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Estudo da natureza do fator de permeabilidade capilar (PF) em culturas de Salmonella typhimurium

Joice Aparecida Soares Gomes
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em //1981 PT
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Quarenta e uma amostras de S. typhimurium e 14 amostras de S. enteritidis foram estudadas quanto à produção de um fator de permeabilidade, semelhante ao observado na pele de coelhos inoculados com a toxina colérica ou sobrenadantes de culturas de amostras de E. coli, produtoras de enterotoxina termo-lábil (LT). A atividade do PF foi encontrada em sobrenadantes de cultivos de salmonelas, quer fossem eles cromatografados ou não em Sephadex G-100. Esta atividade do tipo enterotoxina LT foi estuda através de outros testes, utilizados para a detecção desta enterotoxina. Assim sendo, foram realizados ensaios em linhagem de células Y-1, alça ligada de intestino de coelho, alça ligada de intestino de rato e teste da imunohemólise passiva. A pesquisa da enterotoxina ST em sobrenadantes typhimurium foi feita pelo teste de Dean. de S . A identificação da natureza deste fator foi feita através de tratamentos físicos e químicos (efeito da temperatura, di~lise, pH e enzimas). Paralelamente foram realizadas provas sorol§ gicas para se identificar as características antigênicas deste fator de permeabilidade, bem como foi estudado o envolvimento do LPS presente nesta atividade, através do fenômeno de Sanarelli-Shwartzman. As atividades de PF presentes em S. typhimurium e na toxina colérica foram estudadas comparativamente quanto a seus aspectos histológicos. Os principais resultados obtidos são apresentados a seguir: 1. Pesquisa de enterotoxinas LT e ST. Os testes do PF em coelho...

Pseudo-orbital SO(6) symmetry for pf-shell nuclei

Valencia,J. P.; Wu,H.C.
Fonte: Sociedade Brasileira de Física Publicador: Sociedade Brasileira de Física
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2006 EN
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This work studies the pseudo-orbital SO(6) symmetry for the first half of the {2${ m p}_{frac{1}{2}}$}{2${ m p}_{frac{3}{2}}$}{1${ m f}_{frac{5}{2}}$} shell (denoted as the pf-shell). The spectra and beta decay are calculated for nuclei Ni, Cu and Zn with A=58, and the comparison to experiment prefers the mbox{$widetilde{ m SO}(6)$} limit to the mbox{$widetilde{ m SU}(3)$} one. In the calculation of beta decay two types of transformations are employed and the results seem confirm the adequacy of p-helicity transformation.

Comparison of the BacT/Alert PF Pediatric FAN Blood Culture Bottle with the Standard Pediatric Blood Culture Bottle, the Pedi-BacT

Krisher, Karen K.; Gibb, Patrick; Corbett, Sandra; Church, Deidre
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2001 EN
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The performance of the BacT/Alert PF (Organon-Teknika Corp., Durham, N.C.), a new nonvented pediatric FAN blood culture bottle, was compared to that of the original pediatric bottle, the Pedi-BacT, with matched aerobic cultures obtained from two separate facilities. A total of 244 clinically significant isolates were recovered from 4,015 compliant pairs. Among the positive cultures, 170 (70%) isolates were detected in both the BacT/Alert PF and the Pedi-BacT bottles, while 47 (19%) isolates were recovered in the BacT/Alert PF bottle only and 27 (11%) isolates were recovered in the Pedi-BacT bottle only. Although isolation of specific microorganisms was comparable for the two bottles, the total number of organisms recovered by the BacT/Alert PF was greater than that by the Pedi-BacT (P = 0.0272). In addition, more organisms were recovered by the BacT/Alert PF bottle from the blood of patients receiving antimicrobial therapy (P = 0.0180). Overall time to detection was similar for the two bottles; however, a significantly decreased mean time to detection was recorded for yeast from the BacT/Alert PF bottle (22.9 h; P = 0.0001) and staphylococci from the Pedi-BacT bottle (22.5 h; P = 0.0056). One false-negative culture and five false-positive cultures occurred with the Pedi-BacT bottle...

Effect of PF 10040 on PAF-induced airway responses in neonatally immunized rabbits.

