bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of the NADH Oxidase Gene (
nox
) Reveals an Overlap of the Oxygen- and Acid-Mediated Stress Responses in Streptococcus mutans
Authors: Derr Adam M. , Faustoferri Roberta C. , Betzenhauser Matthew J. , Gonzalez Kaisha , Marquis Robert E. , Quivey Robert G. 
Published: December 2011

ABSTRACT

NADH oxidase (Nox) is a flavin-containing enzyme used by
Streptococcus mutans
to reduce dissolved oxygen encountered during growth in the oral cavity. In this study, we characterized the role of the NADH oxidase in the oxidative and acid stress responses of
S. mutans
. A
nox
-defective mutant strain of
S. mutans
and its parental strain, the genomic type strain UA159, were exposed to various oxygen concentrations at pH values of 5 and 7 to better understand the adaptive mechanisms used by the organism to withstand environmental pressures. With the loss of
nox
, the activities of oxygen stress response enzymes such as superoxide dismutase and glutathione oxidoreductase were elevated compared to those in controls, resulting in a greater adaptation to oxygen stress. In contrast, the loss of
nox
led to a decreased ability to grow in a low-pH environment despite an increased resistance to severe acid challenge. Analysis of the membrane fatty acid composition revealed that for both the
nox
mutant and UA159 parent strain, growth in an oxygen-rich environment resulted in high proportions of unsaturated membrane fatty acids, independent of external pH. The data indicate that
S. mutans
membrane fatty acid composition is responsive to oxidative stress, as well as changes in environmental pH, as previously reported (E. M. Fozo and R. G. Quivey, Jr., Appl. Environ. Microbiol.
70
:929–936, 2004). The heightened ability of the
nox
strain to survive acidic and oxidative environmental stress suggests a multifaceted response system that is partially dependent on oxygen metabolites.
Quantifying the Reduction in Potential Health Risks by Determining the Sensitivity of Poliovirus Type 1 Chat Strain and Rotavirus SA-11 to Electron Beam Irradiation of Iceberg Lettuce and Spinach
Authors: Espinosa Ana Cecilia , Jesudhasan Palmy , Arredondo René , Cepeda Martha , Mazari-Hiriart Marisa , Mena Kristi D. , Pillai Suresh D. 
Published: December 2011

ABSTRACT

Fresh produce, such as lettuce and spinach, serves as a route of food-borne illnesses. The U.S. FDA has approved the use of ionizing irradiation up to 4 kGy as a pathogen kill step for fresh-cut lettuce and spinach. The focus of this study was to determine the inactivation of poliovirus and rotavirus on lettuce and spinach when exposed to various doses of high-energy electron beam (E-beam) irradiation and to calculate the theoretical reduction in infection risks that can be achieved under different contamination scenarios and E-beam dose applications. The D
10
value (dose required to reduce virus titers by 90%) (standard error) of rotavirus on spinach and lettuce was 1.29 (± 0.64) kGy and 1.03 (± 0.05) kGy, respectively. The D
10
value (standard error) of poliovirus on spinach and lettuce was 2.35 (± 0.20) kGy and 2.32 (± 0.08) kGy, respectively. Risk assessment of data showed that if a serving (∼14 g) of lettuce was contaminated with 10 PFU/g of poliovirus, E-beam irradiation at 3 kGy will reduce the risk of infection from >2 in 10 persons to approximately 6 in 100 persons. Similarly, if a serving size (∼0.8 g) of spinach is contaminated with 10 PFU/g of rotavirus, E-beam irradiation at 3 kGy will reduce infection risks from >3 in 10 persons to approximately 5 in 100 persons. The results highlight the value of employing E-beam irradiation to reduce public health risks but also the critical importance of adhering to good agricultural practices that limit enteric virus contamination at the farm and in packing houses.
Differential Targeting of the E-Cadherin/β-Catenin Complex by Gram-Positive Probiotic Lactobacilli Improves Epithelial Barrier Function
Authors: Hummel Stephanie , Veltman Katharina , Cichon Christoph , Sonnenborn Ulrich , Schmidt M. Alexander 
Published: December 2011

