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S Ni

Publications and source records attributed to S Ni.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting.

There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.

Adenoviridae↗
PubMed2006

GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells.

Friend virus induces the development of erythroleukemia in mice through the interaction of a viral glycoprotein, gp55, with a truncated form of the Stk receptor tyrosine kinase, short form-Stk (Sf-Stk), and the EpoR. We have shown previously that the ability of Sf-Stk to participate in the transformation of Friend virus-infected cells requires the kinase activity and Grb2-binding site of Sf-Stk. Here we show that Grb2 heterozygous mice exhibit decreased susceptibility to Friend erythroleukemia and that expansion of erythroid progenitors in response to infection requires the C-terminal SH3 domain of Grb2. A fusion protein in which the Grb2-binding site in Sf-Stk is replaced by Gab2, supports the growth of progenitors from mice lacking Sf-Stk, whereas a Sf-Stk/Gab1 fusion protein does not. Gab2 is expressed in spleens from Friend virus-infected mice, co-immunoprecipitates with Sf-Stk and is tyrosine phosphorylated in the presence of Sf-Stk. Mice with a targeted deletion in Gab2 are less susceptible to Friend erythroleukemia and the expansion of erythroid progenitor cells in response to infection can be rescued by expression of Gab2, but not Gab1. Taken together, these data indicate that a Sf-Stk/Grb2/Gab2 complex mediates the growth of primary erythroid progenitor cells in response to Friend virus.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Deep mantle structure and the postperovskite phase transition.

Seismologists have known for many years that the lowermost mantle of the Earth is complex. Models based on observed seismic phases sampling this region include relatively sharp horizontal discontinuities with strong zones of anisotropy, nearly vertical contrasts in structure, and small pockets of ultralow velocity zones (ULVZs). This diversity of structures is beginning to be understood in terms of geodynamics and mineral physics, with dense partial melts causing the ULVZs and a postperovskite solid-solid phase transition producing regional layering, with the possibility of large-scale variations in chemistry. This strong heterogeneity has significant implications on heat transport out of core, the evolution of the magnetic field, and magnetic field polarity reversals.

Journal Article↗
PubMed2001

Induced apoptosis supports spread of adenovirus vectors in tumors.

Selectively replicating viruses hold promise as anticancer agents. To eliminate the tumor, these viruses must efficiently spread throughout the tumor and induce oncolysis. We hypothesized that viral release and spread could be supported by apoptosis induced after assembly of de novo-produced virions in tumor cells. As a model to test this, we employed an adenovirus vector that replicated in human tumor cell lines. Expression of a dominant-negative I-kappaB from this vector sensitized tumor cells to recombinant human tumor necrosis factor alpha (TNF-alpha)-mediated apoptosis. We found that apoptosis induced during viral DNA replication compromised virus production, whereas apoptosis induced after virion assembly enhanced viral release from infected cells and dissemination. Electron microscopy demonstrated that viral particles were associated with or included in apoptotic bodies whose phagocytosis by neighboring cells provides a potential means for viral spread. Apoptosis induced after viral replication also supported spread in vivo, in subcutaneous tumors or liver metastases, resulting in a delay of tumor growth. Our findings could be applicable to other selectively replicating viruses or antitumor strategies that involve application of proapoptotic or cytolytic agents.

Adenoviridae↗
PubMed2001

Loading estimates of lead, copper, cadmium, and zinc in urban runoff from specific sources.

Urban stormwater runoff is being recognized as a substantial source of pollutants to receiving waters. A number of investigators have found significant levels of metals in runoff from urban areas, especially in highway runoff. As an initiatory study, this work estimates lead, copper, cadmium, and zinc loadings from various sources in a developed area utilizing information available in the literature, in conjunction with controlled experimental and sampling investigations. Specific sources examined include building siding and roofs; automobile brakes, tires, and oil leakage; and wet and dry atmospheric deposition. Important sources identified are building siding for all four metals, vehicle brake emissions for copper and tire wear for zinc. Atmospheric deposition is an important source for cadmium, copper, and lead. Loadings and source distributions depend on building and automobile density assumptions and the type of materials present in the area examined. Identified important sources are targeted for future comprehensive mechanistic studies. Improved information on the metal release and distributions from the specific sources, along with detailed characterization of watershed areas will allow refinements in the predictions.

Automobiles↗
PubMed2001

Tumor-specific gene expression in hepatic metastases by a replication-activated adenovirus vector.