Herd, C. M.; Donigi-Gale, D.; Shoupe, T. S.; Kilfeather, S. A.; Okiji, S. A.; Page, C. P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1994 EN
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1. PF 10040 displaced [3H]-PAF from binding sites on rabbit platelets with an IC50 = 1.07 x 10(-5) M, which was approximately three orders of magnitude below that of a standard PAF antagonist WEB 2086 (IC50 = 4.23 x 10(-9) M). 2. PF 10040 at doses of 5 and 10 mg (direct intratracheal administration) had no effect on the acute bronchoconstriction induced by PAF in neonatally immunized rabbits (airway resistance RL or dynamic compliance Cdyn). However, the PAF-induced increase in airway responsiveness to inhaled histamine was significantly inhibited (RL and Cdyn) by both doses of PF 10040. 3. PF 10040 (5 and 10 mg) significantly inhibited the total pulmonary cell infiltration and neutrophil influx induced by PAF as assessed by bronchoalveolar lavage. PAF-induced eosinophil infiltration into the airways was significantly inhibited in rabbits that received only 10 mg PF 10040. 4. We suggest from the results of the present study that PF 10040 does not exert an inhibitory effect on PAF-induced airway responses solely via antagonism of the PAF receptor located on platelets, as PF 10040 significantly inhibited PAF-induced airway hyperresponsiveness in the absence of an effect on the acute bronchospasm induced by PAF. 5. We provide further evidence that pulmonary eosinophil infiltration and the development of airway hyperresponsiveness are not causally related events as the lower dose of PF 10040 (5 mg) significantly inhibited PAF-induced airway hyperresponsiveness yet was without effect on the eosinophil influx.

Abnormal expression and processing of keratins in pupoid fetus (pf/pf) and repeated epilation (Er/Er) mutant mice

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/10/1987 EN
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The pupoid fetus (pf) and repeated epilation (Er) mutations of mice result in a failure of epidermal differentiation in homozygotes. Expression of the epidermal keratins has been followed in pf/pf and Er/Er mice by two-dimensional gel electrophoresis, and by immunohistochemistry and Western blotting using polyclonal antibodies that are monospecific for individual keratin polypeptides. Our results show that expression of the differentiation-specific keratins (K1 and K10) is delayed in both the pf/pf and Er/Er mutants and that, when these keratins do appear later in development, they are localized in the deeper layers of the thickened mutant epidermis. Conversely, K6 and K16, two keratins found in low abundance in normal epidermis, are abundant in mutant epidermis. In newborn mutant epidermis, K6 and K16 are found to be most abundant in the outermost epidermal cells, a distribution opposite to that of K1 and K10. These findings suggest that the expression of these hyperplastic keratins in mutant mice may occur to the exclusion of the differentiation-specific keratins both during development and in newborn animals. Differentiation, and an apparently normal pattern of keratin expression, occur when whole pf/pf or Er/Er skin is grafted to normal mice. These results suggest that the pf and Er genes may be expressed systemically and that transfer of the mutant skin to a "normal" environment results in the recovery of a normal phenotype.

The sup-pf-2 mutations of Chlamydomonas alter the activity of the outer dynein arms by modification of the gamma-dynein heavy chain

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 02/12/1996 EN
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The sup-pf-2 mutation is a member of a group of dynein regulatory mutations that are capable of restoring motility to paralyzed central pair or radial spoke defective strains. Previous work has shown that the flagellar beat frequency is reduced in sup-pf-2, but little else was known about the sup-pf-2 phenotype (Huang, B., Z. Ramanis, and D.J.L. Luck. 1982. Cell. 28:115-125; Brokaw, C.J., and D.J.L. Luck. 1985. Cell Motil. 5:195-208). We have reexamined sup-pf-2 using improved biochemical and structural techniques and by the analysis of additional sup-pf-2 alleles. We have found that the sup-pf-2 mutations are associated with defects in the outer dynein arms. Biochemical analysis of sup-pf-2-1 axonemes indicates that both axonemal ATPase activity and outer arm polypeptides are reduced by 40-50% when compared with wild type. By thin-section EM, these defects correlate with an approximately 45% loss of outer dynein arm structures. Interestingly, this loss is biased toward a subset of outer doublets, resulting in a radial asymmetry that may reflect some aspect of outer arm assembly. The defects in outer arm assembly do not appear to result from defects in either the outer doublet microtubules or the outer arm docking structures, but rather appear to result from defects in outer dynein arm components. Analysis of new sup-pf-2 mutations indicates that the severity of the outer arm assembly defects varies with different alleles. Complementation tests and linkage analysis reveal that the sup- pf-2 mutations are alleles of the PF28/ODA2 locus...

