bluuebunny/crossref_metadata_2025_split huggingface dataset:
A LytM Domain Dictates the Localization of Proteins to the Mother Cell-Forespore Interface during Bacterial Endospore Formation
Authors: Meisner Jeffrey , Moran Charles P. 
Published: November 2010

ABSTRACT

A large number of proteins are known to reside at specific subcellular locations in bacterial cells. However, the molecular mechanisms by which many of these proteins are anchored at these locations remains unclear. During endospore formation in
Bacillus subtilis
, several integral membrane proteins are located specifically at the interface of the two adjacent cells of the developing sporangium, the mother cell and forespore. The mother cell membrane protein SpoIIIAH recognizes the cell-cell interface through an interaction with the forespore membrane protein SpoIIQ, and then the other proteins are positioned there by the SpoIIIAH-SpoIIQ complex. In this study, we investigated the molecular mechanisms underlying the formation of the SpoIIIAH-SpoIIQ complex. Using gel filtration chromatography and isothermal titration calorimetry, we measured the binding parameters that characterize the SpoIIIAH-SpoIIQ interaction
in vitro
. We also demonstrated that the interaction of SpoIIIAH and SpoIIQ is governed by their YscJ and degenerate LytM domains, respectively. Therefore, the LytM domain of SpoIIQ provides the positional cue that dictates the localization of mother cell membrane proteins to the mother cell-forespore interface.
Complete Genome Sequences of Three
Erwinia amylovora
Phages Isolated in North America and a Bacteriophage Induced from an
Erwinia tasmaniensis
Strain
Authors: Müller I. , Kube M. , Reinhardt R. , Jelkmann W. , Geider K. 
Published: November 2010

ABSTRACT

Fire blight, a plant disease of economic importance caused by
Erwinia amylovora
, may be controlled by the application of bacteriophages. Here, we provide the complete genome sequences and the annotation of three
E. amylovora
-specific phages isolated in North America and genomic information about a bacteriophage induced by mitomycin C treatment of an
Erwinia tasmaniensis
strain that is antagonistic for
E. amylovora
. The American phages resemble two already-described viral genomes, whereas the
E. tasmaniensis
phage displays a singular genomic sequence in BLAST searches.
Complete Genome Sequence of the Haloaromatic Acid-Degrading Bacterium
Achromobacter xylosoxidans
A8
Authors: Strnad Hynek , Ridl Jakub , Paces Jan , Kolar Michal , Vlcek Cestmir , Paces Vaclav 
Published: November 2010

ABSTRACT

Achromobacter xylosoxidans
strain A8 was isolated from soil contaminated with polychlorinated biphenyls. It can use 2-chlorobenzoate and 2,5-dichlorobenzoate as sole sources of carbon and energy. This property makes it a good starting microorganism for further development toward a bioremediation tool. The genome of
A. xylosoxidans
consists of a 7-Mb chromosome and two large plasmids (98 kb and 248 kb). Besides genes for the utilization of xenobiotic organic substrates, it contains genes associated with pathogenesis, toxin production, and resistance. Here, we report the complete genome sequence.
Genome Sequence ofWeissella cibariaKACC 11862
Authors: Kim Dae-Soo , Choi Sang-Haeng , Kim Dong-Wook , Nam Seong-Hyeuk , Kim Ryong Nam , Kang Aram , Kim Aeri , Park Hong-Seog 
Published: November 2010

ABSTRACTWeissella cibariaKACC 11862 is a Gram-positive, heterofermentative,Leuconostoc-like lactic acid bacterium that is widely distributed in Korean traditional foods such as kimchi. Here we report the draft genome sequence of the type strain,W. cibariaKACC 11862 (1,599 known genes, 80 RNA genes), which consists of 72 large contigs (>100 bp in size).
Managing non-response rates for the National Child Safety Seat Survey in Canada
Authors: Yi Wen Tang , Snowdon Anne W , Hussein Abdulkadir , Ahmed S Ejaz 
Published: November 2010

