bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Novel Antistaphylococcal Ectolysin P128 in a Rat Model of Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Channabasappa Shankaramurthy , Durgaiah Murali , Chikkamadaiah Ravisha , Kumar Senthil , Joshi Amruta , Sriram Bharathi 
Published: November 2017

ABSTRACT

Staphylococcus aureus
causes systemic infections with high morbidity and mortality, and the emergence of drug-resistant strains is a rapidly growing clinical concern. Novel therapeutic agents are required to tackle
S. aureus
infections. P128 is a bacteriophage-derived chimeric ectolysin with potent and rapid bactericidal activity against
S. aureus
. In the present study, the efficacy of P128 was evaluated in a newly developed rat model of
S. aureus
bacteremia. Prior to
in vivo
testing, P128 was shown to be stable in whole blood by incubation in rat blood for up to 6 h and testing its bactericidal activity against the methicillin-resistant
S. aureus
isolate USA300. Rats succumbed to intravenous challenge with 10
9
CFU of
S. aureus
USA300, resulting in 80 to 100% mortality by day 14. Evaluation of the bacterial load in various organs at 96 h postinfection revealed high bacterial counts in the kidney, and this correlated with the presence of renal abscesses. Treatment of infected animals with P128 either by intravenous bolus administration via tail vein or by 1-h infusion via the jugular vein at 2 h postinfection resulted in the dose-dependent survival of rats. P128 treatment also resulted in very few or no abscesses in the kidneys. These data show that P128 is stable in the physiological milieu and that intravenous treatment with P128 is highly effective in rescuing rats from
S. aureus
bacteremia. P128 can be a novel therapeutic option for treatment of
S. aureus
systemic infections.
Limited Effects of Variable-Retention Harvesting on Fungal Communities Decomposing Fine Roots in Coastal Temperate Rainforests
Authors: Philpott Timothy J. , Barker Jason S. , Prescott Cindy E. , Grayston Sue J. 
Published: November 2017

ABSTRACT
Fine root litter is the principal source of carbon stored in forest soils and a dominant source of carbon for fungal decomposers. Differences in decomposer capacity between fungal species may be important determinants of fine-root decomposition rates. Variable-retention harvesting (VRH) provides refuge for ectomycorrhizal fungi, but its influence on fine-root decomposers is unknown, as are the effects of functional shifts in these fungal communities on carbon cycling. We compared fungal communities decomposing fine roots (in litter bags) under VRH, clear-cut, and uncut stands at two sites (6 and 13 years postharvest) and two decay stages (43 days and 1 year after burial) in Douglas fir forests in coastal British Columbia, Canada. Fungal species and guilds were identified from decomposed fine roots using high-throughput sequencing. Variable retention had short-term effects on β-diversity; harvest treatment modified the fungal community composition at the 6-year-postharvest site, but not at the 13-year-postharvest site. Ericoid and ectomycorrhizal guilds were not more abundant under VRH, but stand age significantly structured species composition. Guild composition varied by decay stage, with ruderal species later replaced by saprotrophs and ectomycorrhizae. Ectomycorrhizal abundance on decomposing fine roots may partially explain why fine roots typically decompose more slowly than surface litter. Our results indicate that stand age structures fine-root decomposers but that decay stage is more important in structuring the fungal community than shifts caused by harvesting. The rapid postharvest recovery of fungal communities decomposing fine roots suggests resiliency within this community, at least in these young regenerating stands in coastal British Columbia.

IMPORTANCE
Globally, fine roots are a dominant source of carbon in forest soils, yet the fungi that decompose this material and that drive the sequestration or respiration of this carbon remain largely uncharacterized. Fungi vary in their capacity to decompose plant litter, suggesting that fungal community composition is an important determinant of decomposition rates. Variable-retention harvesting is a forestry practice that modifies fungal communities by providing refuge for ectomycorrhizal fungi. We evaluated the effects of variable retention and clear-cut harvesting on fungal communities decomposing fine roots at two sites (6 and 13 years postharvest), at two decay stages (43 days and 1 year), and in uncut stands in temperate rainforests. Harvesting impacts on fungal community composition were detected only after 6 years after harvest. We suggest that fungal community composition may be an important factor that reduces fine-root decomposition rates relative to those of above-ground plant litter, which has important consequences for forest carbon cycling.
Ankyrin-Like Protein AnkB Interacts with CatB, Affects Catalase Activity, and Enhances Resistance of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola to Phenazine-1-Carboxylic Acid
Authors: Pan Xiayan , Xu Shu , Wu Jian , Duan Yabing , Zheng Zhitian , Wang Jianxin , Song Xiushi , Zhou Mingguo 
Published: November 2017