Clinical applications of tumor gene therapy require tumor-specific delivery or expression of therapeutic genes in order to maximize the oncolytic index and minimize side effects. This study demonstrates activation of transgene expression exclusively in hepatic metastases after systemic application of a modified first-generation (E1A/E1B-deleted) adenovirus vector (AdE1-) in mouse tumor models. The discrimination between tumors and normal liver tissue is based on selective DNA replication of AdE1- vectors in tumor cells. This new AdE1- based vector system uses homologous recombination between inverted repeats to mediate precise rearrangements within the viral genome. As a result of these rearrangements, a promoter is brought into conjunction with a reporter gene creating a functional expression cassette. Genomic rearrangements are dependent upon viral DNA replication, which in turn occurs specifically in tumor cells. In a mouse tumor model with liver metastases derived from human tumor cells, a single systemic administration of replication activated AdE1- vectors achieved transgene expression in every metastasis, whereas no extra-tumoral transgene induction was observed. Here we provide a new concept for tumor-specific gene expression that is also applicable for other conditionally replicating adenovirus vectors.

Adenoviridae↗
PubMed2001

[The expression of BDNF and NT-3 in dorsal root ganglion following peripheral and central axotomy--an immunohistochemical study].

OBJECTIVE: To explore the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3(NT-3) in dorsal root ganglion (DRG) following peripheral and central axotomy. METHODS: Fifteen male adult cats were divided into intact group, peripheral axotomy group and central axotomy group. The ten cats of the latter two groups were subjected to unilateral peripheral cut and central processes cut respectively. The animals were allowed to survive 4 days long; L5 DRG was taken from each animal and made into frozen sections 20 microns thick. The sections were stained using antisera of BDNF and NT-3 respectively by immunohistchemical ABC method. The neuronal numbers of BDNF and NT-3 of the three groups were counted and compared. RESULTS: The positive products of BDNF were mainly distributed in small to medium sized neurons (13-57 microns) while those of NT-3 were mainly in large sized neurons (57-100 microns). The neuronal numbers of BDNF and NT-3 in peripheral and central axotomy groups (24.1 +/- 3.5, 29.4 +/- 5.2; 19.4 +/- 2.4, 20.2 +/- 1.9) increased significantly than those of intact group (12.1 +/- 2.2, 13.3 +/- 2.9), P < 0.01. And the neuronal numbers of BDNF and NT-3 in peripheral axotomy groups were more than those of central axotomy group(P < 0.05). CONCLUSION: The results indicate that peripheral axotomy and central axotomy lead to the increase of the expression of BDNF and NT-3 in DRG neurons. And the effect of peripheral axotomy is greater than that of central axotomy.

Animals↗
PubMed2000

[Synthesis and spectroscopic studies of new N-functionalized macrocyclic compounds and complex].

Three new N-functionalized tetraazamacrocyclic compounds, C-messo-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane- N,N',N",N'"-tetrakis (ethyl acetate) (A), C-messo-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetra- azacyclotetradecane-N,N,'N",N'"-tetraacetic acid (H4L) and the hydrobromide of H4L have been synthesized and the complex Na2[NiL].2C2H5OH has been prepared as well. The macroyclic compounds and the complex have been studied by electronic spectrum, infrared spectrum, 1H NMR, MS and elemental analysis.

English Abstract↗
PubMed1999

Electrospray ionization-mass spectrometry study of the interaction of cisplatin-adducted oligonucleotides with human XPA minimal binding domain protein.

Nucleotide excision repair (NER) is the process responsible for eliminating most ultraviolet (UV) radiation damage from DNA, as well as base alterations caused by a variety of mutagens. The xeroderma pigmentosum group A complementing protein (XPA) is believed to be involved in the early step of NER by recognizing and binding damaged DNA. Recent work has suggested that electrospray ionization-mass spectrometry (ESI-MS) can be an effective tool for the study of protein-DNA complexes. We have used ESI-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to examine the cisplatin-adducted oligonucleotide and its interaction with the human XPA minimal binding domain (XPA-MBD). High-resolution FTICR experiments of the binding products showed that both double-stranded damaged 20-mer and double-stranded undamaged 20-mer formed 1:1 noncovalent complexes with XPA-MBD. A 2:1 binding stoichiometry complex was also observed between XPA-MBD and double-stranded damaged 20-mer. Competitive binding experiments indicated only slightly preferential binding of XPA-MBD with the double-stranded damaged 20-mer compared to the undamaged 20-mer. The results demonstrate that ESI-FTICR mass spectrometry provides a fast and efficient approach for characterizing weak protein-DNA interactions such as the binding between XPA-MBD and a 20-mer oligonucleotide system.

Base Sequence↗
PubMed1998

Structural features of the minimal DNA binding domain (M98-F219) of human nucleotide excision repair protein XPA.

