. Hirshfeld surface analysis is carried out to explore the intermolecular interactions. A series of Co(III) and Ni(II) mononuclear transition metal complexes derived from these ligands have been synthesized and characterized by various spectro-analytical methods. The metal to ligand stoichiometry has been found to be 1:2 in all the complexes. The synthesized compounds have been investigated for their in vitro antimicrobial potencies. The compounds are found to be more active than the standard used, in the case of E. coli and A. niger. Additionally, they are also screened for their in vitro antitubercular activity.

Geochronology of archean gneisses in the Lake Helen area, Southwestern Big Horn Mountains, Wyoming

USGS Publications Warehouse

Arth, Joseph G.; Barker, F.; Stern, T.W.

1980-01-01

The RbSr and UPb methods were used to study gneisses in the 7 1 2-minute Lake Helen quadrangle of the Big Horn Mountains, Wyoming. Two episodes of magmatism, deformation and metamorphism occurred during the Archean. Trondhjemitic to tonalitic orthogneisses and amphibolite of the first episode (E-1) are cut by a trondhjemite pluton and a calc-alkaline intrusive series of the second episode (E-2). The E-2 series includes hornblende-biotite quartz diorite, biotite tonalite, biotite granodiorite and biotite granite. A RbSr whole-rock isochron for E-1 gneisses indicates an age of 3007 ?? 34 Ma (1 sigma) and an initial 87Sr/86Sr of 0.7001 ?? 0.0001. UPb determination on zircon from E-1 gneisses yield a concordia intercept age of 2947 ?? 50 Ma. The low initial ratio suggests that the gneisses had no significant crustal history prior to metamorphism, and that the magmas from which they formed had originated from a mafic source. A RbSr whole-rock isochron for E-2 gneisses gives an age of 2801 ?? 31 Ma. The 87Sr/86Sr initial ration is 0.7015 ?? 0.0002 and precludes the existence of the rocks for more than 150 Ma prior to metamorphism. The E-2 magmas may have originated from melting of E-1 gneisses or from a more mafic source. ?? 1980.

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

Metal ion attachment to the matrix meso-tetrakis(pentafluorophenyl)porphyrin, related matrices and analytes: an experimental and theoretical study.

PubMed

van Kampen, Jeroen J A; Luider, Theo M; Ruttink, Paul J A; Burgers, Peter C

2009-11-01

In a previous study [van Kampen et al. Analytical Chemistry 2006; 78: 5403], we found that meso-tetrakis (pentafluorophenyl)porphyrin (F20TPP), in combination with lithium salts, provides an efficient matrix to cationize small molecules by Li+ attachment and that this combination can be successfully applied to the quantitative analysis of drugs, such as antiretroviral compounds using matrix-assisted laser desorption ionization in conjunction with a time-of-flight analyzer (MALDI-TOF). In the present study, we further explore the mechanism of metal ion attachment to F20TPP and analytes by MALDI-FTMS(/MS). To this end, we have studied the interaction of F20TPP and analytes with various mono-, di- and trivalent metal ions (Li+, Na+, K+, Rb+, Cs+, Co2+, Cu2+, Zn2+, Fe2+, Fe3+ and Ga3+). For the alkali cations, we find that F20TPP forms complexes only with Li+ and Na+; in addition, model analyte molecules such as poly(ethyleneglycol)s, mixed with F20TPP and the alkali cations, also only form Li+ and Na+ adducts. This contrasts sharply with the commonly used matrix 2,5-dihydroxybenzoic acid, where analytes are most efficiently cationized by Na+ or K+. Reasons for this difference are delineated. Ab initio calculations on porphyrin itself reveal that even the smallest alkali cation, Li+, does not fit in the porphyrin cavity, but lies on top of it, pushing the 21H and 23 H hydrogen atoms out of and below the plane with concomitant bending of the porphyrin skeleton in the opposite direction, i.e. toward the cation. Thus, the Li+ ion is not effectively sequestered and is in fact exposed and thus accessible for donation to analyte molecules. Interaction of F20TPP with di- and trivalent metal ions leads to protoporphyrin-metal ions, where the metal ion is captured within the protoporphyrin dianion cavity. The most intense signal is obtained when F20TPP is reacted with CuCl2 and then subjected to laser ablation. This method presents an easy general route to study the metal containing protoporphyrin molecules, which could all act as potential MALDI matrices. Copyright 2009 John Wiley & Sons, Ltd.

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

PubMed

Singh, Randeep K; Dagnino, Lina

2016-05-03

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

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

Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operativemore » transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.« less

Optical oscillator strength distribution of amino acids from 3 to 250 eV and examination of the Thomas Reiche Kuhn sum rule

NASA Astrophysics Data System (ADS)

Kamohara, Masumi; Izumi, Yudai; Tanaka, Masafumi; Okamoto, Keiko; Tanaka, Masahito; Kaneko, Fusae; Kodama, Yoko; Koketsu, Toshiyuki; Nakagawa, Kazumichi

2008-10-01

Absorption spectra of thin films of glycine (Gly), alanine (Ala), valine (Val), serine (Ser), leucine (Leu), phenylalanine (Phe) and methinine (Met) were measured in absolute values of absorption cross section σ( E) for the photon energy E from 3 to 250 eV. We translated σ( E) into the optical oscillator strength distribution df/dE and we examined the Thomas-Reiche-Kuhn sum rule [Hirschfelder, J.O., Curtiss, C.F., Bird, R.B., 1954. Molecular Theory of Gases and Liquids. Wiley, New York, p. 890]. We concluded that T-R-K sum rule was correctly applicable for such relatively large size of biomolecules.

Analysis of a Soluble (UreD:UreF:UreG)2 Accessory Protein Complex and its Interactions with Klebsiella aerogenes Urease by Mass Spectrometry

PubMed Central

Farrugia, Mark A.; Han, Linjie; Zhong, Yueyang; Boer, Jodi L.; Ruotolo, Brandon T.; Hausinger, Robert P.

2013-01-01

Maturation of the nickel-containing urease of Klebsiella aerogenes is facilitated by the UreD, UreF, and UreG accessory proteins along with the UreE metallo-chaperone. A fusion of the maltose binding protein and UreD (MBP-UreD) was co-isolated with UreF and UreG in a soluble complex possessing a (MBP-UreD:UreF:UreG)2 quaternary structure. Within this complex a UreF:UreF interaction was identified by chemical cross-linking of the amino termini of its two UreF protomers, as shown by mass spectrometry of tryptic peptides. A pre-activation complex was formed by the interaction of (MBP-UreD:UreF:UreG)2 and urease. Mass spectrometry of intact protein species revealed a pathway for synthesis of the urease pre-activation complex in which individual hetero-trimer units of the (MBP-UreD:UreF:UreG)2 complex bind to urease. Together, these data provide important new insights into the structures of protein complexes associated with urease activation. PMID:23797863

Materials Data on Rb3NaBe2F8 (SG:164) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Characterization of the antigen SO7 during development of Eimeria tenella.

PubMed

Fetterer, R H; Jenkins, M C; Miska, K B; Barfield, R C

2007-10-01

The developmental expression of the antigen SO7, which has been previously shown to protect chickens against infection by several Eimeria species, was investigated. Using RT-PCR, mRNA for SO7 was found to be restricted primarily to unsporulated oocysts (0 hr). Western blot (WB) analysis with an antibody to recombinant SO7 (rbSO7) revealed expression of the protein from 6 to 72 hr (fully sporulated) of sporulation and in sporozoites (SZ). SO7 was absent in host-derived second-stage merozoites (MZ) and was present in culture-derived first-stage MZ but at a level of only 25% of that exhibited by SZ. During invasion of Madin-Darby bovine kidney (MDBK) cells by SZ in vitro, the level of SO7 within cells, as determined by WB analysis, remained relatively constant until 48 hr of development and then decreased by about 40% at the next time point (72 hr). The SO7 secreted into the culture media during in vitro development increased to a relative maximum at 48 hr and then decreased to about 20% of maximum at 72 hr. Immunostaining with anti-rbSO7 indicates that SO7 is highly concentrated in both refractile bodies (RB) of SZ, with some limited distribution in the apical complex. Anti-rbSO7 intensively stained the intracellular parasites and the first-stage schizonts during in vitro development of E. tenella in MDBK cells. Upon release from the schizonts, the first-stage merozoites stained with 1 or 2 bright spots typically at each end. The results suggest that SO7 is closely associated with the SZ RB and is developmentally regulated but may not play a direct role in cellular invasion.

Orientational glasses. II. Calculation of critical thresholds in ACNxMn{1-x} mixtures

NASA Astrophysics Data System (ADS)

Galam, Serge; Depondt, Philippe

1992-10-01

Using a simple steric hindrance based idea, critical thresholds which occur in the phase diagram of ACNxMn{1-x} mixtures, where A stands for K, Na or Rb while Mn represents Br, Cl or I, are calculated. The cyanide density x is divided into a free-to-reorient part x_r, and a frozen-in part x_f. The latter term x_f is calculated from microscopic characteristics of the molecules involved. Two critical thresholds x_c and x_d for the disappearance of respectively, ferroelastic transitions and ferroelastic domains are obtained. The calculated values are in excellent agreement with available experimental results. Predictions are made for additionnal mixtures. Une idée simple d'encombrement stérique permet de calculer des seuils critiques qui apparaissent dans le diagramme de phase de mélanges ACNxMn{1-x}, où A représente K, Na ou Rb, et Mn, des atoms du type Br, Cl ou I. La concentration x du cyanure est divisée en une partie x_r de molécules libres de se réorienter, et une partie de molécules gelées x_f. Ce dernier terme x_f est calculé à partir des caractéristiques microscopiques des molécules concernées. Deux seuils critiques x_c et x_d pour la disparition respectivement des transitions et des domaines ferroelastiques sont obtenus. Les valeurs calculées sont en excellent accord avec les résultats expérimentaux disponibles. Des prédictions sont faites pour d'autres mélanges.

Enhanced Stability of the Fe(II)/Mn(II) State in a Synthetic Model of Heterobimetallic Cofactor Assembly.

