bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Flagellar Protein FliL Is Essential for Swimming in
Rhodobacter sphaeroides
Authors: Suaste-Olmos Fernando , Domenzain Clelia , Mireles-Rodríguez José Cruz , Poggio Sebastian , Osorio Aurora , Dreyfus Georges , Camarena Laura 
Published: October 2010

ABSTRACT

In this work we characterize the function of the flagellar protein FliL in
Rhodobacter sphaeroides
. Our results show that FliL is essential for motility in this bacterium and that in its absence flagellar rotation is highly impaired. A green fluorescent protein (GFP)-FliL fusion forms polar and lateral fluorescent foci that show different spatial dynamics. The presence of these foci is dependent on the expression of the flagellar genes controlled by the master regulator FleQ, suggesting that additional components of the flagellar regulon are required for the proper localization of GFP-FliL. Eight independent pseudorevertants were isolated from the
fliL
mutant strain. In each of these strains a single nucleotide change in
motB
was identified. The eight mutations affected only three residues located on the periplasmic side of MotB. Swimming of the suppressor mutants was not affected by the presence of the wild-type
fliL
allele. Pulldown and yeast two-hybrid assays showed that that the periplasmic domain of FliL is able to interact with itself but not with the periplasmic domain of MotB. From these results we propose that FliL could participate in the coupling of MotB with the flagellar rotor in an indirect fashion.
Copper Stress Targets the Rcs System To Induce Multiaggregative Behavior in a Copper-Sensitive
Salmonella
Strain
Authors: Pontel Lucas B. , Pezza Alejandro , Soncini Fernando C. 
Published: October 2010

ABSTRACT

Salmonella
Δ
cuiD
strains form mucoid colonies on copper-containing solid media. We show here that this multiaggregative behavior is caused by the Rcs-dependent induction of colanic acid extracellular polysaccharide. Deletion of
cps
operon genes in a Δ
cuiD
strain increased the sensitivity to copper, indicating a role for colanic acid in copper resistance.
Specific DNA Binding and Regulation of Its Own Expression by the AidB Protein in
Escherichia coli
Authors: Rippa Valentina , Amoresano Angela , Esposito Carla , Landini Paolo , Volkert Michael , Duilio Angela 
Published: October 2010

ABSTRACT

Upon exposure to alkylating agents,
Escherichia coli
increases expression of
aidB
along with three genes (
ada
,
alkA
, and
alkB
) that encode DNA repair proteins. While the biological roles of the Ada, AlkA, and AlkB proteins have been defined, despite many efforts, the molecular functions of AidB remain largely unknown. In this study, we focused on the biological role of the AidB protein, and we demonstrated that AidB shows preferential binding to a DNA region that includes the upstream element of its own promoter, P
aidB
. The physiological significance of this specific interaction was investigated by
in vivo
gene expression assays, demonstrating that AidB can repress its own synthesis during normal cell growth. We also showed that the domain architecture of AidB is related to the different functions of the protein: the N-terminal region, comprising the first 439 amino acids (AidB “I-III”), possesses FAD-dependent dehydrogenase activity, while its C-terminal domain, corresponding to residues 440 to 541 (AidB “IV”), displays DNA binding activity and can negatively regulate the expression of its own gene
in vivo
. Our results define a novel role in gene regulation for the AidB protein and underline its multifunctional nature.
Independent Segregation of the Two Arms of theEscherichia coli oriRegion Requires neither RNA Synthesis nor MreB Dynamics
Authors: Wang Xindan , Sherratt David J. 
Published: October 2010

ABSTRACTThe mechanism ofEscherichia colichromosome segregation remains elusive. We present results on the simultaneous tracking of segregation of multiple loci in theoriregion of the chromosome in cells growing under conditions in which a single round of replication is initiated and completed in the same generation. Loci segregated as expected for progressive replication-segregation fromoriC, with markers placed symmetrically on either side oforiCsegregating to opposite cell halves at the same time, showing that sister locus cohesion in the origin region is local rather than extensive. We were unable to observe any influence on segregation of the proposed centromeric site,migS, or indeed any other potentialcis-acting element on either replication arm (replichore) in the AB1157 genetic background. Site-specific inhibition of replication close tooriCon one replichore did not prevent segregation of loci on the other replichore. Inhibition of RNA synthesis and inhibition of the dynamic polymerization of the actin homolog MreB did not affectoriand bulk chromosome segregation.
Translational Defects in a Mutant Deficient in YajL, the Bacterial Homolog of the Parkinsonism-Associated Protein DJ-1
Authors: Kthiri Fatoum , Gautier Valérie , Le Hai-Tuong , Prère Marie-Françoise , Fayet Olivier , Malki Abderrahim , Landoulsi Ahmed , Richarme Gilbert 
Published: October 2010