Preclinical Characterization of PF-00868554, a Potent Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase▿ †

Shi, Stephanie T.; Herlihy, Koleen J.; Graham, Joanne P.; Nonomiya, Jim; Rahavendran, Sadayappan V.; Skor, Heather; Irvine, Rebecca; Binford, Susan; Tatlock, John; Li, Hui; Gonzalez, Javier; Linton, Angelica; Patick, Amy K.; Lewis, Cristina
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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PF-00868554 is a nonnucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase, which exerts its inhibitory effect by binding to the thumb base domain of the protein. It is a potent and selective inhibitor, with a mean 50% inhibitory concentration of 0.019 μM against genotype 1 polymerases and a mean 50% effective concentration (EC50) of 0.075 μM against the genotype 1b-Con1 replicon. To determine the in vitro antiviral activity of PF-00868554 against various HCV strains, a panel of chimeric replicons was generated, in which polymerase sequences derived from genotype 1a and 1b clinical isolates were cloned into the 1b-Con1 subgenomic reporter replicon. Our results indicate that PF-00868554 has potent in vitro antiviral activity against a majority (95.8%) of genotype 1a and 1b replicons, with an overall mean EC50 of 0.059 μM. PF-00868554 showed no cytotoxic effect in several human cell lines, up to the highest concentration evaluated (320 μM). Furthermore, the antiviral activity of PF-00868554 was retained in the presence of human serum proteins. An in vitro resistance study of PF-00868554 identified M423T as the predominant resistance mutation, resulting in a 761-fold reduction in susceptibility to PF-00868554 but no change in susceptibility to alpha interferon and a polymerase inhibitor that binds to a different region. PF-00868554 also showed good pharmacokinetic properties in preclinical animal species. Our results demonstrate that PF-00868554 has potent and broad-spectrum antiviral activity against genotype 1 HCV strains...

Determination of PF-04928473 in human plasma using liquid chromatography with tandem mass spectrometry

Jain, Lokesh; Gardner, Erin R.; Venitz, Jürgen; Giaccone, Giuseppe; Houk, Brett E.; Figg, William D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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A simple, rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) analytical method was developed for quantification of Hsp90 inhibitor PF-04928473 in human plasma, following administration of its prodrug, PF-04929113. Sample processing involved protein precipitation by addition of 0.4 mL of methanol containing internal standard (PF-04972487) to 50 μL volume of plasma sample. Chromatographic separation of PF-04928473 and PF-04972487 was achieved on a Phenomenex® Luna C18(2) (2.0×50 mm, 5 μm) column using a gradient elution method with mobile phase solvents: methanol containing 0.1% formic acid and 0.1% formic acid at a flow rate of 0.25 mL/min. Detection was performed in electrospray positive ionization mode, monitoring the ion transitions from m/z 465.1→350.1 (PF-04928473) and m/z 447.0→329.1 (PF-04972487). The retention times for PF-04928473 and PF-04972487 were 1.86 and 2.85 minutes, respectively. Calibration curves were generated in the range of 2–2000 ng/mL. The accuracy and precision ranged from 94.1–99.0% and 86.7–97.6%, respectively, which were calculated using quality control samples of three different concentrations analyzed in quintuplicate on four different days.

Inhibition of Focal Adhesion Kinase by PF-562,271 Inhibits the Growth and Metastasis of Pancreatic Cancer Concomitant with Altering the Tumor Microenvironment