PubMed

Kerber, William D; Goheen, Joshua T; Perez, Kaitlyn A; Siegler, Maxime A

2016-01-19

Heterobimetallic Mn/Fe cofactors are found in the R2 subunit of class Ic ribonucleotide reductases (R2c) and R2-like ligand binding oxidases (R2lox). Selective cofactor assembly is due at least in part to the thermodynamics of M(II) binding to the apoprotein. We report here equilibrium studies of Fe(II)/Mn(II) discrimination in the biomimetic model system H5(F-HXTA) (5-fluoro-2-hydroxy-1,3-xylene-α,α'-diamine-N,N,N',N'-tetraacetic acid). The homobimetallic F-HXTA complexes [Fe(H2O)6][1]2·14H2O and [Mn(H2O)6][2]2·14H2O (1 = [Fe(II)2(F-HXTA)(H2O)4](-); 2 = [Mn(II)2(F-HXTA)(H2O)4](-)) were characterized by single crystal X-ray diffraction. NMR data show that 1 retains its structure in solution (2 is NMR silent). Metal exchange is facile, and the heterobimetallic complex [Fe(II)Mn(II)(F-HXTA)(H2O)4](-) (3) is formed from mixtures of 1 and 2. (19)F NMR was used to quantify 1 and 3 in the presence of excess M(II)(aq) at various metal ratios, and equilibrium constants for Fe(II)/Mn(II) discrimination were calculated from these data. Fe(II) is preferred over Mn(II) with K1 = 182 ± 13 for complete replacement (2 ⇌ 1). This relatively modest preference is attributed to a hard-soft acid-base mismatch between the divalent cations and the polycarboxylate ligand. The stepwise constants for replacement are K2 = 20.1 ± 1.3 (2 ⇌ 3) and K3 = 9.1 ± 1.1 (3 ⇌ 1). K2 > K3 demonstrates enhanced stability of the heterobimetallic state beyond what is expected for simple Mn(II) → Fe(II) replacement. The relevance to Fe(II)/Mn(II) discrimination in R2c and R2lox proteins is discussed.

The H2O-CH3F Complex: a Combined Microwave and Infrared Spectroscopic Study Supported by Structure Calculations

NASA Astrophysics Data System (ADS)

Gnanasekar, Sharon Priya; Goubet, Manuel; Arunan, Elangannan; Georges, Robert; Soulard, Pascale; Asselin, Pierre; Huet, T. R.; Pirali, Olivier

2015-06-01

The H2O-CH3F complex could have two geometries, one with a hydrogen bond and one with the newly proposed carbon bond. While in general carbon bonds are weaker than hydrogen bonds, this complex appears to have comparable energies for the two structures. Infrared (IR) and microwave (MW) spectroscopic measurements using, respectively, the Jet-AILES apparatus and the FTMW spectrometer at the PhLAM laboratory, have been carried out to determine the structure of this complex. The IR spectrum shows the formation of the CH3F- H2O hydrogen bonded complex and small red-shifts in OH frequency most probably due to (CH3F)m-(H2O)n clusters. Noticeably, addition of CH_3F in the mixture promotes the formation of small water clusters. Preliminary MW spectroscopic measurements indicate the formation of the hydrogen bonded complex. So far, we have no experimental evidence for the carbon bonded structure. However, calculations of the Ar-CH3F complex show three energetically equivalent structures: a T-shape, a "fluorine" bond and a carbon bond. The MW spectrum of the (Ar)n-CH3F complexes is currently under analysis. Mani, D; Arunan, E. Phys. Chem. Chem. Phys. 2013, 15, 14377. Cirtog, M; Asselin, P; Soulard, P; Tremblay, B; Madebene, B; Alikhani, M. E; Georges, R; Moudens, A; Goubet, M; Huet, T.R; Pirali, O; Roy, P. J. Phys. Chem. A. 2011, 115, 2523 Kassi, S; Petitprez, D; Wlodarczak, G. J. Mol. Struct. 2000, 517-518, 375

A Study on the Interaction of Rhodamine B with Methylthioadenosine Phosphorylase Protein Sourced from an Antarctic Soil Metagenomic Library

PubMed Central

Bujacz, Anna; Wierzbicka-Woś, Anna; Kur, Józef

2013-01-01

The presented study examines the phenomenon of the fluorescence under UV light excitation (312 nm) of E. coli cells expressing a novel metagenomic-derived putative methylthioadenosine phosphorylase gene, called rsfp, grown on LB agar supplemented with a fluorescent dye rhodamine B. For this purpose, an rsfp gene was cloned and expressed in an LMG194 E. coli strain using an arabinose promoter. The resulting RSFP protein was purified and its UV-VIS absorbance spectrum and emission spectrum were assayed. Simultaneously, the same spectroscopic studies were carried out for rhodamine B in the absence or presence of RSFP protein or native E. coli proteins, respectively. The results of the spectroscopic studies suggested that the fluorescence of E. coli cells expressing rsfp gene under UV illumination is due to the interaction of rhodamine B molecules with the RSFP protein. Finally, this interaction was proved by a crystallographic study and then by site-directed mutagenesis of rsfp gene sequence. The crystal structures of RSFP apo form (1.98 Å) and complex RSFP/RB (1.90 Å) show a trimer of RSFP molecules located on the crystallographic six fold screw axis. The RSFP complex with rhodamine B revealed the binding site for RB, in the pocket located on the interface between symmetry related monomers. PMID:23383268

Geology and mineralization of the Jabal Umm Al Suqian albitized apogranite, southern Najd region, Kingdom of Saudi Arabia

NASA Astrophysics Data System (ADS)

Bokhari, M. Madani; Jackson, Norman J.; Al Oweidi, Khalid

A porphyritic muscovite—albite—microcline microgranite crops out at Jabal Umm Al Suqian, 80 km NE of Bishah. It intrudes alkali-feldspar granite, quartz diorite and a conglomerate composed of dioritic clasts, and is enveloped by a shell of hydrothermally altered, albitized, greisenized and microclinized country rocks. The principal chemical features of the microgranite are: 5-7% Na 2O, Na 2O/K 2O = 1.7, Rb 978 ppm, Sn 94 ppm, and low Ba, Ce, Sr and Zr. Albitized microgranite is highly enriched in F, Nb and Y, and the greisenized assemblages are enriched in F, Li, Rb, Sn and Zn. Mineralization consists of small veins and lenses of fluorite and disseminated minerals such as ixiolite, monazite, bastnaesite, betafite and fluorite, but is not economically significant. The microgranite is probably an apogranite cupola in the roof of an alkali-feldspar granite. Crystallization at about 1 kb total volatile pressure was controlled by (1) variable (0-3 wt. %) F contents which significantly reduced the freezing temperature of the melt and resulted in an albite-rich residue; and (2) progressive decrease in K, which also produced a sodic residuum. K- and F-rich hydrothermal fluids produced the envelope of phyllic alteration. Repetitive increase and decrease in volatile pressure produced rhythmic banding of quartz and alkali feldspar in the upper part of the cupola.

XNP-1/ATR-X acts with RB, HP1 and the NuRD complex during larval development in C. elegans.

PubMed

Cardoso, Carlos; Couillault, Carole; Mignon-Ravix, Cecile; Millet, Anne; Ewbank, Jonathan J; Fontés, Michel; Pujol, Nathalie

2005-02-01

Mutations in the XNP/ATR-X gene cause several X-linked mental retardation syndromes in humans. The XNP/ATR-X gene encodes a DNA-helicase belonging to the SNF2 family. It has been proposed that XNP/ATR-X might be involved in chromatin remodelling. The lack of a mouse model for the ATR-X syndrome has, however, hampered functional studies of XNP/ATR-X. C. elegans possesses one homolog of the XNP/ATR-X gene, named xnp-1. By analysing a deletion mutant, we show that xnp-1 is required for the development of the embryo and the somatic gonad. Moreover, we show that abrogation of xnp-1 function in combination with inactivation of genes of the NuRD complex, as well as lin-35/Rb and hpl-2/HP1 leads to a stereotyped block of larval development with a cessation of growth but not of cell division. We also demonstrate a specific function for xnp-1 together with lin-35 or hpl-2 in the control of transgene expression, a process known to be dependent on chromatin remodelling. This study thus demonstrates that in vivo XNP-1 acts in association with RB, HP1 and the NuRD complex during development.

Static and dynamic investigations of poly(aspartic acid) and Pluronic F127 complex prepared by self-assembling in aqueous solution

NASA Astrophysics Data System (ADS)

Nita, Loredana E.; Chiriac, Aurica P.; Bercea, Maria; Nistor, Manuela T.

2015-12-01

The present investigation is focused on evaluation of self-assembling ability in aqueous solutions of two water soluble polymers: poly(aspartic acid) (PAS) and Pluronic F127 (PL). The intermolecular complexes, realized between polyacid and neutral copolymer surfactant in different ratios, have been studied by combining various characterization techniques as rheology, DLS, spectroscopy, microscopy, chemical imaging, and zeta potential determination, measurements performed in static and/or dynamic conditions. In static conditions, when the equilibrium state between PAS/PL polymeric pair was reached, and depending on the polymers mixture composition, and of experimental rheological conditions, positive or negative deviations from the additive rule are registered. Conformational changes of the macromolecular chains and correspondingly physical interactions are generated between PL and PAS for self-assembly and the formation of interpolymer complex as suprastructure with micellar configuration. The phenomenon was better evidenced in case of 1/1 wt ratio between the two polymers. In dynamic conditions of determination, during ;in situ; evaluation of the hydrodynamic diameter, zeta potential and conductivity, when the equilibrium state is not reached and as result either the intermolecular bonds are not achieved, the self-assembling process is not so obvious evidenced.

