bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in Pseudomonas aeruginosa Biofilms Includes Expression of Ribosome Hibernation Factors in the Antibiotic-Tolerant Subpopulation and Hypoxia-Induced Stress Response in the Metabolically Active Population
Authors: Williamson Kerry S. , Richards Lee A. , Perez-Osorio Ailyn C. , Pitts Betsey , McInnerney Kathleen , Stewart Philip S. , Franklin Michael J. 
Published: February 2012

ABSTRACT

Bacteria growing in biofilms are physiologically heterogeneous, due in part to their adaptation to local environmental conditions. Here, we characterized the local transcriptome responses of
Pseudomonas aeruginosa
growing in biofilms by using a microarray analysis of isolated biofilm subpopulations. The results demonstrated that cells at the top of the biofilms had high mRNA abundances for genes involved in general metabolic functions, while mRNA levels for these housekeeping genes were low in cells at the bottom of the biofilms. Selective green fluorescent protein (GFP) labeling showed that cells at the top of the biofilm were actively dividing. However, the dividing cells had high mRNA levels for genes regulated by the hypoxia-induced regulator Anr. Slow-growing cells deep in the biofilms had little expression of Anr-regulated genes and may have experienced long-term anoxia. Transcripts for ribosomal proteins were associated primarily with the metabolically active cell fraction, while ribosomal RNAs were abundant throughout the biofilms, indicating that ribosomes are stably maintained even in slowly growing cells. Consistent with these results was the identification of mRNAs for ribosome hibernation factors (the
rmf
and PA4463 genes) at the bottom of the biofilms. The dormant biofilm cells of a
P. aeruginosa
Δ
rmf
strain had decreased membrane integrity, as shown by propidium iodide staining. Using selective GFP labeling and cell sorting, we show that the dividing cells are more susceptible to killing by tobramycin and ciprofloxacin. The results demonstrate that in thick
P. aeruginosa
biofilms, cells are physiologically distinct spatially, with cells deep in the biofilm in a viable but antibiotic-tolerant slow-growth state.
RNase III Controls the Degradation ofcorAmRNA in Escherichia coli
Authors: Lim Boram , Sim Se-Hoon , Sim Minji , Kim Kyungsub , Jeon Che Ok , Lee Younghoon , Ha Nam-Chul , Lee Kangseok 
Published: February 2012

ABSTRACTInEscherichia coli, thecorAgene encodes a transporter that mediates the influx of Co2+, Mg2+, and Ni2+into the cell. During the course of experiments aimed at identifying RNase III-dependent genes inE. coli, we observed that steady-state levels ofcorAmRNA as well as the degree of cobalt influx into the cell were dependent on cellular concentrations of RNase III. In addition, changes incorAexpression levels by different cellular concentrations of RNase III were closely correlated with degrees of resistance ofE. colicells to Co2+and Ni2+.In vitroandin vivocleavage analyses ofcorAmRNA identified RNase III cleavage sites in the 5′-untranslated region of thecorAmRNA. The introduction of nucleotide substitutions at the identified RNase III cleavage sites abolished RNase III cleavage activity oncorAmRNA and resulted in prolonged half-lives of the mRNA, which demonstrates that RNase III cleavage constitutes a rate-determining step forcorAmRNA degradation. These findings reveal an RNase III-mediated regulatory pathway that functions to modulatecorAexpression and, in turn, the influx of metal ions transported by CorA inE. coli.
Levels of Germination Proteins in Dormant and Superdormant Spores of Bacillus subtilis
Authors: Ghosh Sonali , Scotland Michelle , Setlow Peter 
Published: February 2012