ABSTRACT

The intestinal ecosystem is balanced by dynamic interactions between resident and incoming microbes, the gastrointestinal barrier, and the mucosal immune system. However, in the context of inflammatory bowel diseases (IBD), where the integrity of the gastrointestinal barrier is compromised, resident microbes contribute to the development and perpetuation of inflammation and disease. Probiotic bacteria have been shown to exert beneficial effects, e.g., enhancing epithelial barrier integrity. However, the mechanisms underlying these beneficial effects are only poorly understood. Here, we comparatively investigated the effects of four probiotic lactobacilli, namely,
Lactobacillus acidophilus
,
L. fermentum
,
L. gasseri
, and
L. rhamnosus
, in a T84 cell epithelial barrier model. Results of DNA microarray experiments indicating that lactobacilli modulate the regulation of genes encoding in particular adherence junction proteins such as E-cadherin and β-catenin were confirmed by quantitative reverse transcription-PCR (qRT-PCR). Furthermore, we show that epithelial barrier function is modulated by Gram-positive probiotic lactobacilli via their effect on adherence junction protein expression and complex formation. In addition, incubation with lactobacilli differentially influences the phosphorylation of adherence junction proteins and the abundance of protein kinase C (PKC) isoforms such as PKCδ that thereby positively modulates epithelial barrier function. Further insight into the underlying molecular mechanisms triggered by these probiotics might also foster the development of novel strategies for the treatment of gastrointestinal diseases (e.g., IBD).
Role of (p)ppGpp in Biofilm Formation by Enterococcus faecalis
Authors: Chávez de Paz Luis E. , Lemos José A. , Wickström Claes , Sedgley Christine M. 
Published: December 2011

ABSTRACT

Enterococcus faecalis
strain OG1RF and its (p)ppGpp-deficient Δ
relA
, Δ
relQ
, and Δ
relA
Δ
relQ
mutants were grown in biofilms and evaluated for growth profiles, biofilm morphology, cell viability, and proteolytic activity.
E. faecalis
lacking (p)ppGpp had a diminished capacity to sustain biofilm formation over an extended period of time and expressed abundant proteolytic activity.
Correlation between Quantitative PCR and Culture-Based Methods for Measuring Enterococcus spp. over Various Temporal Scales at Three California Marine Beaches
Authors: Converse Reagan R. , Griffith John F. , Noble Rachel T. , Haugland Richard A. , Schiff Kenneth C. , Weisberg Stephen B. 
Published: December 2011

ABSTRACT

Several studies have examined how fecal indicator bacteria (FIB) measurements compare between quantitative PCR (qPCR) and the culture methods it is intended to replace. Here, we extend those studies by examining the stability of that relationship within a beach, as affected by time of day and seasonal variations in source.
Enterococcus
spp. were quantified at three southern California beaches in the morning and afternoon using two qPCR assays, membrane filtration, and defined-substrate testing. While qPCR and culture-based measurements were consistently and significantly correlated, strength of the correlation varied both among and within beaches. Correlations were higher in the morning (0.45 < ρ < 0.74 [
P
< 0.002]) than in the afternoon (0.18 < ρ < 0.45 [
P
< 0.021]) and higher when the fecal contamination was concentrated (0.38 < ρ < 0.83 [
P
< 0.001]) than when it was diffuse (0.19 < ρ < 0.34 [
P
< 0.003]). The ratios of culture-based and qPCR results (CFU or most probable number [MPN] per calibrator cell equivalents [CCE]) also varied spatially and temporally. Ratios ranged between 0.04 and 0.85 CFU or MPN per CCE and were lowest at the beach affected by diffuse pollution. Patterns in the ratios over the course of the day were dissimilar across beaches, increasing with time at one beach and decreasing at another. The spatial and temporal variability we observed indicate that the empirical relationship between culture-based and qPCR results is not universal, even within a beach.
Dichloromethane Fermentation by a Dehalobacter sp. in an Enrichment Culture Derived from Pristine River Sediment
Authors: Justicia-Leon Shandra D. , Ritalahti Kirsti M. , Mack E. Erin , Löffler Frank E. 
Published: December 2011

