bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Genome Sequence of
Escherichia coli
ML35
Authors: Casale Angeline , Clark Stephanie , Grasso Melissa , Kryschuk Marta , Ritzer Lukas , Trudeau Madyson , Williams Laura E. 
Published: February 2018

ABSTRACT

We report here the complete genome sequence of
Escherichia coli
strain ML35. We assembled PacBio reads into a single closed contig with 169× mean coverage and then polished this contig using Illumina MiSeq reads, yielding a 4,918,774-bp sequence with 50.8% GC content.
Complete Genome Sequences of Five Foot-and-Mouth Disease Viruses of Serotype A Isolated from Cattle in Nigeria between 2013 and 2015
Authors: Vandenbussche Frank , Mathijs Elisabeth , Ularamu Hussaini G. , Ehizibolo David O. , Haegeman Andy , Lefebvre David , De Vleeschauwer Annebel R. , Van Borm Steven , De Clercq Kris 
Published: February 2018

ABSTRACT
The complete genome sequences of 5 foot-and-mouth disease viruses of serotype A are reported here. These viruses originate from outbreaks in northern Nigeria in 2013 to 2015 and belong to the A/AFRICA/G-IV lineage.
Complete Genome Sequences of
Enterobacter cancerogenus
CR-Eb1 and
Enterococcus
sp. Strain CR-Ec1, Isolated from the Larval Gut of the Greater Wax Moth,
Galleria mellonella
Authors: Chung Joon-hui , Jeong Haeyoung , Ryu Choong-Min 
Published: February 2018

ABSTRACT

Enterobacter cancerogenus
CR-Eb1 and
Enterococcus
sp. CR-Ec1 were isolated from the larval gut of
Galleria mellonella
, the greater wax moth. Here, we report the completed and annotated genome sequences of insect gut-dwelling bacteria.
Analysis of the Complete Genome Sequence of
Cucumber mosaic virus
Strain K
Authors: Moyle Richard , Pretorius Lara-Simone , Shuey Louise S. , Nowak Ekaterina , Schenk Peer M. 
Published: February 2018

ABSTRACT

The complete genome sequence of
Cucumber mosaic virus
strain K was determined by deep RNA sequencing. The tripartite genome consists of a 3,382-nucleotide (nt) RNA1, a 3,050-nt RNA2, and a 2,218-nt RNA3 segment. Phylogenetic analysis placed RNA1 and RNA2 in subgroup IB. However, RNA3 grouped with subgroup IA isolates, indicating a likely recombination event.
Closed Genome Sequence of Phytopathogen Biocontrol Agent
Bacillus velezensis
Strain AGVL-005, Isolated from Soybean
Authors: Pylro Victor Satler , Dias Armando Cavalcante Franco , Andreote Fernando Dini , Morais Daniel Kumazawa , Varani Alessandro de Mello , Andreote Cristiane Cipolla Fasanella , Bernardo Eduardo Roberto de Almeida , Zucchi Tiago 
Published: February 2018

ABSTRACT

We report here the closed and near-complete genome sequence and annotation of
Bacillus velezensis
strain AGVL-005, a bacterium isolated from soybean seeds in Brazil and used for phytopathogen biocontrol.
Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila
Authors: Shokal Upasana , Kopydlowski Hannah , Harsh Sneh , Eleftherianos Ioannis 
Published: February 2018