ABSTRACT

Bacillus subtilis
spores that germinated poorly with saturating levels of nutrient germinants, termed superdormant spores, were separated from the great majority of dormant spore populations that germinated more rapidly. These purified superdormant spores (1.5 to 3% of spore populations) germinated extremely poorly with the germinants used to isolate them but better with germinants targeting germinant receptors not activated in superdormant spore isolation although not as well as the initial dormant spores. The level of β-galactosidase from a
gerA-lacZ
fusion in superdormant spores isolated by germination via the GerA germinant receptor was identical to that in the initial dormant spores. Levels of the germination proteins GerD and SpoVAD were also identical in dormant and superdormant spores. However, levels of subunits of a germinant receptor or germinant receptors activated in superdormant spore isolation were 6- to 10-fold lower than those in dormant spores, while levels of subunits of germinant receptors not activated in superdormant spore isolation were only ≤2-fold lower. These results indicate that (i) levels of β-galactosidase from
lacZ
fusions to operons encoding germinant receptors may not be an accurate reflection of actual germinant receptor levels in spores and (ii) a low level of a specific germinant receptor or germinant receptors is a major cause of spore superdormancy.
The PduM Protein Is a Structural Component of the Microcompartments Involved in Coenzyme B12-Dependent 1,2-Propanediol Degradation by Salmonella enterica
Authors: Sinha Sharmistha , Cheng Shouqiang , Fan Chenguang , Bobik Thomas A. 
Published: February 2012

ABSTRACTDiverse bacteria use proteinaceous microcompartments (MCPs) to optimize metabolic pathways that have toxic or volatile intermediates. MCPs consist of metabolic enzymes encased within a protein shell that provides a defined environment. InSalmonella enterica, a MCP is involved in B12-dependent 1,2-propanediol utilization (Pdu MCP). In this report, we show that the protein PduM is required for the assembly and function of the Pdu MCP. The results of tandem mass spectrometry and Western blot analyses show that PduM is a component of the Pdu MCP. Electron microscopy shows that apduMdeletion mutant forms MCPs with abnormal morphology. Growth tests and metabolite measurements establish that apduMdeletion mutant is unable to form functional MCPs. PduM is unrelated in sequence to proteins of known function and hence may represent a new class of MCP structural proteins. We also report a modified protocol for the purification of Pdu MCP fromSalmonellawhich allows isolation of milligram amounts of MCPs in about 4 h. We believe that this protocol can be extended or modified for the purification of MCPs from diverse bacteria.
CovR Alleviates Transcriptional Silencing by a Nucleoid-Associated Histone-Like Protein in Streptococcus mutans
Authors: Biswas Indranil , Mohapatra Saswat Sourav 
Published: February 2012

ABSTRACT

In
Streptococcus mutans
, the global response regulator CovR plays an important role in biofilm formation, stress tolerance response, and caries production. We have previously demonstrated that CovR activates a large gene cluster, which is a part of a genomic island, TnSmu2. In this article, we have further characterized CovR at the molecular level to understand the gene activation mechanism. Toward this end, we mapped the transcription start site of the operon that lies upstream of the
SMU.1348
gene (P

SMU.1348

), the first gene of the cluster. We constructed a transcriptional reporter fusion and showed that CovR induces expression from P

SMU.1348

. We also demonstrated that purified CovR protects the sequence surrounding the −10 region of P

SMU.1348

. In an
in vitro
transcription assay, we showed that histone-like protein (HLP), a homologue of
Escherichia coli
HU protein, represses transcription from P

SMU.1348

.
In vivo
overexpression of HLP in
trans
also represses transcription from P

SMU.1348

. Addition of CovR to the HLP-repressed P

SMU.1348

resulted in increased transcription from the promoter, suggesting a role for CovR in countering HLP silencing. Moreover, addition of SMU.1349, a transcriptional activator of the operon, to the
in vitro
assay further stimulated the transcription. Based on our
in vivo
and
in vitro
results, we propose a model for transcriptional activation of the operon.
Common Variation atBARD1Results in the Expression of an Oncogenic Isoform That Influences Neuroblastoma Susceptibility and Oncogenicity
Authors: Bosse Kristopher R. , Diskin Sharon J. , Cole Kristina A. , Wood Andrew C. , Schnepp Robert W. , Norris Geoffrey , Nguyen Le B. , Jagannathan Jayanti , Laquaglia Michael , Winter Cynthia , Diamond Maura , Hou Cuiping , Attiyeh Edward F. , Mosse Yael P. , Pineros Vanessa , Dizin Eva , Zhang Yongqiang , Asgharzadeh Shahab , Seeger Robert C. , Capasso Mario , Pawel Bruce R. , Devoto Marcella , Hakonarson Hakon , Rappaport Eric F. , Irminger-Finger Irmgard , Maris John M. 
Published: February 2012

