bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Na
+
:H
+
Antiporter and a Molybdate Transporter Are Essential for Arsenite Oxidation in
Agrobacterium tumefaciens
Authors: Kashyap Des R. , Botero Lina M. , Lehr Corinne , Hassett Daniel J. , McDermott Timothy R. 
Published: February 2006

ABSTRACT

Transposon Tn
5
-B22 mutagenesis was used to identify genetic determinants required for arsenite [As(III)] oxidation in an
Agrobacterium tumefaciens
soil isolate, strain 5A. In one mutant, the transposon interrupted
modB
, which codes for the permease component of a high-affinity molybdate transporter. In a second mutant, the transposon insertion occurred in
mrpB
, which is part of a seven-gene operon encoding an Mrp-type Na
+
:H
+
antiporter complex. Complementation experiments with
mod
and
mrp
operons PCR cloned from the genome-sequenced
A. tumefaciens
strain C58 resulted in complementation back to an As(III)-oxidizing phenotype, confirming that these genes encode activities essential for As(III) oxidation in this strain of
A. tumefaciens
. As expected, the
mrp
mutant was extremely sensitive to NaCl and LiCl, indicating that the Mrp complex in
A. tumefaciens
is involved in Na
+
circulation across the membrane. Gene expression studies (
lacZ
reporter and reverse transcriptase PCR experiments) failed to show evidence of transcriptional regulation of the
mrp
operon in response to As(III) exposure, whereas expression of the
mod
operon was found to be up-regulated by As(III) exposure. In each mutant, the loss of As(III)-oxidizing capacity resulted in conversion to an arsenate [As(V)]-reducing phenotype. Neither mutant was more sensitive to As(III) than the parental strain.
Complete Sequencing and Diversity Analysis of the Enterotoxin-Encoding Plasmids inClostridium perfringensType A Non-Food-Borne Human Gastrointestinal Disease Isolates
Authors: Miyamoto Kazuaki , Fisher Derek J. , Li Jihong , Sayeed Sameera , Akimoto Shigeru , McClane Bruce A. 
Published: February 2006

ABSTRACTEnterotoxin-producingClostridium perfringenstype A isolates are an important cause of food poisoning and non-food-borne human gastrointestinal diseases, e.g., sporadic diarrhea (SPOR) and antibiotic-associated diarrhea (AAD). The enterotoxin gene (cpe) is usually chromosomal in food poisoning isolates but plasmid-borne in AAD/SPOR isolates. Previous studies determined that type A SPOR isolate F5603 has a plasmid (pCPF5603) carryingcpe, IS1151, and the beta2 toxin gene (cpb2), while type A SPOR isolate F4969 has a plasmid (pCPF4969) lackingcpb2and IS1151but carryingcpeand IS1470-like sequences. By completely sequencing these twocpeplasmids, the current study identified pCPF5603 as a 75.3-kb plasmid carrying 73 open reading frames (ORFs) and pCPF4969 as a 70.5-kb plasmid carrying 62 ORFs. These plasmids share an ∼35-kb conserved region that potentially encodes virulence factors and carries ORFs found on the conjugative transposon Tn916. The 34.5-kb pCPF4969 variable region contains ORFs that putatively encode two bacteriocins and a two-component regulator similar to VirR/VirS, while the ∼43.6-kb pCPF5603 variable region contains a functionalcpb2gene and several metabolic genes. Diversity studies indicated that other type A plasmidcpe+/IS1151SPOR/AAD isolates carry a pCPF5603-like plasmid, while other type A plasmidcpe+/IS1470-like SPOR/AAD isolates carry a pCPF4969-like plasmid. Tn916-related ORFs similar to those in pCPF4969 (known to transfer conjugatively) were detected in thecpeplasmids of other type A SPOR/AAD isolates, as well as in representativeC. perfringenstype B to D isolates carrying other virulence plasmids, possibly suggesting that most or allC. perfringensvirulence plasmids transfer conjugatively.
Unusual Extra Space at the Active Site and High Activity for Acetylated Hydroxyproline of Prolyl Aminopeptidase from
Serratia marcescens
Authors: Nakajima Yoshitaka , Ito Kiyoshi , Sakata Makoto , Xu Yue , Nakashima Kanako , Matsubara Futoshi , Hatakeyama Susumi , Yoshimoto Tadashi 
Published: February 2006