ABSTRACT

Drosophila melanogaster
is an outstanding model for studying host antipathogen defense. Although substantial progress has been made in understanding how metabolism and immunity are interrelated in flies, little information has been obtained on the molecular players that regulate metabolism and inflammation in
Drosophila
during pathogenic infection. Recently, we reported that the inactivation of thioester-containing protein 2 (
Tep2
) and
Tep4
promotes survival and decreases the bacterial burden in flies upon infection with the virulent pathogens
Photorhabdus luminescens
and
Photorhabdus asymbiotica
. Here, we investigated physiological and pathological defects in
tep
mutant flies in response to
Photorhabdus
challenge. We find that
tep2
and
tep4
loss-of-function mutant flies contain increased levels of carbohydrates and triglycerides in the presence or absence of
Photorhabdus
infection. We also report that
Photorhabdus
infection leads to higher levels of nitric oxide and reduced transcript levels of the apical caspase-encoding gene
Dronc
in
tep2
and
tep4
mutants. We show that
Tep2
and
Tep4
are upregulated mainly in the fat body rather than the gut in
Photorhabdus
-infected wild-type flies and that
tep
mutants contain decreased numbers of
Photorhabdus
bacteria in both tissue types. We propose that the inactivation of
Tep2
or
Tep4
in adult
Drosophila
flies results in lower levels of inflammation and increased energy reserves in response to
Photorhabdus
, which could confer a survival-protective effect during the initial hours of infection.
Multiplex Immunochromatographic Detection of OXA-48, KPC, and NDM Carbapenemases: Impact of Inoculum, Antibiotics, and Agar
Authors: Saleh Ahmad , Göttig Stephan , Hamprecht Axel G. 
Published: February 2018

ABSTRACT

For the rapid detection of carbapenemase-producing
Enterobacteriaceae
(CPE), immunochromatographic lateral flow tests (ICT) have recently been developed. The aim of this study was to assess the new multiplex ICT Resist-3 O.K.N. and to investigate if it can be performed directly from susceptibility testing plates. Additionally, the impact of the inoculum and carbapenem disks on sensitivity and specificity was evaluated. The new ICT was challenged using 63 carbapenem-resistant
Enterobacteriaceae
(CRE) isolates, including 51 carbapenemase producers. It was assessed under five different conditions directly from Mueller-Hinton agar (MHA): 1 μl or 10 μl of inoculum harvested in the absence of antibiotic pressure or 1 μl taken from the inhibition zone of either an ertapenem, imipenem, or meropenem disk. The sensitivity of the ICT was 100% for OXA-48-like and KPC carbapenemases and 94.4% for the NDM carbapenemase with the 1-μl inoculum. When harvested adjacent to a carbapenem disk, the sensitivity increased to 100%. Additionally, with zinc-supplemented MHA, both the sensitivity increased and the NDM band became visible faster (mean time, 8 ± 3.9 min for MHA compared to 1.9 ± 1.5 min for MHA plus zinc;
P
= 0.0016). The specificity of the ICT was 100%. The Resist-3 O.K.N. ICT is a sensitive and rapid test for the detection of three highly prevalent carbapenemases. However, false-negative results for NDM can occur. We recommend an inoculum of 1 μl that is harvested adjacent to an ertapenem or meropenem disk and the use of agars with sufficient zinc content to achieve the best performance.
Karyopherin Alpha 6 Is Required for Replication of Porcine Reproductive and Respiratory Syndrome Virus and Zika Virus
Authors: Yang Liping , Wang Rong , Yang Shixing , Ma Zexu , Lin Shaoli , Nan Yuchen , Li Qisheng , Tang Qiyi , Zhang Yan-Jin 
Published: February 2018

ABSTRACT
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating the nucleocytoplasmic translocation of proteins through the NPC. In this study, we found that karyopherin α6 (KPNA6; also known as importin α7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The KPNA6 protein level in virus-infected cells was much higher than that in mock-infected controls, whereas the KPNA6 transcript remains stable. Viral infection blocked the ubiquitin-proteasomal degradation of KPNA6, which led to an extension of the KPNA6 half-life and the elevation of the KPNA6 level in comparison to mock-infected cells. PRRSV nsp12 protein induced KPNA6 stabilization. KPNA6 silencing was detrimental to the replication of PRRSV, and KPNA6 knockout impaired ZIKV replication. Moreover, KPNA6 knockout blocked the nuclear translocation of PRRSV nsp1β but had a minimal effect on two other PRRSV proteins with nuclear localization. Exogenous restitution of KPNA6 expression in the KPNA6-knockout cells results in restoration of the nuclear translocation of PRRSV nsp1β and the replication of ZIKV. These results indicate that KPNA6 is an important cellular factor for the replication of PRRSV and ZIKV.

