bluuebunny/crossref_metadata_2025_split huggingface dataset:
The VirAB ABC Transporter Is Required for VirR Regulation of Listeria monocytogenes Virulence and Resistance to Nisin
Authors: Grubaugh Daniel , Regeimbal James M. , Ghosh Pallab , Zhou Yan , Lauer Peter , Dubensky Thomas W. , Higgins Darren E. 
Published: December 2017

ABSTRACT

Listeria monocytogenes
is a Gram-positive intracellular pathogen that causes a severe invasive disease. Upon infecting a host cell,
L. monocytogenes
upregulates the transcription of numerous factors necessary for productive infection. VirR is the response regulator component of a two-component regulatory system in
L. monocytogenes
. In this report, we have identified the putative ABC transporter encoded by genes
lmo1746-lmo1747
as necessary for VirR function. We have designated
lmo1746-lmo1747 virAB
. We constructed an in-frame deletion of
virAB
and determined that the Δ
virAB
mutant exhibited reduced transcription of VirR-regulated genes. The Δ
virAB
mutant also showed defects in
in vitro
plaque formation and
in vivo
virulence that were similar to those of a Δ
virR
deletion mutant. Since VirR is important for innate resistance to antimicrobial agents, we determined the MICs of nisin and bacitracin for Δ
virAB
bacteria. We found that VirAB expression was necessary for nisin resistance but was dispensable for resistance to bacitracin. This result suggested a VirAB-independent mechanism of VirR regulation in response to bacitracin. Lastly, we found that the Δ
virR
and Δ
virAB
mutants had no deficiency in growth in broth culture, intracellular replication, or production of the ActA surface protein, which facilitates actin-based motility and cell-to-cell spread. However, the Δ
virR
and Δ
virAB
mutants produced shorter actin tails during intracellular infection, which suggested that these mutants have a reduced ability to move and spread via actin-based motility. These findings have demonstrated that
L. monocytogenes
VirAB functions in a pathway with VirR to regulate the expression of genes necessary for virulence and resistance to antimicrobial agents.
Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems
Authors: Galperin Michael Y. , Makarova Kira S. , Wolf Yuri I. , Koonin Eugene V. 
Published: December 2017

ABSTRACTThe two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phylaCrenarchaeota,Nanoarchaeota, andKorarchaeota. The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation.IMPORTANCEAlthough theArchaearepresent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online athttp://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html.
Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis
Authors: Martin Nina M. , Griffin Diane E. 
Published: December 2017

ABSTRACTAlphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053–16058, 2014,https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10−/−mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCEAlphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.
Standardised cigarette packaging may reduce the implied safety of Natural American Spirit cigarettes
Authors: Leas Eric Craig , Pierce John P , Dimofte Claudiu V , Trinidad Dennis R , Strong David R 
Published: December 2017

BackgroundOver two-thirds of Natural American Spirit (NAS) smokers believe their cigarettes might be ‘less harmful’, but toxicological evidence does not support this belief. We assessed whether standardised packaging could reduce the possibility of erroneous inferences of ‘safety’ drawn from NAS cigarette packaging.MethodsUS adult smokers (n=909) were recruited to a between-subject survey experiment (3 brands×3 packaging/labelling styles) through Amazon Mechanical Turk and rated their perception of whether a randomly assigned cigarette package conveyed that the brand was ‘safer’ on a three-item scale (Cronbach’s α=0.92). We assessed whether NAS packs were rated higher on the ‘implied safety’ scale than two other brands and estimated the effect that plain packaging (ie, all branding replaced with a drab dark brown colour) and Australian-like packaging (ie, all branding replaced with a drab dark brown colour and a graphic image and text on 75% of the pack surface) had on perceptions of the NAS cigarette package.ResultsSmokers’ ratings of the standard NAS pack on the implied safety scale (mean=4.6; SD=2.9) were 1.9 times (P <0.001) higher than smokers’ ratings of a Marlboro Red pack (mean=2.4; SD=2.3) and 1.7 times (P <0.001) higher than smokers’ ratings of a Newport Menthol pack (mean=2.7; SD=2.4). These perceptions of implied safety were lower when plain packaging was used (Cohen’s d=0.66; P <0.001) and much lower when Australian-like packaging was used (Cohen’s d=1.56; P <0.001).ConclusionThe results suggest that NAS cigarette packaging conveys that its cigarettes are ‘safer’ and that such perceptions are lower with standardised packaging, both with and without warning images.
Physical and optical properties of calcium sulfate ultra-phosphate glass-doped Er2O3
Authors: Aliyu Aliyu Mohammed , Hussin R. , Deraman Karim , Ahmad N. E. , Danmadami Amina M. , Yamusa Y. A. 
Published: December 2017