ABSTRACT

The prolyl aminopeptidase complexes of Ala-TBODA [2-alanyl-5-
tert
-butyl-(1, 3, 4)-oxadiazole] and Sar-TBODA [2-sarcosyl-5-
tert
-butyl-(1, 3, 4)-oxadiazole] were analyzed by X-ray crystallography at 2.4 Å resolution. Frames of alanine and sarcosine residues were well superimposed on each other in the pyrrolidine ring of proline residue, suggesting that Ala and Sar are recognized as parts of this ring of proline residue by the presence of a hydrophobic proline pocket at the active site. Interestingly, there was an unusual extra space at the bottom of the hydrophobic pocket where proline residue is fixed in the prolyl aminopeptidase. Moreover, 4-acetyloxyproline-βNA (4-acetyloxyproline β-naphthylamide) was a better substrate than Pro-βNA. Computer docking simulation well supports the idea that the 4-acetyloxyl group of the substrate fitted into that space. Alanine scanning mutagenesis of Phe139, Tyr149, Tyr150, Phe236, and Cys271, consisting of the hydrophobic pocket, revealed that all of these five residues are involved significantly in the formation of the hydrophobic proline pocket for the substrate. Tyr149 and Cys271 may be important for the extra space and may orient the acetyl derivative of hydroxyproline to a preferable position for hydrolysis. These findings imply that the efficient degradation of collagen fragment may be achieved through an acetylation process by the bacteria.
The Crystal Structure of the Zinc Phosphodiesterase from
Escherichia coli
Provides Insight into Function and Cooperativity of tRNase Z-Family Proteins
Authors: Kostelecky Brenda , Pohl Ehmke , Vogel Andreas , Schilling Oliver , Meyer-Klaucke Wolfram 
Published: February 2006

ABSTRACT

The
elaC
gene product from
Escherichia coli
, ZiPD, is a 3′ tRNA-processing endonuclease belonging to the tRNase Z family of enzymes that have been identified in a wide variety of organisms. In contrast to the
elaC
homologue from
Bacillus subtilis
,
E. coli elaC
is not essential for viability, and although both enzymes process only precursor tRNA (pre-tRNA) lacking a CCA triplet at the 3′ end in vitro, the physiological role of ZiPD remains enigmatic because all pre-tRNA species in
E. coli
are transcribed with the CCA triplet. We present the first crystal structure of ZiPD determined by multiple anomalous diffraction at a resolution of 2.9 Å. This structure shares many features with the tRNase Z enzymes from
B. subtilis
and
Thermotoga maritima
, but there are distinct differences in metal binding and overall domain organization. Unlike the previously described homologous structures, ZiPD dimers display crystallographic symmetry and fully loaded metal sites. The ZiPD exosite is similar to that of the
B. subtilis
enzyme structurally, but its position with respect to the protein core differs substantially, illustrating its ability to act as a clamp in binding tRNA. Furthermore, the ZiPD crystal structure presented here provides insight into the enzyme's cooperativity and assists the ongoing attempt to elucidate the physiological function of this protein.
NnrA Is Required for Full Virulence and Regulates Several
Brucella melitensis
Denitrification Genes
Authors: Haine Valérie , Dozot Marie , Dornand Jacques , Letesson Jean-Jacques , De Bolle Xavier 
Published: February 2006