ABSTRACTXanthomonas oryzaepv. oryzae, which causes rice bacterial leaf blight, andXanthomonas oryzaepv. oryzicola, which causes rice bacterial leaf streak, are important plant-pathogenic bacteria. A member of the adaptor protein family, ankyrin protein, has been investigated largely in humans but rarely in plant-pathogenic bacteria. In this study, a novel ankyrin-like protein, AnkB, was identified inX. oryzaepv. oryzae andX. oryzaepv. oryzicola. The expression ofankBwas significantly upregulated when these bacteria were treated with phenazine-1-carboxylic acid (PCA).ankBis located 58 bp downstream of the genecatB(which encodes a catalase) in both bacteria, and the gene expression ofcatBand catalase activity were reduced followingankBdeletion inX. oryzaepv. oryzae andX. oryzaepv. oryzicola. Furthermore, we demonstrated that AnkB directly interacts with CatB by glutathioneS-transferase (GST) pulldown assays. Deletion ofankBincreased the sensitivity ofX. oryzaepv. oryzae andX. oryzaepv. oryzicola to H2O2and PCA, decreased bacterial biofilm formation, swimming ability, and exopolysaccharide (EPS) production, and also reduced virulence on rice. Together our results indicate that the ankyrin-like protein AnkB has important and conserved roles in antioxidant systems and pathogenicity inX. oryzaepv. oryzae andX. oryzaepv. oryzicola.IMPORTANCEThis study demonstrates that the ankyrin protein AnkB directly interacts with catalase CatB inXanthomonas oryzaepv. oryzae andXanthomonas oryzaepv. oryzicola. Ankyrin protein AnkB can affect the gene expression ofcatB, catalase activity, and sensitivity to H2O2. InXanthomonasspp., the locations of genesankBandcatBand the amino acid sequence of AnkB are highly conserved. It is suggested that in prokaryotes, AnkB plays a conserved role in the defense against oxidative stress.
Silver Nanoparticles Complexed with Bovine Submaxillary Mucin Possess Strong Antibacterial Activity and Protect against Seedling Infection
Authors: Makarovsky Daria , Fadeev Ludmila , Salam Bolaji Babajide , Zelinger Einat , Matan Ofra , Inbar Jacob , Jurkevitch Edouard , Gozin Michael , Burdman Saul 
Published: November 2017

ABSTRACT

A simple method for the synthesis of nanoparticles (NPs) of silver (Ag) in a matrix of bovine submaxillary mucin (BSM) was reported previously by some of the authors of this study. Based on mucin characteristics such as long-lasting stability, water solubility, and surfactant and adhesive characteristics, we hypothesized that these compounds, named BSM-Ag NPs, may possess favorable properties as potent antimicrobial agents. The goal of this study was to assess whether BSM-Ag NPs possess antibacterial activity, focusing on important plant-pathogenic bacterial strains representing both Gram-negative (
Acidovorax
and
Xanthomonas
) and Gram-positive (
Clavibacter
) genera. Growth inhibition and bactericidal assays, as well as electron microscopic observations, demonstrate that BSM-Ag NPs, at relatively low concentrations of silver, exert strong antimicrobial effects. Moreover, we show that treatment of melon seeds with BSM-Ag NPs effectively prevents seed-to-seedling transmission of
Acidovorax citrulli
, one of the most threatening pathogens of cucurbit production worldwide. Overall, our findings demonstrate strong antimicrobial activity of BSM-Ag NPs and their potential application for reducing the spread and establishment of devastating bacterial plant diseases in agriculture.

