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P2
Kinds of P2 Terms modified by P2 Selected AbstractsGrowth and characterisation of potassium cobalt nickel sulfate hexahydrate for UV light filtersCRYSTAL RESEARCH AND TECHNOLOGY, Issue 10 2006Xinxin Zhuang Abstract A new single crystal for ultraviolet light filter, KCNSH (Potassium Cobalt Nickel Sulfate Hexahydrate) was designed and its crystal structure was studied using X-ray diffraction in this paper. The empirical of the title compound is K2Co0.1Ni0.9(SO4)2.6H2O with formula weight 437.15. KCNSH crystal belongs to the monoclinic space group P2(1)/c, a=6.1390(3)Å, b=12.1839(6)Å, c=9.0095(4)Å, ,=,=90°, ,=105.060(2)°, V=650.74(5)Å3, Z=2, Dc=2.231g/cm3. Using the cooling solution method, we have grown a deep green KCNSH crystal with dimension of 12×12×40mm3. The transmission spectrum of KCNSH in the range from UV to near IR wavelengths, its thermal properties, and the relationship between the structure and optical transmission properties are also studied and further discussed in this paper. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Heterogeneous modes of uptake for latex beads revealed through live cell imaging of phagocytes expressing a probe for phosphatidylinositol-(3,4,5)-trisphosphate and phosphatidylinositol-(3,4)-bisphosphateCYTOSKELETON, Issue 9 2008Jennifer Giorgione Abstract Latex beads are the preferred phagocytic substrate in biochemical studies of phagosome composition and maturation. Using living Dictyostelium cells and fluorescent probes, we compared the properties of phagosomes formed to ingest latex beads or digestible prey. Significant differences were found during the initial steps of phagocytosis. During uptake of bacteria or yeast, PHcrac-GFP, a probe that binds to membranes enriched in PI(3,4,5)P3 and PI(3,4)P2, always labeled the nascent phagosome and faded shortly after it sealed. However, labeling of bead-containing phagosomes was highly variable. Beads were engulfed by phagosomes either lacking or displaying the PHcrac-GFP label, and that label, if present, often persisted for many minutes, revealing that early trafficking steps for bead-containing phagosomes are quite heterogeneous. Later stages of the endocytic pathway appeared more similar for phagosomes containing prey and latex beads. Both types of phagosomes fused with acidic endosomes while undergoing transport along microtubules, both acquired the V-ATPase and lost it prior to exocytosis, and both bound the late endosome marker vacuolin B, which was transferred to the plasma membrane upon exocytosis. We conclude that caution is needed in extrapolating results from latex bead phagosomes to phagosomes containing physiological substances, especially in early stages of the endocytic pathway. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Efficacy of laser Doppler flowmetry for the diagnosis of revascularization of reimplanted immature dog teethDENTAL TRAUMATOLOGY, Issue 2 2001Kallaya Yanpiset Abstract , This study was performed to assess if laser Doppler flowmetry (LDF) is an improved method for the detection of revascularization of replanted teeth. Teeth were extracted and reimplanted under different experimental conditions. LDF readings were taken before extraction and weekly for 3 months. In control teeth, LDF baseline readings were taken and then repeated after the apical blood vessels were cut surgically. At the end of 3 months it was determined radiographically and histologically whether revascularization had occurred, i.e. vitality had returned. Results: LDF readings correctly predicted the pulp status (vital vs. non-vital) in 83.7% of the readings. 73.9% (17 of 23) were correct for the vital teeth and 95% (19 of 20) were correct for the non-vital teeth. Fisher's exact test (2-tail) indicated that there was no significant association between the efficacy of LDF and tooth type (P=0.166), although P2 was the least accurate tooth tested. Wilcoxon's matched-pair signed rank test demonstrated that in the revascularized (vital) teeth, the flux value between the baseline and week 2 dropped significantly (P=0.0001), increased significantly from week 2 to week 4 (P=0.0001) and then decreased steadily until week 12. However, at week 12 the flux was still significantly higher than at week 2 (P=0.010). In the teeth that failed to revascularize, the flux value dropped significantly by weeks 1 and 2 (P=0.004 and P=0.0001, respectively). Flux values did not increase from week 2. A Fast Fourier Transform (FFT) analysis confirmed a pulse of dominant frequency of 2 Hz in the teeth that returned to vitality and the lack thereof in those that stayed non-vital. One tooth in which the flux value evaluation indicated a non-vital tooth but the radiographic/histologic findings showed vital (false negative) possessed a pulse of dominant frequency and proved by this method to have successfully revascularized. [source] Influences of postconceptional age and postnatal experience on the development of auditory recognition memory in the newborn infantDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2002Raye-Ann deRegnier Abstract We evaluated the effects of postconceptional age and postnatal experience on the development of neonatal auditory recognition memory. Three groups were tested: a premature newborn group (tested at 35,38 weeks postconceptional age, ,1 week old), a full-term newborn group (tested at 39,42 weeks postconceptional age, ,1 week old), and a full-term experienced group (tested at 39,42 weeks postconceptional age, >1 week old; range 8,30 days). Event-related potentials were collected while infants listened to the maternal voice alternating with a stranger's voice. Postconceptional age was correlated with the development of recognition memory for the maternal voice while there were qualitative effects of postnatal experience on latency measurements. Maturity of auditory cortical responses was not correlated with recognition memory abilities. We conclude that maturation of the recognition memory pathways is primarily a function of postconceptional age with qualitative effects of postnatal experience. Maturation of the auditory recognition memory pathway is not contingent upon maturation of the "P2" peak thought to arise from primary auditory cortex. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 216,225, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10070 [source] Proteomic mapping of the hyperthermophilic and acidophilic archaeon Sulfolobus solfataricus P2ELECTROPHORESIS, Issue 14 2006Richard C. Barry Abstract A proteomic map of Sulfolobus solfataricus,P2, an archaeon that grows optimally at 80°C and pH,3.2, was developed using high-resolution 2-DE and peptide mass fingerprinting. A total of 867,protein spots (659,aqueous Tris-soluble spots and 208,aqueous Tris-insoluble) were mapped over IPG,3,10, 4,7, and 6,11, with second-dimensional gels made of 8,18%,polyacrylamide. Three hundred and twenty-four different gene products were represented by the 867,spots, with 274,gene products being identified in the Tris-soluble fractions and 100,gene products in the Tris-insoluble portion. Fifty gene products were found on gels from both fractions. Additionally, an average of 1.50 ± 0.12 isoforms/protein was identified. This mapping study confirmed the expression of proteins involved in numerous metabolic, transport, energy production, nucleic acid replication, translation, and transcription pathways. Of particular interest, phosphoenolpyruvate carboxykinase,(SSO2537) was detected even though the pathway for gluconeogenesis is unknown for this archaeon. Tris-soluble fractions contained many cytosolic proteins while Tris-insoluble fractions contained many membrane-associated proteins, including ABC transporters and an ATP synthase. This study provides an optimized 2-DE approach for investigating the biochemical pathways and post-translational modifications employed by Sulfolobus to survive in its extreme environment. [source] Emergency department personal protective equipment requirements following out-of-hospital chemical biological or radiological events in AustralasiaEMERGENCY MEDICINE AUSTRALASIA, Issue 2 2007Guy W Sansom Abstract Recent events have led to a revision in ED equipment, preparedness and training for disasters. However, clinicians must still decide when, and what level of personal protection is required when a toxic threat exists. If possible, clear, simple and achievable protocols are required in such situations. Following an off-site Australasian chemical biological or radiological incident, current evidence indicates that the initial receiving ED staff will be adequately protected from all known chemical biological and radiological inhalational threats by wearing a properly fitted P2 (N95) mask, or its equivalent. Protection from serious contact injury is offered by wearing double gloves, disposable fluid-repellent coveralls or gown, eye protection, surgical mask, and ideally, a cap and shoe covers; in conjunction with universal precautions and procedures. [source] Variation in gene content among geographically diverse Sulfolobus isolatesENVIRONMENTAL MICROBIOLOGY, Issue 1 2008Dennis W. Grogan Summary The ability of competitive (i.e., comparative) genomic hybridization (CGH) to assess similarity across entire microbial genomes suggests that it should reveal diversification within and between natural populations of free-living prokaryotes. We used CGH to measure relatedness of genomes drawn from Sulfolobus populations that had been shown in a previous study to be diversified along geographical lines. Eight isolates representing a wide range of spatial separation were compared with respect to gene-specific tags based on a closely related reference strain (Sulfolobus solfataricus P2). For the purpose of assessing genetic divergence, 232 loci identified as polymorphic were assigned one of two alleles based on the corresponding fluorescence intensities from the arrays. Clustering of these binary genotypes was stable with respect to changes in the threshold and similarity criteria, and most of the groupings were consistent with an isolation-by-distance model of diversification. These results indicate that increasing spatial separation of geothermal sites correlates not only with minor sequence polymorphisms in conserved genes of Sulfolobus (demonstrated in the previous study), but also with the regions of difference (RDs) that occur between genomes of conspecifics. In view of the abundance of RDs in prokaryotic genomes and the relevance that some RDs may have for ecological adaptation, the results further suggest that CGH on microarrays may have advantages for investigating patterns of diversification in other free-living archaea and bacteria. [source] Expression of PI(4,5)P2 -binding proteins lowers the PI(4,5)P2 level and inhibits Fc,RIIA-mediated cell spreading and phagocytosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Ewelina Szyma Abstract We found that Fc,RII-mediated cell spreading and phagocytosis were correlated with an increase of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] level in cells. During the spreading, a long-lasting elevation of PI(4,5)P2 and concomitant actin polymerization occurred. Filopodia and lamellae of spreading cells were enriched in phosphatidylinositol 4-phosphate 5-kinase I, (PIP5-kinase I,) that colocalized with PI(4,5)P2 and actin filaments. Both spreading and phagocytosis were inhibited by expression of the C374,440 fragment of PIP5-kinase I, or the pleckstrin homology domain of phospholipase C,1 (PLC,1 -PH), two probes binding PI(4,5)P2. These probes reduced the amount of PI(4,5)P2 in the cells, evoked reorganization of the actin cytoskeleton and abolished PI(4,5)P2 elevation during phagocytosis. Simultaneously, PLC,1 -PH-GFP reduced the amount of PIP5-kinase I, associated with the plasma membrane. In vitro studies demonstrated that PIP5-kinase I,-GST bound PI(4,5)P2, phosphatidylinositol 4-monophosphate, and less efficiently, phosphatidic acid. The data suggest that the PLC,1 -PH domain, and possibly also the C374,440 fragment, when expressed in cells, can compete with endogenous PIP5-kinase I, for PI(4,5)P2 binding in the plasma membrane leading eventually