Spectral Deferred Corrections for Parabolic Partial Differential Equations

DTIC Science & Technology

2015-06-08

n− 1. (5.1) The inverse DFT is given by the formula fj = n−1∑ k=0 f̂` e 2πi`j/n, j = 0, . . . , n− 1 (5.2) (see, e.g., [23, 33]). The n complex...n−1 2∑ `=−n−1 2 f̂` e 2πi`j/n, j = 0, . . . , n− 1. (5.4) While the forms (5.1) and (5.2) are the standard representation for the DFT, the forms...samples on [0, 1], then (5.4) can be restated as f(xj) = n−1 2∑ `=−n−1 2 f̂` e 2πi`tj , j = 0, . . . , n− 1. (5.5) The corresponding trigonometric

Multimeric complexes among ankyrin-repeat and SOCS-box protein 9 (ASB9), ElonginBC, and Cullin 5: insights into the structure and assembly of ECS-type Cullin-RING E3 ubiquitin ligases.

PubMed

Thomas, Jemima C; Matak-Vinkovic, Dijana; Van Molle, Inge; Ciulli, Alessio

2013-08-06

Proteins of the ankyrin-repeat and SOCS-box (ASB) family act as the substrate-recognition subunits of ECS-type (ElonginBC-Cullin-SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that catalyze the specific polyubiquitination of cellular proteins to target them for degradation by the proteasome. Therefore, ASB multimeric complexes are involved in numerous cell processes and pathways; however, their interactions, assembly, and biological roles remain poorly understood. To enhance our understanding of ASB CRL systems, we investigated the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5. Here, we describe the application of several biophysical techniques including differential scanning fluorimetry, isothermal titration calorimetry (ITC), nanoelectrospray ionization, and ion-mobility mass spectrometry (IM-MS) to provide structural and thermodynamic information for a quaternary ASB CRL complex. We find that ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain (Cul5NTD) but not to Cul2NTD. The structure of the monomeric ASB9-EloBC-Cul5NTD quaternary complex is revealed by molecular modeling and is consistent with IM-MS and temperature-dependent ITC data. This is the first experimental study to validate structural information for the assembly of the quaternary N-terminal region of an ASB CRL complex. The results suggest that ASB E3 ligase complexes function and assemble in an analogous manner to that of other CRL systems and provide a platform for further molecular investigation of this important protein family. The data reported here will also be of use for the future development of chemical probes to examine the biological function and modulation of other ECS-type CRL systems.

Multimeric Complexes among Ankyrin-Repeat and SOCS-box Protein 9 (ASB9), ElonginBC, and Cullin 5: Insights into the Structure and Assembly of ECS-type Cullin-RING E3 Ubiquitin Ligases

PubMed Central

2013-01-01

Proteins of the ankyrin-repeat and SOCS-box (ASB) family act as the substrate-recognition subunits of ECS-type (ElonginBC–Cullin–SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that catalyze the specific polyubiquitination of cellular proteins to target them for degradation by the proteasome. Therefore, ASB multimeric complexes are involved in numerous cell processes and pathways; however, their interactions, assembly, and biological roles remain poorly understood. To enhance our understanding of ASB CRL systems, we investigated the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5. Here, we describe the application of several biophysical techniques including differential scanning fluorimetry, isothermal titration calorimetry (ITC), nanoelectrospray ionization, and ion-mobility mass spectrometry (IM–MS) to provide structural and thermodynamic information for a quaternary ASB CRL complex. We find that ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain (Cul5NTD) but not to Cul2NTD. The structure of the monomeric ASB9–EloBC–Cul5NTD quaternary complex is revealed by molecular modeling and is consistent with IM–MS and temperature-dependent ITC data. This is the first experimental study to validate structural information for the assembly of the quaternary N-terminal region of an ASB CRL complex. The results suggest that ASB E3 ligase complexes function and assemble in an analogous manner to that of other CRL systems and provide a platform for further molecular investigation of this important protein family. The data reported here will also be of use for the future development of chemical probes to examine the biological function and modulation of other ECS-type CRL systems. PMID:23837592

Microwave-induced three-photon coherence of Rydberg atomic states

NASA Astrophysics Data System (ADS)

Kwak, Hyo Min; Jeong, Taek; Lee, Yoon-Seok; Moon, Han Seb

2016-12-01

We investigate the three-photon coherence (TPC) effects of the Rydberg state in a Doppler-broadened four-level ladder-type atomic system for the 5S1/2(F=3)-5P3/2(F‧=4)-50D5/2-51P3/2 transition of 85Rb atoms. Upon interaction of the Rydberg Rb atom of the ladder-type electromagnetically induced transparency (EIT) scheme with a resonant microwave (MW) field, we numerically analyze the spectral features of the Rydberg TPC from two viewpoints, Autler-Townes splitting (AT-splitting) of the Rydberg EIT and three-photon electromagnetically induced absorption (TPEIA). We determine the criterion to differentiate between AT-splitting of the Rydberg EIT and TPEIA in the Doppler-broadened ladder-type atomic system.

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

Malliakas, Christos D.; Chung, Duck Young; Claus, Helmut

Superconductivity was discovered in the layered compound RbBi 11/3Te 6, featuring Bi vacancies and a narrow band gap of 0.25(2) eV at room temperature. In addition, a sharp superconducting transition at similar to 3.2 K was observed in polycrystalline ingots. The superconducting volume fraction of oriented single crystals is almost 100%, confirming bulk superconductivity. Systematic Se and Sb substitutions in RbBi 11/3-ySb ySe xTe 6-x, revealed a dependence of the superconducting transition on composition that can increase the T c up to similar to 10%. The RbBi 11/3Te 6 system is the first member of the new homologous series Rb[Bimore » 2n+11/3Te 3n+6] with infinite Bi 2Te 3-like layers. Lastly, the large degree of chemical tunability of the electronic structure of the homology via doping and/or substitution gives rise to a new family of superconductors.« less

Spatial and temporal variations of Rb/Sr ratios of the bulk surface sediments in Lake Qinghai

PubMed Central

2010-01-01

The Rb/Sr ratios of lake sediments have been suggested as indicators of weathering intensity by increasing work. However, the geochemistry of Rb/Sr ratios of lake sediments is variable between different lakes. In this study, we investigated the spatial and temporal patterns of Rb/Sr ratios, as well as those of other major elements in surface sediments of Lake Qinghai. We find that the spatial pattern of Rb/Sr ratios of the bulk sediments correlates well with that of the mass accumulation rate, and those of the terrigenous fractions, e.g., SiO2, Ti, and Fe. The temporal variations of Rb/Sr ratios also synchronize with those of SiO2, Ti, and Fe of each individual core. These suggest that Rb/Sr ratios of the surface sediments are closely related to terrigenous input from the catchment. Two out of eight cores show similar trends between Rb/Sr ratios and precipitation indices on decadal scales; however, the other cores do not show such relationship. The result of this study suggests that physical weathering and chemical weathering in Lake Qinghai catchment have opposite influence on Rb/Sr ratios of the bulk sediments, and they compete in dominating the Rb/Sr ratios of lake sediments on different spatial and temporal scales. Therefore, it is necessary to study the geochemistry of Rb/Sr ratio of lake sediments (especially that on short term timescales) particularly before it is used as an indicator of weathering intensity of the catchment. PMID:20615264

Gonadal expression of aromatase and estrogen receptor alpha genes in two races of Tunisian mice and their hypofertile hybrids.

PubMed

Saïd, Lamia; Delalande, Christelle; Britton-Davidian, Janice; Saïd, Khaled; Saad, Ali; Carreau, Serge

2007-07-01

House mice (Mus musculus domesticus) in Tunisia consists of two races, one carries the 40-acrocentric standard karyotypes and the other one is a robertsonian race (2n=22) homozygous for nine centric fusions (Rb). The F1 hybrids between the two chromosomal races showed a significant decrease in reproductive success and litter size. Such results can be related to the formation of meiotic trivalent in the hybrids leading to the production of viable aneuploid gametes and post-zygotic elimination of embryos due to chromosomal non disjunction events at meiosis. Moreover, testicular histology of F1 and backcross males showed in some cases a breakdown in spermatogenesis. In both females and males, androgens but also estrogens play an important role in gametogenesis. In this study, we have studied aromatase and estrogen receptor alpha (ERalpha) gene expression in the gonads of the two parental races and their chromosomal hybrids. The results showed that aromatase and ERalpha mRNAs are expressed in hybrid males of inter-racial crosses (female22Rb x male40Std and female40Std x male22Rb) and in hybrid females of inter-racial crosses (female22Rb x male40Std) as in the two parental races. However, in hybrid females of inter-racial crosses (female40Std x male22Rb) the amount of aromatase transcripts decreased sharply suggesting that this gene is involved in the breakdown of hybrid fertility in females, but not in males. However, in hybrid males, a putative post-translational modification of this enzyme, in terms of activity, should be verified.

CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes

PubMed Central

Singh, Randeep K.; Dagnino, Lina

2017-01-01

The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation. PMID:27903963

CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

PubMed

Singh, Randeep K; Dagnino, Lina

2017-01-17

The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

Prompt and easy activation by specific thioredoxins of calvin cycle enzymes of Arabidopsis thaliana associated in the GAPDH/CP12/PRK supramolecular complex.

PubMed

Marri, Lucia; Zaffagnini, Mirko; Collin, Valérie; Issakidis-Bourguet, Emmanuelle; Lemaire, Stéphane D; Pupillo, Paolo; Sparla, Francesca; Miginiac-Maslow, Myroslawa; Trost, Paolo

2009-03-01

The Calvin cycle enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) can form under oxidizing conditions a supramolecular complex with the regulatory protein CP12. Both GAPDH and PRK activities are inhibited within the complex, but they can be fully restored by reduced thioredoxins (TRXs). We have investigated the interactions of eight different chloroplast thioredoxin isoforms (TRX f1, m1, m2, m3, m4, y1, y2, x) with GAPDH (A(4), B(4), and B(8) isoforms), PRK and CP12 (isoform 2), all from Arabidopsis thaliana. In the complex, both A(4)-GAPDH and PRK were promptly activated by TRX f1, or more slowly by TRXs m1 and m2, but all other TRXs were ineffective. Free PRK was regulated by TRX f1, m1, or m2, while B(4)- and B(8)-GAPDH were absolutely specific for TRX f1. Interestingly, reductive activation of PRK caged in the complex was much faster than reductive activation of free oxidized PRK, and activation of A(4)-GAPDH in the complex was much faster (and less demanding in terms of reducing potential) than activation of free oxidized B(4)- or B(8)-GAPDH. It is proposed that CP12-assembled supramolecular complex may represent a reservoir of inhibited enzymes ready to be released in fully active conformation following reduction and dissociation of the complex by TRXs upon the shift from dark to low light. On the contrary, autonomous redox-modulation of GAPDH (B-containing isoforms) would be more suited to conditions of very active photosynthesis.