IMPORTANCE
Positive-sense, single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected cells. The roles of transport factors in the nucleocytoplasmic trafficking system for the replication of +ssRNA viruses are not known. In this study, we discovered that PRRSV and ZIKV viruses needed karyopherin α6 (KPNA6), one of the transport factors, to enhance the virus replication. Our data showed that viral infection induced an elevation of the KPNA6 protein level due to an extension of the KPNA6 half-life via viral interference of the ubiquitin-proteasomal degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV. PRRSV nsp1β depended on KPNA6 to translocate into the nucleus. In addition, exogenous restitution of KPNA6 expression in KPNA6-knockout cells led to the restoration of nsp1β nuclear translocation and ZIKV replication. These results reveal a new aspect in the virus-cell interaction and may facilitate the development of novel antiviral therapeutics.
Optical study of interactions among propagation waves of neural excitation in the rat somatosensory cortex evoked by forelimb and hindlimb stimuli
Authors: Hama Noriyuki , Kawai Minako , Ito Shin-Ichi , Hirota Akihiko 
Published: February 2018

Multisite optical recording has revealed that the neural excitation wave induced by a sensory stimulation begins at a focus and propagates in the cortex. This wave is considered to be important for computation in the sensory cortex, particularly the integration of sensory information; however, the nature of this wave remains largely unknown. In the present study, we examined the interaction between two waves in the rat sensory cortex induced by hindlimb and forelimb stimuli with different interstimulus intervals. We classified the resultant patterns as follows: 1) the collision of two waves, 2) the hindlimb response being evoked while the forelimb-induced wave is passing the hindlimb focus, and 3) the hindlimb response being evoked after the forelimb-induced wave has passed the hindlimb focus. In pattern 1, the two waves fused into a single wave, but the propagation pattern differed from that predicted by the superimposition of two singly induced propagation courses. In pattern 2, the state of the interaction between the two waves varied depending on the phase of optical signals constituting the forelimb-induced wave around the hindlimb focus. Although no hindlimb-induced wave was observed in the rising phase, the propagating velocity of the forelimb-induced wave increased. At the peak, neither the hindlimb-induced response nor a modulatory effect on the forelimb-induced wave was detected. In pattern 3, the hindlimb-induced wave showed a reduced amplitude and spatial extent. These results indicate that the state of the interaction between waves was strongly influenced by the relative timing of sensory inputs. NEW & NOTEWORTHY Sensory stimulation-induced cortical excitation propagates as a wave and spreads over a wide area of the sensory cortex. To elucidate the characteristics of this relatively unknown phenomenon, we examined the interaction between two individually induced waves in the somatosensory cortex. Either the waves collided or the preceding wave affected the emergence of the following one. Our results indicate that the state of the interaction was strongly influenced by the relative timing of sensory inputs.
Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes
Authors: Mohme Malte , Schliffke Simon , Maire Cecile L. , Rünger Alessandra , Glau Laura , Mende Klaus C. , Matschke Jakob , Gehbauer Christina , Akyüz Nuray , Zapf Svenja , Holz Mareike , Schaper Miriam , Martens Tobias , Schmidt Nils O. , Peine Sven , Westphal Manfred , Binder Mascha , Tolosa Eva , Lamszus Katrin 
Published: February 2018

Abstract
Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion.
Experimental Design: We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM.
Results: We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8+ T cells.
Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187–200. ©2018 AACR.
See related commentary by Jackson and Lim, p. 4059
A Correlative Analysis of PD-L1, PD-1, PD-L2, EGFR, HER2, and HER3 Expression in Oropharyngeal Squamous Cell Carcinoma
Authors: Steuer Conor E. , Griffith Christopher C. , Nannapaneni Sreenivas , Patel Mihir R. , Liu Yuan , Magliocca Kelly R. , El-Deiry Mark W. , Cohen Cynthia , Owonikoko Taofeek K. , Shin Dong M. , Chen Zhuo G. , Saba Nabil F. 
Published: February 2018