to PI(4,5)P2 depletion. [source] Better Performance of Monodentate P -Stereogenic Phosphanes Compared to Bidentate Analogues in Pd-Catalyzed Asymmetric Allylic AlkylationsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2010Arnald Grabulosa Abstract The cationic allylpalladium complexes 3a,3f, 4a, 4e, 5e of type [Pd(,3 -2-Me-C3H4)P2]PF6 were synthesized using a group of monodentate P -stereogenic phosphanes, P=PPhRR, (a,f) and diphosphanes (PhRPCH2)2 (1a, 1e) or PhRPCH2Si(Me)2CH2PPhR (2e). The analogous cationic complexes with the disubstituted allyl group (,3 -1,3-Ph2 -C3H3) and monodentate phosphanes were not isolated as stable solids; only [PdCl(,3 -1,3-Ph2 -C3H3)P] (6a, 6d) were obtained. Palladium allyl complexes were screened as precatalysts in the allylic substitution of rac -3-acetoxy-1,3-diphenyl-1-propene (I) and (E)-3-acetoxy-1-phenyl-1-propene (III) with dimethyl malonate as the nucleophile. The various catalytic precursors showed a wide range of activity and selectivity. The bismonodentate phosphane complexes 3 are more active than the bidentate analogues. With regard to the regioselectivity, precursors containing monodentate phosphanes favour the formation of the linear product in the allylic substitution of cinnamyl acetate (III) compared with those containing bidentate phosphanes. With substrate I, compounds with the diphosphanes 1a and 1e, containing a five-membered chelate ring, gave low enantioselectivities (less than 10,% ee), but those with the diphosphane 2e, forming a six-membered chelate ring or with two monodentate phosphanes, afforded products with moderate enantioselectivity under standard conditions (ee up to 74,%). The results show that the performance of precursors containing monodentate phosphanes was superior to those containing bidentate ligands in both activity and selectivity. [source] Synthesis and Structural Characterisation of Palladium and Group-12 Metal Complexes with a Hybrid Phosphanylphosphonate Ferrocene LigandEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 5 2006Abstract Diethyl [1,-(diphenylphosphanyl)ferrocenyl]phosphonate (1) was synthesised by stepwise metallation/functionalisation of 1,1,-dibromoferrocene and studied as a ligand for palladium(II) and group-12 metals. Treatment of [PdCl2(cod)] (cod = ,2:,2 -cycloocta-1,5-diene) with 1 in 1:1 or 1:2 molar ratios gave, respectively, the dinuclear, chloride-bridged complex [{Pd(,-Cl)Cl(1 -,P2)}2] (2) and the mononuclear complex trans -[PdCl2(1 -,P2)2] (3), where 1 coordinates exclusively through the phosphane function. The reactions between 1 and group-12 metal bromides MBr2 in a 1:1 molar ratio gave the adducts [MBr2(1)] [M = Zn (4), Cd (5), and Hg (6)], whose crystal structures change considerably with the metal ion. Thus, whereas 4 is a molecular complex with 1 coordinating as an O1,P2 -chelate, its cadmium(II) analogue is a polymer built up from symmetric {CdBr(,-Br)}2 units interconnected by pairs of O1,P2 -bridging phosphanylphosphonate ligands. Finally, the mercury(II) complex 6 is a halide-bridged dimer, [{Hg(,-Br)Br(1 -,P2)}2]. However, this compound is structurally fluxional in solution (NMR spectra) and, in the crystal, it attains a structure similar to 5 owing to weak interactions between mercury and phosphonate-O1 atoms from adjacent molecules. An isomer to 6, [{HgBr2(1 -,2O1,P2)}2] (7), was isolated from attempted alkylation of 6 and structurally characterised as a dimer, where ligands 1 bridge two {HgBr2} units. All compounds were studied by spectroscopic methods (IR, NMR, mass) and the solid-state structures of 1, 2·,H2O, 3·4,CHCl3, 4, 5, 6·5,C6H6, and 7 have been determined by single-crystal X-ray diffraction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Early life modulators and predictors of adult synaptic plasticityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Katherine G. Akers Abstract Early life experience can induce long-lasting changes in brain and behaviour that are opposite in direction, such as enhancement or impairment in regulation of stress response, structural and functional integrity of the hippocampus, and learning and memory. To explore how multiple early life events jointly determine developmental outcome, we investigated the combined effects of neonatal trauma (anoxia on postnatal day 1, P1) and neonatal novelty exposure (P2,21) on adult social recognition memory (3 months of age) and synaptic plasticity in the CA1 of the rat hippocampus (4.5,8 months of age). While neonatal anoxia selectively reduced post-tetanic potentiation (PTP), neonatal novel exposure selectively increased long-term potentiation (LTP). No interaction between anoxia and novelty exposure was found on either PTP or LTP. These findings suggest that the two contrasting neonatal events have selective and distinct effects on two different forms of synaptic plasticity. At the level of behaviour, the effect of novelty exposure on LTP was associated with increased social memory, and the effect of anoxia on PTP was not accompanied by changes in social memory. Such a finding suggests a bias toward the involvement of LTP over PTP in social memory. Finally, we report a surprising finding that an early behavioural measure of emotional response to a novel environment obtained at 25 days of age can predict adult LTP measured several months later. Therefore, individual differences in emotional responses present during the juvenile stage may contribute to adult individual differences in cellular mechanisms that underlie learning and memory. [source] A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] Subsite specificity of trypanosomal cathepsin L-like cysteine proteasesFEBS JOURNAL, Issue 9 2001Probing the S2 pocket with phenylalanine-derived amino acids The S2 subsite of mammalian cysteine proteinases of the papain family is essential for specificity. Among natural amino acids, all these enzymes prefer bulky hydrophobic residues such as phenylalanine at P2. This holds true for their trypanosomal counterparts: cruzain from Trypanosoma cruzi and congopain from T. congolense. A detailed analysis of the S2 specificity of parasitic