Testing Properties of Boolean Functions

DTIC Science & Technology

2012-01-01

Applying the Hermite decomposition of f and linearity of expectation, E x,y [f(x)f(y) 〈x, y〉] = n∑ i=1 ∑ S,T∈Nn f̂(S)f̂(T )E x [HS(x)xi]E y [ HT (y)yi...otherwise it takes the value 0. Similarly, Ey[ HT (y)yi] = 1 iff T = ei. 38 Part I Exact Query Complexity 39 Chapter 5 Testing Juntas We begin by studying the...1− 2e− 6m /2 = 1− 2e−O( √ n). The estimate ν̃ is a U-statistic with kernel ψ∗f . This kernel satisfies ‖ψ∗f − Eψ∗f‖∞ ≤ 2‖ψ∗f‖∞ = 2 √ 4n log(4n/3

MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb repressive complex PRC1.6

PubMed Central

Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten

2018-01-01

Diverse Polycomb repressive complexes 1 (PRC1) play essential roles in gene regulation, differentiation and development. Six major groups of PRC1 complexes that differ in their subunit composition have been identified in mammals. How the different PRC1 complexes are recruited to specific genomic sites is poorly understood. The Polycomb Ring finger protein PCGF6, the transcription factors MGA and E2F6, and the histone-binding protein L3MBTL2 are specific components of the non-canonical PRC1.6 complex. In this study, we have investigated their role in genomic targeting of PRC1.6. ChIP-seq analysis revealed colocalization of MGA, L3MBTL2, E2F6 and PCGF6 genome-wide. Ablation of MGA in a human cell line by CRISPR/Cas resulted in complete loss of PRC1.6 binding. Rescue experiments revealed that MGA recruits PRC1.6 to specific loci both by DNA binding-dependent and by DNA binding-independent mechanisms. Depletion of L3MBTL2 and E2F6 but not of PCGF6 resulted in differential, locus-specific loss of PRC1.6 binding illustrating that different subunits mediate PRC1.6 loading to distinct sets of promoters. Mga, L3mbtl2 and Pcgf6 colocalize also in mouse embryonic stem cells, where PRC1.6 has been linked to repression of germ cell-related genes. Our findings unveil strikingly different genomic recruitment mechanisms of the non-canonical PRC1.6 complex, which specify its cell type- and context-specific regulatory functions. PMID:29381691

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection.

PubMed

Subramanian, T; Zhao, Ling-Jun; Chinnadurai, G

2013-09-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

PubMed Central

Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G.

2013-01-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. PMID:23747199

Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S

PubMed Central

Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Rivera, Alicia; Heneghan, John F.; Li, Xiaojin; Hsu, Ann; Karpatkin, Margaret; O'Neill, Allison F.; Bauer, Daniel E.; Heeney, Matthew M.; John, Kathryn; Kuypers, Frans A.; Gallagher, Patrick G.; Lux, Samuel E.; Brugnara, Carlo; Westhoff, Connie M.

2011-01-01

Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li+ and 86Rb+, with secondarily increased 86Rb+ influx sensitive to ouabain and to bumetanide. Increased RhAG-associated 14C-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li+, 86Rb+, and 14C-MA were pharmacologically distinct, and Li+ uptakes associated with RhAG and RhAG F65S were differentially inhibited by NH4+ and Gd3+. RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH3/NH4+, but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA+). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH4Cl, but MA/MA+ elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li+ substitution or bath addition of 5 mM NH4Cl or MA/MA+. These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH3/NH4+ and MA/MA+; 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA+ transport, and decreased NH3/NH4+-associated depolarization; and 3) RhAG transports NH3/NH4+ and MA/MA+ by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms. PMID:21849667

Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes.

PubMed

Zaragoza, Katrin; Bégay, Valérie; Schuetz, Anja; Heinemann, Udo; Leutz, Achim

2010-05-01

The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/EBPalpha transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity toward DNA and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 4, Volume 3, Appendix 11: Final Pathology Report

DTIC Science & Technology

1984-04-01

bladder 1 muscle, s k e l e t a l 5 bone marrow smear --- 3 nasal t u rb ina tes *ti ~ s u e masses ,- and any o the r t i ssues w i t h...Lymphoma, lymphocytic type .__ - __ __ ___ .____. . _ - --- Fibrosarcoma , me ta s t a t i c - __ .._._- _ __._ - - .- Granulosa-cell Carcinoma... Fibrosarcoma , m e t a s t a t i c . -- RENAL LYMPH NODE -- E ’ L - --.I- t Malignant Lymphoma, mixed type Malignant

Word Frequency Analysis MOS: 15E. Skill Levels 1 and 2.

DTIC Science & Technology

1982-05-01

AR 34 ARE I I AREA1 L 5 15 ARM 1 .: 𔃻A’FNT 3 AROL D 25 AS 12 ASSEI 3LE 12 ASSEPALED11 iES b8 ASSEMBLY 4 ASSISTA CE27 ASSISTANT13 1’A T . SSISTED 29 ...CABLE31 CA3Lr.P 2, C.ABLES . . 1 L.BLI"IG I CAM C>; 4 CA’"UT 2 CANvA S 29 CAP2 CYPSCRE ,S 4 CAPTIVE A , L I AR o,7 CAREFiULLY .... CARRY IG 2 LA.TELL 1...1 (l. 5 1 jS I E (f r I FR I 5 IP E V PEET ~ (F I 4 3 E X P N A WL S q 6 XPL11S VE E EXPIUSIVS I z~ SE 17 *.!GU I 5 EXTE nrEC 3 WI’S1. lltj 3 29 ~Il

Phase Behavior of Complex Superprotonic Solid Acids

NASA Astrophysics Data System (ADS)

Panithipongwut, Chatr

Superprotonic phase transitions and thermal behaviors of three complex solid acid systems are presented, namely Rb3H(SO4) 2-RbHSO4 system, Rb3H(SeO4)2-Cs 3H(SeO4)2 solid solution system, and Cs6 (H2SO4)3(H1.5PO4) 4. These material systems present a rich set of phase transition characteristics that set them apart from other, simpler solid acids. A.C. impedance spectroscopy, high-temperature X-ray powder diffraction, and thermal analysis, as well as other characterization techniques, were employed to investigate the phase behavior of these systems. Rb3H(SO4)2 is an atypical member of the M3H(XO4)2 class of compounds (M = alkali metal or NH4+ and X = S or Se) in that a transition to a high-conductivity state involves disproportionation into two phases rather than a simple polymorphic transition [1]. In the present work, investigations of the Rb3H(SO4)2-RbHSO4 system have revealed the disproportionation products to be Rb2SO 4 and the previously unknown compound Rb5H3(SO 4)4. The new compound becomes stable at a temperature between 25 and 140 °C and is isostructural to a recently reported trigonal phase with space group P3m of Cs5H 3(SO4)4 [2]. At 185 °C the compound undergoes an apparently polymorphic transformation with a heat of transition of 23.8 kJ/mol and a slight additional increase in conductivity. The compounds Rb3H(SeO4)2 and Cs 3H(SeO4)2, though not isomorphous at ambient temperatures, are quintessential examples of superprotonic materials. Both adopt monoclinic structures at ambient temperatures and ultimately transform to a trigonal (R3m) superprotonic structure at slightly elevated temperatures, 178 and 183 °C, respectively. The compounds are completely miscible above the superprotonic transition and show extensive solubility below it. Beyond a careful determination of the phase boundaries, we find a remarkable 40-fold increase in the superprotonic conductivity in intermediate compositions rich in Rb as compared to either end-member. The compound Cs6(H2SO4)3(H 1.5PO4)4 is unusual amongst solid acid compounds in that it has a complex cubic structure at ambient temperature and apparently transforms to a simpler cubic structure of the CsCl-type (isostructural with CsH2PO4) at its transition temperature of 100-120 °C [3]. Here it is found that, depending on the level of humidification, the superprotonic transition of this material is superimposed with a decomposition reaction, which involves both exsolution of (liquid) acid and loss of H2O. This reaction can be suppressed by application of sufficiently high humidity, in which case Cs6(H2SO4)3(H 1.5PO4)4 undergoes a true superprotonic transition. It is proposed that, under conditions of low humidity, the decomposition/dehydration reaction transforms the compound to Cs6(H2-0.5xSO 4)3(H1.5PO4)4-x, also of the CsCl structure type at the temperatures of interest, but with a smaller unit cell. With increasing temperature, the decomposition/dehydration proceeds to greater and greater extent and unit cell of the solid phase decreases. This is identified to be the source of the apparent negative thermal expansion behavior. References: [1] L.A. Cowan, R.M. Morcos, N. Hatada, A. Navrotsky, S.M. Haile, Solid State Ionics 179 (2008) (9-10) 305. [2] M. Sakashita, H. Fujihisa, K.I. Suzuki, S. Hayashi, K. Honda, Solid State Ionics 178 (2007) (21-22) 1262. [3] C.R.I. Chisholm, Superprotonic Phase Transitions in Solid Acids: Parameters affecting the presence and stability of superprotonic transitions in the MHnXO4 family of compounds (X=S, Se, P, As; M=Li, Na, K, NH4, Rb, Cs), Materials Science, California Institute of Technology, Pasadena, California (2003).

Synthesis and structure of the first discrete dinuclear cationic aluminum complexes.