BackgroundCanada has a Road Safety Vision of having the safest roads in the world, yet vehicle crashes have remained the leading cause of death of Canadian children for a number of years.ObjectivesDetermine the influence of high rates of non-participation on the estimates for correct use of safety seats for child occupants in vehicles. Examine the impact of three different criteria for determining correct safety seat use on the estimates of correct use of safety seats for children in Canada.MethodsA national child seat safety survey was conducted in 200 randomly selected sites across Canada that included both naturalistic observation of child seat safety use at intersections and a detailed vehicle inspection in nearby parking lots. Non-participation in the detailed parking lot study was high. This study reports on statistical methods for managing high rates of non-response and compared estimates of correct use using three different criteria.Results and conclusionsResults revealed that high non-participation rates introduced bias into the raw estimates of correct safety seat use. Correct use estimates also varied substantially depending on which criterion (more stringent or less stringent) for correct use was applied in the analysis. When child age was the only criterion for correct use, estimates were higher than when more stringent criteria of child height and weight were applied to estimate rates of correct use. This study identifies the importance of managing high rates of non-response in safety seat observation studies using statistical techniques. Stringent criteria for correct use may provide more accurate estimates of the correct use of safety seats. Studies of child seat use in vehicles (using voluntary participation) may benefit from the use of naturalistic observation to capture non-participants' use of child occupant restraints, as it may more accurately estimate the rates of correct use in populations.
Fine needle aspiration cytology is a valuable adjunct to axillary ultrasound in the preoperative staging of breast cancer
Authors: MacNeill Morna , Arnott Isobel , Thomas Jeremy 
Published: November 2010

AimsTo compare the predictive values of axillary ultrasound (US) combined with fine needle aspiration (FNA) cytology with tumour size (T stage) and grade in the preoperative staging of breast cancer. More precise definition of axillary FNA reporting nomenclature is also presented.Patients and Methods314 patients: 119 patients had suspicious US investigated by FNA, 195 patients had normal US not investigated further preoperatively. This study examined the node-positive and node-negative cases in these two groups, calculating predictive values for cytology, US, T stage and tumour grade, and tested comparisons for significance.ResultsAxillary FNA has a positive predictive value of 84.8% compared with US (66.7%). The difference is significant (p=0.008). Negative US has a negative predictive value of 81.0% compared with a negative predictive value for cytology of 66.7%, but the difference is not significant (p=0.08). 43% of patients with unsatisfactory cytology were node positive. Of 195 patients with negative axillary US, 37 (19%) had metastatic nodal disease. Fewer than 20% of these patients had micrometastases alone. Tumour size and grade influenced node status in US-suspicious cases only.ConclusionAxillary FNA adds significantly to the positive predictive value provided by US. US gives false-negative results in 19% of cases and only a small proportion of these can be explained by micrometastases. Unsatisfactory cytology needs to be repeated because of a high rate of positive nodes in this group.
Reversible heart failure: the role of inflammatory activation
Authors: Robinson Tim , Smith Alyson , Channer Kevin S 
Published: November 2010

ABSTRACT
Heart failure is increasingly common in western populations and is an inevitable consequence of the improved survival after myocardial infarction, and of an ageing population. Heart failure is usually relentlessly progressive as the maladaptive processes triggered by the physiological changes of the condition lead to further deterioration. However, in certain circumstances, heart failure is transient or potentially reversible when it occurs as part of intense systemic inflammatory activation. This review considers the role of inflammation in the aetiology of heart failure, and illustrates the strategies which have been used to modify the inflammatory response with anonymised clinical case reports.
PDGFR Signaling Blockade in Marrow Stroma Impairs Lung Cancer Bone Metastasis
Authors: Catena Raúl , Luis-Ravelo Diego , Antón Iker , Zandueta Carolina , Salazar-Colocho Pablo , Larzábal Leyre , Calvo Alfonso , Lecanda Fernando 
Published: November 2010

