bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoor-Air Microbiome in an Urban Subway Network: Diversity and Dynamics
Authors: Leung Marcus H. Y. , Wilkins David , Li Ellen K. T. , Kong Fred K. F. , Lee Patrick K. H. 
Published: August 2014

ABSTRACT
Subway systems are indispensable for urban societies, but microbiological characteristics of subway aerosols are relatively unknown. Previous studies investigating microbial compositions in subways employed methodologies that underestimated the diversity of microbial exposure for commuters, with little focus on factors governing subway air microbiology, which may have public health implications. Here, a culture-independent approach unraveling the bacterial diversity within the urban subway network in Hong Kong is presented. Aerosol samples from multiple subway lines and outdoor locations were collected. Targeting the 16S rRNA gene V4 region, extensive taxonomic diversity was found, with the most common bacterial genera in the subway environment among those associated with skin. Overall, subway lines harbored different phylogenetic communities based on α- and β-diversity comparisons, and closer inspection suggests that each community within a line is dependent on architectural characteristics, nearby outdoor microbiomes, and connectedness with other lines. Microbial diversities and assemblages also varied depending on the day sampled, as well as the time of day, and changes in microbial communities between peak and nonpeak commuting hours were attributed largely to increases in skin-associated genera in peak samples. Microbial diversities within the subway were influenced by temperature and relative humidity, while carbon dioxide levels showed a positive correlation with abundances of commuter-associated genera. This Hong Kong data set and communities from previous studies conducted in the United States formed distinct community clusters, indicating that additional work is required to unravel the mechanisms that shape subway microbiomes around the globe.
Circular Bacteriocins: Biosynthesis and Mode of Action
Authors: Gabrielsen Christina , Brede Dag A. , Nes Ingolf F. , Diep Dzung B. 
Published: August 2014

ABSTRACT

Circular bacteriocins are a group of N-to-C-terminally linked antimicrobial peptides, produced by Gram-positive bacteria of the phylum
Firmicutes
. Circular bacteriocins generally exhibit broad-spectrum antimicrobial activity, including against common food-borne pathogens, such as
Clostridium
and
Listeria
spp. These peptides are further known for their high pH and thermal stability, as well as for resistance to many proteolytic enzymes, properties which make this group of bacteriocins highly promising for potential industrial applications and their biosynthesis of particular interest as a possible model system for the synthesis of highly stable bioactive peptides. In this review, we summarize the current knowledge on this group of bacteriocins, with emphasis on the recent progress in understanding circular bacteriocin genetics, biosynthesis, and mode of action; in addition, we highlight the current challenges and future perspectives for the application of these peptides.
Impact of Fertilizing with Raw or Anaerobically Digested Sewage Sludge on the Abundance of Antibiotic-Resistant Coliforms, Antibiotic Resistance Genes, and Pathogenic Bacteria in Soil and on Vegetables at Harvest
Authors: Rahube Teddie O. , Marti Romain , Scott Andrew , Tien Yuan-Ching , Murray Roger , Sabourin Lyne , Zhang Yun , Duenk Peter , Lapen David R. , Topp Edward 
Published: August 2014

ABSTRACT
The consumption of crops fertilized with human waste represents a potential route of exposure to antibiotic-resistant fecal bacteria. The present study evaluated the abundance of bacteria and antibiotic resistance genes by using both culture-dependent and molecular methods. Various vegetables (lettuce, carrots, radish, and tomatoes) were sown into field plots fertilized inorganically or with class B biosolids or untreated municipal sewage sludge and harvested when of marketable quality. Analysis of viable pathogenic bacteria or antibiotic-resistant coliform bacteria by plate counts did not reveal significant treatment effects of fertilization with class B biosolids or untreated sewage sludge on the vegetables. Numerous targeted genes associated with antibiotic resistance and mobile genetic elements were detected by PCR in soil and on vegetables at harvest from plots that received no organic amendment. However, in the season of application, vegetables harvested from plots treated with either material carried gene targets not detected in the absence of amendment. Several gene targets evaluated by using quantitative PCR (qPCR) were considerably more abundant on vegetables harvested from sewage sludge-treated plots than on vegetables from control plots in the season of application, whereas vegetables harvested the following year revealed no treatment effect. Overall, the results of the present study suggest that producing vegetable crops in ground fertilized with human waste without appropriate delay or pretreatment will result in an additional burden of antibiotic resistance genes on harvested crops. Managing human exposure to antibiotic resistance genes carried in human waste must be undertaken through judicious agricultural practice.
Mutation of the
Erwinia amylovora argD
Gene Causes Arginine Auxotrophy, Nonpathogenicity in Apples, and Reduced Virulence in Pears
Authors: Ramos Laura S. , Lehman Brian L. , Peter Kari A. , McNellis Timothy W. 
Published: August 2014