ABSTRACT

We identified two regulators of denitrification genes in
Brucella melitensis
16M: NarR, which regulates the nitrate reductase (
nar
) operon, and NnrA, which is involved in the expression of the last three reductases of the denitrification pathway (
nirK
,
norB
, and
nosZ
). NnrA is required for virulence in mice and for intracellular resistance to nitric oxide.
Apyrase, the Product of the Virulence Plasmid-Encoded
phoN2
(
apy
) Gene of
Shigella flexneri
, Is Necessary for Proper Unipolar IcsA Localization and for Efficient Intercellular Spread
Authors: Santapaola D. , Del Chierico F. , Petrucca A. , Uzzau S. , Casalino M. , Colonna B. , Sessa R. , Berlutti F. , Nicoletti M. 
Published: February 2006

ABSTRACT

The role in virulence of the
Shigella flexneri ospB
-
phoN2
operon has been evaluated. Here we confirm that OspB is an effector and show that apyrase, the product of
phoN2
, may be a virulence factor, since it is required for efficient intercellular spreading. Apyrase may be important in a deoxynucleoside triphosphate-hydrolyzing activity-independent manner, suggesting that it may act as an interaction partner in the process of IcsA localization.
A Eukaryotic-Type Serine/Threonine Protein Kinase Is Required for Biofilm Formation, Genetic Competence, and Acid Resistance in
Streptococcus mutans
Authors: Hussain Haitham , Branny Pavel , Allan Elaine 
Published: February 2006

ABSTRACT

We report an operon encoding a eukaryotic-type serine/threonine protein kinase (STPK) and its cognate phosphatase (STPP) in
Streptococcus mutans
. Mutation of the gene encoding the STPK produced defects in biofilm formation, genetic competence, and acid resistance, determinants important in caries pathogenesis.
Transcriptome Profiling of
Shewanella oneidensis
Gene Expression following Exposure to Acidic and Alkaline pH
Authors: Leaphart Adam B. , Thompson Dorothea K. , Huang Katherine , Alm Eric , Wan Xiu-Feng , Arkin Adam , Brown Steven D. , Wu Liyou , Yan Tingfen , Liu Xueduan , Wickham Gene S. , Zhou Jizhong 
Published: February 2006

ABSTRACT

The molecular response of
Shewanella oneidensis
MR-1 to variations in extracellular pH was investigated based on genomewide gene expression profiling. Microarray analysis revealed that cells elicited both general and specific transcriptome responses when challenged with environmental acid (pH 4) or base (pH 10) conditions over a 60-min period. Global responses included the differential expression of genes functionally linked to amino acid metabolism, transcriptional regulation and signal transduction, transport, cell membrane structure, and oxidative stress protection. Response to acid stress included the elevated expression of genes encoding glycogen biosynthetic enzymes, phosphate transporters, and the RNA polymerase sigma-38 factor (
rpoS
), whereas the molecular response to alkaline pH was characterized by upregulation of
nhaA
and
nhaR
, which are predicted to encode an Na
+
/H
+
antiporter and transcriptional activator, respectively, as well as sulfate transport and sulfur metabolism genes. Collectively, these results suggest that
S. oneidensis
modulates multiple transporters, cell envelope components, and pathways of amino acid consumption and central intermediary metabolism as part of its transcriptome response to changing external pH conditions.
Global Transcriptome Analysis ofStaphylococcus aureusResponse to Hydrogen Peroxide
Authors: Chang Wook , Small David A. , Toghrol Freshteh , Bentley William E. 
Published: February 2006

ABSTRACTStaphylococcus aureusresponds with protective strategies against phagocyte-derived reactive oxidants to infect humans. Herein, we report the transcriptome analysis of the cellular response ofS. aureusto hydrogen peroxide-induced oxidative stress. The data indicate that the oxidative response includes the induction of genes involved in virulence, DNA repair, and notably, anaerobic metabolism.
MurQ Etherase Is Required by
Escherichia coli
in Order To Metabolize Anhydro-
N
-Acetylmuramic Acid Obtained either from the Environment or from Its Own Cell Wall
Authors: Uehara Tsuyoshi , Suefuji Kyoko , Jaeger Tina , Mayer Christoph , Park James T. 
Published: February 2006