ABSTRACT

Dichloromethane (DCM) as the sole substrate supported growth of a
Dehalobacter
sp. in an enrichment culture derived from noncontaminated river sediment. DCM was not reductively dechlorinated, and acetate was produced, indicating DCM fermentation and further suggesting
Dehalobacter
growth is not limited to organohalide respiration.
Characterization of Mono- and Mixed-Culture Campylobacter jejuni Biofilms
Authors: Ica Tuba , Caner Vildan , Istanbullu Ozlem , Nguyen Hung Duc , Ahmed Bulbul , Call Douglas R. , Beyenal Haluk 
Published: December 2011

ABSTRACT

Campylobacter jejuni
, one of the most common causes of human gastroenteritis, is a thermophilic and microaerophilic bacterium. These characteristics make it a fastidious organism, which limits its ability to survive outside animal hosts. Nevertheless,
C. jejuni
can be transmitted to both humans and animals via environmental pathways, especially through contaminated water. Biofilms may play a crucial role in the survival of the bacterium under unfavorable environmental conditions. The goal of this study was to investigate survival strategies of
C. jejuni
in mono- and mixed-culture biofilms. We grew monoculture biofilms of
C. jejuni
and mixed-culture biofilms of
C. jejuni
with
Pseudomonas aeruginosa
. We found that mono- and mixed-culture biofilms had significantly different structures and activities. Monoculture
C. jejuni
biofilms did not consume a measurable quantity of oxygen. Using a confocal laser scanning microscope (CLSM), we found that cells from monoculture biofilms were alive according to live/dead staining but that these cells were not culturable. In contrast, in mixed-culture biofilms,
C. jejuni
remained in a culturable physiological state. Monoculture
C. jejuni
biofilms could persist under lower flow rates (0.75 ml/min) but were unable to persist at higher flow rates (1 to 2.5 ml/min). In sharp contrast, mixed-culture biofilms were more robust and were unaffected by higher flow rates (2.5 ml/min). Our results indicate that biofilms provide an environmental refuge that is conducive to the survival of
C. jejuni
.
Phylogenetic Diversities and Community Structure of Members of the Extremely Halophilic Archaea (Order Halobacteriales) in Multiple Saline Sediment Habitats
Authors: Youssef Noha H. , Ashlock-Savage Kristen N. , Elshahed Mostafa S. 
Published: December 2011

ABSTRACT

We investigated the phylogenetic diversity and community structure of members of the halophilic
Archaea
(order
Halobacteriales
) in five distinct sediment habitats that experience various levels of salinity and salinity fluctuations (sediments from Great Salt Plains and Zodletone Spring in Oklahoma, mangrove tree sediments in Puerto Rico, sediment underneath salt heaps in a salt-processing plant, and sediments from the Great Salt Lake northern arm) using
Halobacteriales
-specific 16S rRNA gene primers. Extremely diverse
Halobacteriales
communities were encountered in all habitats, with 27 (Zodletone) to 37 (mangrove) different genera identified per sample, out of the currently described 38
Halobacteriales
genera. With the exception of Zodletone Spring, where the prevalent geochemical conditions are extremely inhospitable to
Halobacteriales
survival, habitats with fluctuating salinity levels were more diverse than permanently saline habitats. Sequences affiliated with the recently described genera
Halogranum
,
Halolamina
,
Haloplanus
,
Halosarcina
, and
Halorientalis
, in addition to the genera
Halorubrum
,
Haloferax
, and
Halobacterium
, were among the most abundant and ubiquitous genera, suggesting a wide distribution of these poorly studied genera in saline sediments. The
Halobacteriales
sediment communities analyzed in this study were more diverse than and completely distinct from communities from typical hypersaline water bodies. Finally, sequences unaffiliated with currently described genera represented a small fraction of the total
Halobacteriales
communities, ranging between 2.5% (Zodletone) to 7.0% (mangrove and Great Salt Lake). However, these novel sequences were characterized by remarkably high levels of alpha and beta diversities, suggesting the presence of an enormous, yet-untapped supply of novel
Halobacteriales
genera within the rare biosphere of various saline ecosystems.
Nature and Intensity of Selection Pressure on CRISPR-Associated Genes
Authors: Takeuchi Nobuto , Wolf Yuri I. , Makarova Kira S. , Koonin Eugene V. 
Published: December 2011