Abstract
Bone microenvironment and cell–cell interactions are crucial for the initiation and development of metastasis. By means of a pharmacologic approach, using the multitargeted tyrosine kinase inhibitor sunitinib, we tested the relevance of the platelet-derived growth factor receptor (PDGFR) axis in the bone marrow (BM) stromal compartment for the initiation and development of lung cancer metastasis to bone. PDGFRβ was found to be the main tyrosine kinase target of sunitinib expressed in BM stromal ST-2 and MC3T3-E1 preosteoblastic cells. In contrast, no expression of sunitinib-targeted receptors was found in A549M1 and low levels in H460M5 lung cancer metastatic cells. Incubation of ST-2 and human BM endothelial cells with sunitinib led to potent cell growth inhibition and induction of apoptosis in a dose-dependent manner. Similarly, sunitinib induced a robust proapoptotic effect in vivo on BM stromal PDGFRβ+ cells and produced extensive disruption of tissue architecture and vessel leakage in the BM cavity. Pretreatment of ST-2 cells with sunitinib also hindered heterotypic adhesion to lung cancer cell lines. These effects were correlated with changes in cell–cell and cell–matrix molecules in both stromal and tumor cells. Pretreatment of mice with sunitinib before intracardiac inoculation of A549M1 or H460M5 cells caused marked inhibition of tumor cells homing to bone, whereas no effect was found when tumor cells were pretreated before inoculation. Treatment with sunitinib dramatically increased overall survival and prevented tumor colonization but not bone lesions, whereas combination with zoledronic acid resulted in marked reduction of osteolytic lesions and osseous tumor burden. Thus, disruption of the PDGFR axis in the BM stroma alters heterotypic tumor–stromal and tumor–matrix interactions, thereby preventing efficient engagement required for bone homing and osseous colonization. These results support the notion that concomitant targeting of the tumor and stromal compartment is a more effective approach for blocking bone metastasis. Cancer Res; 71(1); 164–74. ©2010 AACR.
Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing
Authors: Zang Zhi Jiang , Ong Choon Kiat , Cutcutache Ioana , Yu Willie , Zhang Shen Li , Huang Dachuan , Ler Lian Dee , Dykema Karl , Gan Anna , Tao Jiong , Lim Siyu , Liu Yujing , Futreal P. Andrew , Grabsch Heike , Furge Kyle A. , Goh Liang Kee , Rozen Steve , Teh Bin Tean , Tan Patrick 
Published: November 2010

AbstractGenetic alterations in kinases have been linked to multiple human pathologies. To explore the landscape of kinase genetic variation in gastric cancer (GC), we used targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide kinases in 14 GC cell lines. We identified 10,604 single-nucleotide variants (SNV) in kinase exons including greater than 300 novel nonsynonymous SNVs. Family-wise analysis of the nonsynonymous SNVs revealed a significant enrichment in mitogen-activated protein kinase (MAPK)-related genes (P &lt; 0.01), suggesting a preferential involvement of this kinase family in GC. A potential antioncogenic role for MAP2K4, a gene exhibiting recurrent alterations in 2 lines, was functionally supported by siRNA knockdown and overexpression studies in wild-type and MAP2K4 variant lines. The deep sequencing data also revealed novel, large-scale structural rearrangement events involving kinases including gene fusions involving CDK12 and the ERBB2 receptor tyrosine kinase in MKN7 cells. Integrating SNVs and copy number alterations, we identified Hs746T as a cell line exhibiting both splice-site mutations and genomic amplification of MET, resulting in MET protein overexpression. When applied to primary GCs, we identified somatic mutations in 8 kinases, 4 of which were recurrently altered in both primary tumors and cell lines (MAP3K6, STK31, FER, and CDKL5). These results demonstrate that how targeted deep sequencing approaches can deliver unprecedented multilevel characterization of a medically and pharmacologically relevant gene family. The catalog of kinome genetic variants assembled here may broaden our knowledge on kinases and provide useful information on genetic alterations in GC. Cancer Res; 71(1); 29–39. ©2011 AACR.
Tumor Growth Inhibition by Olaparib in BRCA2 Germline-Mutated Patient-Derived Ovarian Cancer Tissue Xenografts
Authors: Kortmann Ursula , McAlpine Jessica N. , Xue Hui , Guan Jun , Ha Gavin , Tully Sophie , Shafait Sharaz , Lau Alan , Cranston Aaron N. , O'Connor Mark J. , Huntsman David G. , Wang Yuzhuo , Gilks C. Blake 
Published: November 2010