XPA, an essential protein in nucleotide excision repair (NER), interacts with damaged DNA and other proteins (RPA, ERCC1 and TFIIH) to remove a wide variety of chemically and structurally distinct DNA lesions from the eukaryotic genome. To understand the structural basis for the role of XPA in the repair process, the structure of the minimal DNA binding domain of human XPA [XPA-MBD (M98-F219)] was studied by NMR spectroscopy. A three-dimensional structure for XPA-MBD was generated using distance geometry and simulated annealing methods from NOE-based distance restraints, hydrogen bond and Zn-S distance restraints, and dihedral restraints. The structure calculations indicate that XPA-MBD contains elements of well-defined secondary structure interspaced with disordered loops organized into two non-interactive sub-domains: a zinc-binding core (D101-K137) and a loop-rich domain (L138-F219). The zinc-associated core contains an antiparallel beta-sheet (Y102-C105 and K110-M113) and an alpha-helix (C126-K137) separated by a poorly defined turn, reminiscent of the structure of the zinc-binding domain of the chicken erythroid transcription factor GATA-1 when bound to its cognate DNA sequence. The loop-rich domain contains a triple-strand antiparallel beta-sheet (L138-T140, L182-M178 and K163-K167), three loops (K151-L162, N169-D177 and Q208-F219) and three alpha-helices (K141-L150, K183-W194 and Q197-R207). The XPA-MBD structure is discussed in terms of known functions: binding single- and double-stranded DNA and binding RPA.

Amino Acid Sequence↗
PubMed1998

Human nucleotide excision repair protein XPA: extended X-ray absorption fine-structure evidence for a metal-binding domain.

The ubiquitous, multi-enzyme, nucleotide excision repair (NER) pathway is responsible for correcting a wide range of chemically and structurally distinct DNA lesions in the eukaryotic genome. Human XPA, a 31 kDa, zinc-associated protein, is thought to play a major NER role in the recognition of damaged DNA and the recruitment of other proteins, including RPA, ERCC1, and TFIIH, to repair the damage. Sequence analyses and genetic evidence suggest that zinc is associated with a C4-type motif, C105-X2-C108-X17-C126-X2-C129, located in the minimal DNA binding region of XPA (M98-F219). The zinc-associated motif is essential for damaged DNA recognition. Extended X-ray absorption fine structure (EXAFS) spectra collected on the zinc associated minimal DNA-binding domain of XPA (ZnXPA-MBD) show directly, for the first time, that the zinc is coordinated to the sulfur atoms of four cysteine residues with an average Zn-S bond length of 2.34+/-0.01 A. XPA-MBD was also expressed in minimal medium supplemented with cobalt nitrate to yield a blue-colored protein that was primarily (>95%) cobalt associated (CoXPA-MBD). EXAFS spectra collected on CoXPA-MBD show that the cobalt is also coordinated to the sulfur atoms of four cysteine residues with an average Co-S bond length of 2.33+/-0.02 A.

Absorptiometry, Photon↗
PubMed1998

[Applied anatomy of insular skin flap of nasolabial groove with retrograde superior labial artery].

In order to study the feasibiliy of the insular skin flap of the nasolabial groove with the retrograde superior labial artery, 8 adult cadavers were dissected and the relation between the superior labial artery and the skin of nasolabial groove was observed. The result revealed that superior labial artery was one of the branches of the facial artery and could be found in every cadaver. The diameter of the artery was 0.8 +/- 0.1 mm and the length was about 90 mm. The left and right facial arteries were connected with each other in the mid-line in the formation of the arcuate artery. The arcuate artery lay within the submucous tissue beyond the vermilion border about 6 mm. The concomitant veins were constant. If the facial artery being sectioned was beyond its initial site of superior labial artery, the skin of nasolabial groove on the same side could receive blood supply from contralateral supperior labial artery. The conclusion was that the insular skin flap of the nasolabial groove with the retrograde superior labial artery could be used in patients, because it had support from anatomical research.

Adult↗
PubMed1997

Purification, characterization and gene sequence analysis of a novel cytochrome c co-induced with reductive dechlorination activity in Desulfomonile tiedjei DCB-1.

The sulfate-reducing bacterium, Desulfomonile tiedjei DCB-1, conserves energy for growth from reductive dechlorination of 3-chlorobenzoate via halorespiration. To understand this respiratory process better, we examined electron carriers from different cellular compartments of D. tiedjei. A 50-kDa cytochrome from the membrane fraction was found to be co-induced with dechlorination activity. This inducible cytochrome was extracted from the membrane fractions by Tris-HCl buffer containing ammonium sulfate at 35% saturation and was purified to electrophoretic homogeneity by phenyl superose, Mono Q, and hydroxyapatite chromatography. The purified cytochrome had a high-spin absorption spectrum. In a pH titration experiment, the absorption spectrum of the inducible cytochrome shifted to low spin at pH 13.2. The midpoint potential of the inducible cytochrome at pH 7.0 was -342 mV. The NH2-terminal amino acid sequence of the inducible cytochrome was determined and was used to obtain inverse PCR products containing the sequence of the gene encoding the inducible cytochrome. The ORF was 1398 bp and coded for a protein of 52.6 kDa. Two c-type heme-binding domains were identified in the COOH-terminal half of the protein. A putative signal peptide of 26 residues was found at the NH2-terminal end. The protein sequence was not found to have substantial sequence similarity to any other sequence in GenBank. We conclude that this is a c-type cytochrome substantially different from previously characterized c-type cytochromes.