ABSTRACT

We report here that YajL is associated with ribosomes and interacts with many ribosomal proteins and that a
yajL
mutant of
Escherichia coli
displays decreased translation accuracy, as well as increased dissociation of 70S ribosomes into 50S and 30S subunits after oxidative stress.
Genome Sequence of the Marine Alphaproteobacterium HTCC2150, Assigned to the
Roseobacter
Clade
Authors: Kang Ilnam , Oh Hyun-Myung , Vergin Kevin L. , Giovannoni Stephen J. , Cho Jang-Cheon 
Published: October 2010

ABSTRACT

Here we announce the genome sequence of a marine bacterium, HTCC2150, that was isolated off the Oregon coast using dilution-to-extinction culturing and that is affiliated with the
Roseobacter
clade. The 16S rRNA phylogeny showed that the strain was closely related to members of the RCA clade. The genome sequence suggests that strain HTCC2150 is an organoheterotroph carrying diverse metabolic potential, including a close relationship with phytoplankton.
Excessive RNA Splicing and Inhibition of HIV-1 Replication Induced by Modified U1 Small Nuclear RNAs
Authors: Mandal Dibyakanti , Feng Zehua , Stoltzfus C. Martin 
Published: October 2010

ABSTRACTHIV-1 RNA undergoes a complex splicing process whereby over 40 different mRNA species are produced by alternative splicing. In addition, approximately half of the RNA transcripts remain unspliced and either are used to encode Gag and Gag-Pol proteins or are packaged into virions as genomic RNA. It has previously been shown that HIV-1 splicing is regulated byciselements that bind to cellular factors. These factors either enhance or repress definition of exons that are flanked by the HIV-1 3′ splice sites. Here we report that expression of modified U1 snRNPs with increased affinity to HIV-1 downstream 5′ splice sites and to sequences within the firsttatcoding exon act to selectively increase splicing at the upstream 3′ splice sites in cotransfected 293T cells. This results in a decrease of unspliced viral RNA levels and an approximately 10-fold decrease in virus production. In addition, excessive splicing of viral RNA is concomitant with a striking reduction in the relative amounts of Gag processing intermediates and products. We also show that T cell lines expressing modified U1 snRNAs exhibit reduced HIV-1 replication. Our results suggest that induction of excessive HIV-1 RNA splicing may be a novel strategy to inhibit virus replication in human patients.
Association between wearing a personal floatation device and death by drowning among recreational boaters: a matched cohort analysis of United States Coast Guard data
Authors: Cummings P , Mueller B A , Quan L 
Published: October 2010

ObjectiveTo estimate the association between wearing a personal floatation device (PFD) and death by drowning among recreational boaters.DesignMatched cohort study analysis of Coast Guard data.SettingUnited States.SubjectsRecreational boaters during 2000–2006.Main outcome measuresRisk ratio (RR) for drowning death comparing boaters wearing a PFD with boaters not wearing a PFD.ResultsApproximately 4915 boater records from 1809 vessels may have been eligible for our study, but because of missing records and other problems, the analysis was restricted to 1597 boaters in 625 vessels with 878 drowning deaths. The adjusted RR was 0.51 (95% CI 0.35 to 0.74).ConclusionsIf the estimated association is causal, wearing a PFD may potentially prevent one in two drowning deaths among recreational boaters. However, this estimate may be biased because many vessels had to be excluded from the analysis.
Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth
Authors: Muramatsu Masashi , Yamamoto Seiji , Osawa Tsuyoshi , Shibuya Masabumi 
Published: October 2010

Abstract
Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1–expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)–deficient (Flt-1 TK−/−) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK−/− mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK−/− mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK−/− mice. Pericyte marker+ cells were also reduced in Flt-1 TK−/− mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK−/− mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK−/− mice implanted with Flt-1 TK−/− BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression. Cancer Res; 70(20); 8211–21. ©2010 AACR.
In silicoModeling andIn vivoEfficacy of Cancer-Preventive Vaccinations
Authors: Palladini Arianna , Nicoletti Giordano , Pappalardo Francesco , Murgo Annalisa , Grosso Valentina , Stivani Valeria , Ianzano Marianna L. , Antognoli Agnese , Croci Stefania , Landuzzi Lorena , De Giovanni Carla , Nanni Patrizia , Motta Santo , Lollini Pier-Luigi 
Published: October 2010