Abstract
We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by IHC on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0 to 4 within the tumor mass and peritumoral stroma. Associations between biomarkers and patient outcomes were tested using descriptive and inferential statistics, logistic regression, and Cox proportional hazards models. We analyzed tissue samples from 97 OPSCC cases: median age 59 years, p16+ (71%), male (83.5%), never smokers (18%), stage 3 to 4 disease (77%). Twenty-five percent of cases were PD-L1 positive. The proportion of PD-L1+ tumors was higher in p16+ (29%) than p16− OPSCC (11%, P = 0.047). There was no correlation between PD-L1, PD-L2, PD-1, EGFR, HER2, or HER3 expression. Positive PD-L1 status correlated with advanced nodal disease on multivariate analysis (OR 5.53; 95% CI, 1.06–28.77; P = 0.042). Negative PD-L2 expression was associated with worse survival (HR 3.99; 95% CI, 1.37–11.58; P = 0.011) in p16− OPSCC. Lower density of PD-1 positive lymphocytes in peritumoral stroma was associated with significantly increased risk of death on multivariate analysis (HR 3.17; 95% CI, 1.03–9.78; P = 0.045) after controlling for prognostic factors such as stage and p16 status. PD-L1 expression on tumor cells correlates with p16 status and advanced nodal status in OPSCC. PD-1 positive lymphocytes in peritumoral stroma serve as an independent prognostic factor for overall survival. Mol Cancer Ther; 17(3); 710–6. ©2018 AACR.
A Spatio-Temporal Model of Macrophage-Mediated Drug Resistance in Glioma Immunotherapy
Authors: Zheng Yongjiang , Bao Jiguang , Zhao Qiyi , Zhou Tianshou , Sun Xiaoqiang 
Published: February 2018

Abstract
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas. In this study, we developed a spatio-temporal model to quantitatively describe the interplay between glioma cells and CSF1R inhibitor–targeted macrophages through CSF1 and IGF1 pathways. Our model was used to investigate the evolutionary kinetics of the tumor regrowth and the associated dynamic adaptation of the tumor microenvironment in response to the CSF1R inhibitor treatment. The simulation result obtained using this model was in agreement with the experimental data. The sensitivity analysis revealed the key parameters involved in the model, and their potential impacts on the model behavior were examined. Moreover, we demonstrated that the drug resistance is dose-dependent. In addition, we quantitatively evaluated the effects of combined CSFR inhibition and IGF1 receptor (IGF1R) inhibition with the goal of designing more effective therapies for gliomas. Our study provides quantitative and mechanistic insights into the microenvironmental adaptation mechanisms that operate during macrophage-targeted immunotherapy and has implications for drug dose optimization and the design of more effective combination therapies. Mol Cancer Ther; 17(4); 814–24. ©2018 AACR.
Small Molecule–Mediated Activation of RAS Elicits Biphasic Modulation of Phospho-ERK Levels that Are Regulated through Negative Feedback on SOS1
Authors: Howes Jennifer E. , Akan Denis T. , Burns Michael C. , Rossanese Olivia W. , Waterson Alex G. , Fesik Stephen W. 
Published: February 2018

