bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance
Authors: Gudeta Dereje Dadi , Bortolaia Valeria , Amos Greg , Wellington Elizabeth M. H. , Brandt Kristian K. , Poirel Laurent , Nielsen Jesper Boye , Westh Henrik , Guardabassi Luca 
Published: October 2015

ABSTRACT

The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in
Escherichia coli
, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive
Pedobacter roseus
(PEDO-1),
Pedobacter borealis
(PEDO-2),
Pedobacter kyungheensis
(PEDO-3),
Chryseobacterium piscium
(CPS-1),
Epilithonimonas tenax
(ESP-1),
Massilia oculi
(MSI-1), and
Sphingomonas
sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in
Chryseobacterium
and
Epilithonimonas
, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in
E. coli
significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria.
Complete Genome Sequence of Polyvinyl Alcohol-Degrading Strain
Sphingopyxis
sp. 113P3 (NBRC 111507)
Authors: Ohtsubo Yoshiyuki , Nagata Yuji , Numata Mitsuru , Tsuchikane Kieko , Hosoyama Akira , Yamazoe Atsushi , Tsuda Masataka , Fujita Nobuyuki , Kawai Fusako 
Published: October 2015

ABSTRACT

Strain 113P3 was isolated from activated sludge and identified as a polyvinyl alcohol (PVA)-degrading
Pseudomonas
species; it was later reidentified as
Sphingopyxis
species. Only three genes are directly relevant to the metabolism of PVA and comprise the
pva
operon, which was deposited as accession no. AB190228. Here, we report the complete genome sequence of strain 113P3, which has been conserved as a stock culture (NBRC 111507) at the Biological Resource Center, National Institute of Technology and Evaluation (NITE) (Tokyo, Japan). The genome of strain 113P3 is composed of a 4.4-Mb circular chromosome and a 243-kb plasmid. The whole finishing was conducted
in silico
except for four PCRs. The sequence corresponding to AB190288 exists on the chromosome.
Characterization of the Whole-Genome Sequence of an H3N6 Avian Influenza Virus, Isolated from a Domestic Duck in Guangxi, Southern China
Authors: Liu Tingting , Xie Zhixun , Luo Sisi , Xie Liji , Deng Xianwen , Xie Zhiqing , Huang Li , Huang Jiaoling , Zhang Yanfang , Zeng Tingting , Wang Sheng 
Published: October 2015

ABSTRACT
A field strain of H3N6 avian influenza virus (AIV), A/duck/Guangxi/175D12/2014(H3N6), was isolated from a native duck in Guangxi Province, southern China, in 2014. All of the eight AIV gene segments were sequenced, and sequence results revealed that there were 11 amino acid deletions at the NA stalk region. The NA, PB2, and NP genes showed highest homology to H5N6 AIV, and the PA gene showed highest homology to H7N2 AIV. Phylogenetic analysis indicated that the eight AIV gene segments belonged to the Eurasian lineage. These findings provide scientific evidence of possible or potential mutations of H3N6 AIV circulating in waterfowl in southern China.
Draft Genome Sequence of Rhodococcus rhodochrous Strain KG-21, a Soil Isolate from Oil Fields of Krishna-Godavari Basin, India
Authors: Dawar Chhavi , Aggarwal Ramesh K. 
Published: October 2015

ABSTRACT

Here, we present the 6.1-Mb draft genome sequence of
Rhodococcus rhodochrous
strain KG-21, a soil isolate from the oil fields of Krishna-Godavari Basin in Andhra Pradesh, India. This genomic resource may help in the identification of the gene(s) involved in hydrocarbon degradation and their possible deployment for bioremediation.
Insights into the experiences of patients with cancer in London: framework analysis of free-text data from the National Cancer Patient Experience Survey 2012/2013 from the two London Integrated Cancer Systems
Authors: Wiseman Theresa , Lucas Grace , Sangha Amrit , Randolph Anuska , Stapleton Sarah , Pattison Natalie , O'Gara Geraldine , Harris Katherine , Pritchard-Jones Kathy , Dolan Shelley 
Published: October 2015