The influence of erbium on physical and optical properties of calcium sulfate ultra-phosphate glass was investigated using conventional melt quench process. Selected samples of composition 20CaSO4 (80 – x) P2O5– xEr2O3 with 0.1 [Formula: see text]x [Formula: see text] 0.9 mol.% were prepared and assessed. X-ray diffraction (XRD) techniques were used to confirm the amorphous nature of the said samples. The structural units of phosphate-based glass were assessed from Raman spectra as ultra-(Q3), meta-(Q2), pyro-(Q1) and orthophosphate (Q0) units. Depolymerization process of the glasses was testified for higher calcium oxide content and UV-visible for optical measurement. Thermal analysis have been investigated by means of thermogravimetric analysis. The results show the decomposition of materials in the temperature range of 25[Formula: see text]C–1000[Formula: see text]C. Er[Formula: see text] absorption spectra were measured in the range of 400–1800[Formula: see text]nm. PL measurement was carried out in order to obtain the excitation and emission spectra of the samples. The emission spectra excited at 779[Formula: see text]nm comprises of 518[Formula: see text]nm, 550[Formula: see text]nm and 649[Formula: see text]nm of transition 4F[Formula: see text], 4S[Formula: see text] and 2H[Formula: see text] excited states to 4I[Formula: see text] ground state. In physical properties, the density calculated using Archimedes method is inversely proportional to molar volume with increase in Er[Formula: see text] ions. Optical bandgap (E[Formula: see text]) were determined using Tauc’s plots for direct transitions where E[Formula: see text] (direct) decreases with increase in erbium content. The refractive index increases with decreasing molar volume; this may have a tendency for larger optical bandgap. The result obtained from the glass matrix indicates that erbium oxide-doped calcium sulfate ultra-phosphate may give important information for wider development of functional glasses.
Characterization of signed Gauss paragraphs and skew-symmetric graded matrices
Authors: Rodríguez-Nieto José Gregorio 
Published: December 2017

In this paper, we use theory of embedded graphs on oriented and compact [Formula: see text]-surfaces to construct minimal realizations of signed Gauss paragraphs. We prove that the genus of the ambient surface of these minimal realizations can be seen as a function of the maximum number of Carter’s circles. For the case of signed Gauss words, we use a generating set of [Formula: see text], given in [G. Cairns and D. Elton, The Planarity problem for signed Gauss world, J. Knots Theor. Ramif. 2(4) (1993) 359–367], and the intersection pairing of immersed [Formula: see text]-normal curves to present a short solution of the signed Gauss word problem. We relate this solution with the one given by Cairns and Elton. Moreover, we define the join operation on signed Gauss paragraphs to produce signed Gauss words such that both can be realized on the same minimal genus [Formula: see text]-surface. We connect the characterization of signed Gauss paragraph with the recognition virtual links problem. Also we present a combinatorial algorithm to compute, in an easier way, skew-symmetric graded matrices [V. Turaev, Cobordism of knots on surfaces, J. Topol. 1(2) (2008) 285–305] for virtual knots through the concept of triplets [M. Toro and J. Rodríguez, Triplets associated to virtual knot diagrams, Rev. Integración (2011)]. Therefore, we can prove that the Kishino’s knot is not classical, moreover, we prove that the virtual knots of the family [Formula: see text] given in [H. A. Dye, Virtual knots undetected by [Formula: see text] and [Formula: see text]-strand bracket polynomials, Topol. Appl. 153 (2005) 141–160] are not classical knots.
Games with Symmetric Incomplete Information and Asymmetric Computational Resources
Authors: Gavrilovich Misha , Kreps Victoria 
Published: December 2017