Abstract
Purpose: Most patients with ovarian carcinomas succumb to their disease and there is a critical need for improved therapeutic approaches. Carcinomas arising in BRCA mutation carriers display defective DNA double-strand break repair that can be therapeutically exploited by inhibition of PARP-1, a key enzyme in the repair of DNA single-strand breaks, creating synthetic lethality in tumor cells.
Experimental Design: To investigate synthetic lethality in vivo, we established a BRCA2 germline-mutated xenograft model that was developed directly from human ovarian cancer tissue, treated with the PARP inhibitor olaparib (AZD2281) alone and in combination with carboplatin.
Results: We show that olaparib alone and in combination with carboplatin greatly inhibit growth in BRCA2-mutated ovarian serous carcinoma. This effect was not observed in a serous carcinoma with normal BRCA function, showing a specific antitumor effect of olaparib in mutation carriers. Immunohistochemistry (cleaved caspase-3 and Ki-67 stains) of remnant tissue after olaparib treatment revealed significantly decreased proliferation and increased apoptotic indices in these tumors compared with untreated controls. Furthermore, olaparib-treated tumors showed highly reduced PARP-1 activity that correlated with olaparib levels.
Conclusions: We established a BRCA2-mutated human ovarian cancer xenograft model suitable for experimental drug testing. The demonstrated in vivo efficacy of olaparib extends on the preclinical rationale for further clinical trials targeting ovarian cancer patients with BRCA mutations. Clin Cancer Res; 17(4); 783–91. ©2010 AACR.
Genetic Polymorphisms Associated with a Prolonged Progression-Free Survival in Patients with Metastatic Renal Cell Cancer Treated with Sunitinib
Authors: van der Veldt Astrid A.M. , Eechoute Karel , Gelderblom Hans , Gietema Jourik , Guchelaar Henk-Jan , van Erp Nielka P. , van den Eertwegh Alfons J.M. , Haanen John B. , Mathijssen Ron H.J. , Wessels Judith A.M. 
Published: November 2010

Abstract
Purpose: The objective of this study was to identify genetic polymorphisms related to the pharmacokinetics and pharmacodynamics of sunitinib that are associated with a prolonged progression-free survival (PFS) and/or overall survival (OS) in patients with clear-cell metastatic renal cell cancer (mRCC) treated with sunitinib.
Experimental design: A retrospective multicenter pharmacogenetic association study was performed in 136 clear-cell mRCC patients treated with sunitinib. A total of 30 polymorphisms in 11 candidate genes, together with clinical characteristics were tested univariately for association with PFS as primary and OS as secondary outcome. Candidate variables with P &lt; 0.1 were analyzed in a multivariate Cox regression model.
Results: Multivariate analysis showed that PFS was significantly improved when an A-allele was present in CYP3A5 6986A/G [hazard ratio (HR), 0.27; P = 0.032], a CAT copy was absent in the NR1I3 haplotype (5719C/T, 7738A/C, 7837T/G; HR, 1.76; P = 0.017) and a TCG copy was present in the ABCB1 haplotype (3435C/T, 1236C/T, 2677G/T; HR, 0.52; P = 0.033). Carriers with a favorable genetic profile (n = 95) had an improved PFS and OS as compared with noncarriers (median PFS and OS: 13.1 versus 7.5 months and 19.9 versus 12.3 months). Next to the genetic variants, the Memorial Sloan-Kettering Cancer Center prognostic criteria were associated with PFS and OS (HR, 1.99 and 2.27; P &lt; 0.001).
Conclusions: This exploratory study shows that genetic polymorphisms in three genes involved in sunitinib pharmacokinetics are associated with PFS in mRCC patients treated with this drug. These findings advocate prospective validation and further elucidation of these genetic determinants in relation to sunitinib exposure and efficacy. Clin Cancer Res; 17(3); 620–9. ©2010 AACR.
Extent and Patterns ofMGMTPromoter Methylation in Glioblastoma- and Respective Glioblastoma-Derived Spheres
Authors: Sciuscio Davide , Diserens Annie-Claire , van Dommelen Kristof , Martinet Danielle , Jones Greg , Janzer Robert-Charles , Pollo Claudio , Hamou Marie-France , Kaina Bernd , Stupp Roger , Levivier Marc , Hegi Monika E. 
Published: November 2010

AbstractPurpose: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma.Experimental Design: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), cultured under stem cell conditions, were analyzed for the degree and pattern of MGMT promoter methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin status, and respective effects on MGMT expression and MGMT activity.Results: In glioblastoma, MGMT-methylated alleles ranged from 10% to 90%. In contrast, methylated alleles were highly enriched (100% of clones) in respective GS, even when 2 MGMT alleles were present, with 1 exception (&lt;50%). The CpG methylation patterns were characteristic for each glioblastoma exhibiting 25% to 90% methylated CpGs of 28 sites interrogated. Furthermore, MGMT promoter methylation was associated with a nonpermissive chromatin status in accordance with very low MGMT transcript levels and undetectable MGMT activity.Conclusions: In MGMT-methylated glioblastoma, MGMT promoter methylation is highly enriched in GS that supposedly comprise glioma-initiating cells. Thus, even a low percentage of MGMT methylation measured in a glioblastoma sample may be relevant and predict benefit from an alkylating agent therapy. Clin Cancer Res; 17(2); 255–66. ©2010 AACR.
High Impact of Oatp1a/1b Transporters on In Vivo Disposition of the Hydrophobic Anticancer Drug Paclitaxel
Authors: van de Steeg Evita , van Esch Anita , Wagenaar Els , van der Kruijssen Cornelia M.M. , van Tellingen Olaf , Kenworthy Kathryn E. , Schinkel Alfred H. 
Published: November 2010

