bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Microarray-Based Identification of Different
mecA
Alleles in Staphylococci
Authors: Monecke Stefan , Müller Elke , Schwarz Stefan , Hotzel Helmut , Ehricht Ralf 
Published: August 2012

ABSTRACT

To screen isolates and to identify
mecA
alleles, published
mecA
sequences were analyzed, and a microarray for the rapid discrimination of
mecA
alleles was designed. A GenBank analysis yielded 135 full-length gene sequences annotated as
mecA
. These sequences clustered into 32 different alleles corresponding to 28 unique amino acid sequences and to 15 distinct hybridization patterns on this microarray. A collection of 78 clinical and veterinary isolates of
Staphylococcus
spp. was characterized using this assay. Nine of the 15 expected patterns, as well as one as-yet-unknown pattern, were identified. These patterns were detected in various epidemic methicillin-resistant
Staphylococcus aureus
strains, in
S. pseudintermedius
, and in coagulase-negative species such as
S. epidermidis
,
S. fleurettii
, or
S. haemolyticus
. There was no correlation between the different
mecA
hybridization patterns and the SCC
mec
type. Determination of MICs showed that
mecA
alleles corresponding to only four of these nine patterns were associated with β-lactam resistance. The
mecA
alleles that did not confer β-lactam resistance were largely restricted to coagulase-negative staphylococci of animal origin, such as
S. sciuri
and
S. vitulinus
. Because of the diversity of sequences and the different impact on β-lactam susceptibility, the existence of different
mecA
alleles needs to be taken into account when designing diagnostic assays for the detection of
mecA
.
The Putative Lactococcal Extracytoplasmic Function Anti-Sigma Factor Llmg2447 Determines Resistance to the Cell Wall-Active Bacteriocin Lcn972
Authors: Roces Clara , Pérez Verónica , Campelo Ana B. , Blanco Diego , Kok Jan , Kuipers Oscar P. , Rodríguez Ana , Martínez Beatriz 
Published: August 2012

ABSTRACT

Lactococcin 972 (Lcn972) is a cell wall-active bacteriocin that inhibits cell wall biosynthesis in
Lactococcus lactis
. In this work, the transcriptomes of the Lcn972-resistant (Lcn
r
) mutant
L. lactis
D1 and its parent strain were compared to identify factors involved in Lcn972 resistance. Upregulated genes included members of the cell envelope stress (CesSR) regulon, the penicillin-binding protein
pbpX
gene and gene
llmg2447
, which may encode a putative extracytoplasmic function (ECF) anti-sigma factor. The gene
llmg2447
is located downstream of the nonfunctional ECF gene

sigX
pseudo

. Nisin-controlled expression of
llmg2447
led to high Lcn972 resistance in
L. lactis
, with no cross-resistance to other cell wall-active antimicrobials. Upregulation of
llmg2447
in
L. lactis
D1 (Lcn
r
) was linked to the integration of insertion element IS
981
into the
llmg2447
promoter region, replacing the native −35 box and activating the otherwise silent promoter P

2447

. This is the first example of an orphan ECF anti-sigma factor involved in bacteriocin resistance. This new role in neutralizing cell wall-active compounds (e.g., Lcn972) could have evolved from a putative primary function of Llmg2447 in sensing cell envelope stress.
Trichinella spiralis Secreted Enzymes Regulate Nucleotide-Induced Mast Cell Activation and Release of Mouse Mast Cell Protease 1
Authors: Afferson Holly C. , Eleftheriou Emily , Selkirk Murray E. , Gounaris Kleoniki 
Published: August 2012