ObjectiveTo shed light on experiences of patients with cancer in London National Health Service (NHS) trusts that may not be fully captured in national survey data, to inform improvement action plans by these trusts.DesignFramework analysis of free-text data from 2012/2013 National Cancer Patient Experience Survey (NCPES) from the 2 London Integrated Cancer Systems.Setting and participantsPatients with a cancer diagnosis treated by the NHS across 27 trusts in London.Main outcome measuresFree-text data received from patients categorised into what patients found good about their cancer care and what could be improved.MethodsUsing Framework analysis, a thematic framework was created for 15 403 comments from over 6500 patients. Themes were identified across the London data set, by tumour group and by trust.ResultsTwo-thirds of free-text comments from patients in London were positive and one-third of those related to the good quality of care those patients received. However, the majority of comments for improvement related to quality of care, with a focus on poor care, poor communication and waiting times in outpatient departments. Additionally, 577 patients (9% of those who returned free-text data in London) commented on issues pertaining to the questionnaire itself. Some patients who experienced care from multiple trusts were unclear on how to complete the questionnaire for the single trust whose care they were asked to comment on, others said the questions did not fit their experiences.ConclusionsNCPES free-text analysis can shed light on the experiences of patients that closed questions might not reveal. It further indicates that there are issues with the survey itself, in terms of ambiguities in the questionnaire and difficulties in identifying patients within specific trusts. Both of these issues have the potential to contribute to knowledge and understanding of the uses and limitations of free-text data in improving cancer services.
The quantum gravitational field theory and the domains of its fix points for inflationary or low-redshift universe
Authors: Xue She-Sheng 
Published: October 2015

We study a quantum field theory for the Einstein–Cartan gravity and the domain of its ultraviolet unstable (stable) fixed point [Formula: see text] [Formula: see text] of running gravitational constant [Formula: see text], where inflationary (low-redshift) universe can be realized as the basic space-time cutoff [Formula: see text] approaching to the Planck length [Formula: see text]. Because the fundamental operators of quantum gravitational field theory are dimension-2 area operators, the cosmological constant is inversely proportional to the squared correlation length [Formula: see text]. The correlation length [Formula: see text] characterizes an infrared size of a causally correlate patch of the universe. The quantitative description of low-redshift universe in the scaling-invariant region of fixed point [Formula: see text] is given, and its deviation from the [Formula: see text]CDM can be examined by recent cosmological observations, such as supernova Type Ia.
Modeling and validating self-adaptive service-oriented applications
Authors: Arcaini Paolo , Riccobene Elvinia , Scandurra Patrizia 
Published: October 2015

Self-adaptive and autonomous behaviors are becoming more and more important in the context of service-oriented applications, and formal modeling self-adaptive service-oriented components is highly required to assure quality properties.
This paper enhances the formal framework SCA-ASM for modeling and validating distributed self-adaptive service-oriented applications. We explain how modeling an SCA-ASM component able to monitor and react to environmental changes (context-awareness) and to internal changes (self-awareness), and present the operators for expressing and coordinating self-adaptive behaviors in a distributed setting. We also support techniques for validating adaptation scenarios, and getting feedback of the correctness of the adaptation logic as implemented by the managing SCA-ASM components over the managed ones. As a proof-of-concepts, we use self-adaptive SCA-ASMs for modeling and validating a decentralized traffic monitoring system.
Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas
Authors: Verreault Maite , Schmitt Charlotte , Goldwirt Lauriane , Pelton Kristine , Haidar Samer , Levasseur Camille , Guehennec Jeremy , Knoff David , Labussière Marianne , Marie Yannick , Ligon Azra H. , Mokhtari Karima , Hoang-Xuan Khê , Sanson Marc , Alexander Brian M. , Wen Patrick Y. , Delattre Jean-Yves , Ligon Keith L. , Idbaih Ahmed 
Published: October 2015