We consider random public signals on the state of two-person zero-sum game with incomplete information on both sides (both players do not know the state of the game). To learn the state, each player chooses a finite automaton which receives the public signal; the player only sees the output of the automaton chosen. Supposing that the size of automata available to Player 1 is essentially bigger than that available to Player 2, we give an example of public signal with random length of output strings where the posterior belief of Player 1 is the state and the posterior belief of Player 2 is close to his original belief. Thus, we demonstrate that asymmetric information about the state of a game may appear not only due to a private signal but as a result of a public signal and asymmetric computational resources of players. Besides, for a class of random signals with fixed length of output strings, we estimate the fraction of signals such that some automaton of given size may help Player 2 to significantly reestimate prior probability of the state. We show that this fraction is negligible if the size of automata of Player 2 is sufficiently smaller than length of output strings.
Associated Factors and Outcome of Uterine Rupture at Suhul General Hospital, Shire Town, North West Tigray, Ethiopia 2016: A Case-Control Study
Authors: Marie Bereka Tefera , Mulat Aweke Amlaku , Eshetie Wondie Tewodrose 
Published: December 2017

Background. Uterine rupture is tearing of the uterine wall during pregnancy or delivery. It may extend to partial or whole thickness of the uterine wall. It is usually a case where obstetric care is poor. In extensive damage, death of the baby and sometimes even maternal death are evident.Objective. This study assesses associated factors and outcome of uterine rupture at Suhul General Hospital, Tigray Region, Ethiopia, 2016.Methodology. A case-control study was conducted by review of data from September 2012 to August 2016. A total of 336 samples were studied after calculating by EPI-INFO using proportion of multiparity (53%) and ratio of 1 : 2 for cases and controls, respectively. Analysis was done using SPSS version 20. Bivariate and multivariate logistic regression was applied withp<0.05.Result. ANC, grand multiparity, malpresentation, and obstructed labor had association, but previous cesarean delivery was not significant. Perinatal mortality was 105 (93%) versus 13 (5.8%) in cases and controls, respectively. Anemia was highest for both groups (53.7% versus 32.1%).Conclusion. Majority of uterine rupture is attributed to prolonged or obstructed labor. Cases of uterine rupture had prompt management preventing maternal mortality, but burden of perinatal death is still high.
New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome
Authors: Wilson Leah J. , Linley Adam , Hammond Dean E. , Hood Fiona E. , Coulson Judy M. , MacEwan David J. , Ross Sarah J. , Slupsky Joseph R. , Smith Paul D. , Eyers Patrick A. , Prior Ian A. 
Published: December 2017

AbstractThe human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates. While a major research focus of the last 30 years has been cancer-associated Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at least one disease or developmental disorder. Despite this remarkable statistic, for the majority of protein kinases and pseudokinases, there are currently no inhibitors progressing toward the clinic, and in most cases, details of their physiologic and pathologic mechanisms remain at least partially obscure. By curating and annotating data from the literature and major public databases of phosphorylation sites, kinases, and disease associations, we generate an unbiased resource that highlights areas of unmet need within the kinome. We discuss strategies and challenges associated with characterizing catalytic and noncatalytic outputs in cells, and describe successes and new frontiers that will support more comprehensive cancer-targeting and therapeutic evaluation in the future. Cancer Res; 78(1); 15–29. ©2017 AACR.
“Future-Proofing” Blood Processing for Measurement of Circulating miRNAs in Samples from Biobanks and Prospective Clinical Trials
Authors: Murray Matthew J. , Watson Hannah L. , Ward Dawn , Bailey Shivani , Ferraresso Marta , Nicholson James C. , Gnanapragasam Vincent J. , Thomas Benjamin , Scarpini Cinzia G. , Coleman Nicholas 
Published: December 2017