ABSTRACT

Extracellular nucleotides are important triggers of innate immunity, acting on a wide variety of cells via signaling through purinergic receptors. Mucosal mast cells contribute to expulsion of a number of gastrointestinal nematode parasites, and mouse mast cell protease 1 has been shown to have a critical role in clearance of
Trichinella spiralis
from the intestinal tract. We show here that adenosine, ADP, ATP, UDP, and UTP all stimulate calcium mobilization in bone marrow-derived mast cells with a mucosal phenotype. Secreted proteins from
T. spiralis
infective larvae inhibit nucleotide-induced mast cell activation, and that induced by ADP and UDP is specifically blocked by parasite secretory 5′-nucleotidase. Release of mouse mast cell protease 1 is stimulated by ADP and ATP. Both parasite secreted products and the 5′-nucleotidase inhibit ADP-induced release of mast cell protease, whereas that stimulated by ATP is partially inhibited by secreted products alone. This indicates that the 5′-nucleotidase contributes to but is not solely responsible for inhibition of nucleotide-mediated effects on mast cell function. Secretion of nucleotide-metabolizing enzymes by parasitic nematodes most likely evolved as a strategy for suppression of innate immune responses and is discussed in this context.
Role of Interleukin-32 in Helicobacter pylori-Induced Gastric Inflammation
Authors: Sakitani Kosuke , Hirata Yoshihiro , Hayakawa Yoku , Serizawa Takako , Nakata Wachiko , Takahashi Ryota , Kinoshita Hiroto , Sakamoto Kei , Nakagawa Hayato , Akanuma Masao , Yoshida Haruhiko , Maeda Shin , Koike Kazuhiko 
Published: August 2012

ABSTRACTHelicobacter pyloriinfection is associated with gastritis and gastric cancer. AnH. pylorivirulence factor, thecagpathogenicity island (PAI), is related to host cell cytokine induction and gastric inflammation. Since elucidation of the mechanisms of inflammation is important for therapy, the associations between cytokines and inflammatory diseases have been investigated vigorously. Levels of interleukin-32 (IL-32), a recently described inflammatory cytokine, are increased in various inflammatory diseases, such as rheumatoid arthritis and Crohn's disease, and in malignancies, including gastric cancer. In this report, we examined IL-32 expression in human gastric disease. We also investigated the function of IL-32 in activation of the inflammatory cytokines in gastritis. IL-32 expression paralleled human gastric tissue pathology, with low IL-32 expression inH. pylori-uninfected gastric mucosa and higher expression levels in gastritis and gastric cancer tissues.H. pyloriinfection increased IL-32 expression in human gastric epithelial cell lines.H. pylori-induced IL-32 expression was dependent on the bacterialcagPAI genes and on activation of nuclear factor κB (NF-κB). IL-32 expression induced byH. pyloriwas not detected in the supernatant of AGS cells but was found in the cytosol. Expression of theH. pylori-induced cytokines CXCL1, CXCL2, and IL-8 was decreased in IL-32-knockdown AGS cell lines compared to a control AGS cell line. We also found that NF-κB activation was decreased inH. pylori-infected IL-32-knockdown cells. These results suggest that IL-32 has important functions in the regulation of cytokine expression inH. pylori-infected gastric mucosa.
Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae
Authors: Reeves Angela E. , Koenigsknecht Mark J. , Bergin Ingrid L. , Young Vincent B. 
Published: August 2012

ABSTRACT

The indigenous microbial community of the gastrointestinal (GI) tract determines susceptibility to
Clostridium difficile
colonization and disease. Previous studies have demonstrated that antibiotic-treated mice challenged with
C. difficile
either developed rapidly lethal
C. difficile
infection or were stably colonized with mild disease. The GI microbial community of animals with mild disease was dominated by members of the bacterial family
Lachnospiraceae
, while the gut community in moribund animals had a predominance of
Escherichia coli
. We investigated the roles of murine
Lachnospiraceae
and
E. coli
strains in colonization resistance against
C. difficile
in germfree mice. Murine
Lachnospiraceae
and
E. coli
isolates were cultured from wild-type mice. The ability of each of these isolates to interfere with
C. difficile
colonization was tested by precolonizing germfree mice with these bacteria 4 days prior to experimental
C. difficile
challenge. Mice precolonized with a murine
Lachnospiraceae
isolate, but not those colonized with
E. coli
, had significantly decreased
C. difficile
colonization, lower intestinal cytotoxin levels and exhibited less severe clinical signs and colonic histopathology. Infection of germfree mice or mice precolonized with
E. coli
with
C. difficile
strain VPI 10463 was uniformly fatal by 48 h, but only 20% mortality was seen at 2 days in mice precolonized with the
Lachnospiraceae
isolate prior to challenge with VPI 10463. These findings confirm that a single component of the GI microbiota, a murine
Lachnospiraceae
isolate, could partially restore colonization resistance against
C. difficile
. Further study of the members within the
Lachnospiraceae
family could lead to a better understanding of mechanisms of colonization resistance against
C. difficile
and novel therapeutic approaches for the treatment and prevention of
C. difficile
infection.
Photometry of dayside auroras during solar minimum 1This article is part of a Special issue that honours the work of Dr. Donald M. Hunten FRSC who passed away in December 2010 after a very illustrious career.
Authors: McEwen D.J. , Sivjee G.G. 
Published: August 2012