IMPORTANCE
Bacterial plant diseases challenge agricultural production, and the means available to manage them are limited. Importantly, many plant-pathogenic bacteria have the ability to colonize seeds, and seed-to-seedling transmission is a critical route by which bacterial plant diseases spread to new regions and countries. The significance of our study resides in the following aspects: (i) the simplicity of the method of BSM-Ag NP synthesis, (ii) the advantageous chemical properties of BSM-Ag NPs, (iii) the strong antibacterial activity of BSM-Ag NPs at relatively low concentrations of silver, and (iv) the fact that, in contrast to most studies on the effects of metal NPs on plant pathogens, the proof of concept for the novel compound is supported by
in planta
assays. Application of this technology is not limited to agriculture; BSM-Ag NPs potentially could be exploited as a potent antimicrobial agent in a wide range of industrial areas, including medicine, veterinary medicine, cosmetics, textiles, and household products.
Pseudouridine-Free Escherichia coli Ribosomes
Authors: O'Connor Michael , Leppik Margus , Remme Jaanus 
Published: November 2017

ABSTRACT

Pseudouridine (Ψ) is present at conserved, functionally important regions in the ribosomal RNAs (rRNAs) from all three domains of life. Little, however, is known about the functions of Ψ modifications in bacterial ribosomes. An
Escherichia coli
strain has been constructed in which all seven rRNA Ψ synthases have been inactivated and whose ribosomes are devoid of all Ψs. Surprisingly, this strain displays only minor defects in ribosome biogenesis and function, and cell growth is only modestly affected. This is in contrast to a strong requirement for Ψ in eukaryotic ribosomes and suggests divergent roles for rRNA Ψ modifications in these two domains.

IMPORTANCE
Pseudouridine (Ψ) is the most abundant posttranscriptional modification in RNAs. In the ribosome, Ψ modifications are typically located at conserved, critical regions, suggesting they play an important functional role. In eukarya and archaea, rRNAs are modified by a single pseudouridine synthase (PUS) enzyme, targeted to rRNA via a snoRNA-dependent mechanism, while bacteria use multiple stand-alone PUS enzymes. Disruption of Ψ modification of rRNA in eukarya seriously impairs ribosome function and cell growth. We have constructed an
E. coli
multiple deletion strain lacking all Ψ modifications in rRNA. In contrast to the equivalent eukaryotic mutants, the
E. coli
strain is only modestly affected in growth, decoding, and ribosome biogenesis, indicating a differential requirement for Ψ modifications in these two domains.
Accelerated in vitro model for occlusion of biliary stents: investigating the role played by dietary fibre
Authors: Surwase Sachin , Balakrishnan Harishankar , Acharya Subrat K , Makharia Govind K , Kumaraswamy Guruswamy , Prasad Bhagavatula L V 
Published: November 2017

BackgroundTo develop a new accelerated in vitro model that has implications for investigating the mechanism of biliary stent occlusion and help in the development of new materials that can alleviate this problem.MethodsWe employ a combination of reconstituted animal bile, bacteria and cellulose fibres optimised to reproducibly generate accelerated occlusion of stents, and produce occlusions that closely mimic those found in clinical studies.ResultsOur model affords repeatable, highly accelerated occlusion (within 2–3 days, compared with between about a week to 2 months in previous models). Our results highlight the role of dietary fibre in blockage of stents and demonstrate their importance in the onset of occlusion.ConclusionsThis accelerated model may have implications for developing biliary stents with enhanced patency.
Cost-effectiveness of a preferred intensity exercise programme for young people with depression compared with treatment as usual: an economic evaluation alongside a clinical trial in the UK
Authors: Turner David , Carter Tim , Sach Tracey , Guo Boliang , Callaghan Patrick 
Published: November 2017