AbstractThe mechanisms underlying genetic susceptibility at loci discovered by genome-wide association study (GWAS) approaches in human cancer remain largely undefined. In this study, we characterized the high-risk neuroblastoma association at the BRCA1-related locus, BARD1, showing that disease-associated variations correlate with increased expression of the oncogenically activated isoform, BARD1β. In neuroblastoma cells, silencing of BARD1β showed genotype-specific cytotoxic effects, including decreased substrate-adherence, anchorage-independence, and foci growth. In established murine fibroblasts, overexpression of BARD1β was sufficient for neoplastic transformation. BARD1β stabilized the Aurora family of kinases in neuroblastoma cells, suggesting both a mechanism for the observed effect and a potential therapeutic strategy. Together, our findings identify BARD1β as an oncogenic driver of high-risk neuroblastoma tumorigenesis, and more generally, they illustrate how robust GWAS signals offer genomic landmarks to identify molecular mechanisms involved in both tumor initiation and malignant progression. The interaction of BARD1β with the Aurora family of kinases lends strong support to the ongoing work to develop Aurora kinase inhibitors for clinically aggressive neuroblastoma. Cancer Res; 72(8); 2068–78. ©2012 AACR.
FGFR2 Isoforms Support Epithelial–Stromal Interactions in Thyroid Cancer Progression
Authors: Guo Miao , Liu Wei , Serra Stefano , Asa Sylvia L. , Ezzat Shereen 
Published: February 2012

Abstract
Alternate splicing yields two distinct isoforms of the fibroblast growth factor (FGF) receptor FGFR2-IIIb and FGFR2-IIIc varying their extracellular structure in human thyroid cancer, in which FGFR expression is commonly dysregulated. In this study, we characterized the function of these variants in modulating thyroid cancer behavior. Enforced expression of either FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer cells reduced expression of fibronectin, MAGE-A3 and MMP9, while increasing p21 and enhancing Rb dephosphorylation. Consistent with these tumor-suppressive properties, FGFR2-IIIb and FGFR2-IIIc each diminished invasive behavior in vitro and reduced tumor growth and metastasis in vivo. Notably, these effects contrasted with those produced by expression of these FGFR isoforms in fibroblasts, in which they both stimulated cell growth. Moreover, in xenograft tumors generated by coimplantation of epithelial and fibroblast cells expressing that same isoform, there was no significant effect on tumor progression. Conversely, FGFR2-IIIb expression in epithelial cells yielded higher FGF4/FGF7 expression that, in the presence of FGFR2-IIIc–expressing fibroblasts, enhanced tumor progression. Together, our findings highlight the importance of cellular context in assigning growth properties to growth factor receptor isoforms. More specifically, they show how alternative splicing of FGFR2 yields heteroisoforms critical to the growth-promoting actions of FGFs that exert distinct epithelial–stromal effects in thyroid cancer. Cancer Res; 72(8); 2017–27. ©2012 AACR.
Mesothelin-Targeted Agents in Clinical Trials and in Preclinical Development
Authors: Kelly Ronan J. , Sharon Elad , Pastan Ira , Hassan Raffit 
Published: February 2012