AbstractCancer vaccine feasibility would benefit from reducing the number and duration of vaccinations without diminishing efficacy. However, the duration of in vivo studies and the huge number of possible variations in vaccination protocols have discouraged their optimization. In this study, we employed an established mouse model of preventive vaccination using HER-2/neu transgenic mice (BALB-neuT) to validate in silico–designed protocols that reduce the number of vaccinations and optimize efficacy. With biological training, the in silico model captured the overall in vivo behavior and highlighted certain critical issues. First, although vaccinations could be reduced in number without sacrificing efficacy, the intensity of early vaccinations was a key determinant of long-term tumor prevention needed for predictive utility in the model. Second, after vaccinations ended, older mice exhibited more rapid tumor onset and sharper decline in antibody levels than young mice, emphasizing immune aging as a key variable in models of vaccine protocols for elderly individuals. Long-term studies confirmed predictions of in silico modeling in which an immune plateau phase, once reached, could be maintained with a reduced number of vaccinations. Furthermore, that rapid priming in young mice is required for long-term antitumor protection, and that the accuracy of mathematical modeling of early immune responses is critical. Finally, that the design and modeling of cancer vaccines and vaccination protocols must take into account the progressive aging of the immune system, by striving to boost immune responses in elderly hosts. Our results show that an integrated in vivo–in silico approach could improve both mathematical and biological models of cancer immunoprevention. Cancer Res; 70(20); 7755–63. ©2010 AACR.
Carcinoembryonic Antigen Interacts with TGF-β Receptor and Inhibits TGF-β Signaling in Colorectal Cancers
Authors: Li Ying , Cao Hong , Jiao Zhongxian , Pakala Suresh B. , Sirigiri Divijendra Natha Reddy , Li Wenpin , Kumar Rakesh , Mishra Lopa 
Published: October 2010

Abstract
As a tumor marker for colorectal cancers, carcinoembryonic antigen (CEA) enhances the metastatic potential of cancer cells. CEA functions as an intercellular adhesion molecule and is upregulated in a wide variety of human cancers. However, the molecular mechanisms by which CEA mediates metastasis remain to be understood. Transforming growth factor-β (TGF-β) signaling regulates both tumor suppression and metastasis, and also contributes to the stimulation of CEA transcription and secretion in colorectal cancer cells. However, it remains unknown whether CEA, in turn, influences TGF-β functions and if a regulatory cross-talk exists between CEA and the TGF-β signaling pathway. Here, we report that CEA directly interacts with TGF-β receptor and inhibits TGF-β signaling. Targeting CEA with either CEA-specific antibody or siRNA rescues TGF-β response in colorectal cancer cell lines with elevated CEA, thereby restoring the inhibitory effects of TGF-β signaling on proliferation. CEA also enhances the survival of colorectal cancer cells in both local colonization and liver metastasis in animal study. Our study provides novel insights into the interaction between CEA and TGF-β signaling pathway and establishes a negative feedback loop in amplifying the progression of colon cancer cells to more invasive phenotypes. These findings offer new therapeutic opportunities to inhibit colorectal cancer cell proliferation by cotargeting CEA in promoting tumor-inhibitory action of the TGF-β pathway. Cancer Res; 70(20); 8159–68. ©2010 AACR.
hsa-miR-191 Is a Candidate Oncogene Target for Hepatocellular Carcinoma Therapy
Authors: Elyakim Eran , Sitbon Einat , Faerman Alexander , Tabak Sarit , Montia Eve , Belanis Liron , Dov Avital , Marcusson Eric G. , Bennett C. Frank , Chajut Ayelet , Cohen Dalia , Yerushalmi Noga 
Published: October 2010