ObjectivesTo assess the cost-effectiveness of preferred intensity exercise programme for young people with depression compared with a treatment as usual control group.DesignA ‘within trial’ cost-effectiveness and cost-utility analysis conducted alongside a randomised controlled trial. The perspective of the analysis was the UK National Health Service and social services.SettingThe intervention was provided in a community leisure centre setting.Participants86 young people aged 14–17 years attending Tier 2 and Tier 3 CAMHS (Child and Adolescent Mental Health Services) outpatient services presenting with depression.InterventionsThe intervention comprised 12 separate sessions of circuit training over a 6-week period. Sessions were supervised by a qualified exercise therapist. Participants also received treatment as usual. The comparator group received treatment as usual.ResultsWe found improvements in the Children’s Depression Inventory-2 (CDI-2) and estimated cost-effectiveness at £61 per point improvement in CDI-2 for the exercise group compared with control. We found no evidence that the exercise intervention led to differences in quality-adjusted life years (QALY). QALYs were estimated using the EQ-5D-5L (5-level version of EuroQol-5 dimension).ConclusionsThere is evidence that exercise can be an effective intervention for adolescents with depression and the current study shows that preferred intensity exercise could also represent a cost-effective intervention in terms of the CDI-2.Trial registration numberNCT01474837.
To sell or not to sell: cigarette sales in alcohol-licenced premises
Authors: Burton Suzan , Ludbrooke Mark , Williams Kelly , Walsberger Scott C , Egger Sam 
Published: November 2017

ObjectiveTo obtain insight into tobacco retailing by alcohol-licenced premises, in order to understand the financial importance of tobacco sales for such retailers.MethodData were collected by a telephone survey of 1042 clubs, hotels and packaged liquor outlets in New South Wales, Australia. The response rate was 86.1%. Qualitative and quantitative data were obtained. Logistic and linear regression were used to determine factors associated with the probability of selling and stopping selling and the importance of cigarette sales.ResultsMore than a third (36.4%) of premises contacted did not sell cigarettes. 147 (an estimated 18.1% of those who had ever sold) had stopped selling. There were significant differences in the probability of selling, in the reported importance of cigarette sales and in the probability of stopping selling, between different outlet types and other outlet characteristics (number of gaming machines, proximity of nearest alternative tobacco retailer and remoteness). Outlets where alcohol can be consumed were more likely to rate cigarette sales as ‘not important’ than ‘important’.ConclusionsDespite claims by tobacco companies that tobacco sales are important for many Australian retailers, tobacco sales appear to be of limited importance for alcohol-licenced premises. This means that opposition to stopping tobacco sales where alcohol is consumed and/or sold may be less than expected.
Diversity of parasitoid and parasitic wasps across a latitudinal gradient: Using public DNA records to work within a taxonomic impediment
Authors: Eagalle Thanushi , Smith M. Alex 
Published: November 2017

The diversity of insect parasitoids (Hymenoptera) has long been thought to be anomalous because it doesn’t appear to increase rapidly with decreasing latitude. However, due to the presence of undiscovered cryptic species and the under-sampling of hyper-diverse tropical areas, such apparently anomalous gradients may, in fact, be artifacts of limited geographic and taxonomic sampling. We attempted to circumvent such taxonomic impediments by elucidating a diversity/latitude relationship for parasitoid wasps, using publicly available DNA sequences to quantify diversity (via a species proxy molecular operational taxonomic unit (the DNA Barcode Index Number) and phylogenetic diversity) across a latitudinal gradient of ∼5000 km. We compared these diversity values to the abiotic factors (temperature and precipitation) that may drive the diversity/latitude relationship. We found no significant relationship between either diversity measure with latitude or with the environmental variables. Although ours is the first work to enumerate different DNA-based measures of parasitoid diversity across this geographic scale in a standardized fashion using publicly available sequences, further standardized collections over long time periods and a rapid movement of sequences into the public arena are needed to facilitate the further testing of macroecological trends elucidated with public DNA sequence libraries.
MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels
Authors: Lu Yunqi , Hu Zhongyi , Mangala Lingegowda S. , Stine Zachary E. , Hu Xiaowen , Jiang Dahai , Xiang Yan , Zhang Youyou , Pradeep Sunila , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , DeMarzo Angelo M. , Sood Anil K. , Zhang Lin , Dang Chi V. 
Published: November 2017