ABSTRACT

MurQ is an
N
-acetylmuramic acid-phosphate (MurNAc-P) etherase that converts MurNAc-P to
N
-acetylglucosamine-phosphate and is essential for growth on MurNAc as the sole source of carbon (T. Jaegar, M. Arsic, and C. Mayer, J. Biol. Chem.
280:
30100-30106, 2005). Here we show that MurQ is the only MurNAc-P etherase in
Escherichia coli
and that MurQ and AnmK kinase are required for utilization of anhydro-MurNAc derived either from cell wall murein or imported from the medium.
Repressor of Phage
16
-
3
with Altered Binding Specificity Indicates Spatial Differences in Repressor-Operator Complexes
Authors: Ferenczi Szilamér , Orosz László , Papp Péter P. 
Published: February 2006

ABSTRACT

The C repressor protein of phage
16-3
, which is required for establishing and maintaining lysogeny, recognizes structurally different operators which differ by 2 bp in the length of the spacer between the conserved palindromic sequences. A “rotationally flexible protein homodimers” model has been proposed in order to explain the conformational adaptivity of the
16-3
repressor. In this paper, we report on the isolation of a repressor mutant with altered binding specificity which was used to identify a residue-base pair contact and to monitor the spatial relationship of the recognition helix of C repressor to the contacting major groove of DNA within the two kinds of repressor-operator complexes. Our results indicate spatial differences at the interface which may reflect different docking arrangements in recognition of the structurally different operators by the
16-3
repressor.
B7-H4 Is a Novel Membrane-Bound Protein and a Candidate Serum and Tissue Biomarker for Ovarian Cancer
Authors: Simon Iris , Zhuo Shaoqiu , Corral Laura , Diamandis Eleftherios P. , Sarno Mark J. , Wolfert Robert L. , Kim Nam W. 
Published: February 2006

Abstract
Using cDNA database mining strategies and real-time quantitative reverse transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in ovarian and breast cancer tissues when compared with normal tissues. The gene encodes a protein of 282 amino acids with a signal sequence, an immunoglobulin domain, and a COOH-terminal hydrophobic transmembrane domain. Immunohistochemistry experiments show plasma membrane staining in serous ovarian and breast cancer, confirming the tissue specificity and cell surface localization. We have developed a sensitive dual monoclonal antibody sandwich ELISA to analyze the level of B7-H4 protein in &gt;2,500 serum samples, ascites fluids, and tissue lysates. High levels of B7-H4 protein were detected in ovarian cancer tissue lysates when compared with normal tissues. B7-H4 was present at low levels in all sera but showed an elevated level in serum samples from ovarian cancer patients when compared with healthy controls or women with benign gynecologic diseases. The median B7-H4 concentration in endometrioid and serous histotypes was higher than in mucinous histotypes, consistent with results of immunohistochemical staining. The multivariate logistic regression analysis of B7-H4 and CA125 measured in the same sample set resulted in an area under the curve (AUC) of 0.86 for all stages and 0.86 for stage I/II patients, which was significantly higher than the AUC for either marker alone. In early-stage patients, the sensitivity at 97% specificity increased from 52% for CA125 alone to 65% when used in combination with B7-H4. We conclude that B7-H4 is a promising new biomarker for ovarian carcinoma. (Cancer Res 2006; 66(3): 1570-5)
An Essential Role of Alternative Splicing of c-myc Suppressor FUSE-Binding Protein–Interacting Repressor in Carcinogenesis
Authors: Matsushita Kazuyuki , Tomonaga Takeshi , Shimada Hideaki , Shioya Ayumi , Higashi Morihiro , Matsubara Hisahiro , Harigaya Kenichi , Nomura Fumio , Libutti Daniel , Levens David , Ochiai Takenori 
Published: February 2006