PubMed

Wang, Xingbao; Dorcet, Vincent; Luo, Yi; Carpentier, Jean-Francois; Kirillov, Evgueni

2016-08-02

The reactions of the charge neutral dinuclear aluminum tetraalkyl complexes of di-Schiff base ligands, i.e. [AlMe2{ON}-R-{ON}AlMe2] (1a, R = 1,3-propylene; 1b, R = 1,3-cyclohexylene) with B(C6F5)3 and [H(Et2O)2](+)[H2N{B(C6F5)3}2](-) were investigated. When B(C6F5)3 was used as the cationizing agent (1 or 2 equiv. vs. Al), only monocationic dinuclear complexes [2a,b]+[MeB(C6F5)3]- were obtained. In contrast, with [H(Et2O)2](+)[H2N{B(C6F5)3}2](-), both mixed-dicationic [3a,b·(OEt2)2]2+[MeB(C6F5)3]-[H2N{B(C6F5)3}2]- and homo-dicationic [3a,b·(OEt2)2]2+[H2N{B(C6F5)3}2]-2 ion-pairs were prepared. All cationic complexes were characterized by (1)H, (13)C, (19)F and (11)B NMR spectroscopy, and an X-ray diffraction study was performed for [3b·(OEt2)2]2+[H2N{B(C6F5)3}2]-2.

Ab Initio Study of Chemical Reactions of Cold SrF and CaF Molecules with Alkali-Metal and Alkaline-Earth-Metal Atoms: The Implications for Sympathetic Cooling.

PubMed

Kosicki, Maciej Bartosz; Kędziera, Dariusz; Żuchowski, Piotr Szymon

2017-06-01

We investigate the energetics of the atom exchange reaction in the SrF + alkali-metal atom and CaF + alkali-metal atom systems. Such reactions are possible only for collisions of SrF and CaF with the lithium atoms, while they are energetically forbidden for other alkali-metal atoms. Specifically, we focus on SrF interacting with Li, Rb, and Sr atoms and use ab initio methods to demonstrate that the SrF + Li and SrF + Sr reactions are barrierless. We present potential energy surfaces for the interaction of the SrF molecule with the Li, Rb, and Sr atoms in their energetically lowest-lying electronic spin states. The obtained potential energy surfaces are deep and exhibit profound interaction anisotropies. We predict that the collisions of SrF molecules in the rotational or Zeeman excited states most likely have a strong inelastic character. We discuss the prospects for the sympathetic cooling of SrF and CaF molecules using ultracold alkali-metal atoms.

Role of XIAP in Therapeutic Resistance in Inflammatory Breast Cancer

DTIC Science & Technology

2009-07-01

antibody a nd l apatinib , a s mall m olecule E rbB1/2 kinase inhibitor. However, acquired resistance is a common outcome even in those IBC patients...t rastuzumab a nd G W583340 ( a l apatinib a nalog) i n a n i n vi vo S UM190 xenograft i mageable t umor m odel. In s tudies c onducted t o d ate...trastuzumab, an anti-ErbB2 antibody a nd l apatinib , a s mall molecule E rbB1/2 ki nase i nhibitor. H owever, acquired resistance is a common

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS, HIGH BAY AREA. ...

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

Photocopy of drawing. VEHICLE ASSEMBLY BUILDING MODIFICATIONS, HIGH BAY AREA. NASA John F. Kennedy Space Center, Florida. File Number 79K05424, Seelye Stevenson Value & Knecht, March 1975. TRANSFER AISLE NORTH DOOR,ARCHITECTURAL NORTH ELEVATION AND MISC. DETAILS. Sheet 78 of 207 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed Central

Deaton, J D; Guerrero, T; Howard, T H

1992-01-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin independent. PMID:1337290

Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils.

PubMed

Deaton, J D; Guerrero, T; Howard, T H

1992-12-01

In vitro Ca++ activates gelsolin to sever F-actin and form a gelsolin-actin (GA) complex at the+end of F-actin that is not dissociated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) but is separated by EGTA+PIP/PIP2. The gelsolin blocks the+end on the actin filament, but the-end of the filament can still initiate actin polymerization. In thrombin activated platelets, evidence suggests that severing of F-actin by gelsolin increases GA complex, creates one-end actin nucleus and one cryptic+end actin nucleus per cut, and then dissociates to yield free+ends to nucleate rapid actin assembly. We examined the role of F-actin severing in creation and regulation of nuclei and polymerization in polymorphonuclear neutrophils (PMNs). At 2-s intervals after formyl peptide (FMLP) activation of endotoxin free (ETF) PMNs, change in GA complex was correlated with change in+end actin nuclei,-end actin nuclei, and F-actin content. GA complex was quantitated by electrophoretograms of proteins absorbed by antigelsolin from cells lysed in 10 mM EGTA,+end actin nuclei as cytochalasin (CD) sensitive and-end actin nuclei as CD insensitive increases in G-pyrenyl actin polymerization rates induced by the same PMNs, and F-actin content by NBDphallacidin binding to fixed cells. Thirty three percent of gelsolin was in GA complex in basal ETF PMNs; from 2-6 s, GA complexes dissociate (low = 15% at 10 s) and sequentially+end nuclei and F-actin content and then-end nuclei increase to a maximum at 10 s. At > s GA complex increase toward basal and + end nuclei and F-actin content returned toward basal. These kinetic data show gelsolin regulates availability of + end nuclei and actin polymerization in FMLP. However, absence of an initial increase in GA complex or - end nucleating activity shows FMLP activation does not cause gelsolin to sever F- or to bind G-actin to create cryptic + end nuclei in PMNs; the results suggest the + nucleus formation is gelsolin independent.

dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes

PubMed Central

Korenjak, Michael; Kwon, Eunjeong; Morris, Robert T.; Anderssen, Endre; Amzallag, Arnaud; Ramaswamy, Sridhar; Dyson, Nicholas J.

2014-01-01

dREAM complexes represent the predominant form of E2F/RBF repressor complexes in Drosophila. dREAM associates with thousands of sites in the fly genome but its mechanism of action is unknown. To understand the genomic context in which dREAM acts we examined the distribution and localization of Drosophila E2F and dREAM proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM sites and binding sites for the insulator-binding proteins CP190 and Beaf-32. Genetic assays show that these components functionally co-operate and chromatin immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is important for association of CP190 with chromatin. dE2F2/dREAM binding sites are enriched at divergently transcribed genes, and the majority of genes upregulated by dE2F2 depletion represent the repressed half of a differentially expressed, divergently transcribed pair of genes. Analysis of mutant animals confirms that dREAM and CP190 are similarly required for transcriptional integrity at these gene pairs and suggest that dREAM functions in concert with CP190 to establish boundaries between repressed/activated genes. Consistent with the idea that dREAM co-operates with insulator-binding proteins, genomic regions bound by dREAM possess enhancer-blocking activity that depends on multiple dREAM components. These findings suggest that dREAM functions in the organization of transcriptional domains. PMID:25053843

Assembly and Transfer of Iron–Sulfur Clusters in the Plastid

PubMed Central

Lu, Yan

2018-01-01

Iron-Sulfur (Fe-S) clusters and proteins are essential to many growth and developmental processes. In plants, they exist in the plastids, mitochondria, cytosol, and nucleus. Six types of Fe-S clusters are found in the plastid: classic 2Fe-2S, NEET-type 2Fe-2S, Rieske-type 2Fe-2S, 3Fe-4S, 4Fe-4S, and siroheme 4Fe-4S. Classic, NEET-type, and Rieske-type 2Fe-2S clusters have the same 2Fe-2S core; similarly, common and siroheme 4Fe-4S clusters have the same 4Fe-4S core. Plastidial Fe-S clusters are assembled by the sulfur mobilization (SUF) pathway, which contains cysteine desulfurase (EC 2.8.1.7), sulfur transferase (EC 2.8.1.3), Fe-S scaffold complex, and Fe-S carrier proteins. The plastidial cysteine desulfurase-sulfur transferase-Fe-S-scaffold complex system is responsible for de novo assembly of all plastidial Fe-S clusters. However, different types of Fe-S clusters are transferred to recipient proteins via respective Fe-S carrier proteins. This review focuses on recent discoveries on the molecular functions of different assembly and transfer factors involved in the plastidial SUF pathway. It also discusses potential points for regulation of the SUF pathway, relationships among the plastidial, mitochondrial, and cytosolic Fe-S assembly and transfer pathways, as well as several open questions about the carrier proteins for Rieske-type 2Fe-2S, NEET-type 2Fe-2S, and 3F-4S clusters. PMID:29662496

BAR Proteins PSTPIP1/2 Regulate Podosome Dynamics and the Resorption Activity of Osteoclasts

PubMed Central

Sztacho, Martin; Segeletz, Sandra; Sanchez-Fernandez, Maria Arantzazu; Czupalla, Cornelia; Niehage, Christian; Hoflack, Bernard

2016-01-01

Bone resorption in vertebrates relies on the ability of osteoclasts to assemble F-actin-rich podosomes that condense into podosomal belts, forming sealing zones. Sealing zones segregate bone-facing ruffled membranes from other membrane domains, and disassemble when osteoclasts migrate to new areas. How podosome/sealing zone dynamics is regulated remains unknown. We illustrate the essential role of the membrane scaffolding F-BAR-Proline-Serine-Threonine Phosphatase Interacting Proteins (PSTPIP) 1 and 2 in this process. Whereas PSTPIP2 regulates podosome assembly, PSTPIP1 regulates their disassembly. PSTPIP1 recruits, through its F-BAR domain, the protein tyrosine phosphatase non-receptor type 6 (PTPN6) that de-phosphophorylates the phosphatidylinositol 5-phosphatases SHIP1/2 bound to the SH3 domain of PSTPIP1. Depletion of any component of this complex prevents sealing zone disassembly and increases osteoclast activity. Thus, our results illustrate the importance of BAR domain proteins in podosome structure and dynamics, and identify a new PSTPIP1/PTPN6/SHIP1/2-dependent negative feedback mechanism that counterbalances Src and PI(3,4,5)P3 signalling to control osteoclast cell polarity and activity during bone resorption. PMID:27760174

[Active constituents reducing side-effects of prednisone acetate in leaves of Panax ginseng C.A.Mey].