An examination is made of Antarctic dayside auroras to establish how they relate to solar wind strength under the quiet conditions of the recent extended solar minimum when the solar wind pressure was weak and the interplanetary magnetic field Bz is small. It is found that, during the many days of observation, the aurora is detected even with the most stable and quiet conditions. On such occasions the 630 nm OI emission can be as low as 50 R, but is unambiguously and continuously detectable through each noon. This is above an airglow intensity of about 30 R. For these quiet conditions there is no evident relation between the solar wind dynamic pressure or interplanetary magnetic field Bz and dayside auroral intensity. This suggests that there is no effective reconnection under these minimal conditions and the particle source for the dayside aurora could be within the magnetosphere.
Saturn upper atmospheric structure from Cassini EUV and FUV occultations 1This article is part of a Special Issue that honours the work of Dr. Donald M. Hunten FRSC who passed away in December 2010 after a very illustrious career.
Authors: Shemansky D.E. , Liu X. 
Published: August 2012

Stellar occultations of the Saturn atmosphere using the Cassini ultraviolet imaging spectrograph (UVIS) experiment have provided vertical structure at a range of latitudes. The transmission spectra in the extreme–far ultraviolet (EUV–FUV) range allow extraction of vertical profiles of H2 and hydrocarbon abundances from the top of the atmosphere to about 300 km above the 1 bar (1 bar = 100 kPa) pressure level. A reanalysis of the Voyager 2 δSco occultation in 1981 is consistent with the original report. The hydrocarbon homopause is near a pressure of 0.2 μbar in the UVIS analysis, compared to ∼0.01 μbar obtained from the Voyager occultation. Measured hydrocarbon abundances are obtained in the pressure range 600–0.1 μbar in the Cassini UVIS experiment. The combined UVIS results provide evidence for significant latitudinal dependence of vertical temperature profile. The confinement of the hydrocarbons in the current observations compared to published models and the Voyager ultraviolet spectrograph (UVS) results at solar maximum, infer smaller eddy diffusion coefficients in this epoch. Model calculations indicate that the latitudinal dependence of H2 vertical displacements is caused primarily by the combined effects of gravitational potential and evident differences in electron energy deposition at the top of the atmosphere affecting the temperature profile. The derived H2 density profiles from ~–40° latitude and others close to the equator, are found to be nearly identical on a pressure scale below the exobase. The inference is that that the pressure profile of H2 density at Saturn is unchanged over a broad range of latitudes.
The lunar sodium atmosphere: April–May 1998 1This article is part of a Special Issue that honours the work of Dr. Donald M. Hunten FRSC who passed away in December 2010 after a very illustrious career.
Authors: Sprague A.L. , Sarantos M. , Hunten D.M. , Hill R.E. , Kozlowski R.W.H. 
Published: August 2012

Atmospheric sodium at the Moon was observed for altitudes from the ground up to 1800 km from 18 April to 13 May 1998, a period including an entire lunar month. Because of bad weather, coverage was incomplete but we present the analysis of 36 spectra largely from near first and third quarter phases and passage through full moon. The apparatus used was the specially built clear aperture 16.5 cm, 203 cm focal length, Mt. Lemmon Lunar Coronagraph on Mt. Lemmon in the Catalina Mountains of Tucson, Arizona. Data are interpreted in terms of Chamberlain fits to the observed emission rate using both one equivalent temperature and two source components (with both cold and hot density distributions). The extent and equivalent temperatures of the exosphere during this period trended towards an extended coma with very little fraction in the thermally accommodated regime, even near the surface. Preliminary data–model comparisons suggest that these measurements are consistent with rates and spatial distributions expected from a photon-stimulated desorption source, although evidence for one, or possibly two, periods of notable meteoroid impact source might be present. A compilation of new and previously published observations illustrates an increased emission by sodium at third quarter over that of first quarter, a result that suggests that the dayside exospheric content increases, at least occasionally, following transit of the Moon through the Earth’s magnetosphere.
The O2(b1Σ) dayglow emissions: application to middle and upper atmosphere remote sensing 1This article is part of a Special issue that honours the work of Dr. Donald M. Hunten FRSC who passed away in December 2010 after a very illustrious career.
Authors: Yee Jeng-Hwa , DeMajistre R. , Morgan F. 
Published: August 2012