Abstract
Hepatocellular carcinoma (HCC) is generally a fatal disease due to a paucity of effective treatment options. The identification of oncogenic microRNAs that exert pleiotropic effects in HCC cells may offer new therapeutic targets. In this study, we have identified the human microRNA miR-191 as a potential target for HCC therapy. Inhibition of miR-191 decreased cell proliferation and induced apoptosis in vitro and significantly reduced tumor masses in vivo in an orthotopic xenograft mouse model of HCC. Additionally, miR-191 was found to be upregulated by a dioxin, a known liver carcinogen, and was found to be a regulator of a variety of cancer-related pathways. Our findings offer a preclinical proof of concept for miR-191 targeting as a rational strategy to pursue for improving HCC treatment. Cancer Res; 70(20); 8077–87. ©2010 AACR.
Contextual Synthetic Lethality of Cancer Cell Kill Based on the Tumor Microenvironment
Authors: Chan Norman , Pires Isabel M. , Bencokova Zuzana , Coackley Carla , Luoto Kaisa R. , Bhogal Nirmal , Lakshman Minalini , Gottipati Ponnari , Oliver F. Javier , Helleday Thomas , Hammond Ester M. , Bristow Robert G. 
Published: October 2010

Abstract
Acute and chronic hypoxia exists within the three-dimensional microenvironment of solid tumors and drives therapy resistance, genetic instability, and metastasis. Replicating cells exposed to either severe acute hypoxia (16 hours with 0.02% O2) followed by reoxygenation or moderate chronic hypoxia (72 hours with 0.2% O2) treatments have decreased homologous recombination (HR) protein expression and function. As HR defects are synthetically lethal with poly(ADP-ribose) polymerase 1 (PARP1) inhibition, we evaluated the sensitivity of repair-defective hypoxic cells to PARP inhibition. Although PARP inhibition itself did not affect HR expression or function, we observed increased clonogenic killing in HR-deficient hypoxic cells following chemical inhibition of PARP1. This effect was partially reversible by RAD51 overexpression. PARP1−/− murine embryonic fibroblasts (MEF) showed a proliferative disadvantage under hypoxic gassing when compared with PARP1+/+ MEFs. PARP-inhibited hypoxic cells accumulated γH2AX and 53BP1 foci as a consequence of altered DNA replication firing during S phase–specific cell killing. In support of this proposed mode of action, PARP inhibitor–treated xenografts displayed increased γH2AX and cleaved caspase-3 expression in RAD51-deficient hypoxic subregions in vivo, which was associated with decreased ex vivo clonogenic survival following experimental radiotherapy. This is the first report of selective cell killing of HR-defective hypoxic cells in vivo as a consequence of microenvironment-mediated “contextual synthetic lethality.” As all solid tumors contain aggressive hypoxic cells, this may broaden the clinical utility of PARP and DNA repair inhibition, either alone or in combination with radiotherapy and chemotherapy, even in tumor cells lacking synthetically lethal, genetic mutations. Cancer Res; 70(20); 8045–54. ©2010 AACR.
Baseline Plasma Total Homocysteine and Adenoma Recurrence: Results from a Double Blind Randomized Clinical Trial of Aspirin and Folate Supplementation
Authors: Levine A. Joan , Grau Maria V. , Mott Leila A. , Ueland Per Magne , Baron John A. 
Published: October 2010

AbstractBackground: Elevated plasma total homocysteine (tHcy) is an accepted marker of functional folate deficiency but may have independent effects on colorectal neoplasia risk. It is uncertain whether plasma tHcy is associated with risk at the low levels common in a folate-fortified population.Methods: Study subjects, about half of whom were recruited after fortification of grain products with folic acid in the United States and Canada, consisted of 871 individuals with a recent history of one or more colorectal adenomas who were randomized to receive either a 1 mg/day folic acid supplement or a placebo within one of three randomly assigned aspirin treatment groups (placebo, 81, or 325 mg/day). Nonfasting plasma tHcy was determined by a gas chromatograph mass chromatography method. We estimated adjusted risk ratios and 95% confidence intervals (95% CI) for one or more adenoma recurrences for each quartile of baseline plasma tHcy using generalized linear regression with an overdispersed Poisson approximation to the binomial.Results: The Q4/Q1 adjusted risk ratio for any adenoma was 0.98 (95% CI, 0.70-1.38; P trend = 0.17) in the placebo group, and 0.81 (95% CI, 0.58-1.12; P-trend = 0.17) in the folic acid group. Results were similar for adenomas with advanced features. There was no modification by sex, aspirin treatment group or MTHFR 677C&gt;T genotype.Conclusions: Plasma tHcy is not an independent marker for an increase in colorectal adenoma recurrence risk in postfortification populations in which plasma tHcy levels are in the lower range of values.Impact: Controlling plasma tHcy levels is unlikely to favorably modify adenoma recurrence risk in folate-fortified populations. Cancer Epidemiol Biomarkers Prev; 19(10); 2541–8. ©2010 AACR.
Transduction of Tumor-Specific T Cells with CXCR2 Chemokine Receptor Improves Migration to Tumor and Antitumor Immune Responses
Authors: Peng Weiyi , Ye Yang , Rabinovich Brian A. , Liu Chengwen , Lou Yanyan , Zhang Minying , Whittington Mayra , Yang Yan , Overwijk Willem W. , Lizée Gregory , Hwu Patrick 
Published: October 2010