ABSTRACT

Fire blight is caused by
Erwinia amylovora
and is the most destructive bacterial disease of apples and pears worldwide. In this study, we found that
E. amylovora
argD
(
1000
)::Tn
5
, an
argD
Tn
5
transposon mutant that has the Tn
5
transposon inserted after nucleotide 999 in the
argD
gene-coding region, was an arginine auxotroph that did not cause fire blight in apple and had reduced virulence in immature pear fruits. The
E. amylovora
argD
gene encodes a predicted
N
-acetylornithine aminotransferase enzyme, which is involved in the production of the amino acid arginine. A plasmid-borne copy of the wild-type
argD
gene complemented both the nonpathogenic and the arginine auxotrophic phenotypes of the
argD
(
1000
)::Tn
5
mutant. However, even when mixed with virulent
E. amylovora
cells and inoculated onto immature apple fruit, the
argD
(
1000
)::Tn
5
mutant still failed to grow, while the virulent strain grew and caused disease. Furthermore, the pCR2.1-
argD
complementation plasmid was stably maintained in the
argD
(
1000
)::Tn
5
mutant growing in host tissues without any antibiotic selection. Therefore, the pCR2.1-
argD
complementation plasmid could be useful for the expression of genes, markers, and reporters in
E. amylovora
growing
in planta
, without concern about losing the plasmid over time. The ArgD protein cannot be considered an
E. amylovora
virulence factor because the
argD
(
1000
)::Tn
5
mutant was auxotrophic and had a primary metabolism defect. Nevertheless, these results are informative about the parasitic nature of the fire blight disease interaction, since they indicate that
E. amylovora
cannot obtain sufficient arginine from apple and pear fruit tissues or from apple vegetative tissues, either at the beginning of the infection process or after the infection has progressed to an advanced state.
Acquisition and Role of Molybdate in Pseudomonas aeruginosa
Authors: Pederick Victoria G. , Eijkelkamp Bart A. , Ween Miranda P. , Begg Stephanie L. , Paton James C. , McDevitt Christopher A. 
Published: August 2014

ABSTRACT

In microaerophilic or anaerobic environments,
Pseudomonas aeruginosa
utilizes nitrate reduction for energy production, a process dependent on the availability of the oxyanionic form of molybdenum, molybdate (MoO
4
2−
). Here, we show that molybdate acquisition in
P. aeruginosa
occurs via a high-affinity ATP-binding cassette permease (ModABC). ModA is a cluster D-III solute binding protein capable of interacting with molybdate or tungstate oxyanions. Deletion of the
modA
gene reduces cellular molybdate concentrations and results in inhibition of anaerobic growth and nitrate reduction. Further, we show that conditions that permit nitrate reduction also cause inhibition of biofilm formation and an alteration in fatty acid composition of
P. aeruginosa
. Collectively, these data highlight the importance of molybdate for anaerobic growth of
P. aeruginosa
and reveal novel consequences of nitrate reduction on biofilm formation and cell membrane composition.
PCR and Culture Identification of Pathogenic Leptospira spp. from Coastal Soil in Leyte, Philippines, after a Storm Surge during Super Typhoon Haiyan (Yolanda)
Authors: Saito Mitsumasa , Miyahara Satoshi , Villanueva Sharon Y. A. M. , Aramaki Natsumi , Ikejiri Mami , Kobayashi Yoshie , Guevarra Jonathan P. , Masuzawa Toshiyuki , Gloriani Nina G. , Yanagihara Yasutake , Yoshida Shin-ichi 
Published: August 2014