proteases was performed to gain information that might be of interest for the design of more selective pseudopeptidyl inhibitors. Nonproteogenic phenylalanyl analogs (Xaa) have been introduced into position P2 of fluorogenic substrates dansyl-Xaa-Arg-Ala-Pro-Trp, and their kinetic constants (Km, kcat/Km) have been determined with congopain and cruzain, and related host cathepsins B and L. Trypanosomal cysteine proteases are poorly stereoselective towards d/l -Phe, the inversion of chirality modifying the efficiency of the reaction but not the Km. Congopain binds cyclohexylalanine better than aromatic Phe derivatives. Another characteristic feature of congopain compared to cruzain and cathepsins B and L was that it could accomodate a phenylglycyl residue (kcat/Km = 1300 mm,1·s,1), while lengthening of the side chain by a methylene group only slightly impaired the specificity constant towards trypanosomal cysteine proteases. Mono- and di-halogenation or nitration of Phe did not affect Km for cathepsin L-like enzymes, but the presence of constrained Phe derivatives prevented a correct fitting into the S2 subsite. A model of congopain has been built to study the fit of Phe analogs within the S2 pocket. Phe analogs adopted a positioning within the S2 pocket similar to that of the Tyr of the cruzain/Z-Tyr-Ala-fluoromethylketone complex. However, cyclohexylalanine has an energetically favorable chair-like conformation and can penetrate deeper into the subsite. Fitting of modeled Phe analogs were in good agreement with kinetic parameters. Furthermore, a linear relationship could be established with logP, supporting the suggestion that fitting into the S2 pocket of trypanosomal cysteine proteases depends on the hydrophobicity of Phe analogs. [source] Multifunctional Mesoporous Silica Material Used for Detection and Adsorption of Cu2+ in Aqueous Solution and Biological Applications in vitro and in vivoADVANCED FUNCTIONAL MATERIALS, Issue 12 2010Qingtao Meng Abstract An inorganic,organic silica material (SBA,P2), prepared by immobilization of the 1,8-naphthalimide-based receptor P2 within the channels of the mesoporous silica material SBA-15, is characterized by transmission electron microscopy and several spectroscopic methods. SBA,P2 features a high affinity Cu2+ -specific fluorescence response in aqueous solution with a detection limit for Cu2+ of ca. 0.65,ppb (10,×,10,9,M) under optimized conditions. It can extract Cu2+ from the solution with only trace amounts remaining. Through isolating of the toxic ions within the mesopores of the silica, SBA,P2 has the potential to work as a toxicide for Cu2+ in living systems. The fluorogenical responses are reversible and do not vary over a broad (4.0 to 9.0) pH range suitable for application under physiological conditions. The fluorescence responses of Cu2+ in vitro (human breast cancer cells) and in vivo (five-day-old zebrafish) demonstrate the possibility of further application in biology. [source] Coxibs: evolution of prescription's behaviour in FranceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2007Julie Biga Abstract The aim of the present study was, first to characterize profiles of coxibs' prescribers [general practitioners (GPs) and rheumatologists] in 2002 in France and, secondly, to identify factors associated with modification of this profile 1 year later. All GPs and rheumatologists from Midi-Pyrenees, Aquitaine, Languedoc-Roussillon and Pays de Loire areas (South of France: 11 050 000 inhabitants) were included in the study. For each practitioner, we used data concerning all non-steroidal anti-inflammatory drugs (NSAIDs) including coxibs reimbursed during period 1 (P1; January,March 2002) and period 2 (P2; January,March 2003). The ratio between the number of coxibs' prescriptions and the total number of NSAIDs' prescriptions (including coxibs) was used to define the two profiles of prescribers, one with a low level of coxibs' prescriptions and another one with a high level of coxibs' prescriptions. Characteristics of practitioners and characteristics of their practices were compared according to this profile. In the second step, we investigated the characteristics (of practitioners and practices) associated with an increase in the level of coxibs' prescriptions in P2 for practitioners with a low level of coxibs' prescriptions in P1. Results are expressed as odds ratio with their 95% confidence intervals. A positive statistical link was found between a high level of coxibs' prescriptions, the speciality of rheumatologist or extra costs for consultation. In contrast, a negative association was observed with female gender or age below 44 years. No relationship was found with the status of referent. Concerning practices' characteristics of practitioners, there was a positive statistical link between a high ratio of coxibs' prescriptions and high co-prescriptions of gastroprotective agents and a negative association with a high number of acts, a high proportion of patients with chronic disabling diseases (CDD) or a high number of patients between 15 and 64 years. There was no statistical link with proportion of patients covered by Universal Medical Coverage (UMC) or aged more than 65 years. Among the factors involved in the increase in the ratio (between P1 and P2), no relationship was found with practitioners' characteristics. In contrast, some factors related to practices (level of gastroprotective co-prescriptions, number of acts, number of CDD patients) were related to a change in coxibs' prescriptions between P1 and P2. This study allowed to discuss some relationships between coxibs' prescription and practitioners' (age, gender, medical speciality or extra costs for consultation) or practices' (level of medical practice, patients' age, number of CDD patients or level of gastroprotective prescriptions) characteristics. In contrast, some other factors like the referent status or the number of patients with UMC are not related. Physicians, initially low prescribers of coxibs and increasing their coxibs' prescriptions during the period of our study, were those with a high level of