Abstract
Background: Quantifying circulating nucleic acids is an important new approach to cancer diagnosis/monitoring.
Methods: We compared the suitability of serum versus plasma for measuring miRNAs using qRT-PCR and assessed how preanalytic variables that can affect circulating tumor DNA (ctDNA) quantification in plasma also influence miRNA levels.
Results: Across 62 blood-derived specimens, plasma samples in EDTA, Streck-DNA, and Streck-RNA tubes showed significantly higher Ct values for multiple housekeeping miRNAs, compared with serum samples. For the EDTA-plasma tubes, this difference was only seen when including the high-speed centrifugation protocol used to optimize ctDNA extraction. In plasma samples derived from blood stored at room temperature for up to 14 days (conditions that typically apply to samples processed for biobanking), levels of endogenous housekeeping miRNAs gradually increased, in parallel with the hemolysis marker hsa-miR-451a, consistent with release from blood cells/platelets. It was necessary to normalize levels of the housekeeping miRNAs to those of hsa-miR-451a, to obtain the stable values needed for referencing test miRNA levels.
Conclusions: Our data indicate that plasma samples prepared for ctDNA extraction are suboptimal for miRNA quantification and require the incorporation of multiple data normalization steps. For prospective studies designed to measure both miRNAs and ctDNA, the most suitable approach would be to obtain both serum (for miRNAs) and plasma (for ctDNA). If only plasma can be collected, we recommend an initial low-speed centrifugation step, followed by aliquoting the supernatant into parallel samples, one for direct miRNA quantification, and the other for a further high-speed centrifugation step to optimize ctDNA retrieval.
Impact: These recommendations will help “future-proof” clinical studies in which quantification of circulating miRNAs is a component. Cancer Epidemiol Biomarkers Prev; 27(2); 208–18. ©2017 AACR.
Association of Pancreatic Cancer Susceptibility Variants with Risk of Breast Cancer in Women of European and African Ancestry
Authors: Wang Shengfeng , Zheng Yonglan , Ogundiran Temidayo O. , Ojengbede Oladosu , Zheng Wei , Nathanson Katherine L. , Nemesure Barbara , Ambs Stefan , Olopade Olufunmilayo I. , Huo Dezheng 
Published: December 2017

Abstract
Background: Pancreatic cancer mutation signatures closely resemble breast cancer, suggesting that both cancers may have common predisposition mechanisms that may include commonly inherited SNPs.
Methods: We examined 23 genetic variants known to be associated with pancreatic cancer as breast cancer risk factors in the Root genome-wide association study (GWAS; 1,657 cases and 2,029 controls of African diaspora) and GAME-ON/DRIVE GWAS (16,003 cases and 41,335 controls of European ancestry).
Results: None of the pancreatic cancer susceptibility variants were individually associated with breast cancer risk after adjustment for multiple testing (at α = 0.002) in the two populations. In Root GWAS, a change by one SD in the polygenic risk score (PRS) was not significantly associated with breast cancer. In addition, we did not observe a trend in the relationship between PRS percentiles and breast cancer risk.
Conclusions: The association between reported pancreatic cancer genetic susceptibility variants and breast cancer development in women of African or European ancestry is likely weak, if it does exist.
Impact: Known GWAS-derived susceptibility variants of pancreatic cancer do not explain its shared genetic etiology with breast cancer. Cancer Epidemiol Biomarkers Prev; 27(1); 116–8. ©2017 AACR.
Novel Targeting of Transcription and Metabolism in Glioblastoma
Authors: Su Yu-Ting , Chen Robert , Wang Herui , Song Hua , Zhang Qi , Chen Li-Yuan , Lappin Hallie , Vasconcelos Gabriel , Lita Adrian , Maric Dragan , Li Aiguo , Celiku Orieta , Zhang Wei , Meetze Kristan , Estok Thomas , Larion Mioara , Abu-Asab Mones , Zhuang Zhengping , Yang Chunzhang , Gilbert Mark R. , Wu Jing 
Published: December 2017

Abstract
Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become an effective therapeutic for GBM patients.
Experimental Design: To investigate TG02, an agent with known penetration of the blood–brain barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We used human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02. Mechanistic studies included TG02-induced transcriptional regulation, apoptosis, and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays.
Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of antiapoptotic proteins and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue.
Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Clin Cancer Res; 24(5); 1124–37. ©2017 AACR.