PubMed

Dou, D; Wen, Y; Pei, Y; Chen, Y; Ma, Z

1997-03-01

The rise of total lipid, triglyceride and total cholesterol, and the drop of cortisol in serum induced by PA can be significantly inhibited by total ginsenosides in the leaves of Panax ginseng [GSL, 60 mg/(kg.d)]. From GSL ten compounds have been isolated and identified as ginsenoside-Rb2, -Rc, -Rd, -Re, -Rg1 -F3, F2, -Rg2, 20(R)-Rg2 and -Rh1, respectively. Pharmacological study has proved ginsenoside-Re to be the chief active constituent of GSL.

Structure of UreG/UreF/UreH Complex Reveals How Urease Accessory Proteins Facilitate Maturation of Helicobacter pylori Urease

PubMed Central

Fong, Yu Hang; Wong, Ho Chun; Yuen, Man Hon; Lau, Pak Ho; Chen, Yu Wai; Wong, Kam-Bo

2013-01-01

Urease is a metalloenzyme essential for the survival of Helicobacter pylori in acidic gastric environment. Maturation of urease involves carbamylation of Lys219 and insertion of two nickel ions at its active site. This process requires GTP hydrolysis and the formation of a preactivation complex consisting of apo-urease and urease accessory proteins UreF, UreH, and UreG. UreF and UreH form a complex to recruit UreG, which is a SIMIBI class GTPase, to the preactivation complex. We report here the crystal structure of the UreG/UreF/UreH complex, which illustrates how UreF and UreH facilitate dimerization of UreG, and assembles its metal binding site by juxtaposing two invariant Cys66-Pro67-His68 metal binding motif at the interface to form the (UreG/UreF/UreH)2 complex. Interaction studies revealed that addition of nickel and GTP to the UreG/UreF/UreH complex releases a UreG dimer that binds a nickel ion at the dimeric interface. Substitution of Cys66 and His68 with alanine abolishes the formation of the nickel-charged UreG dimer. This nickel-charged UreG dimer can activate urease in vitro in the presence of the UreF/UreH complex. Static light scattering and atomic absorption spectroscopy measurements demonstrated that the nickel-charged UreG dimer, upon GTP hydrolysis, reverts to its monomeric form and releases nickel to urease. Based on our results, we propose a mechanism on how urease accessory proteins facilitate maturation of urease. PMID:24115911

A Simulation Model Depicting Fleet Expansion Effects on the Fire Control Technicians Training Pipeline.

DTIC Science & Technology

1982-06-01

35 682 SSIO S GN* I TR B(I NOW; NIE* 3uE 663 t010 JsUjUE(4.g),7,. SEL4 ; O-IE* UU 665 * SR T 2; TRAVEL To a SCHOOL 666 AO9 1j( ),jQ35:SLI; FJTfSL JAT...INPUT 66a tET. .ATR 4 .Q 36 SSLI; E 5LT ~u 664 ICT,,,PIPL; 87’ OPL As 5IGNvATRISI4)*S:5Tl SLI AS I’NATR1413IUT4Ow; Qk~~ UU 672 all Q3UE’Jf(4’.1 ,, SEL4 ...WAT RB() FLEE INPU m3; 689 012 OUQUEE52).,,, SEL4 ; LE -PT;EJ bQ0 T126 rREA TE9289O; 691 TgF54 692 CAEAtE*159a,1; OSVET INPUT IOENTIFIED 643 ACT: 694

Reconstitution of the Recombinant RanBP2 SUMO E3 Ligase Complex.

PubMed

Ritterhoff, Tobias; Das, Hrishikesh; Hao, Yuqing; Sakin, Volkan; Flotho, Annette; Werner, Andreas; Melchior, Frauke

2016-01-01

One of the few proteins that have SUMO E3 ligase activity is the 358 kDa nucleoporin RanBP2 (Nup358). While small fragments of RanBP2 can stimulate SUMOylation in vitro, the physiologically relevant E3 ligase is a stable multi-subunit complex comprised of RanBP2, SUMOylated RanGAP1, and Ubc9. Here, we provide a detailed protocol to in vitro reconstitute the RanBP2 SUMO E3 ligase complex. With the exception of RanBP2, reconstitution involves untagged full-length proteins. We describe the bacterial expression and purification of all complex components, namely an 86 kDa His-tagged RanBP2 fragment, the SUMO E2-conjugating enzyme Ubc9, RanGAP1, and SUMO1, and we provide a protocol for quantitative SUMOylation of RanGAP1. Finally, we present details for the assembly and final purification of the catalytically active RanBP2/RanGAP1*SUMO1/Ubc9 complex.

Penetration of alkali atoms throughout a graphene membrane: theoretical modeling

NASA Astrophysics Data System (ADS)

Boukhvalov, D. W.; Virojanadara, C.

2012-02-01

Theoretical studies of penetration of various alkali atoms (Li, Na, Rb, Cs) throughout a graphene membrane grown on a silicon carbide substrate are reported and compared with recent experimental results. Results of first principles modeling demonstrate a rather low (about 0.8 eV) energy barrier for the formation of temporary defects in the carbon layer required for the penetration of Li at a high concentration of adatoms, a higher (about 2 eV) barrier for Na, and barriers above 4 eV for Rb and Cs. Experiments prove migration of lithium adatoms from the graphene surface to the buffer layer and SiC substrate at room temperature, sodium at 100 °C and impenetrability of the graphene membrane for Rb and Cs. Differences between epitaxial and free-standing graphene for the penetration of alkali ions are also discussed.

Penetration of alkali atoms throughout a graphene membrane: theoretical modeling.

PubMed

Boukhvalov, D W; Virojanadara, C

2012-03-07

Theoretical studies of penetration of various alkali atoms (Li, Na, Rb, Cs) throughout a graphene membrane grown on a silicon carbide substrate are reported and compared with recent experimental results. Results of first principles modeling demonstrate a rather low (about 0.8 eV) energy barrier for the formation of temporary defects in the carbon layer required for the penetration of Li at a high concentration of adatoms, a higher (about 2 eV) barrier for Na, and barriers above 4 eV for Rb and Cs. Experiments prove migration of lithium adatoms from the graphene surface to the buffer layer and SiC substrate at room temperature, sodium at 100 °C and impenetrability of the graphene membrane for Rb and Cs. Differences between epitaxial and free-standing graphene for the penetration of alkali ions are also discussed.

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

PubMed Central

Singh, Randeep K.; Dagnino, Lina

2016-01-01

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

Variation in 12 porcine genes involved in the carbohydrate moiety assembly of glycosphingolipids does not account for differential binding of F4 Escherichia coli and their fimbriae.

PubMed

Goetstouwers, Tiphanie; Van Poucke, Mario; Coddens, Annelies; Nguyen, Van Ut; Melkebeek, Vesna; Deforce, Dieter; Cox, Eric; Peelman, Luc J

2014-10-03

Glycosphingolipids (GSLs) are important membrane components composed of a carbohydrate structure attached to a hydrophobic ceramide. They can serve as specific membrane receptors for microbes and microbial products, such as F4 Escherichia coli (F4 ETEC) and isolated F4 fimbriae. The aim of this study was to investigate the hypothesis that variation in genes involved in the assembly of the F4 binding carbohydrate moiety of GSLs (i.e. ARSA, B4GALT6, GAL3ST1, GALC, GBA, GLA, GLB1, GLB1L, NEU1, NEU2, UGCG, UGT8) could account for differential binding of F4 ETEC and their fimbriae. RT-PCR could not reveal any differential expression of the 12 genes in the jejunum of F4 receptor-positive (F4R(+)) and F4 receptor-negative (F4R(-)) pigs. Sequencing the complete open reading frame of the 11 expressed genes (NEU2 was not expressed) identified 72 mutations. Although some of them might have a structural effect, none of them could be associated with a F4R phenotype. We conclude that no regulatory or structural variation in any of the investigated genes is responsible for the genetic susceptibility of pigs towards F4 ETEC.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

PubMed Central

Siefker-Radtke, Arlene; Zhang, Xin-qiao; Guo, Charles C; Shen, Yu; Pirollo, Kathleen F; Sabir, Sharjeel; Leung, Chris; Leong-Wu, Cindy; Ling, Chi-Ming; Chang, Esther H; Millikan, Randall E; Benedict, William F

2016-01-01

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy. PMID:27480598

New Metacentric Populations and Phylogenetic Hypotheses Involving Whole-Arm Reciprocal Translocation in Mus musculus domesticus from Sicily, Southern Italy.

PubMed

Castiglia, Riccardo; Capanna, Ernesto; Bezerra, Alexandra M R; Bizzoco, Domenico; Zambigli, Emanuela; Solano, Emanuela

2015-01-01

The house mouse Mus musculus domesticus is characterized by more than 100 metacentric populations, due to the occurrence of Robertsonian (Rb) fusions, together with the standard all-telocentric karyotype (2n = 40). We examined G-banded karyotypes of 18 mice from 10 localities in Sicily and describe 3 new metacentric populations: 'Ragusa Ibla' (IRAG), 2n = 33-36, Rb(2.4), Rb(5.6), Rb(9.16), Rb(13.17); 'Piana degli Albanesi' (IPIA), 2n = 23, Rb(1.18), Rb(2.15), Rb(3.5), Rb(4.12), Rb(6.11), Rb(7.8), Rb(9.16), Rb(10.14), Rb(13.17); 'Trapani' (ITRA), 2n = 22, Rb(1.18), Rb(2.15), Rb(3.7), Rb(4.12), Rb(5.9), Rb(6.11), Rb(8.16), Rb(10.14), Rb(13.17). Three mice belonged to the previously reported 'Castelbuono' race (ICAS), 2n = 24, which is very similar to the nearby 'Palermo' (IPAL) race, 2n = 26. Three Rb fusions not yet observed in wild mouse populations were identified: Rb(3.5), Rb(3.7) and Rb(5.9). Rb fusions shared among 4 races (IPIA, IRAG, ICAS, and IPAL) allowed us to describe their potential phylogenetic relationships. We obtained 2 alternative phylogenetic trees. The differences between them are mainly due to various modes of formation of IPIA and ITRA. In the first hypothesis, the specific Rb fusions occurred independently. In the second, those of IRAG originated from those of IPIA via whole-arm reciprocal translocations. © 2015 S. Karger AG, Basel.