Stokes, Jayme B.; Adair, Sara J.; Slack-Davis, Jill K.; Walters, Dustin M.; Tilghman, Robert W.; Hershey, E. Dan; Lowrey, Bryce; Thomas, Keena S.; Bouton, Amy H.; Hwang, Rosa F.; Stelow, Edward B.; Parsons, J. Thomas; Bauer, Todd W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Current therapies for pancreatic ductal adenocarcinoma (PDA) target individual tumor cells. Focal adhesion kinase (FAK) is activated in PDA and levels are inversely associated with survival. We investigated the effects of PF-562,271 (a small molecule inhibitor of FAK/PYK2) on a) in vitro migration, invasion and proliferation, b) tumor proliferation, invasion and metastasis in a murine model, and c) stromal cell composition in the PDA microenvironment. Migration assays were performed to assess tumor and stromal cell migration in response to cellular factors, collagen and the effects of PF-562,271. An orthotopic murine model was used to assess the effects of PF-562,271 on tumor growth, invasion and metastasis. Proliferation assays measured PF-562,271 effects on in vitro growth. Immunohistochemistry was used to examine the effects of FAK inhibition on the cellular composition of the tumor microenvironment. FAK and PYK2 are activated and expressed in patient-derived PDA tumors, stromal components and human PDA cell lines. PF-562,271 blocked phosphorylation of FAK Y397 in a dose-dependent manner. PF-562,271 inhibited migration of tumor cells, cancer associated fibroblasts, and macrophages. Treatment of mice with PF-562,271 resulted in reduced tumor growth...

I-PfoP3I: A Novel Nicking HNH Homing Endonuclease Encoded in the Group I Intron of the DNA Polymerase Gene in Phormidium foveolarum Phage Pf-WMP3

Kong, Shuanglei; Liu, Xinyao; Fu, Liwen; Yu, Xiangchun; An, Chengcai
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 27/08/2012 EN
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Homing endonucleases encoded in a group I self-splicing intron in a protein-coding gene in cyanophage genomes have not been reported, apart from some free-standing homing edonucleases. In this study, a nicking DNA endonuclease, I-PfoP3I, encoded in a group IA2 intron in the DNA polymerase gene of a T7-like cyanophage Pf-WMP3, which infects the freshwater cyanobacterium Phormidium foveolarum is described. The Pf-WMP3 intron splices efficiently in vivo and self-splices in vitro simultaneously during transcription. I-PfoP3I belongs to the HNH family with an unconventional C-terminal HNH motif. I-PfoP3I nicks the intron-minus Pf-WMP3 DNA polymerase gene more efficiently than the Pf-WMP4 DNA polymerase gene that lacks any intervening sequence in vitro, indicating the variable capacity of I-PfoP3I. I-PfoP3I cleaves 4 nt upstream of the intron insertion site on the coding strand of EXON 1 on both intron-minus Pf-WMP3 and Pf-WMP4 DNA polymerase genes. Using an in vitro cleavage assay and scanning deletion mutants of the intronless target site, the minimal recognition site was determined to be a 14 bp region downstream of the cut site. I-PfoP3I requires Mg2+, Ca2+ or Mn2+ for nicking activity. Phylogenetic analysis suggests that the intron and homing endonuclease gene elements might be inserted in Pf-WMP3 genome individually after differentiation from Pf-WMP4. To our knowledge...

Ferric-Pyoverdine Recognition by Fpv Outer Membrane Proteins of Pseudomonas protegens Pf-5

Hartney, Sierra L.; Mazurier, Sylvie; Girard, Maëva K.; Mehnaz, Samina; Davis, Edward W.; Gross, Harald; Lemanceau, Philippe; Loper, Joyce E.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2013 EN
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The soil bacterium Pseudomonas protegens Pf-5 (previously called P. fluorescens Pf-5) produces two siderophores, enantio-pyochelin and a compound in the large and diverse pyoverdine family. Using high-resolution mass spectroscopy, we determined the structure of the pyoverdine produced by Pf-5. In addition to producing its own siderophores, Pf-5 also utilizes ferric complexes of some pyoverdines produced by other strains of Pseudomonas spp. as sources of iron. Previously, phylogenetic analysis of the 45 TonB-dependent outer membrane proteins in Pf-5 indicated that six are in a well-supported clade with ferric-pyoverdine receptors (Fpvs) from other Pseudomonas spp. We used a combination of phylogenetics, bioinformatics, mutagenesis, pyoverdine structural determinations, and cross-feeding bioassays to assign specific ferric-pyoverdine substrates to each of the six Fpvs of Pf-5. We identified at least one ferric-pyoverdine that was taken up by each of the six Fpvs of Pf-5. Functional redundancy of the Pf-5 Fpvs was also apparent, with some ferric-pyoverdines taken up by all mutants with a single Fpv deletion but not by a mutant having deletions in two of the Fpv-encoding genes. Finally, we demonstrated that phylogenetically related Fpvs take up ferric complexes of structurally related pyoverdines...