ABSTRACT

Leptospirosis is a zoonosis caused by pathogenic
Leptospira
spp. Most of the outbreaks of leptospirosis occur after floods caused by heavy rain in countries where
Leptospira
spp. are endemic. It has been believed that the overflow of seawater rarely causes outbreaks of leptospirosis because the leptospires are killed by salt water. On 8 November 2013, a storm surge caused by Super Typhoon Haiyan (Yolanda) inundated the entire coastal areas of Tacloban and Palo in Leyte, Philippines. The present study was carried out in order to determine whether the environmental leptospires in soil were able to survive after the storm surge in the affected areas. We collected 23 wet soil samples along the coastal areas of Tacloban and Palo 2 months after the storm surge. The samples were suspended in HEPES buffer, and the supernatants were cultured in liquid or semisolid Korthof's medium supplemented with five antimicrobial agents to inhibit the growth of contaminants. Leptospires were isolated from primary cultures of 22 out of 23 samples. The DNA of pathogenic
Leptospira
species was detected in 11 samples (47.8%) by analysis of
flaB
by nested PCR. Eventually, two pathogenic
Leptospira
strains were isolated and showed the highest 16S rRNA gene sequence similarity to
Leptospira kmetyi
. When these isolates were experimentally mixed with soil, they were found to survive in seawater for 4 days. These results show the possibility that leptospires living in soil survived after the storm surge. Our findings may serve as a warning that when seawater inundates the land during a storm surge or a tsunami, an outbreak of leptospirosis could occur in the disaster-stricken area.
Functional Implications and Ubiquitin-Dependent Degradation of the Peptide Transporter Ptr2 in Saccharomyces cerevisiae
Authors: Kawai Ken , Moriya Atsuto , Uemura Satoshi , Abe Fumiyoshi 
Published: August 2014

ABSTRACT

The peptide transporter Ptr2 plays a central role in di- or tripeptide import in
Saccharomyces cerevisiae
. Although
PTR2
transcription has been extensively analyzed in terms of upregulation by the Ubr1-Cup9 circuit, the structural and functional information for this transporter is limited. Here we identified 14 amino acid residues required for peptide import through Ptr2 based on the crystallographic information of
Streptococcus thermophilus
peptide transporter PepT
st
and based on the conservation of primary sequences among the proton-dependent oligopeptide transporters (POTs). Expression of Ptr2 carrying one of the 14 mutations of which the corresponding residues of PepT
st
are involved in peptide recognition, salt bridge interaction, or peptide translocation failed to enable
ptr2
Δ
trp1
cell growth in alanyl-tryptophan (Ala-Trp) medium. We observed that Ptr2 underwent rapid degradation after cycloheximide treatment (half-life, approximately 1 h), and this degradation depended on Rsp5 ubiquitin ligase. The ubiquitination of Ptr2 most likely occurs at the N-terminal lysines 16, 27, and 34. Simultaneous substitution of arginine for the three lysines fully prevented Ptr2 degradation. Ptr2 mutants of the presumed peptide-binding site (E92Q, R93K, K205R, W362L, and E480D) exhibited severe defects in peptide import and were subjected to Rsp5-dependent degradation when cells were moved to Ala-Trp medium, whereas, similar to what occurs in the wild-type Ptr2, mutant proteins of the intracellular gate were upregulated. These results suggest that Ptr2 undergoes quality control and the defects in peptide binding and the concomitant conformational change render Ptr2 subject to efficient ubiquitination and subsequent degradation.
Improving pre-operative medicines reconciliation
Authors: Brunswicker Annemarie , Yogarajah Amieth 
Published: August 2014