ABSTRACTThe recently discovered CRISPR-Cas adaptive immune system is present in almost all archaea and many bacteria. It consists of cassettes of CRISPR repeats that incorporate spacers homologous to fragments of viral or plasmid genomes that are employed as guide RNAs in the immune response, along with numerous CRISPR-associated (cas) genes that encode proteins possessing diverse, only partially characterized activities required for the action of the system. Here, we investigate the evolution of thecasgenes and show that they evolve under purifying selection that is typically much weaker than the median strength of purifying selection affecting genes in the respective genomes. The exceptions are thecas1andcas2genes that typically evolve at levels of purifying selection close to the genomic median. Thus, although these genes are implicated in the acquisition of spacers from alien genomes, they do not appear to be directly involved in an arms race between bacterial and archaeal hosts and infectious agents. These genes might possess functions distinct from and additional to their role in the CRISPR-Cas-mediated immune response. Taken together with evidence of the frequent horizontal transfer ofcasgenes reported previously and with the wide-spread microscale recombination within these genes detected in this work, these findings reveal the highly dynamic evolution ofcasgenes. This conclusion is in line with the involvement of CRISPR-Cas in antiviral immunity that is likely to entail a coevolutionary arms race with rapidly evolving viruses. However, we failed to detect evidence of strong positive selection in any of thecasgenes.
Rapid Detection of the Marek's Disease Viral Genome in Chicken Feathers by Loop-Mediated Isothermal Amplification
Authors: Angamuthu Raja , Baskaran Subasty , Gopal Dhinakar Raj , Devarajan Jeyanthi , Kathaperumal Kumanan 
Published: December 2011

ABSTRACT
A loop-mediated isothermal amplification (LAMP) method for the rapid detection of serotype 1 Marek's disease virus (MDV) was developed. The method used a set of three pairs of primers to amplify the MEQ gene for detecting serotype 1 MDV. The MDV LAMP method did not cross-react with serotype 2 and serotype 3, nor did the LAMP primers have binding sites for the common avian DNA viruses (reticuloendotheliosis virus, chicken anemia virus, subgroup J of the avian leukosis virus). Additionally, the assay could detect up to 10 copies of the MEQ gene in the MD viral genome, and it had 10 times higher sensitivity than the traditional PCR methods. The LAMP master mix was stable for 90 days at −20°C. Furthermore, the efficiency of LAMP for detection of serotype 1 MDV in clinical samples was comparable to those of PCR and viral isolation. The LAMP procedure is simple and does not rely on any special equipment. The detection of serotype 1 MDV by LAMP will be useful for detecting and controlling oncogenic Marek's disease.
Detection of Yeasts in Blood Cultures by the Luminex xTAG Fungal Assay
Authors: Balada-Llasat Joan-Miquel , LaRue Heidi , Kamboj Kamal , Rigali Lisa , Smith Debra , Thomas Keelie , Pancholi Preeti 
Published: December 2011