Abstract
Elevated expression of c-myc has been detected in a broad range of human cancers, indicating a key role for this oncogene in tumor development. Recently, an interaction between FUSE-binding protein–interacting repressor (FIR) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and might be important for suppressing tumor formation. In this study, we showed that enforced expression of FIR induced apoptosis. Deletion of the NH2-terminal repression domain of FIR rescued the cells from apoptosis as did coexpression of c-Myc with FIR; thus, repression of Myc mediates FIR-driven apoptosis. Surprisingly, a splicing variant of FIR unable to repress c-myc or to drive apoptosis was frequently discovered in human primary colorectal cancers but not in the adjacent normal tissues. Coexpression of this splicing variant with repressor-competent FIR, either in HeLa cells or in the colon cancer cell line SW480, not only abrogated c-Myc suppression but also inhibited apoptosis. These results strongly suggest the expression of this splicing variant promotes tumor development by disabling FIR repression and sustaining high levels of c-Myc and opposing apoptosis in colorectal cancer. (Cancer Res 2006; 66(3): 1409-17)
ErbB3-Dependent Motility and Intravasation in Breast Cancer Metastasis
Authors: Xue Chengsen , Liang Fubo , Mahmood Radma , Vuolo Magalis , Wyckoff Jeffrey , Qian Hong , Tsai Kun-Lin , Kim Mimi , Locker Joseph , Zhang Zhong-Yin , Segall Jeffrey E. 
Published: February 2006

AbstractA better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin β1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth. (Cancer Res 2006; 66(3): 1418-26)
Application of Bayesian Modeling of Autologous Antibody Responses against Ovarian Tumor-Associated Antigens to Cancer Detection
Authors: Erkanli Al , Taylor Douglas D. , Dean Deyrick , Eksir Faria , Egger Daniel , Geyer James , Nelson Brad H. , Stone Brad , Fritsche Herbert A. , Roden Richard B.S. 
Published: February 2006

Abstract
Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125. (Cancer Res 2006; 66(3): 1792-8)
Arachidonic Acid Activates Phosphatidylinositol 3-Kinase Signaling and Induces Gene Expression in Prostate Cancer
Authors: Hughes-Fulford Millie , Li Chai-Fei , Boonyaratanakornkit Jim , Sayyah Sina 
Published: February 2006

Abstract
Essential fatty acids are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase and other genes. Using gene chip analysis, we have found that arachidonic acid, an ω-6 fatty acid, induced 11 genes that are regulated by nuclear factor-κB (NF-κB). We verified gene induction by ω-6 fatty acid, including COX-2, IκBα, NF-κB, GM-CSF, IL-1β, CXCL-1, TNF-α, IL-6, LTA, IL-8, PPARγ, and ICAM-1, using quantitative reverse transcription-PCR. Prostaglandin E2 (PGE2) synthesis was increased within 5 minutes of addition of arachidonic acid. Analysis of upstream signal transduction showed that within 5 minutes of fatty acid addition, phosphatidylinositol 3-kinase (PI3K) was significantly activated followed by activation of Akt at 30 minutes. Extracellular signal-regulated kinase 1 and 2, p38 and stress-activated protein kinase/c-Jun-NH2-kinase were not phosphorylated after ω-6 fatty acid addition. Thirty minutes after fatty acid addition, we found a significant 3-fold increase in translocation of NF-κB transcription factor to the nucleus. Addition of a nonsteroidal anti-inflammatory drug (NSAID) caused a decrease in COX-2 protein synthesis, PGE2 synthesis, as well as inhibition of PI3K activation. We have previously shown that NSAIDs cause an inhibition of arachidonic acid–induced proliferation; here, we have shown that arachidonic acid–induced proliferation is also blocked (P &lt; 0.001) by PI3K inhibitor LY294002. LY294002 also significantly inhibited the arachidonic acid–induced gene expression of COX-2, IL-1β, GM-CSF, and ICAM1. Taken together, the data suggest that arachidonic acid via conversion to PGE2 plays an important role in stimulation of growth-related genes and proliferation via PI3K signaling and NF-κB translocation to the nucleus. (Cancer Res 2006; 66(3): 1427-33)