Abstract
Purpose: p53 pathway alterations are key molecular events in glioblastoma (GBM). MDM2 inhibitors increase expression and stability of p53 and are presumed to be most efficacious in patients with TP53 wild-type and MDM2-amplified cancers. However, this biomarker hypothesis has not been tested in patients or patient-derived models for GBM.
Experimental Design: We performed a preclinical evaluation of RG7112 MDM2 inhibitor, across a panel of 36 patient-derived GBM cell lines (PDCL), each genetically characterized according to their P53 pathway status. We then performed a pharmacokinetic (PK) profiling of RG7112 distribution in mice and evaluated the therapeutic activity of RG7112 in orthotopic and subcutaneous GBM models.
Results: MDM2-amplified PDCLs were 44 times more sensitive than TP53-mutated lines that showed complete resistance at therapeutically attainable concentrations (avg. IC50 of 0.52 μmol/L vs. 21.9 μmol/L). MDM4-amplified PDCLs were highly sensitive but showed intermediate response (avg. IC50 of 1.2 μmol/L), whereas response was heterogeneous in TP53 wild-type PDCLs with normal MDM2/4 levels (avg. IC50 of 7.7 μmol/L). In MDM2-amplified lines, RG7112 restored p53 activity inducing robust p21 expression and apoptosis. PK profiling of RG7112-treated PDCL intracranial xenografts demonstrated that the compound significantly crosses the blood–brain and the blood–tumor barriers. Most importantly, treatment of MDM2-amplified/TP53 wild-type PDCL-derived model (subcutaneous and orthotopic) reduced tumor growth, was cytotoxic, and significantly increased survival.
Conclusions: These data strongly support development of MDM2 inhibitors for clinical testing in MDM2-amplified GBM patients. Moreover, significant efficacy in a subset of non–MDM2-amplified models suggests that additional markers of response to MDM2 inhibitors must be identified. Clin Cancer Res; 22(5); 1185–96. ©2015 AACR.
Is It Better to Be Rich or Relaxed? Sociobiology Meets Bone Marrow Transplant
Authors: Turcotte Lucie M. , Verneris Michael R. 
Published: October 2015

Abstract
Low socioeconomic status in hematopoietic cell transplant recipients is associated with increased treatment-related mortality and relapse, resulting in reduced survival. No biologic mechanism has been identified for these associations. The stress-related gene expression profile, termed the “conserved transcriptional response to adversity,” may be a predictor of these negative outcomes. Clin Cancer Res; 22(1); 6–8. ©2015 AACR.
See related article by Knight et al., p. 69
Abstract A02: The epigenetic modifier CHAF1A opposes neuroblastoma differentiation via metabolic reprogramming
Authors: Barbieri Eveline , Chen Zaowen , Moreno-Smith Mirthala , Shohet Jason M. 
Published: October 2015

Abstract
Background. Neuroblastoma (NB) arises from embryonal neural crest secondary to a block in differentiation and long-term survival inversely correlates with degree of neuronal differentiation. Metabolic rewiring is an important feature of undifferentiated NB tumors. Interestingly, MYCN down regulation precedes differentiation of NB cells induced by retinoic acid (RA) and genetic MYCN silencing leads to neuronal differentiation. We have recently demonstrated a novel function for the histone chaperone CHAF1A in blocking NB differentiation. CHAF1A is a subunit of the Chromatin Assembly Factor-1 (CAF1), which regulates H3K9-trimethylation and DNA methylation.
Methods. Morphological and molecular evaluations of NB differentiation were assessed upon CHAF1A silencing in RA-sensitive and RA-resistant lines by neurite outgrowth assays and Q-PCR for mature neuronal markers. Gene expression profiling of CHAF1A knockdown and control cell lines was performed on the Affymetrix U133+2.0 arrays. GSEA (Gene Set Enrichment Analysis) defined the transcriptional response to CHAF1A silencing in RA sensitive lines. Quantitative-PCR assays were used to validate the most significant enriched metabolic gene sets and MYCN western blotting was performed at different time points after CHAF1A silencing.
Results. CHAFIA suppression in MYCN-amplified RA-sensitive and RA-resistant lines results in NB differentiation and inhibition of cell proliferation. CHAF1A silencing significantly (nominal p-value &lt;0.05 and FDR q-value &lt;0.25) enriches for cell metabolism pathways (valine, leucine, and isoleucine degradation, glutamate metabolism and insulin pathways) and suppresses pathways with known oncogenic function in neuroblastoma (KRAS, ALK, Akt and BMI1). Q-PCR studies confirmed the regulation by CHAF1A of gene sets regulating glucose and glutamine metabolism. Importantly, MYCN protein levels were profoundly suppressed upon CHAF1A silencing.
Conclusions. We have shown that differentiation of NB cells upon CHAF1A silencing: 1) induces metabolic reprogramming by decreasing glucose and glutamine uptakes, 2) inhibits cell proliferation, and 3) reduces MYCN protein levels. We hypothesize that CHAF1A plays a critical role in the MYCN-mediated metabolic reprogramming of undifferentiated NB tumors. Future studies will further dissect this link and guide the development of novel differentiating therapies for high-risk NB.
Citation Format: Eveline Barbieri, Zaowen Chen, Mirthala Moreno-Smith, Jason M. Shohet. The epigenetic modifier CHAF1A opposes neuroblastoma differentiation via metabolic reprogramming. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A02.
Abstract A08: Identification of c-MYC SUMOylation by mass spectrometry
Authors: Kalkat Manpreet , Chan Pak-Kei , Wasylishen Amanda R. , Srikumar Tharan , Kim Sam S. , Ponzielli Romina , Bazett-Jones David P. , Raught Brian , Penn Linda Z. 
Published: October 2015