Abstract
Purpose: Organic anion-transporting polypeptides (OATP) mediate the cellular uptake of a broad range of drugs. The hydrophobic anticancer drug, paclitaxel (PTX), was recently identified as a substrate for OATP1B3 in vitro. We investigated the role of Oatp1a/1b transporters in the pharmacokinetics of PTX in vivo, as well as their impact at different dose levels of PTX and methotrexate (MTX).
Experimental Design: Recently generated Slco1a/1b−/− (lacking all Oatp1a/1b transporters) and wild-type mice were intravenously dosed with 2, 10, or 50 mg/kg of PTX, or with 10, 50, or 500 mg/kg of MTX, and plasma and tissue drug concentrations were measured.
Results: In spite of its hydrophobicity, PTX systemic exposure (at 10 mg/kg) was increased by greater than 2-fold in Slco1a/1b−/− mice compared with wild-type, whereas PTX liver uptake was reduced by about 2-fold. Oatp1a/1b transporters displayed a high impact on PTX and MTX pharmacokinetics over a broad dose range. For MTX, even at 500 mg/kg, saturation of Oatp1a/1b was not observed, with a 3.4-fold increase in plasma and 30-fold decrease in liver levels in Slco1a/1b−/− mice compared with wild-type. Although beginning saturation of Oatp1a/1b was observed at the highest dose of PTX, plasma levels in Slco1a/1b−/− mice were still 1.7-fold increased and liver levels 1.5-fold decreased compared with wild-type.
Conclusion: Oatp1a/1b transporters play a pronounced role in determining plasma levels and tissue distribution of MTX and PTX, thus affecting even highly hydrophobic drugs. Variation in OATP1A/1B transporter activity, due to genetic variation, inhibition, and/or tumor expression might affect toxicity and therapeutic efficacy of these anticancer drugs. Clin Cancer Res; 17(2); 294–301. ©2010 AACR. Clin Cancer Res; 17(2); 294–301. ©2010 AACR.
NSAID Inhibition of Prostate Cancer Cell Migration Is Mediated by Nag-1 Induction via the p38 MAPK-p75NTR Pathway
Authors: Wynne Shehla , Djakiew Daniel 
Published: November 2010

Abstract
The nonsteroidal anti-inflammatory drugs (NSAID) R-flurbiprofen and ibuprofen have been shown to induce expression of p75NTR (neurotrophin receptor) in prostate cancer cell lines. p75NTR, a tumor necrosis factor receptor superfamily member, is a proapoptotic protein that functions as a tumor suppressor in the human prostate. Expression of p75NTR is lost as prostate cancer progresses and is minimal in several metastatic prostate cancer cell lines. NSAIDs induce p75NTR through activation of the p38 mitogen-activated protein kinase (MAPK) pathway, with a concomitant decrease in cell survival. Here, we show that treatment with R-flurbiprofen and ibuprofen induces expression of the NSAID-activated gene-1 (Nag-1) protein, a divergent member of the TGF beta (TGF-β) family, in PC-3 cells. Using the selective pharmacologic inhibitor of p38 MAPK, SB202190, and p38 MAPK-specific siRNA (small interfering RNA), we show that Nag-1 induction following NSAID treatment is mediated by the p38 MAPK pathway. p75NTR-specific siRNA pretreatment shows that Nag-1 induction by NSAIDs is downstream of p75NTR induction. Decreased survival of NSAID-treated cells is rescued by p75NTR-specific siRNA but not by Nag-1 siRNA. Transwell chamber and in vitro wound healing assays demonstrate decreased cell migration upon NSAID treatment. Pretreatment of PC-3 cells with p75NTR and Nag-1–specific siRNA shows that NSAID inhibition of cell migration is mediated by Nag-1 and p75NTR. These results demonstrate a role for Nag-1 in NSAID inhibition of cell migration, but not survival. Mol Cancer Res; 8(12); 1656–64. ©2010 AACR.