Structural Studies of the pRB Tumor Suppressor Complexed with Human Papillomavirus E7 Proteins.

DTIC Science & Technology

1999-06-01

HAT 1 (yeast histone acetyltransferase 1) and SmAAT ( Serratia marcescens aminoglycoside 3 N-acetyltransferase), implicates the mode of substrate...of PCAF appears to be similar for both free and nuclecsomal histories . Surprisingly, PCAF has also been reported to acetylate noa-histone substrates...FAX +44 1865 267798 OUP SMJ JNLS @009 Cd\\c> s Crystal structurt of th« PCAF-eoenzym« A complex B Fig. 4. Historie ncetyltransferwe active site

On the molecular and supramolecular properties of N,N‧-disubstituted iminoisoindolines: Synthesis, spectroscopy, X-ray structure and Hirshfeld surface analyses, and DFT calculations of two (E)-N,N‧-bis(aryl)iminoisoindolines (aryl = 2-tert-butylphenyl or perfluorophenyl)

NASA Astrophysics Data System (ADS)

Bitzer, Rodrigo S.; Visentin, Lorenzo C.; Hörner, Manfredo; Nascimento, Marco A. C.; Filgueiras, Carlos A. L.

2017-02-01

Supramolecular studies of iminoisoindoline-derived compounds have been prompted by their biological and photophysical properties. In this article, we report the synthesis, spectroscopy, X-ray structural characterization, and DFT study of two N,N‧-(aryl)-disubstituted 1-iminoisoindolines, namely (E)-N,N‧-bis(2-tert-butylphenyl)iminoisoindoline (2-t-BuPhimiso) and (E)-N,N‧-bis(perfluorophenyl)iminoisoindoline (F5Phimiso). Our X-ray structural analyses have shown that the isoindoline N2 atom of 2-t-BuPhimiso is slightly pyramidalized whereas the respective atom of F5Phimiso displays the expected trigonal planar geometry. The supramolecular arrangement of 2-t-BuPhimiso comprises one-dimensional chains along the [101] direction formed by Csbnd H···πarene interactions, in which the isoindoline ring behaves as a hydrogen-bond donor. For 2-t-BuPhimiso, DFT calculations at the B97-D3/6-311G** level have shown that the dimer formed by this Csbnd H···πarene contact displays a binding energy of -12.83 kcal mol-1. Product F5Phimiso assembles in the crystal state through type-I F3 synthons in addition to Csbnd H⋯F, C-Fδ-···πF+, and πarene/F-πarene/F stacking interactions. Accordingly, our DFT-D3 calculations have confirmed that these interactions synergistically play a dominating role in the crystal packing of F5Phimiso. Finally, the relative stability of the (Z) and (E) isomers of each product has been evaluated at the DFT level of theory. Our calculations have shown that the (E) forms are the most stable ones.

Lactation performance of Holstein cows treated with 2 formulations of recombinant bovine somatotropin in a large commercial dairy herd in Brazil.

PubMed

de Morais, J P G; da S Cruz, A P; Minami, N S; Veronese, L P; Del Valle, T A; Aramini, J

2017-07-01

The objectives of this controlled study were to compare the effects of 2 different formulations of recombinant bovine somatotropin (rbST) on milk yield, milk composition (fat and protein), milk somatic cell count, and body condition score (BCS) among dairy cattle in a large commercial herd. Regulatory approved 500-mg zinc sesame oil base rbST (ZSO-rbST; Elanco Animal Health, Greenfield, IN) and vitamin E lecithin base rbST (VEL-rbST; LG Life Sciences, Seoul, South Korea) formulations were administered per the manufacturers' recommendations every 14 d over 17 injection cycles starting at 57 to 70 d of lactation (90 cows per rbST group). Control cows (n = 60) received no rbST. Somatotropin-treated animals (VEL-rbST and ZSO-rbST combined) had increased average milk yield and protein percentage and lower average BCS compared with control cows. For primiparous cows, average milk yield was 37.75 kg/d with the ZSO-rbST treatment and 35.72 kg/d with the VEL-rbST treatment. For multiparous cows, average milk yield was 40.13 kg/d with the ZSO-rbST treatment and 38.81 kg/d with the VEL-rbST treatment. There were no differences in milk fat percentage between VEL-rbST and ZSO-rbST treatments, but milk protein content was greater with VEL-rbST treatment than with ZSO-rbST treatment. Nonetheless, cows treated with ZSO-rbST yielded more kilograms of fat and protein per day than cows treated with VEL-rbST. No significant differences in BCS were found between both rbST treatment groups. The differential increase in milk yield between cows treated with ZSO-rbST and VEL-rbST was driven by rbST response differences both within the 14-d cycle and throughout the 17 injection cycles. The cows treated with VEL-rbST demonstrated a more variable 14-d milk yield response curve, with more pronounced valleys between injections compared with the ZSO-rbST formulation. In addition, only the ZSO-rbST treatment was effective in modifying the lactation persistency compared with control cows. Compared with the VEL-rbST formulation, the ZSO-rbST formulation yielded more kilograms of milk, fat, and protein with less milk variation throughout the seventeen 14-d lactation cycles for both primiparous and multiparous cows. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Effects of guest atomic species on the lattice thermal conductivity of type-I silicon clathrate studied via classical molecular dynamics

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

Kumagai, Tomohisa, E-mail: kumagai@criepi.denken.or.jp; Nakamura, Kaoru; Yamada, Susumu

The effects of guest atomic species in Si clathrates on the lattice thermal conductivity were studied using classical molecular dynamics calculations. The interaction between a host atom and a guest atom was described by the Morse potential function while that between host atoms was described by the Tersoff potential. The parameters of the potentials were newly determined for this study such that the potential curves obtained from first-principles calculations for the insertion of a guest atom into a Si cage were successfully reproduced. The lattice thermal conductivities were calculated by using the Green-Kubo method. The experimental lattice thermal conductivity ofmore » Ba{sub 8}Ga{sub 16}Si{sub 30} can be successfully reproduced using the method. As a result, the lattice thermal conductivities of type-I Si clathrates, M{sub 8}Si{sub 46} (M = Na, Mg, K, Ca Rb, Sr, Cs, or Ba), were obtained. It is found that the lattice thermal conductivities of M{sub 8}Si{sub 46}, where M is IIA elements (i.e., M = Mg, Ca, Sr, or Ba) tend to be lower than those of M{sub 8}Si{sub 46}, where M is IA elements (i.e., M = Na, K, Rb, or Cs). Those of {sup m}M{sub 8}Si{sub 46}, where m was artificially modified atomic weight were also obtained. The obtained lattice thermal conductivity can be regarded as a function of a characteristic frequency, f{sub c}. That indicates minimum values around f{sub c}=2-4 THz, which corresponds to the center of the frequencies of the transverse acoustic phonon modes associated with Si cages.« less

Effect of alkaline metal cations on the ionic structure of cryolite melts: Ab-initio NpT MD study.

PubMed

Bučko, Tomáš; Šimko, František

2018-02-14

Ab initio molecular dynamics simulations in an NpT ensemble have been performed to study the role of alkaline metal cations (Me = Li, Na, K, Rb) on the structure and vibrational properties of melts of Me-cryolites (Me 3 AlF 6 ) at T = 1300 K. In all melts examined in this work, the species AlF 5 2- has been found to be formed at the highest abundance [from 58% (Li) to 70% (Na)] among the Al-containing anionic clusters. The concentration of clusters AlF 4 - increases with the size of cations while that of anions AlF 6 3- follows the opposite trend and it becomes negligible in the melts of the K- and Rb-cryolites. The computed percentage of the Al atoms participating in the formation of dimers Al 2 F m 6-m bridged via common F atoms is significant only in the case of Li- and Na-cryolites (16% and 10%, respectively) and the formation of even larger aggregates is found to be unlikely in all four melts. The percentage of the F atoms that are not bound to Al is ∼20% in all four melts and the ions formed by Me + and F - are found to be only short-lived. Vibrational analysis has been performed using the velocity autocorrelation functions computed for the Cartesian and selected internal coordinates describing Raman-active symmetric stretching vibrations of different AlF n species. The results of vibrational analysis allowed us to identify trends in the variation of positions and shapes of peaks corresponding to the anionic fragments AlF 4 - , AlF 5 2- , and AlF 6 3- with the size of cations, and these trends are found to be consistent with those deduced from the available Raman spectroscopy experiments. Our findings represent a new insight into the properties of cryolite melts, which will be useful for the interpretation of experimental data.

Rare earth abundances and Rb-Sr systematics of basalts, gabbro, anorthosite and minor granitic rocks from the Indian Ocean Ridge System, Western Indian Ocean

USGS Publications Warehouse

Hedge, C.E.; Futa, K.; Engel, C.G.; Fisher, R.L.

1979-01-01

Basalts dredged from the Mid-Indian Ocean Ridge System have rare earth, Rb, and Sr concentrations like those from other mid-ocean ridges, but have slightly higher Sr87/Sr86 ratios. Underlying gabbroic complexes are similar to the basalts in Sr87/Sr86, but are poorer K, Rb, and in rare earths. The chemical and isotopic data, as well as the geologic relations suggest a cumulate origin for the bulk of the gabbroic complexes. ?? 1979 Springer-Verlag.