Abstract
The c-MYC transcription factor is a master regulator of many cellular processes and deregulation of this oncogene has been linked to more than 50% of all cancers. In normal cells, MYC is tightly controlled at a number of steps, including at the transcriptional, translational and post-translational levels. Altered regulation at any of these steps can result in deregulated, oncogenic MYC. One well-studied canonical pathway that is known to regulate MYC activity and stability at the post-translational level is the GSK3 pathway. The GSK3-FBXW7 axis regulates MYC via phosphorylation at T58, followed by ubiquitylation of MYC by the E3 ubiquitin ligase complex SCF-FBXW7 and subsequent proteasomal degradation. Accordingly, substituting threonine 58 with alanine (T58A) confers increased stability and transformative potential. Thus, characterizing the post-translational modifications (PTMs) of MYC can lead to a better understanding of the regulatory mechanisms controlling this potent oncogene. SUMOylation is a post-translational modification that utilizes a series of E1, E2 and E3 proteins for conjugation of a small ubiquitin-like modifier (SUMO) moiety to its target protein. Growing evidence indicates that SUMOylation has many important roles in the cell, such as response to cellular stressors and transcriptional regulation. Moreover, recent reports have unveiled a potential role for SUMOylation in MYC-driven tumourigenesis. Here, using immunoprecipitation combined with mass spectrometry, we identified a MYC SUMOylation site (K326). Abrogation of signaling through this residue by substitution with arginine (K326R) has no obvious effects on MYC half-life, intracellular localization, transcriptional targets, nor on the biological effects of MYC overexpression in three different cell systems assessed for soft agar colony formation, proliferation, and apoptosis. While we have definitively demonstrated that MYC SUMOylation can occur on K326, future work will be needed to elucidate the mechanisms and biological significance of MYC regulation by SUMOylation.
Citation Format: Manpreet Kalkat, Pak-Kei Chan, Amanda R. Wasylishen, Tharan Srikumar, Sam S. Kim, Romina Ponzielli, David P. Bazett-Jones, Brian Raught, Linda Z. Penn. Identification of c-MYC SUMOylation by mass spectrometry. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A08.
Abstract A12: Identifying MYC post-translational modifications using a mass spectrometry-based approach
Authors: Resetca Diana , Kalkat Manpreet , Lourenco Corey , Chan Pak-Kei , Srikumar Tharan , Raught Brian , Penn Linda 
Published: October 2015