AbstractAn audit of 143 surgical admissions showed that only 30% of general surgery and urology patients have complete medication charts on the day of surgery prior to going to theatre, compared to 94% of orthopaedic patients. This was despite having been seen previously in the pre-operative assessment clinic (POAC). These patients went to the wards post-operatively, where many then missed doses of their life-sustaining medications. Orthopaedic patients see a prescribing pharmacist in POAC who undertakes medicines reconciliation; this is performed by junior doctors for surgical patients.We designed three interventions to improve drug chart completion by junior doctors, and gathered prospective data for 22 weeks in the POAC. We also recorded attendance of junior doctors in the POAC and reasons for absence. Daily and weekly percentages of drug chart completion were plotted on a run chart.The baseline completion rate was 43%. This rose to 45% after the first and second interventions, and 51% after the third intervention. However, the completion rate remained markedly below our target of 94%. Junior doctors attended only 44% of POACs. They reported being "too busy to attend" 41% of the time, and could not be contacted on 11% of occasions.Junior doctors reported that they were unable to attend to both unwell inpatients and the POAC, the latter seeming less of a priority. This was despite a rota allocating doctors to attend POAC sessions free from clinical or teaching commitments.We were unable to increase the rate of drug chart completion with the resources available. We therefore recommend the employment of prescribing pharmacists in the POAC for general surgery and urology patients.
CXM: A New Tool for Mapping Breast Cancer Risk in the Tumor Microenvironment
Authors: Flister Michael J. , Endres Bradley T. , Rudemiller Nathan , Sarkis Allison B. , Santarriaga Stephanie , Roy Ishan , Lemke Angela , Geurts Aron M. , Moreno Carol , Ran Sophia , Tsaih Shirng-Wern , De Pons Jeffery , Carlson Daniel F. , Tan Wenfang , Fahrenkrug Scott C. , Lazarova Zelmira , Lazar Jozef , North Paula E. , LaViolette Peter S. , Dwinell Michael B. , Shull James D. , Jacob Howard J. 
Published: August 2014

Abstract
The majority of causative variants in familial breast cancer remain unknown. Of the known risk variants, most are tumor cell autonomous, and little attention has been paid yet to germline variants that may affect the tumor microenvironment. In this study, we developed a system called the Consomic Xenograft Model (CXM) to map germline variants that affect only the tumor microenvironment. In CXM, human breast cancer cells are orthotopically implanted into immunodeficient consomic strains and tumor metrics are quantified (e.g., growth, vasculogenesis, and metastasis). Because the strain backgrounds vary, whereas the malignant tumor cells do not, any observed changes in tumor progression are due to genetic differences in the nonmalignant microenvironment. Using CXM, we defined genetic variants on rat chromosome 3 that reduced relative tumor growth and hematogenous metastasis in the SS.BN3IL2Rγ consomic model compared with the SSIL2Rγ parental strain. Paradoxically, these effects occurred despite an increase in the density of tumor-associated blood vessels. In contrast, lymphatic vasculature and lymphogenous metastasis were unaffected by the SS.BN3IL2Rγ background. Through comparative mapping and whole-genome sequence analysis, we narrowed candidate variants on rat chromosome 3 to six genes with a priority for future analysis. Collectively, our results establish the utility of CXM to localize genetic variants affecting the tumor microenvironment that underlie differences in breast cancer risk. Cancer Res; 74(22); 6419–29. ©2014 AACR.
Emerging Potential of Therapeutic Targeting of Ubiquitin-Specific Proteases in the Treatment of Cancer
Authors: Pal Anupama , Young Matthew A. , Donato Nicholas J. 
Published: August 2014

Abstract
The ubiquitin–proteasome system (UPS) has emerged as a therapeutic focus and target for the treatment of cancer. The most clinically successful UPS-active agents (bortezomib and lenalidomide) are limited in application to hematologic malignancies, with only marginal efficacy in solid tumors. Inhibition of specific ubiquitin E3 ligases has also emerged as a valid therapeutic strategy, and many targets are currently being investigated. Another emerging and promising approach in regulation of the UPS involves targeting deubiquitinases (DUB). The DUBs comprise a relatively small group of proteins, most with cysteine protease activity that target several key proteins involved in regulation of tumorigenesis, apoptosis, senescence, and autophagy. Through their multiple contacts with ubiquitinated protein substrates involved in these pathways, DUBs provide an untapped means of modulating many important regulatory proteins that support oncogenic transformation and progression. Ubiquitin-specific proteases (USP) are one class of DUBs that have drawn special attention as cancer targets, as many are differentially expressed or activated in tumors or their microenvironment, making them ideal candidates for drug development. This review attempts to summarize the USPs implicated in different cancers, the current status of USP inhibitor–mediated pharmacologic intervention, and future prospects for USP inhibitors to treat diverse cancers. Cancer Res; 74(18); 4955–66. ©2014 AACR.
Sonic Hedgehog Signaling in Basal Cell Nevus Syndrome
Authors: Athar Mohammad , Li Changzhao , Kim Arianna L. , Spiegelman Vladimir S. , Bickers David R. 
Published: August 2014