gastroprotective prescriptions, a low number of acts or a small proportion of CDD patients. [source] A role for Connexin43 during neurodevelopmentGLIA, Issue 7 2007Amy E. Wiencken-Barger Abstract Connexin43 (Cx43) is the predominant gap junction protein expressed in premitotic radial glial cells and mature astrocytes. It is thought to play a role in many aspects of brain development and physiology, including intercellular communication, the release of neuroactive substances, and neural and glial proliferation and migration. To investigate the role of Cx43 in brain physiology, we generated a conditional knockout (cKO) mouse expressing Cre recombinase driven by the human GFAP promoter and a floxed Cx43 gene. The removal of Cx43 from GFAP-expressing cells affects the behavior of the mice and the development of several brain structures; however, the severity of the phenotype varies depending on the mouse background. One mouse subline, hereafter termed Shuffler, exhibits cellular disorganization of the cortex, hippocampus, and cerebellum, accompanied by ataxia and motor deficits. The Shuffler cerebellum is most affected and displays altered distribution and lamination of glia and neurons suggestive of cell migration defects. In all Shuffler mice by postnatal day two (P2), the hippocampus, cortex, and cerebellum are smaller. Disorganization of the ventricular and subventricular zone of the cortex is also evident. Given that these are sites of early progenitor cell proliferation, we suspect production and migration of neural progenitors may be altered. In conclusion, neurodevelopment of Shuffler/Cx43 cKO mice is abnormal, and the observed cellular phenotype may explain behavioral disturbances seen in these animals as well as in humans carrying Cx43 mutations. © 2007 Wiley-Liss, Inc. [source] Diet selection of dry and lactating beef cows grazing extensive pastures in late autumnGRASS & FORAGE SCIENCE, Issue 4 2006A. Farruggia Abstract The diet selection, made by twelve dry and twelve lactating spring-calving Salers beef cows at the end of the grazing season on an extensively grazed natural mountain pasture in central France, was compared. Sward structure, selection bites, daily grazing time and digestibility of the diet were measured in mid-October (P1) and mid-November (P2). Live weights were measured twice monthly throughout the experiment. Daily milk production was assessed in the week before the grazing behaviour measurements. Lactating cows grazed more selectively than dry cows: they took more bites on green patches (0·20 vs. 0·13 of total bites, P < 0·01; Jacob's selectivity index: 0·13 vs. ,0·25, P < 0·001), which is consistent with the higher overall nitrogen concentration in faeces (18·1 vs. 17·3 g kg,1 DM, P < 0·05). Lactating cows tended to slightly increase their daily grazing time compared with dry cows (on average 9·9 vs. 9·5 h, P = 0·07) and grazed faster in mid-November (74 vs. 69 bites min,1, P < 0·05). The lactating cows lost more live weight (,24 vs. ,12 kg cow,1, P < 0·05) between P1 and P2. A positive correlation was found between consumption of green patches by lactating cows and their daily milk production in P2 (r = 0·574, P = 0·05), whereas no correlation occurred between individual milk production and liveweight loss. Dry cows were less selective, which supports management practices that promote the use of cows with low requirements on extensively grazed pastures in late season. [source] Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2002Christopher J. O'Brien MS, FRACS Abstract Background Metastatic cutaneous cancer is the most common parotid malignancy in Australia, with metastatic squamous carcinoma (SCC) occurring most frequently. There are limitations in the current TNM staging system for metastatic cutaneous malignancy, because all patients with nodal metastases are simply designated N1, irrespective of the extent of disease. The aim of this study was to analyze the influence of clinical stage, extent of surgery, and pathologic findings on outcome after parotidectomy for metastatic SCC by applying a new staging system that separates metastatic disease in the parotid from metastatic disease in the neck. Methods A prospectively documented series of 87 patients treated by one of the authors (COB) over 12 years for clinical metastatic cutaneous SCC involving the parotid gland and a minimum of 2 years follow-up was analyzed. These patients were all previously untreated and were restaged according to the clinical extent of disease in the parotid gland in the following manner. P1, metastatic SCC of the parotid up to 3 cm in diameter; P2, tumor greater than 3 cm up to 6 cm in diameter or multiple metastatic parotid nodes; P3, tumor greater than 6 cm in diameter, VII nerve palsy, or skull base invasion. Neck disease was staged in the following manner: N0, no clinical metastatic disease in the neck; N1, a single ipsilateral metastatic neck node less than 3 cm in diameter; N2, multiple metastatic nodes or any node greater than 3 cm in diameter. Results Clinical P stages were P1, 43 patients; P2, 35 patients; and P3, 9 patients. A total of 21 patients (24%) had clinically positive neck nodes. Among these, 11 were N1, and 10 were N2. Conservative parotidectomies were carried out in 71 of 87 patients (82%), and 8 of these had involved surgical margins (11%). Radical parotidectomy sacrificing the facial nerve was performed in 16 patients, and 6 (38%) had positive margins, (p < .01 compared with conservative resections). Margins were positive in 12% of patients staged P1, 14% of those staged P2, and 44% of those staged P3 (p < .05). Multivariate analysis demonstrated that increasing P stage, positive margins, and a failure to have postoperative radiotherapy independently predicted for decreased control in the parotid region. Survival did not correlate with P stage; however, many patients staged P1 and P2 also had metastatic disease in the neck. Clinical and pathologic N stage both significantly influenced survival, and patients with N2 disease had a much worse prognosis than patients with negative necks or only a single positive