Abstract
MYC activity is regulated by a complex network of signaling cascades and protein interactions, some of which result in post-translation modifications (PTMs). For example, phosphorylation of the regulatory threonine 58 (T58) and serine 62 (S62) plays a pivotal role in regulating MYC stability and activity. Loss of this regulatory pathway in cancer can lead to MYC dysregulation and contribute to tumorigenesis. Despite their important role, the majority of MYC PTMs arising downstream of different signaling cascades and their consequences on regulating MYC activity remain largely unknown.
To capture the broad spectrum of MYC PTMs, a mass spectrometry (MS)-based approach is being pursued to attain high sequence coverage and enable the identification of PTMs throughout the protein. MYC was overexpressed in the HEK293T cell line, immunoprecipitated, digested, and analyzed on the Velos Orbitrap MS. This analysis facilitated the identification of a range of MYC PTMs, including phosphorylation, sumoylation, ubiquitination and acetylation. Phosphorylation was readily detectable at residues T58 and S62, consistent with previous reports. Additionally, we also observed a previously reported phosphorylation cluster involving residues T343/S344/S347/S348, suggesting that these sites might play a role in regulating MYC function. Indeed, converting these residues to alanine to prevent phosphorylation resulted in a gain-of-function mutant (See Penn Lab poster Lorenco et al.). Another phosphorylation was observed mapping to residues S71 and/or S81. Mutating these sites to alanine also potentiated MYC transformation, highlighting the role of PTMs in regulating MYC function. A MYC sumoylation site was identified on lysine 326 (K326) and is subject of ongoing investigation (See Penn Lab poster Kalkat et al.). Additionally, we will discuss approaches presently underway to increase sequence coverage and identify additional MYC PTMs.
PTMs play an important role in regulating the activity of transcription factors, including that of MYC. Moreover, PTMs can contribute to the dysregulation of its activity in cancer. Thus, mapping the array of PTMs in MYC, understanding their role in regulating MYC function, and elucidating the pathways that converge on these PTMs may pave the way for the development of novel therapeutic strategies aimed at targeting MYC-induced tumorigenesis.
Citation Format: Diana Resetca, Manpreet Kalkat, Corey Lourenco, Pak-Kei Chan, Tharan Srikumar, Brian Raught, Linda Penn. Identifying MYC post-translational modifications using a mass spectrometry-based approach. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A12.
Abstract A34: The stress response transcription factor ATF4 mediates cytoprotective pathways in c-Myc overexpressing cells
Authors: Tameire Feven Tameire , Koumenis Costas 
Published: October 2015

Abstract
The proto-oncogene c-Myc is often deregulated in human tumors and its overexpression associates with poor prognosis in patients. While c-Myc is a potent activator of pro-tumorigenic pathways, it can also induce anti-tumorgenic pathways such as apoptosis. However, in c-Myc driven cancers the anti-tumorigenic state is evaded via a yet poorly understood pro-survival mechanism. We previously reported that activation of the PERK arm of the Unfolded Protein Response (UPR) is one such pro-survival mechanism induced by c-Myc to bypass c-Myc induced apoptosis. We also demonstrated enhanced activation of the PERK/p-eIF2α arm of the UPR in a mouse model of lymphoma and in B-cells from human lymphoma patients compared to normal tissues. ATF4, one of the main downstream effectors of PERK, regulates amino acid metabolism, antioxidant response and autophagy. Using the CRISPR/CAS9 genome-editing tool we were able to ablate portions of the ATF4 gene in DLD-1, human colon carcinoma cell line, preventing ATF4 protein expression. Here, we show ATF4 expression is induced in Myc overexpressing ATF4-WT DLD-1 cells. Activation of c-Myc in ATF4-deficient DLD-1 cells resulted in decreased clonogenic survival and reduced autophagy. Addition of Trolox, an antioxidant, conferred protection in ATF4 deficient cells. These findings indicate that the transcription factor ATF4 activates pro-survival pathways such as antioxidant response and autophagy during c-Myc overexpression to promote survival. Therefore, therapeutically targeting these pathways would switch the balance towards cell death in c-Myc dependent tumors.
Citation Format: Feven Tameire Tameire, Costas Koumenis. The stress response transcription factor ATF4 mediates cytoprotective pathways in c-Myc overexpressing cells. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A34.