Abstract
Mesothelin is a tumor differentiation antigen that is highly expressed in several malignant diseases in humans, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. The limited expression of mesothelin on normal human tissues and its high expression in many common cancers make it an attractive candidate for cancer therapy. Several agents, including an immunotoxin, monoclonal antibody, antibody drug conjugate, and tumor vaccine, are in various stages of development to treat patients with mesothelin-expressing tumors. This review highlights ongoing clinical trials, as well as other approaches to exploit mesothelin for cancer therapy, that are in preclinical development. Mol Cancer Ther; 11(3); 517–25. ©2012 AACR.
Novel Therapies for Metastatic Renal Cell Carcinoma: Efforts to Expand beyond the VEGF/mTOR Signaling Paradigm
Authors: Pal Sumanta Kumar , Williams Stephen , Josephson David Y. , Carmichael Courtney , Vogelzang Nicholas J. , Quinn David I. 
Published: February 2012

AbstractWith six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease. However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues. Mol Cancer Ther; 11(3); 526–37. ©2012 AACR.
The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center: A Unique Resource for Defining the “Molecular Histology” of the Breast
Authors: Sherman Mark E. , Figueroa Jonine D. , Henry Jill E. , Clare Susan E. , Rufenbarger Connie , Storniolo Anna Maria 
Published: February 2012

Abstract
“Molecular histology” of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website. Cancer Prev Res; 5(4); 528–35. ©2012 AACR.
Pentoxifylline Lowers Plasminogen Activator Inhibitor 1 Levels in Obese Individuals: A Pilot Study
Authors: Muldowney James A. S. , Chen Qingxia , Blakemore Dana L. , Vaughan Douglas E. 
Published: February 2012

Plasminogen activator inhibitor 1 (PAI-1), the primary inhibitor of fibrinolysis and C-reactive protein (CRP), is a predictor of myocardial infarction. Both are upregulated by tumor necrosis factor-alpha (TNF-α) within the obese population. This pilot study tested the hypothesis that TNF-α blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP (hsCRP) in obese individuals. Twenty participants were treated with pentoxifylline for 8 weeks. A proportional odds model was used to compare the change in PAI-1 and CRP in the pentoxifylline and placebo groups. Plasminogen activator inhibitor 1, but not hsCRP levels, decreased over the 8-week period of the study ( P = .025 and P = NS). There was significant dropout of participants due to drug tolerability. These findings suggest that these markers of cardiovascular risk are differentially regulated in obesity and that PAI-1 levels can be reduced by pentoxifylline in this population.
Endoscopic Nasoseptal Flap Repair of Skull Base Defects
Authors: Eloy Jean Anderson , Choudhry Osamah J. , Friedel Mark E. , Kuperan Arjuna B. , Liu James K. 
Published: February 2012

ObjectiveWe compared the incidence of postoperative cerebrospinal fluid (CSF) leaks in patients undergoing endoscopic skull base repair with a pedicled nasoseptal flap (PNSF) with or without the addition of a dural sealant.Study Design and SettingRetrospective analysis at a tertiary care medical center.MethodsA retrospective analysis was performed at our tertiary care medical center on patients who underwent endoscopic repair of high‐flow CSF leaks using a PNSF between December 2008 and August 2011. Repair materials, incidence of postoperative CSF leaks, and demographic data were collected.ResultsThirty‐two high‐flow CSF leaks were repaired with a PNSF alone without dural sealant (group A), and 42 were repaired with a PNSF with the addition of a dural sealant (group B). In group A, there were no postoperative CSF leaks (0%), whereas in group B, there was 1 delayed postoperative CSF leak, resulting in a 2.4% leak rate. The incidence of postoperative CSF leakage was not significantly different between the 2 groups (P =. 38). The overall postoperative CSF leak rate was 1.4%.ConclusionsThe use of dural sealants when performing endoscopic PNSF repair of high‐flow CSF leaks is not supported by our data. In addition, this practice may significantly increase surgical cost. We encountered no postoperative CSF leaks in patients with high‐flow CSF leaks treated with PNSF alone without dural sealants. Meticulous surgical technique and proper positioning of the PNSF seem to obviate the need for dural sealants during endoscopic skull base reconstruction of high‐flow CSF leaks.
Long‐Term Performance of Cochlear Implants in Postlingually Deafened Adults
Authors: Lenarz Minoo , Sönmez Hasibe , Joseph Gert , Büchner Andreas , Lenarz Thomas 
Published: February 2012