AbstractThe hedgehog (Hh) signaling pathway is considered to be a major signal transduction pathway during embryonic development, but it usually shuts down after birth. Aberrant Sonic hedgehog (Shh) activation during adulthood leads to neoplastic growth. Basal cell carcinoma (BCC) of the skin is driven by this pathway. Here, we summarize information related to the pathogenesis of this neoplasm, discuss pathways that crosstalk with Shh signaling, and the importance of the primary cilium in this neoplastic process. The identification of the basic/translational components of Shh signaling has led to the discovery of potential mechanism-driven druggable targets and subsequent clinical trials have confirmed their remarkable efficacy in treating BCCs, particularly in patients with nevoid BCC syndrome (NBCCS), an autosomal dominant disorder in which patients inherit a germline mutation in the tumor-suppressor gene Patched (Ptch). Patients with NBCCS develop dozens to hundreds of BCCs due to derepression of the downstream G-protein–coupled receptor Smoothened (SMO). Ptch mutations permit transposition of SMO to the primary cilium followed by enhanced expression of transcription factors Glis that drive cell proliferation and tumor growth. Clinical trials with the SMO inhibitor, vismodegib, showed remarkable efficacy in patients with NBCCS, which finally led to its FDA approval in 2012. Cancer Res; 74(18); 4967–75. ©2014 AACR.
A Prospective Cohort Study of Body Size and Risk of Head and Neck Cancers in the NIH–AARP Diet and Health Study
Authors: Etemadi Arash , O'Doherty Mark G. , Freedman Neal D. , Hollenbeck Albert R. , Dawsey Sanford M. , Abnet Christian C. 
Published: August 2014

Abstract
Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies.
Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI).
Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P &lt; 0.01).
Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height.
Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.
Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer
Authors: Pusztai Lajos , Moulder Stacy , Altan Mehmet , Kwiatkowski Danielle , Valero Vicente , Ueno Naoto T. , Esteva Francisco J. , Avritscher Rony , Qi Yuan , Strauss Lewis , Hortobagyi Gabriel N. , Hatzis Christos , Symmans W. Fraser 
Published: August 2014

Abstract
Purpose: Dasatinib has limited single-agent activity in unselected patients with metastatic breast cancer. Several gene signatures predictive of dasatinib response in vitro have been reported. The purpose of this three-arm, phase II study was to prospectively assess the utility of three previously published gene signatures to select patients with clinical benefit from dasatinib.
Experimental Design: Patients with metastatic breast cancer underwent biopsy for gene expression profiling in an academic CLIA laboratory; those who were positive for any one of three predictive gene signatures (dasatinib sensitivity signature, SRC pathway activity signature, and dasatinib target index) received dasatinib 100 mg orally daily. The three marker-defined cohorts were analyzed separately, using early stopping rules for futility.
Results: Ninety-seven patients were enrolled, 93 underwent biopsy, and 80% of the biopsies were sufficient for molecular testing. Thirty patients were positive for at least one signature and received treatment. Only 1 patient experienced clinical benefit and had stable disease over 300 days. All three arms were closed early for futility. There was one serious biopsy-related adverse event (hematoma and pain following a liver biopsy). There were no unexpected toxicities from dasatinib.
Conclusion: None of the three predictive gene signatures, although supported by preclinical evidence, defined tumors clinically sensitive to dasatinib as a single agent. Clin Cancer Res; 20(20); 5265–71. ©2014 AACR.