Abstract
Oncogenic mutation of RAS results in aberrant cellular signaling and is responsible for more than 30% of all human tumors. Therefore, pharmacologic modulation of RAS has attracted great interest as a therapeutic strategy. Our laboratory has recently discovered small molecules that activate Son of Sevenless (SOS)–catalyzed nucleotide exchange on RAS and inhibit downstream signaling. Here, we describe how pharmacologically targeting SOS1 induced biphasic modulation of RAS-GTP and ERK phosphorylation levels, which we observed in a variety of cell lines expressing different RAS-mutant isoforms. We show that compound treatment caused an increase in phosphorylation at ERK consensus motifs on SOS1 that was not observed with the expression of a non-phosphorylatable S1178A SOS1 mutant or after pretreatment with an ERK inhibitor. Phosphorylation at S1178 on SOS1 is known to inhibit the association between SOS1 and GRB2 and disrupt SOS1 membrane localization. Consistent with this, we show that wild-type SOS1 and GRB2 dissociated in a time-dependent fashion in response to compound treatment, and conversely, this interaction was enhanced with the expression of an S1178A SOS1 mutant. Furthermore, in cells expressing either S1178A SOS1 or a constitutively membrane-bound CAAX box tagged SOS1 mutant, we observed elevated RAS-GTP levels over time in response to compound, as compared with the biphasic changes in RAS-GTP exhibited in cells expressing wild-type SOS1. These results suggest that small molecule targeting of SOS1 can elicit a biphasic modulation of RAS-GTP and phospho-ERK levels through negative feedback on SOS1 that regulates the interaction between SOS1 and GRB2. Mol Cancer Ther; 17(5); 1051–60. ©2018 AACR.
Prior Percutaneous Coronary Intervention and Mortality in Patients Undergoing Surgical Myocardial Revascularization
Authors: Mariscalco Giovanni , Rosato Stefano , Serraino Giuseppe F. , Maselli Daniele , Dalén Magnus , Airaksinen Juhani K.E. , Reichart Daniel , Zanobini Marco , Onorati Francesco , De Feo Marisa , Gherli Riccardo , Santarpino Giuseppe , Rubino Antonino S. , Gatti Giuseppe , Nicolini Francesco , Santini Francesco , Perrotti Andrea , Bruno Vito D. , Ruggieri Vito G. , Biancari Fausto , Ahmed Aamer , Masala Nicola , Dominici Carmelo , Nardella Saverio , Khodabandeh Sorosh , Svenarud Peter , Gulbins Helmut , Saccocci Matteo , Faggian Giuseppe , Franzese Ilaria , Bancone Ciro , Della Ratta Ester E. , Musumeci Francesco , Gazdag Laszlo , Fischlein Theodor , Mignosa Carmelo , Pappalardo Aniello , Gherli Tiziano , Salsano Antonio , Olivieri Guido , Bounader Karl , Verhoye Jean P. , Chocron Sidney , Tauriainen Tuomas , Kinnunen Eeva-Maija 
Published: February 2018

Background—
The clinical impact of prior percutaneous coronary intervention (PCI) in patients requiring coronary artery bypass grafting (CABG) remains unsettled. We sought to determine whether prior PCI is associated with adverse outcome after CABG.

Methods and Results—

Data from the prospective E-CABG (European Multicenter Study on Coronary Artery Bypass Grafting) conducted between January 2015 and March 2016 at 16 European centres were analyzed using propensity weighted methodology to adjust for confounding. A parallel systematic review/meta-analysis (MEDLINE, Embase, SCOPUS, and Cochrane Library) through September 2017 was accomplished. Of a total of 3641 adult patients included in the E-CABG study, 685 (19%) patients had a history of PCI. At multivariable level, prior PCI was not associated with an increased hospital mortality in both unweighted and weighted patient groups (odds ratio, 0.73; 95% confidence interval, 0.29–1.38;
P
=0.33 and odds ratio, 0.90; 95% confidence interval, 0.39–2.08;
P
=0.81, respectively). Subgroup analyses confirmed that prior PCI had no impact on hospital mortality and morbidity, including reexploration for bleeding, blood transfusion, hospital resource use, and neurological, renal, and cardiac complications. The systematic review provided a total of 71 366 individuals and showed a trend toward higher in-hospital/30-day mortality (adjusted odds ratio, 1.30; 95% confidence interval, 0.99–1.70; I
2
=43.1%) in patients with prior PCI.

Conclusions—
Our prospective multicenter study showed that prior PCI was not associated with an increased risk of mortality or other adverse outcomes in patients undergoing CABG. In light of a trend toward increased mortality observed in the meta-analysis, further studies are needed to ascertain the prognostic impact of prior PCI in the outcome after CABG.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02319083.