Abstract
Purpose: One of the most important rate-limiting steps in adoptive cell transfer (ACT) is the inefficient migration of T cells to tumors. Because melanomas specifically express the chemokines CXCL1 and CXCL8 that are known to facilitate the CXCR2-dependent migration by monocytes, our aim is to evaluate whether introduction of the CXCR2 gene into tumor-specific T cells could further improve the effectiveness of ACT by enhancing T-cell migration to tumor.
Experimental Design: In this study, we used transgenic pmel-1 T cells, which recognize gp100 in the context of H-2Db, that were transduced with luciferase gene to monitor the migration of transferred T cells in vivo. To visualize luciferase-expressing T cells within a tumor, a nonpigmented tumor is required. Therefore, we used the MC38 tumor model, which naturally expresses CXCL1.
Results: Mice bearing MC38/gp100 tumor cells treated with CXCR2/luciferase-transduced pmel-1 T cells showed enhanced tumor regression and survival compared with mice receiving control luciferase-transduced pmel-1 T cells. We also observed preferential accumulation of CXCR2-expressing pmel-1 T cells in the tumor sites of these mice using bioluminescence imaging. A similar enhancement in tumor regression and survival was observed when CXCR2-transduced pmel-1 T cells were transferred into mice bearing CXCL1-transduced B16 tumors compared with mice treated with control pmel-1 T cells.
Conclusions: These results implicate that the introduction of the CXCR2 gene into tumor-specific T cells can enhance their localization to tumors and improve antitumor immune responses. This strategy may ultimately enable personalization of cancer therapies based on chemokine expression by tumors. Clin Cancer Res; 16(22); 5458–68. ©2010 AACR.
A Synergistic Interaction between Lapatinib and Chemotherapy Agents in a Panel of Cell Lines Is Due to the Inhibition of the Efflux Pump BCRP
Authors: Perry Jackie , Ghazaly Essam , Kitromilidou Christiana , McGrowder Eva H. , Joel Simon , Powles Thomas 
Published: October 2010

AbstractLapatinib is a specific HER1 and 2 targeted tyrosine kinase inhibitor now widely used in combination with chemotherapy in the clinical setting. In this work, we investigated the interactions between lapatinib and specific chemotherapy agents (cisplatin, SN-38, topotecan) in a panel of cell lines [breast (n = 2), lung (n = 2), testis (n = 4)]. A high-sensitivity cell proliferation/cytotoxicity ATP assay and flow cytometry were used to determine cell viability, apoptosis, and the effect of the drugs on cell-cycle distribution. CalcuSyn analysis was employed to formally identify synergistic interactions between drugs. Intracellular concentrations of SN-38 were measured using a novel high-performance liquid chromatography (HPLC) technique. Flow cytometry and HPLC techniques were used to identify the effect of lapatinib on drug influx and efflux pumps, using specific substrates and inhibitors of these pumps. Results showed significant synergy between SN-38, and lapatinib in the majority of cell lines (combination index &lt; 0.75), associated with increased apoptosis. This synergy was not universal but, when observed (Susa S/R, H1975, H358, and MDA-MB-231 cell lines), was related to SN-38 intracellular accumulation (2.2- to 4.8-fold increase, P &lt; 0.05 for each), attributable to the inhibition of the breast cancer–related protein (BCRP) efflux pump by lapatinib. Flow cytometry analysis showed that lapatinib (10 μmol/L) inhibited the efflux of mitoxantrone, a specific substrate of the BCRP pump, in a manner similar to fumitremorgin C, a known BCRP inhibitor, confirming lapatinib as a BCRP inhibitor. This work shows that lapatinib has a direct inhibitory effect on BCRP accounting for the synergistic findings. The synergy is cell line dependent and related to the activity of specific efflux pumps. Mol Cancer Ther; 9(12); 3322–9. ©2010 AACR.