The O2 atmospheric band transition is observed in the altitude region between ∼40 and 200 km in the dayglow and between ∼80 and 100 km in the nightglow. Wallace and Hunten (J. Geophys. Res. 73, 4813 (1968)) presented the first detailed analysis of the sources and sinks of this O2 airglow emitting state. Because of its extended altitude coverage, bright signal, and spectral and photometric properties, this emission provides an important means to remotely sense the thermal, dynamical, and compositional structures of the upper atmosphere. In this paper we present a photochemical and emission–absorption model that calculates the spectral brightnesses of the four brightest vibrational manifolds of this band system that, for the first time, extends from the mesosphere to the thermosphere. This model incorporates the latest rate constants, cross sections, and spectral parameters relevant to this emission, some of which were not considered in previous remote sensing retrieval applications. The model results are compared with our previous rocket experiments to assess the utility of this emission for upper atmospheric remote sensing and to identify key future measurement challenges. This model, together with improved instrument capabilities, permits us to study the atmosphere from 40 up to 200 km, a region where the strongest coupling between the lower atmosphere and upper atmosphere occurs.
Hypoxia-Induced Gene Expression in Chemoradioresistant Cervical Cancer Revealed by Dynamic Contrast-Enhanced MRI
Authors: Halle Cathinka , Andersen Erlend , Lando Malin , Aarnes Eva-Katrine , Hasvold Grete , Holden Marit , Syljuåsen Randi G. , Sundfør Kolbein , Kristensen Gunnar B. , Holm Ruth , Malinen Eirik , Lyng Heidi 
Published: August 2012

Abstract
Knowledge of the molecular background of functional magnetic resonance (MR) images is required to fully exploit their potential in cancer management. We explored the prognostic impact of dynamic contrast-enhanced MR imaging (DCE-MRI) parameters in cervical cancer combined with global gene expression data to reveal their underlying molecular phenotype and construct a representative gene signature for the relevant parameter. On the basis of 78 patients with cervical cancer subjected to curative chemoradiotherapy, we identified the prognostic DCE-MRI parameter ABrix by pharmacokinetic analysis of pretreatment images based on the Brix model, in which tumors with low ABrix appeared to be most aggressive. Gene set analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to other tumor phenotypes were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including both targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response, were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. On the basis of the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Our findings reveal the molecular basis of an aggressive hypoxic phenotype and suggest the use of DCE-MRI to noninvasively identify patients with hypoxia-related chemoradioresistance. Cancer Res; 72(20); 5285–95. ©2012 AACR.
Secreted Protein Acidic and Rich in Cysteines-like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers
Authors: Hu Hanguang , Zhang Hang , Ge Weiting , Liu Xiyong , Loera Sofia , Chu Peiguo , Chen Huarong , Peng Jiaping , Zhou Lun , Yu Shujing , Yuan Ying , Zhang Suzhan , Lai Lily , Yen Yun , Zheng Shu 
Published: August 2012