Tumor P-Glycoprotein Correlates with Efficacy of PF-3758309 in in vitro and in vivo Models of Colorectal Cancer

Bradshaw-Pierce, Erica Lynn; Pitts, Todd M.; Tan, Aik-Choon; McPhillips, Kelly; West, Mark; Gustafson, Daniel L.; Halsey, Charles; Nguyen, Leslie; Lee, Nathan V.; Kan, Julie L. C.; Murray, Brion William; Eckhardt, S. Gail
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 22/03/2013 EN
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P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter family, is overexpressed in a number of different cancers and some studies show that P-gp overexpression can be correlated to poor prognosis or therapeutic resistance. Here we sought to elucidate if PF-3758309 (PF-309), a novel p-21 activated kinase inhibitor, efficacy was influenced by tumor P-gp. Based on in vitro proliferation data, a panel of colorectal cancer cell lines were ranked as sensitive or resistant and ABCB1 (P-gp) expression was evaluated by microarray for these cell lines. P-gp expression was determined by western blot and activity determined by rhodamine efflux assay. Knock down of P-gp and pharmacologic inhibition of P-gp to restore PF-309 activity was performed in vitro. PF-309 activity was evaluated in vivo in cell line xenograft models and in primary patient derived tumor xenografts (PDTX). Mice were treated with 25 mg/kg PF-309 orally, twice daily. On the last day of treatment, tumor and plasma were collected for PF-309 analysis. Here we show that ABCB1 gene expression correlates with resistance to PF-309 treatment in vitro and the expression and activity of P-gp was verified in a panel of resistant cells. Furthermore, inhibition of P-gp increased the sensitivity of resistant cells...

The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation

Wiemer, Andrew J.; Wernimont, Sarah A.; Cung, Thai-duong; Bennin, David A.; Beggs, Hilary E.; Huttenlocher, Anna
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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The focal adhesion kinase inhibitor, PF-562,271, is currently in clinical development for cancer, however it is not known how PF-562,271 affects T cell function. Here, we demonstrate inhibitory effects of PF-562,271 on the activation of primary human and mouse T cells. PF-562,271 inhibits T cell receptor signaling-induced T cell adhesion to intercellular adhesion molecule-1 and T cell interactions with antigen-presenting cells. An additional focal adhesion kinase inhibitor, PF-573,228, and genetic depletion of focal adhesion kinase also impair T cell conjugation with antigen-presenting cells. PF-562,271 blocks phosphorylation of the signaling molecules zeta chain associate protein of 70 kDa, linker of activated T cells, and extracellular signal-regulated kinase, and impairs T cell proliferation. The effects observed on T cell proliferation cannot solely be attributed to focal adhesion kinase inhibition, as genetic depletion did not alter proliferation. The effect of PF-562,271 on T cell proliferation is not rescued when proximal T cell receptor signaling is bypassed by stimulation with phorbol-12-myristate-13-acetate and ionomycin. Taken together, our findings demonstrate that focal adhesion kinase regulates integrin-mediated T cell adhesion following T cell receptor activation. Moreover...

The AP-1 transcription factor homolog Pf-AP-1 activates transcription of multiple biomineral proteins and potentially participates in Pinctada fucata biomineralization

Zheng, Xiangnan; Cheng, Minzhang; Xiang, Liang; Liang, Jian; Xie, Liping; Zhang, Rongqing
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 25/09/2015 EN
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27.04%
Activator protein-1 (AP-1) is an important bZIP transcription factor that regulates a series of physiological processes by specifically activating transcription of several genes, and one of its well-chartered functions in mammals is participating in bone mineralization. We isolated and cloned the complete cDNA of a Jun/AP-1 homolog from Pinctada fucata and called it Pf-AP-1. Pf-AP-1 had a highly conserved bZIP region and phosphorylation sites compared with those from mammals. A tissue distribution analysis showed that Pf-AP-1 was ubiquitously expressed in P. fucata and the mRNA level of Pf-AP-1 is extremely high in mantle. Pf-AP-1 expression was positively associated with multiple biomineral proteins in the mantle. The luciferase reporter assay in a mammalian cell line showed that Pf-AP-1 significantly up-regulates the transcriptional activity of the promoters of KRMP, Pearlin, and Prisilkin39. Inhibiting the activity of Pf-AP-1 depressed the expression of multiple matrix proteins. Pf-AP-1 showed a unique expression pattern during shell regeneration and pearl sac development, which was similar to the pattern observed for biomineral proteins. These results suggest that the Pf-AP-1 AP-1 homolog is an important transcription factor that regulates transcription of several biomineral proteins simultaneously and plays a role in P. fucata biomineralization...