Amino Acid Sequence↗
PubMed1995

Purification and characterization of a novel 3-chlorobenzoate-reductive dehalogenase from the cytoplasmic membrane of Desulfomonile tiedjei DCB-1.

Although reductive dehalogenation by anaerobic microorganisms offers great potential for the degradation of halocarbons, little is known about the biochemical mechanisms involved. It has previously been demonstrated that the dehalogenase activity involved in 3-chlorobenzoate dehalogenation by Desulfomonile tiedjei DCB-1 is present in the membrane fraction of the cell extracts. We report herein the purification of a 3-chlorobenzoate-reductive dehalogenase from the cytoplasmic membrane of D. tiedjei DCB-1. The dehalogenase activity was monitored by the conversion of 3-chlorobenzoate to benzoate with reduced methyl viologen as a reducing agent. The membrane fraction of the cell extracts was obtained by ultracentrifugation, and the membrane proteins were solubilized with either the detergent CHAPS (3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) or Triton X-100 in the presence of glycerol. The solubilized dehalogenase was purified by ammonium sulfate fractionation and a combination of anion exchange, hydroxyapatite, and hydrophobic interaction chromatographies. This procedure yielded about 7% of the total dehalogenase activity with a 120-fold increase in specific activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the purified dehalogenase consisted of two subunits with molecular weights of 64,000 and 37,000. The enzyme converted 3-chlorobenzoate to benzoate at its highest specific activity in 10 mM potassium phosphate buffer (pH 7.2) at 38 degrees C. The enzyme was yellow and probably a heme protein. The enzyme had an adsorbance peak at 408 nm. The dithionite-reduced enzyme displayed absorbance peaks at 416, 522, and 550 nm. The dithionite-reduced enzyme was able to complex with carbon monoxide. The nature of the heme chromophore is currently unknown.

Benzoates↗
PubMed1994

Transfer of Methanolobus siciliae to the genus Methanosarcina, naming it Methanosarcina siciliae, and emendation of the genus Methanosarcina.

A sequence analysis of the 16S rRNA of Methanolobus siciliae T4/M(T) (T = type strain) showed that this strain is closely related to members of the genus Methanosarcina, especially Methanosarcina acetivorans C2A(T). Methanolobus siciliae T4/M(T) and HI350 were morphologically more similar to members of the genus Methanosarcina than to members of the genus Methanolobus in that they both formed massive cell aggregates with pseudosarcinae. Thus, we propose that Methanolobus siciliae should be transferred to the genus Methanosarcina as Methanosarcina siciliae.

Methanosarcina↗
PubMed1994

Potassium extrusion by the moderately halophilic and alkaliphilic methanogen methanolobus taylorii GS-16 and homeostasis of cytosolic pH.

Methanolobus taylorii GS-16, a moderately halophilic and alkaliphilic methanogen, grows over a wide pH range, from 6.8 to 9.0. Cells suspended in medium with a pH above 8.2 reversed their transmembrane pH gradient (delta pH), making their cytosol more acidic than the medium. The decreased energy in the proton motive force due to the reversed delta pH was partly compensated by an increased electric membrane potential (delta psi). The cytosolic acidification by M. taylorii at alkaline pH values was accompanied by K+ extrusion. The cytosolic K+ concentration was 110 mM in cells suspended at pH 8.7, but it was 320 mM in cells suspended at neutral pH values. High external K+ concentrations (210 mM or higher) inhibited the growth of M. taylorii at alkaline pH values, perhaps by preventing K+ extrusion. Cells suspended at pH 8.5 and 300 mM external K+ failed to acidify their cytosol. The key observation indicative of the involvement of K+ transport in cytosolic acidification was that valinomycin (0.8 microM), a K+ uniporter, inhibited the growth of M. taylorii only at alkaline pH values. Experiments with resting cells indicated that at alkaline pH values valinomycin uncoupled catabolic reactions from ATP synthesis. Thus, K+/H+ antiport activity was proposed to account for the K+ extrusion and the uncoupling effect of valinomycin at alkaline pH values. Such antiport activity was demonstrated by the sharp drop in pH of the bulk medium of the cell suspension upon the addition of 0.1 M KCl. The antiporter appeared to be active only at alkaline pH values, which was in accordance with a possible role in pH homeostasis by M. taylorii growing at alkaline pH values.

Alkalies↗