ABSTRACT

A multiplex-PCR Luminex xMAP bead probe fluid array using xTAG analyte-specific reagents (multiplex xTAG fungal ASR assay) was employed for detection of clinically significant
Candida
species,
Cryptococcus neoformans
,
Histoplasma capsulatum
, and
Blastomyces dermatitidis
from blood cultures. We tested 132 blood cultures negative (
n
= 10) or positive (
n
= 97) for yeasts and/or bacteria (
n
= 25). The assay showed sensitivity and specificity of 100% and 99%, respectively. The xTAG fungal ASR assay is a rapid assay that allows simultaneous identification of multiple yeast species.
Transcriptional and Nontranscriptional Functions of E2F1 in Response to DNA Damage
Authors: Biswas Anup K. , Johnson David G. 
Published: December 2011

Abstract
E2F is a family of transcription factors that regulate the expression of genes involved in a wide range of cellular processes, including cell-cycle progression, DNA replication, DNA repair, differentiation, and apoptosis. E2F1, the founding member of the family, undergoes posttranslational modifications in response to DNA damage, resulting in E2F1 stabilization. In some cases, E2F1 is important for DNA damage–induced apoptosis through the transcriptional activation of p73 and perhaps other proapoptotic target genes. However, in other contexts, E2F1 can stimulate DNA repair and promote survival in response to DNA damage. The E2F1 protein accumulates at sites of both DNA double-strand breaks and UV radiation–induced damage, indicating that E2F1 has a nontranscriptional function at sites of damage. This review summarizes recent progress made in understanding the role of E2F1 in the DNA damage response, including transcription-independent activities that facilitate DNA repair in the context of chromatin. Cancer Res; 72(1); 13–7. ©2011 AACR.
Antitumor Activity of BRAF Inhibitor Vemurafenib in Preclinical Models of BRAF-Mutant Colorectal Cancer
Authors: Yang Hong , Higgins Brian , Kolinsky Kenneth , Packman Kathryn , Bradley William D. , Lee Richard J. , Schostack Kathleen , Simcox Mary Ellen , Kopetz Scott , Heimbrook David , Lestini Brian , Bollag Gideon , Su Fei 
Published: December 2011

Abstract
The protein kinase BRAF is a key component of the RAS–RAF signaling pathway which plays an important role in regulating cell proliferation, differentiation, and survival. Mutations in BRAF at codon 600 promote catalytic activity and are associated with 8% of all human (solid) tumors, including 8% to 10% of colorectal cancers (CRC). Here, we report the preclinical characterization of vemurafenib (RG7204; PLX4032; RO5185426), a first-in-class, specific small molecule inhibitor of BRAFV600E in BRAF-mutated CRC cell lines and tumor xenograft models. As a single agent, vemurafenib shows dose-dependent inhibition of ERK and MEK phosphorylation, thereby arresting cell proliferation in BRAFV600-expressing cell lines and inhibiting tumor growth in BRAFV600E bearing xenograft models. Because vemurafenib has shown limited single-agent clinical activity in BRAFV600E-mutant metastatic CRC, we therefore explored a range of combination therapies, with both standard agents and targeted inhibitors in preclinical xenograft models. In a BRAF-mutant CRC xenograft model with de novo resistance to vemurafenib (RKO), tumor growth inhibition by vemurafenib was enhanced by combining with an AKT inhibitor (MK-2206). The addition of vemurafenib to capecitabine and/or bevacizumab, cetuximab and/or irinotecan, or erlotinib resulted in increased antitumor activity and improved survival in xenograft models. Together, our findings suggest that the administration of vemurafenib in combination with standard-of-care or novel targeted therapies may lead to enhanced and sustained clinical antitumor efficacy in CRCs harboring the BRAFV600E mutation. Cancer Res; 72(3); 779–89. ©2011 AACR.
Monofunctional Platinum–DNA Adducts Are Strong Inhibitors of Transcription and Substrates for Nucleotide Excision Repair in Live Mammalian Cells
Authors: Zhu Guangyu , Myint MyatNoeZin , Ang Wee Han , Song Lina , Lippard Stephen J. 
Published: December 2011