Clinical neurosciences in the decade of the brain: hypotheses in neuro-oncology. VEG/PF acts upon the actin cytoskeleton and is inhibited by dexamethasone: relevance to tumor angiogenesis and vasogenic edema.

Criscuolo, G. R.; Balledux, J. P.
Fonte: Yale Journal of Biology and Medicine Publicador: Yale Journal of Biology and Medicine
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
Relevância na Pesquisa
27.09%
HYPOTHESIS: We have proposed that VEG/PF acts by transforming the cytoskeletal architecture of microvascular endothelial cells. BACKGROUND: Evidence supporting a pivotal role for vascular endothelial growth/permeability factor (VEG/PF) in tumor angiogenesis and edemagenesis is compelling. VEG/PF exhibits specific endothelial cell mitogenicity and is expressed by brain tumors exhibiting increased vascularity and microvascular extravasation. The mechanistic cascade that follows VEG/PF-tyrosine kinase receptor binding remains uncertain, however. Actin is a cytoskeletal protein that regulates cellular motility, shape and vesicular transport. Regulation of actin stress fibers, cell-surface focal adhesions and plasmalemmal "ruffles" is mediated by tyrosine kinase activation of GTP-binding proteins that are in turn linked to intracellular calcium flux. As VEG/PF is known to induce cytosolic calcium ion transients in endothelial cells, actin microfilaments would appear to be logical candidates for study of a cytocontractile response mediated by calcium signal transduction. METHODS: VEG/PF-induced endothelial actin cytoskeletal changes were studied using rhodamine phalloidin staining and fluorescence photomicrography. RESULTS: When exposed to VEG/PF...

The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus▿

Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 Å. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.

Characterization of Human Herpesvirus 8 ORF59 Protein (PF-8) and Mapping of the Processivity and Viral DNA Polymerase-Interacting Domains

Chan, Szeman Ruby; Chandran, Bala
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2000 EN
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27.1%
Human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus (KSHV) ORF59 protein (PF-8) is a processivity factor for HHV-8 DNA polymerase (Pol-8) and is homologous to processivity factors expressed by other herpesviruses, such as herpes simplex virus type 1 UL42 and Epstein-Barr virus BMRF1. The interaction of UL42 and BMRF1 with their corresponding DNA polymerases is essential for viral DNA replication and the subsequent production of infectious virus. Using HHV-8-specific monoclonal antibody 11D1, we have previously identified the cDNA encoding PF-8 and showed that it is an early-late gene product localized to HHV-8-infected cell nuclei (S. R. Chan, C. Bloomer, and B. Chandran, Virology 240:118–126, 1998). Here, we have further characterized PF-8. This viral protein was phosphorylated both in vitro and in vivo. PF-8 bound double-stranded DNA (dsDNA) and single-stranded DNA independent of DNA sequence; however, the affinity for dsDNA was approximately fivefold higher. In coimmunoprecipitation reactions, PF-8 also interacted with Pol-8. In in vitro processivity assays with excess poly(dA):oligo(dT) as a template, PF-8 stimulated the production of elongated DNA products by Pol-8 in a dose-dependent manner. Functional domains of PF-8 were determined using PF-8 truncation mutants. The carboxyl-terminal 95 amino acids (aa) of PF-8 were dispensable for all three functions of PF-8: enhancing processivity of Pol-8...