node. Independent risk factors for survival by multivariate analysis were positive surgical margins and the presence of advanced (N2) clinical and pathologic neck disease. Conclusions The results of this study demonstrate that patients with metastatic cutaneous SCC in both the parotid gland and neck have a significantly worse prognosis than those with disease in the parotid gland alone. Furthermore, patients with cervical nodes larger than 3 cm in diameter or with multiple positive neck nodes have a significantly worse prognosis than those with only a single positive node. Also, the extent of metastatic disease in the parotid gland correlated with the local control rate. The authors recommend that the clinical staging system for cutaneous SCC of the head and neck should separate parotid (P) and neck disease (N) and that the proposed staging system should be tested in a larger study population. © 2002 Wiley Periodicals, Inc. [source] Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion,,HEPATOLOGY, Issue 3 2010Wei Ding Epithelial-to-mesenchymal transition (EMT) is predicted to play a critical role in metastatic disease in hepatocellular carcinoma. In this study, we used a novel murine model of EMT to elucidate a mechanism of tumor progression and metastasis. A total of 2 × 106 liver cells isolated from Ptenloxp/loxp/Alb-Cre+ mice, expanded from a single CD133+CD45, cell clone, passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, P1 and P2. Cells were analyzed for gene expression using microarray and real-time polymerase chain reaction. Functional analysis included cell proliferation, migration, and invasion in vitro and orthotopic tumor metastasis assays in vivo. Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to P0 cells and cells with fibroblastoid morphology. These P2 mesenchymal cells demonstrated increased locomotion on wound healing; increased cell invasion on Matrigel basement membrane; increased EMT-associated gene expression of Snail1, Zeb1, and Zeb2; and down-regulated E-cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth in vivo compared with P2 epithelial counterparts, with invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of hepatocyte growth factor (HGF), which we propose acts in a paracrine fashion to drive epithelial cells to undergo EMT. In addition, a second murine liver cancer stem cell line with methionine adenosyltransferase 1a deficiency acquired EMT after sequential transplantations, indicating that EMT was not restricted to Pten-deleted tumors. Conclusion: EMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in vivo, which is driven by HGF secreted from mesenchymal tumor cells in a feed-forward mechanism. (HEPATOLOGY 2010) [source] Efficient preconditioning techniques for finite-element quadratic discretization arising from linearized incompressible Navier,Stokes equationsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 12 2010A. El Maliki Abstract We develop an efficient preconditioning techniques for the solution of large linearized stationary and non-stationary incompressible Navier,Stokes equations. These equations are linearized by the Picard and Newton methods, and linear extrapolation schemes in the non-stationary case. The time discretization procedure uses the Gear scheme and the second-order Taylor,Hood element P2,P1 is used for the approximation of the velocity and the pressure. Our purpose is to develop an efficient preconditioner for saddle point systems. Our tools are the addition of stabilization (penalization) term r,(div(·)), and the use of triangular block matrix as global preconditioner. This preconditioner involves the solution of two subsystems associated, respectively, with the velocity and the pressure and have to be solved efficiently. Furthermore, we use the P1,P2 hierarchical preconditioner recently proposed by the authors, for the block matrix associated with the velocity and an additive approach for the Schur complement approximation. Finally, several numerical examples illustrating the good performance of the preconditioning techniques are presented. Copyright © 2009 John Wiley & Sons, Ltd. [source] Inhibition of endive (Cichorium endivia L.) polyphenoloxidase by a Carica papaya latex preparationINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 6 2001David De Rigal When endive polyphenoloxidase (PPO) was incubated with a crude papaya latex extract, it rapidly lost its activity. Inactivation was ascribed to thermostable nonenzymatic factors of low molecular weight. These factors were partially purified by a two step protocol including gel filtration chromatography on Biogel P2 and ion exchange chromatography using DEAE Sephadex A25. The PPO-inactivation rate was first order, when either inactivating agent or proton concentration was evaluated. Inactivation could be partially reversed by CuSO4, which suggested that the inactivating factor(s) bound to the copper site of the enzyme. On a more rapid time scale than inactivation, papaya latex extract acted also as a weak noncompetitive PPO inhibitor. [source] Regulation of phosphoinositide signaling by the inositol polyphosphate 5-phosphatasesIUBMB LIFE, Issue 8 2006Megan V. Astle Abstract Phosphoinositide signaling molecules control cellular growth, proliferation and differentiation, intracellular vesicle trafficking, and cytoskeletal rearrangement. The inositol polyphosphate 5-phosphatase family remove the D-5 position phosphate from PtdIns(3,4,5)P3, PtdIns(4,5)P2 and PtdIns(3,5)P2 forming PtdIns(3,4)P2, PtdIns(4)P and PtdIns(3)P respectively. This enzyme family, comprising ten mammalian members, exhibit seemingly non-redundant functions including the regulation of synaptic vesicle recycling, hematopoietic cell function and insulin signaling. Here we highlight recently established insights into the functions of two well characterized 5-phosphatases OCRL and SHIP2, which have been the subject of extensive functional studies, and the characterization of recently identified members, SKIP and PIPP, in order to highlight the diverse and complex functions of this enzyme family. iubmb Life, 58: 451 - 456, 2006 [source] PDK1 and PKB/Akt: Ideal Targets for Development of New Strategies to Structure-Based Drug DesignIUBMB LIFE, Issue 3 2003Thomas Harris Abstract Growth factor binding events to receptor tyrosine kinases result in activation of phosphatidylinositol 3-kinase (PI3K), and activated PI3K generates the membrane-bound second messengers phosphatidylinositol 3,4-diphosphate [PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (PKB, also known as Akt). In addition to the kinase domain, PDK1 and PKB contain a pleckstrin homology (PH) domain that binds to the second messenger, resulting in the phosphorylation and activation of PKB by PDK1. Recent evidence indicates that constitutive activation of PKB contributes to cancer progression by promoting proliferation and increased cell survival. The indicating of PDK1 and PKB as primary targets for discovery of anticancer drugs, together with the observations that both PDK1 and PKB contain small-molecule regulatory binding sites that may be in proximity to the kinase active site, make PDK1 and PKB ideal targets for the development of new strategies to structure-based drug design. While X-ray structures have been reported for the kinase domains of PDK1 and PKB, no suitable crystals have been obtained for either PDK1 or PKB with their PH domains intact. In this regard, a novel structure-based strategy is proposed, which utilizes segmental isotopic labeling of the PH domain in combination with site-directed spin labeling of the kinase active site. Then, long-range distance restraints between the 15N-labeled backbone amide groups of the PH domain and the unpaired electron of the active site spin label can be determined from magnetic resonance studies of the enhancement effect that the paramagnetic spin label has on the nuclear relaxation rates of the amide protons. The determination of the structure and position of the PH domain with respect to the known X-ray structure of the kinase active site could be useful in the rational design of potent and selective inhibitors of PDK1 and PKB by 'linking' the free energies of binding of substrate (ATP) analogs with analogs of the inositol polar head group of the phospholipid second messenger. The combined use of X-ray crystallography, segmental isotopic and spin labeling, and magnetic resonance studies can be further extended to the study of other dynamic multidomain proteins and targets for structure-based drug design. IUBMB Life, 55: 117-126, 2003 [source] Propofol has anti-inflammatory effects on alveolar type II epithelial cellsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010L. MA Background: We investigated whether lipopolysaccharide (LPS) induced inflammation in alveolar epithelial type II (ATII) cells is through cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4) and the effect of different dosages of propofol on the inflammation in primary cultured rat ATII cells. Methods: Cultured ATII cells were randomly assigned to one of the following five groups: Group C: untreated group (control) cultured in the absence of propofol and LPS; Group LPS: treated with 1 ,g/ml LPS; Group P1: treated with 1 ,g/ml LPS and 25 ,M propofol; Group P2: treated with 1 ,g/ml LPS and 50 ,M propofol; Group P3: treated with 1 ,g/ml LPS and 100 ,M propofol. ATII cells in all groups were cultured at 37 °C for 3 h. CD14 and TLR4 mRNA was detected using real-time polymerase chain reaction. Western blot was used to detect CD14 and TLR4 protein expression. CD14 and TLR4 expression on the ATII cells was imaged using immunofluorescence. Tumor necrosis factor-, (TNF-,) production was determined using an ELISA kit. Results: LPS stimulation resulted in an increased CD14 and TLR4 expression and increased TNF-, production in ATII cells. Propofol, at concentrations ,50 ,M, significantly (P<0.05) and dose-dependently decreased CD14 and TLR4 mRNA expression and protein expression in ATII cells. This was accompanied by a decrease in TNF-, production (P<0.05). Conclusion: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS-induced ATII cells injury through downregulation of CD14 and TLR4 expression. [source] Effects of Fertilizer Phosphorus on Yield Traits of Dekoko (Pisum sativum var. abyssinicum) Under Field ConditionsJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 1 2003A. Yemane Abstract Cool-season food legumes (CSFLs) are important supplementary protein sources and soil fertility restorers for subsistence farmers in Ethiopia. Yields of CSFLs, however, are limited by low soil fertility, as they are grown in poor soils, often without fertilizer. Dekoko (Pisum sativum var. abyssinicum) is one of the CSFLs cultivated in Tigray, Northern Ethiopia. It is highly appreciated by the local people for its taste. This paper reports on the effect of phosphorus (P) on the yield and nutrition value of Dekoko under field conditions, and compares the results with those obtained for Ater (Pisum sativum var. sativum). The experiment was conducted in the 1998 and 1999 growing seasons. Three rates of P equivalent to zero, 30, and 60 kg ha,1 P2O5 were tested. Biomass, leaf area index, branches/plant, pods/m2 and yield responded positively while seeds/pod and seed weight were not significantly affected by P. Tissue P contents in shoots and roots increased with an increase in P application rate, while P in the nodules was not affected. Crude protein (CP) content increased from 24.9 % of dry matter (DM) at P0 to 26.2 % at P2, and from 24.3 % at P0 to 25.2 % at P2, in Dekoko and Ater seeds, respectively, while total sugars decreased with an increase in P application rate. Cysteine in Dekoko and asparagine and threonine in both varieties decreased, while lysine and other amino acids were not significantly affected by P. P improved seed yield and CP content without greatly affecting the amino acid profile of Dekoko, when compared with that of the FAO/WHO (1991, Protein Quality Evaluation. Food and Nutrition, Paper 51. FAO/WHO, Rome) standard pattern of amino acid for children 2,5 years of age. Thus, improving yield through fertilization may help to improve nutritional quality and household food security