Abstract
The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers.
Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64–74. ©2017 AACR.
Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is Independent of BRCA Status in Triple-Negative Breast Cancer
Authors: Carey Jason. P.W. , Karakas Cansu , Bui Tuyen , Chen Xian , Vijayaraghavan Smruthi , Zhao Yang , Wang Jing , Mikule Keith , Litton Jennifer K. , Hunt Kelly K. , Keyomarsi Khandan 
Published: November 2017

Abstract
PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several of those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are associated with worse overall survival. Combining MYC blockade with PARPi yielded synthetic lethality in MYC-driven TNBC cells. Using the cyclin-dependent kinase inhibitor dinaciclib, which downregulates MYC expression, we found that combination with the PARPi niraparib increased DNA damage and downregulated homologous recombination, leading to subsequent downregulation of the epithelial–mesenchymal transition and cancer stem-like cell phenotypes. Notably, dinaciclib resensitized TBNC cells, which had acquired resistance to niraparib. We found that the synthetic lethal strategy employing dinaciclib and niraparib was also highly efficacious in ovarian, prostate, pancreatic, colon, and lung cancer cells. Taken together, our results show how blunting MYC oncogene addiction can leverage cancer cell sensitivity to PARPi, facilitating the clinical use of c-myc as a predictive biomarker for this treatment.
Significance: Dual targeting of MYC-regulated homologous recombination and PARP-mediated DNA repair yields potent synthetic lethality in triple-negative breast tumors and other aggressive tumors characterized by MYC overexpression. Cancer Res; 78(3); 742–57. ©2017 AACR.
Classifying Colorectal Cancer by Tumor Location Rather than Sidedness Highlights a Continuum in Mutation Profiles and Consensus Molecular Subtypes
Authors: Loree Jonathan M. , Pereira Allan A.L. , Lam Michael , Willauer Alexandra N. , Raghav Kanwal , Dasari Arvind , Morris Van. K , Advani Shailesh , Menter David G. , Eng Cathy , Shaw Kenna , Broaddus Russell , Routbort Mark J. , Liu Yusha , Morris Jeffrey S. , Luthra Rajyalakshmi , Meric-Bernstam Funda , Overman Michael J. , Maru Dipen , Kopetz Scott 
Published: November 2017

AbstractPurpose: Colorectal cancers are classified as right/left-sided based on whether they occur before/after the splenic flexure, with established differences in molecular subtypes and outcomes. However, it is unclear if this division is optimal and whether precise tumor location provides further information.Experimental Design: In 1,876 patients with colorectal cancer, we compared mutation prevalence and overall survival (OS) according to side and location. Consensus molecular subtype (CMS) was compared in a separate cohort of 608 patients.Results: Mutation prevalence differed by side and location for TP53, KRAS, BRAFV600, PIK3CA, SMAD4, CTNNB1, GNAS, and PTEN. Within left- and right-sided tumors, there remained substantial variations in mutation rates. For example, within right-sided tumors, RAS mutations decreased from 70% for cecal, to 43% for hepatic flexure location (P = 0.0001), while BRAFV600 mutations increased from 10% to 22% between the same locations (P &lt; 0.0001). Within left-sided tumors, the sigmoid and rectal region had more TP53 mutations (P = 0.027), less PIK3CA (P = 0.0009), BRAF (P = 0.0033), or CTNNB1 mutations (P &lt; 0.0001), and less MSI (P &lt; 0.0001) than other left-sided locations. Despite this, a left/right division preceding the transverse colon maximized prognostic differences by side and transverse colon tumors had K-modes mutation clustering that appeared more left than right sided. CMS profiles showed a decline in CMS1 and CMS3 and rise in CMS2 prevalence moving distally.Conclusions: Current right/left classifications may not fully recapitulate regional variations in tumor biology. Specifically, the sigmoid-rectal region appears unique and the transverse colon is distinct from other right-sided locations. Clin Cancer Res; 24(5); 1062–72. ©2017 AACR.See related commentary by Dienstmann, p. 989