Revisão metodológica da PIM-PF e impactos sobre a trajetória da produção industrial; Methodological revision of the Monthly Industrial Research - Physical Production (PIM-PF) and impacts on the industrial production trajectory

Carvalho, Leonardo Mello de
Fonte: Instituto de Pesquisa Econômica Aplicada (Ipea) Publicador: Instituto de Pesquisa Econômica Aplicada (Ipea)
Tipo: Carta de Conjuntura - Artigos
PT-BR
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O Instituto Brasileiro de Geografia e Estatística (IBGE) divulgou em abril último, através da sua Coordenação de Indústria, a reformulação implementada na Pesquisa Industrial Mensal-Produção Física (PIM-PF). No mês seguinte, foram divulgados os dados referentes a março de 2014. Dentre as mudanças metodológicas introduzidas, visando retratar de maneira mais fiel a evolução da produção do setor industrial brasileiro, destacam-se: i) reclassificação das atividades de acordo com a Classificação Nacional de Atividades Econômicas (CNAE) na sua versão 2.0; ii) atualização do sistema de ponderação dos produtos, tendo como base a pesquisa Produção Industrial Anual (PIA) em nível de empresa e produto, cuja referência passa a ser o ano de 2010; e iii) atualização da amostra de produtos, setores e informantes. Em relação aos aspectos metodológicos, a migração para o sistema de classificação das atividades industriais com base na CNAE 2.0 provocou algumas alterações importantes na pesquisa.; p. 105-110 : il.

Low temperature structural effects in the (TMTSF)$_2$PF$_6$ and AsF$_6$ Bechgaard salts

Foury-Leylekian, P.; Petit, S.; Mirebeau, I.; Andre, G.; de Souza, M.; Lang, M.; Ressouche, E.; Moradpour, A.; Pouget, J. -P.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
27.04%
We present a detailed low-temperature investigation of the statics and dynamics of the anions and methyl groups in the organic conductors (TMTSF)$_2$PF$_6$ and (TMTSF)$_2$AsF$_6$ (TMTSF : tetramethyl-tetraselenafulvalene). The 4 K neutron scattering structure refinement of the fully deuterated (TMTSF)$_2$PF$_6$-D12 salt allows locating precisely the methyl groups at 4 K. This structure is compared to the one of the fully hydrogenated (TMTSF)$_2$PF$_6$-H12 salt previously determined at the same temperature. Surprisingly it is found that deuteration corresponds to the application of a negative pressure of 5 x 10$^2$ MPa to the H12 salt. Accurate measurements of the Bragg intensity show anomalous thermal variations at low temperature both in the deuterated PF$_6$ and AsF$_6$ salts. Two different thermal behaviors have been distinguished. Low-Bragg-angle measurements reflect the presence of low-frequency modes at characteristic energies {\theta}$_E$ = 8.3 K and {\theta}$_E$ = 6.7 K for the PF$_6$-D12 and AsF$_6$-D12 salts, respectively. These modes correspond to the low-temperature methyl group motion. Large-Bragg-angle measurements evidence an unexpected structural change around 55 K which probably corresponds to the linkage of the anions to the methyl groups via the formation of F...D-CD2 bonds observed in the 4 K structural refinement. Finally we show that the thermal expansion coefficient of (TMTSF)$_2$PF$_6$ is dominated by the librational motion of the PF$_6$ units. We quantitatively analyze the low-temperature variation of the lattice expansion via the contribution of Einstein oscillators...

Structural validity of the mood and behavior rating scale for youth – Parent Form (MBRSY-PF): A Parent informant questionnaire to assess bipolar disorder in children and adolescents

Nemcek, Laura A.
Fonte: Rochester Instituto de Tecnologia Publicador: Rochester Instituto de Tecnologia
Tipo: Tese de Doutorado
EN_US
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Empirically validated techniques to reliably assess for bipolar disorder in children and adolescents are crucial toward timely and effective treatment efforts. Rating scales and behavior checklists are often considered a valuable alternative to the semi-structured interview, as they can provide quantified information regarding symptom experience, and values can be compared to both age and gender norms as a supplement to clinical expertise (Kahana, Youngstrom, Findling, & Calabrese, 2003). Converse to semistructured interviews, rating scales are brief and time efficient, inexpensive, simple to administer, require much less training to deliver and interpret, and can be utilized for screening purpose by a wide variety of practitioners (Kahana et al.). For these reasons, high quality and psychometrically sound rating scale measures that address the specific assessment issues for pediatric bipolar disorder, and possess the advantages listed above, would have valuable clinical utility. However, while a number of promising such measures do exist and have been subjected to some psychometric study, definitively rigorous instruments meeting these qualifications are deficient within the literature overall (Kahana et al.). To address this missing aspect within the literature as a whole...