for subsistence farmers. [source] Instrument-independent specification of the diffraction geometry and polarization state of the incident X-ray beamJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 1 2009Marc Schiltz This work augments the proposal of Schwarzenbach & Flack [J. Appl. Cryst. (1989), 22, 601,605], who have advocated the use of a diffractometer-independent definition of the azimuthal angle , to specify the diffraction geometry of a Bragg reflection. It is here proposed that one additional angle ,, which is also based on a diffractometer-independent definition, is needed to encode the direction of linear polarization for those experiments where this quantity is of importance. This definition is then extended to the cases of partially and/or elliptically polarized X-ray beams, and the use of three normalized Stokes parameters, P1, P2 and P3, together with ,, is advocated in order to characterize exhaustively the polarization state of the incident beam. The conventions proposed here present a general, unambiguous and economical means of encoding the information about the diffraction geometry, without the need to record any further information about the instrument, crystal orientation matrix and goniometer angles. Data-processing software using these definitions to analyse polarization-dependent phenomena becomes instrument-independent and completely general. These methods have been implemented in the macromolecular phasing program SHARP for exploiting the polarization anisotropy of anomalous scattering in protein crystals. [source] The cofilin activity cycle in lamellipodia and invadopodiaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Matthew Oser Abstract The actin severing protein cofilin is essential for directed cell migration and chemotaxis, in many cell types and is also important for tumor cell invasion during metastasis. Through its severing activity, cofilin increases the number of free barbed ends to initiate actin polymerization for actin-based protrusion in two distinct subcellular compartments in invasive tumor cells: lamellipodia and invadopodia. Cofilin severing activity is tightly regulated and multiple mechanisms are utilized to regulate cofilin activity. In this prospect, we have grouped the primary on/off regulation into two broad categories, both of which are important for inhibiting cofilin from binding to F-actin or G-actin: (1) Blocking cofilin activity by the binding of cofilin to either PI(4,5)P2 at lamellipodia, or cortactin at invadopodia. (2) Blocking cofilin's ability to bind to actin via serine phosphorylation. Although the literature suggests that these cofilin regulatory mechanisms may be cell-type dependent, we propose the existence of a common cofilin activity cycle in which both operate. In this common cycle, the mechanism used to initiate cofilin activity is determined by the starting point in the cycle in a given subcellular compartment. J. Cell. Biochem. 108: 1252,1262, 2009. © 2009 Wiley-Liss, Inc. [source] Tissue alterations after tooth extraction with and without surgical trauma: a volumetric study in the beagle dogJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2008Stefan Fickl Abstract Objectives: The aim of this study is to evaluate whether tooth extraction without the elevation of a muco-periosteal flap has advantageous effects on the resorption rate after tooth extraction. Material and Methods: In five beagle dogs polyether impressions were taken before the surgery. The roots of the first and second pre-molars (P1 and P2) were extracted and the sites were assigned to one of the following treatments: treatment group (Tx) 1, no treatment; Tx 2, surgical trauma (flap elevation and repositioning); Tx 3, the extraction socket was filled with BioOss Collagen® and closed with a free soft-tissue graft; Tx 4, after flap elevation and repositioning, the extraction socket was treated with BioOss Collagen® and a free soft-tissue graft. Impressions were taken 2 and 4 months after surgery. The casts were scanned, matched together with baseline casts and evaluated with digital image analysis. Results: The "flapless groups" demonstrated significant lower resorption rates both when using socket-preservation techniques and without. Furthermore, socket-preservation techniques yielded better results compared with not treating the socket. Conclusion: The results demonstrate that leaving the periosteum in place decreases the resorption rate of the extraction socket. Furthermore, the treatment of the extraction socket with BioOss Collagen® and a free gingival graft seems beneficial in limiting the resorption process after tooth extraction. [source] Theoretical study on the mechanism of the 1CHCl + NO2 reactionsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2004Jia-Xu Zhang Abstract The radical-molecule reaction mechanism of 1CHCl with NO2 has been explored theoretically at the B3LYP/6-311G(d, p) and CCSD(T)/6-311G(d, p) (single-point) levels of theory. Thirteen minimum isomers and 29 transition states are located. The initial association between 1CHCl and NO2 proceeds most likely through the carbon-to-middle-nitrogen attack leading to an energy-rich adduct a (HClCNO2), which is found to be a barrierless process. Staring from a, the most feasible channel is to undergo a concerted O-shift and CN bond rupture leading to product P2 (NO + HClCO). The minor product pathways are the direct O-extrusion of a to P3 (O + HClCNO- cis) as well as the 1,3-H-shift of a to isomer b (ClCNOOH) followed by a concerted OH-shift leading to d (HOClCNO), which will dissociate to product P8 (NO + ClCOH) via CN cleavage. Because the transition states and isomers involved in the most feasible channel all lie below the reactants, the title reaction is expected to be rapid, as is consistent with the measured rate constant at 296 K. The comparison with the analogous reactions 3CH2 + NO2 are discussed. The present study may be useful for further experimental investigation of the title reaction. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1184,1190, 2004 [source] | ||||||||||||||||||||||||||||||||||||||||