Abstract
To overcome drug resistance and reduce the side effects of cisplatin, a widely used antineoplastic agent, major efforts have been made to develop next generation platinum-based anticancer drugs. Because cisplatin–DNA adducts block RNA polymerase II unless removed by transcription-coupled excision repair, compounds that react similarly but elude repair are desirable. The monofunctional platinum agent pyriplatin displays antitumor activity in mice, a cytotoxicity profile in cell cultures distinct from that of cisplatin, and a unique in vitro transcription inhibition mechanism. In this study, we incorporated pyriplatin globally or site specifically into luciferase reporter vectors to examine its transcription inhibition profiles in live mammalian cells. Monofunctional pyriplatin reacted with plasmid DNA as efficiently as bifunctional cisplatin and inhibited transcription as strongly as cisplatin in various mammalian cells. Using repair-defective nucleotide excision repair (NER)-, mismatch repair-, and single-strand break repair–deficient cells, we show that NER is mainly responsible for removal of pyriplatin–DNA adducts. These findings reveal that the mechanism by which pyriplatin generates its antitumor activity is very similar to that of cisplatin, despite the chemically different nature of their DNA adducts, further supporting a role for monofunctional platinum anticancer agents in human cancer therapy. This information also provides support for the validity of the proposed mechanism of action of cisplatin and provides a rational basis for the design of more potent platinum anticancer drug candidates using a monofunctional DNA-damaging strategy. Cancer Res; 72(3); 790–800. ©2011 AACR.
Phase I Study of Bosutinib, a Src/Abl Tyrosine Kinase Inhibitor, Administered to Patients with Advanced Solid Tumors
Authors: Daud Adil I. , Krishnamurthi Smitha S. , Saleh Mansoor N. , Gitlitz Barbara J. , Borad Mitesh J. , Gold Philip J. , Chiorean Elena G. , Springett Gregory M. , Abbas Richat , Agarwal Shefali , Bardy-Bouxin Nathalie , Hsyu Poe-Hirr , Leip Eric , Turnbull Kathleen , Zacharchuk Charles , Messersmith Wells A. 
Published: December 2011

Abstract
Purpose: Bosutinib, a potent ATP-competitive, quinolinecarbonitrile Src/Abl kinase inhibitor, was tested in this first-in-human phase I trial in patients with advanced solid tumor malignancies.
Patients and Methods: This trial was conducted in 2 parts. In part 1 (dose escalation), increasing oral bosutinib doses were administered using a 3 + 3 design. In part 2 (dose expansion), approximately 30 patients each with refractory colorectal, pancreas, or non–small cell lung cancer were treated at the recommended phase II dose (RP2D). Primary efficacy endpoints for part 2 were median progression-free survival (colorectal and non–small cell lung) and median overall survival (pancreas).
Results: In part 1, dose-limiting toxicities of grade 3 diarrhea (two patients) and grade 3 rash occurred with bosutinib 600 mg/day and the maximum tolerated dose identified was 500 mg/day. However, the majority of patients treated with 500 mg/day had grade 2 or greater gastrointestinal toxicity, and 400 mg/day was identified as the RP2D. The most common bosutinib-related adverse events were nausea (60% patients), diarrhea (47%), vomiting (40%), fatigue (38%), and anorexia (36%). Bosutinib had a mean half-life of 19 to 20 hours at the RP2D. A partial response (breast) and unconfirmed complete response (pancreas) were observed; 8 of 112 evaluable patients had stable disease for 22 to 101 weeks. However, the primary efficacy endpoints for part 2 were not met.
Conclusions: Bosutinib was generally well tolerated in patients with solid tumors, with the main toxicity being gastrointestinal. The RP2D was 400 mg/day orally. Further study of bosutinib is planned in combination regimens. Clin Cancer Res; 18(4); 1092–100. ©2011 AACR.