Abstract
Purpose: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is an extracellular matrix glycoprotein with malignancy-suppressing potential. The hypothesis that SPARCL1 reduces cancer invasiveness and predicts better survival in colorectal cancers (CRC) was investigated.
Experimental Design: Stable SPARCL1 transfectants, RKO-SPARCL1, and corresponding vector control were constructed and implanted into nude mice to generate a mouse xenograft model of liver metastasis. Also, a retrospective outcome study was conducted on the COH set (222 CRCs) and ZJU set (412 CRCs). The protein expression level of SPARCL1 was determined by immunohistochemistry. The Kaplan–Meier and Cox analyses were used for survival analysis. The association of SPARCL1 with mesenchymal–epithelial transition (MET) was examined by reverse transcription PCR (RT-PCR) and Western blot analysis.
Results: The ectopic expression of SPARCL1 significantly reduced the potential for anchorage-independent growth, migration, invasion and induced cell differentiation in RKO and SW620 cells. In mouse xenograft model, the expression of SPARCL1 significantly reduced the liver metastasis (P &lt; 0.01). The patient-based studies revealed that the expression of SPARCL1 was related to better differentiation (P &lt; 0.01), less lymph node involvement [OR, 0.67; 95% confidence interval (CI), 0.45–1.00], and less distant metastasis (OR, 0.38; 95% CI, 0.18–0.79). The Kaplan–Meier and Cox analysis showed that the expression of SPARCL1 was associated with better overall survival (log-rank: P &lt; 0.01; HR, 0.57; 95% CI, 0.39–0.84). Transfection of SPARCL1 induced MET of colon cancer cells.
Conclusion: SPARCL1 functions as a tumor suppressor promoting differentiation possibly via MET, which inhibits the aggressiveness of CRCs. Clin Cancer Res; 18(19); 5438–48. ©2012 AACR.
The Inhibitor of Histone Deacetylases Sodium Butyrate Enhances the Cytotoxicity of Mitomycin C
Authors: Gospodinov Anastas , Popova Stanislava , Vassileva Ivelina , Anachkova Boyka 
Published: August 2012

AbstractThe use of histone deacetylase inhibitors has been proposed as a promising approach to increase the cell killing effect of DNA damage–inducing drugs in chemotherapy. However, the molecular mechanism of their action remains understudied. In the present article, we have assessed the effect of the histone deacetylase inhibitor sodium butyrate on the DNA damage response induced by the crosslinking agent mitomycin C. Sodium butyrate increased mitomycin C cytotoxicity, but did not impair the repair pathways required to remove mitomycin C-induced lesions as neither the rate of nucleotide excision repair nor the homologous recombination repair rate were diminished. Sodium butyrate treatment abrogated the S-phase cell-cycle checkpoint in mitomycin C-treated cells and induced the G2–M checkpoint. However, sodium butyrate treatment alone resulted in accumulation of reactive oxygen species, double-strand breaks in DNA, and apoptosis. These results imply that the accumulation of reactive oxygen species–mediated increase in DNA lesion burden may be the major mechanism by which sodium butyrate enhances the cytotoxicity of mitomycin C. Mol Cancer Ther; 11(10); 2116–26. ©2012 AACR.
Active Efflux of Dasatinib from the Brain Limits Efficacy against Murine Glioblastoma: Broad Implications for the Clinical Use of Molecularly Targeted Agents
Authors: Agarwal Sagar , Mittapalli Rajendar K. , Zellmer David M. , Gallardo Jose L. , Donelson Randy , Seiler Charlie , Decker Stacy A. , SantaCruz Karen S. , Pokorny Jenny L. , Sarkaria Jann N. , Elmquist William F. , Ohlfest John R. 
Published: August 2012

Abstract
The importance of the blood–brain barrier in preventing effective pharmacotherapy of glioblastoma has been controversial. The controversy stems from the fact that vascular endothelial cell tight junctions are disrupted in the tumor, allowing some systemic drug delivery. P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) efflux drugs from brain capillary endothelial cells into the blood. We tested the hypothesis that although the tight junctions are “leaky” in the core of glioblastomas, active efflux limits drug delivery to tumor-infiltrated normal brain and consequently, treatment efficacy. Malignant gliomas were induced by oncogene transfer into wild-type (WT) mice or mice deficient for Pgp and BCRP (knockout, KO). Glioma-bearing mice were orally dosed with dasatinib, a kinase inhibitor and dual BCRP/PgP substrate that is being currently tested in clinical trials. KO mice treated with dasatinib survived for twice as long as WT mice. Microdissection of the tumor core, invasive rim, and normal brain revealed 2- to 3-fold enhancement in dasatinib brain concentrations in KO mice relative to WT. Analysis of signaling showed that poor drug delivery correlated with the lack of inhibition of a dasatinib target, especially in normal brain. A majority of human glioma xenograft lines tested expressed BCRP or PgP and were sensitized to dasatinib by a dual BCRP/Pgp inhibitor, illustrating a second barrier to drug delivery intrinsic to the tumor itself. These data show that active efflux is a relevant obstacle to treating glioblastoma and provide a plausible mechanistic basis for the clinical failure of numerous drugs that are BCRP/Pgp substrates. Mol Cancer Ther; 11(10); 2183–92. ©2012 AACR.