ObjectiveTo evaluate the stability of long‐term hearing performance after cochlear implantation (CI) in postlingually deafened adults and to explore the boundaries and limitations of the present test batteries for adult CI patients.Study DesignCase series with chart review.SettingTertiary referral center.Subjects and MethodsA cohort of 1005 postlingually deafened adult cochlear implantees, who received their implants after age 18 years, was unilaterally implanted and had no inner ear malformations or cochlear ossification. Hearing performance with cochlear implant was evaluated with the help of 5 standard German speech tests.ResultsThe average performance improved significantly during the first 6 months in all tests (learning phase) and afterward entered a plateau phase in which no statistically significant improvements or deteriorations were observed for more than 20 years of follow‐up. For each test, the average performance of the cohort, the ceiling effect, and the average results for high and low performers are presented.ConclusionsIn this study, postlingually deafened adults required about 6 months to learn how to process the artificial signals delivered by the cochlear implant. After this learning phase, the hearing performance entered a stable plateau phase for more than 20 years. This stability reveals the long‐term reliability of the technology and the biological stability of the electrode‐nerve interface over years. In this study, the authors also evaluated the “ceiling effect” with 5 standard German speech tests, used for evaluation of postlingually deafened adult CI patients.
The New Baha Implant
Authors: D’Eredità Riccardo , Caroncini Matteo , Saetti Roberto 
Published: February 2012

ObjectivesTo assess stability of a new‐design titanium implant (Cochlear Baha BAI300) in bone‐anchored hearing aid (Baha) recipients over time.Study Design and SettingProspective case series with planned data collection at a tertiary care institution. Twelve patients who underwent Baha surgery over 12 months were analyzed.SubjectsAll patients (3 children, age range 6‐10 years, mean 7.7 years, median 7.3 years; 9 adults, age range 34‐73 years, mean 52.8 years, median 48 years) underwent the 1‐stage procedure following the standard Brånemark technique. In all procedures, the single‐skin incision was applied.MethodsThe stability of the implant was measured with implant stability quotient (ISQ) measurement tests. All patients were tested at surgery and every week after for 1 year. Wound‐healing time, degree of soft tissue reactions around the abutment, and need for revision surgery were examined. Two‐tailed Student t test and χ2 for all comparisons were calculated; P <. 05 values were considered significant.ResultsThe new implant showed a steep increase of ISQ values over the first 2 weeks and reached stable ISQ values 3 weeks after surgery. Complete skin healing time was obtained in 8 days on average (range, 7‐12 days; median 7.6 days). Neither implant extrusion nor skin revision surgery was observed in our patients during the first year of follow‐up.ConclusionsThis new implant revealed stability and fast integration. The data from the present study suggest the new implant may be suitable for early loading protocols.
WIC Infant Food Package Issuance Data Are a Valid Measure of Infant Feeding Practices
Authors: Whaley Shannon E. , Koleilat Maria , Jiang Lu 
Published: February 2012

Background: Multiple datasets collect breastfeeding data in the United States (US), but a coordinated monitoring and surveillance system does not currently exist. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) reaches over 50% of all infants in the US and provides a potential wealth of administrative data about the breastfeeding practices of low-income women. Objective: The objective of this research was to assess whether WIC administrative data are a valid source of information about breastfeeding practices. Methods: A phone survey of 2015 postpartum WIC mothers in Southern California was conducted to assess the feeding practices of mothers with infants 2-12 months old. Survey data were linked with WIC administrative records from the same month in order to assess the percent agreement between feeding behavior as reported by survey methods and as documented in WIC administrative records. Results: The unweighted κ test statistic was used to test the agreement between survey responses and WIC administrative data. Substantial to almost perfect agreement was found between the two measures. Conclusions: WIC administrative data are a valid source of information about breastfeeding. With appropriate funding support, WIC administrative data should be considered for use in nationwide breastfeeding surveillance and monitoring systems.