High-Temperature Transitions in Metallopolymers Crosslinked With 2,6-bis(1’-methylbenzimidazolyl)pyridine Metal-Ligand Complex

DTIC Science & Technology

2013-10-01

2005, 127 (51), 18202–18211. 9. Cordier, P.; Tournilhac, F.; Soulie-Ziakovic, C.; Leibler, L. Self - Healing And Thermoreversible Rubber From...Supramolecular Assembly. Nature 2008, 451 (7181), 977–980. 10. Colquhoun, H. M. Self -Repairing Ploymers: Materials that Heal Themselves. Nat. Chem. 2012, 4...theory of rubber elasticity (27). The work described in this report proposes bond scission of the ML complex and softening of the ML-rich phase as two

The influence of different cucumariosides on immunogenicity of OmpF porin from Yersinia pseudotuberulosis as a model protein antigen of tubular immunostimulating complex

NASA Astrophysics Data System (ADS)

Sanina, N. M.; Chopenko, N. S.; Davydova, L. A.; Mazeika, A. N.; Portnyagina, O. Yu.; Kim, N. Yu.; Golotin, V. A.; Kostetsky, E. Y.; Shnyrov, V. L.

2017-09-01

Nanoparticulate tubular immunostimulating complex (TI-complex) is a novel promising adjuvant carrier of antigens allowing to create safe and effective vaccines of new generation. The adjuvant activity of TI-complexes based on monogalactosyldyacylglycerol (MGDG) from the sea alga Ulva lactuca and different triterpene glycosides cucumariosides (CDs) from marine invertebrate Cucumaria japonica and their fractions was studied to assess effects of different CDs on the immunogenicity of porin OmpF from Yersinia pseudotuberculosis (YOmpF). TI-complexes with cucumarioside A2-2 (CDA2-2) maximally stimulated anti-porin antibody production. Studies of protein intrinsic fluorescence showed that all CDs had a relaxing effect on the conformation of YOmpF, loosening peripheral region of protein and promoting exposure of the protein antigenic determinants to the water environment. The greatest immunostimulating effect of TI-complexes comprising CDA2-2 was accompanied by mild effect of this CD on the tertiary structure of protein antigen YOmpF, whereas cucumarioside E (CDE) and cucumarioside A2-4 (CDA2-4) caused especially sharp redistribution of spectral form of the YOmpF corresponding to the emission of an intrinsic protein fluorophore tryptophan.

Rose bengal-grafted biodegradable microcapsules: singlet-oxygen generation and cancer-cell incapacitation.

PubMed

Wang, Xiao-Lei; Zeng, Yu; Zheng, Yan-Zhen; Chen, Jian-Feng; Tao, Xia; Wang, Ling-Xuan; Teng, Yan

2011-09-26

Rose bengal-grafted chitosan (RB-CHI), synthesized through dehydration between amino and carboxyl functional groups under mild conditions, was coated onto the outer layer of preformed biodegradable microcapsules consisting of sodium alginate and chitosan. The fabricated photosensitive microcapsules were characterized by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The assembled materials maintained intact spherical morphology and thus showed good ability to form thin films. Electron spin resonance spectroscopy allowed direct observation of the generation of singlet oxygen ((1)O(2)) from photosensitive microcapsules under light excitation at about 545 nm. Furthermore, with increasing light radiation, the content of (1)O(2) increased, as detected by a chemical probe. In vitro cellular toxicity assays showed that RB-CHI-coated photosensitive microcapsules exhibit good biocompatibility in darkness and high cytotoxicity after irradiation, and could provide new photoresponsive drug-delivery vehicles. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human Pyruvate Dehydrogenase Complex E2 and E3BP Core Subunits: New Models and Insights from Molecular Dynamics Simulations.

PubMed

Hezaveh, Samira; Zeng, An-Ping; Jandt, Uwe

2016-05-19

Targeted manipulation and exploitation of beneficial properties of multienzyme complexes, especially for the design of novel and efficiently structured enzymatic reaction cascades, require a solid model understanding of mechanistic principles governing the structure and functionality of the complexes. This type of system-level and quantitative knowledge has been very scarce thus far. We utilize the human pyruvate dehydrogenase complex (hPDC) as a versatile template to conduct corresponding studies. Here we present new homology models of the core subunits of the hPDC, namely E2 and E3BP, as the first time effort to elucidate the assembly of hPDC core based on molecular dynamic simulation. New models of E2 and E3BP were generated and validated at atomistic level for different properties of the proteins. The results of the wild type dimer simulations showed a strong hydrophobic interaction between the C-terminal and the hydrophobic pocket which is the main driving force in the intertrimer binding and the core self-assembly. On the contrary, the C-terminal truncated versions exhibited a drastic loss of hydrophobic interaction leading to a dimeric separation. This study represents a significant step toward a model-based understanding of structure and function of large multienzyme systems like PDC for developing highly efficient biocatalyst or bioreaction cascades.

Quenching Capabilities of Long-Chain Carotenoids in Light-Harvesting-2 Complexes from Rhodobacter sphaeroides with an Engineered Carotenoid Synthesis Pathway.

PubMed

Dilbeck, Preston L; Tang, Qun; Mothersole, David J; Martin, Elizabeth C; Hunter, C Neil; Bocian, David F; Holten, Dewey; Niedzwiedzki, Dariusz M

2016-06-23

Six light-harvesting-2 complexes (LH2) from genetically modified strains of the purple photosynthetic bacterium Rhodobacter (Rb.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. These strains were engineered to incorporate carotenoids for which the number of conjugated groups (N = NC═C + NC═O) varies from 9 to 15. The Rb. sphaeroides strains incorporate their native carotenoids spheroidene (N = 10) and spheroidenone (N = 11), as well as longer-chain analogues including spirilloxanthin (N = 13) and diketospirilloxantion (N = 15) normally found in Rhodospirillum rubrum. Measurements of the properties of the carotenoid first singlet excited state (S1) in antennas from the Rb. sphaeroides set show that carotenoid-bacteriochlorophyll a (BChl a) interactions are similar to those in LH2 complexes from various other bacterial species and thus are not significantly impacted by differences in polypeptide composition. Instead, variations in carotenoid-to-BChl a energy transfer are primarily regulated by the N-determined energy of the carotenoid S1 excited state, which for long-chain (N ≥ 13) carotenoids is not involved in energy transfer. Furthermore, the role of the long-chain carotenoids switches from a light-harvesting supporter (via energy transfer to BChl a) to a quencher of the BChl a S1 excited state B850*. This quenching is manifested as a substantial (∼2-fold) reduction of the B850* lifetime and the B850* fluorescence quantum yield for LH2 housing the longest carotenoids.

Structures and electron affinities of the di-arsenic fluorides As2Fn/As2Fn- (n=1-8).

PubMed

Kasalová, Veronika; Schaefer, Henry F

2005-04-15

Developments in the preparation of new materials for microelectronics are focusing new attention on molecular systems incorporating several arsenic atoms. A systematic investigation of the As2Fn/As2Fn- systems was carried out using Density Functional Theory methods and a DZP++ quality basis set. Global and low-lying local geometric minima and relative energies are discussed and compared. The three types of neutral-anion separations reported in this work are: the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). Harmonic vibrational frequencies pertaining to the global minimum for each compound are reported. From the first four studied species (As2Fn, n=1-4), all neutral molecules and their anions are shown to be stable with respect to As-As bond breaking. The neutral As2F molecule and its anion are predicted to have Cs symmetry. We find the trans F-As-As-F isomer of C2h symmetry and a pyramidalized vinylidene-like As-As-F2- isomer of Cs symmetry to be the global minima for the As2F2 and As2F2- species, respectively. The lowest lying minima of As2F3 and As2F3- are vinyl radical-like structures F-As-As-F2 of Cs symmetry. The neutral As2F4 global minimum is a trans-bent (like Si2H4) F2-As-As-F2 isomer of C2 symmetry, while its anion is predicted to have an unusual fluorine-bridged (C(1)) structure. The global minima of the neutral As2Fn species, n=5-8, are weakly bound complexes, held together by dipole-dipole interactions. All such structures have the AsFm-AsFn form, where (m,n) is (2,3) for As2F5, (3,3) for As2F6, (4,3) for As2F7), and (5,3) for As2F8. For As2F8 the beautiful pentavalent F4As-AsF4 structure (analogous to the stable AsF5 molecule) lies about 30 kcal/mol above the AsF3 . . . AsF5 complex. The stability of AsF(5) depends crucially on the strong As-F bonds, and replacing one of these with an As-As bond (in F4As-AsF4) has a very negative impact on the molecule's stability. The anions As2Fn-, n=5-8, are shown to be stable with respect to the As-As bond breaking, and we predict that all of them have fluorine-bridged or fluorine-linked structures. The zero-point vibrational energy corrected adiabatic electron affinities are predicted to be 2.28 eV (As2F), 1.95 eV (As2F2), 2.39 eV (As2F3), 1.71 eV (As2F4), 2.72 eV (As2F5), 1.79 eV (As2F6), 5.26 eV (As2F7), and 3.40 eV (As2F8) from the BHLYP method. Vertical detachment energies are rather large, especially for species with fluorine-bridged global minima, having values up to 6.45 eV (As2F7, BHLYP).

Chaperoning 5S RNA assembly

PubMed Central

Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

2015-01-01

In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2–Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2–Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2–Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. PMID:26159998

Geometrical tile design for complex neighborhoods.

PubMed

Czeizler, Eugen; Kari, Lila

2009-01-01

Recent research has showed that tile systems are one of the most suitable theoretical frameworks for the spatial study and modeling of self-assembly processes, such as the formation of DNA and protein oligomeric structures. A Wang tile is a unit square, with glues on its edges, attaching to other tiles and forming larger and larger structures. Although quite intuitive, the idea of glues placed on the edges of a tile is not always natural for simulating the interactions occurring in some real systems. For example, when considering protein self-assembly, the shape of a protein is the main determinant of its functions and its interactions with other proteins. Our goal is to use geometric tiles, i.e., square tiles with geometrical protrusions on their edges, for simulating tiled paths (zippers) with complex neighborhoods, by ribbons of geometric tiles with simple, local neighborhoods. This paper is a step toward solving the general case of an arbitrary neighborhood, by proposing geometric tile designs that solve the case of a "tall" von Neumann neighborhood, the case of the f-shaped neighborhood, and the case of a 3 x 5 "filled" rectangular neighborhood. The techniques can be combined and generalized to solve the problem in the case of any neighborhood, centered at the tile of reference, and included in a 3 x (2k + 1) rectangle.