bluuebunny/crossref_metadata_2025_split huggingface dataset:
BtaE, an Adhesin That Belongs to the Trimeric Autotransporter Family, Is Required for Full Virulence and Defines a Specific Adhesive Pole of Brucella suis
Authors: Ruiz-Ranwez Verónica , Posadas Diana M. , Van der Henst Charles , Estein Silvia M. , Arocena Gastón M. , Abdian Patricia L. , Martín Fernando A. , Sieira Rodrigo , De Bolle Xavier , Zorreguieta Angeles 
Published: January 2013

ABSTRACT

Brucella
is responsible for brucellosis, one of the most common zoonoses worldwide that causes important economic losses in several countries. Increasing evidence indicates that adhesion of
Brucella
spp. to host cells is an important step to establish infection. We have previously shown that the BmaC unipolar monomeric autotransporter mediates the binding of
Brucella suis
to host cells through cell-associated fibronectin. Our genome analysis shows that the
B. suis
genome encodes several additional potential adhesins. In this work, we characterized a predicted trimeric autotransporter that we named BtaE. By expressing
btaE
in a nonadherent
Escherichia coli
strain and by phenotypic characterization of a
B. suis
Δ
btaE
mutant, we showed that BtaE is involved in the binding of
B. suis
to hyaluronic acid. The
B. suis
Δ
btaE
mutant exhibited a reduction in the adhesion to HeLa and A549 epithelial cells compared with the wild-type strain, and it was outcompeted by the wild-type strain in the binding to HeLa cells. The knockout
btaE
mutant showed an attenuated phenotype in the mouse model, indicating that BtaE is required for full virulence. BtaE was immunodetected on the bacterial surface at one cell pole. Using old and new pole markers, we observed that both the BmaC and BtaE adhesins are consistently associated with the new cell pole, suggesting that, in
Brucella
, the new pole is functionally differentiated for adhesion. This is consistent with the inherent polarization of this bacterium, and its role in the invasion process.
Influenza-Induced Inflammation Drives Pneumococcal Otitis Media
Authors: Short Kirsty R. , Reading Patrick C. , Brown Lorena E. , Pedersen John , Gilbertson Brad , Job Emma R. , Edenborough Kathryn M. , Habets Marrit N. , Zomer Aldert , Hermans Peter W. M. , Diavatopoulos Dimitri A. , Wijburg Odilia L. 
Published: January 2013

ABSTRACT

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium
Streptococcus pneumoniae
(the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.
Chlamydia trachomatis Plasmid-Encoded Pgp4 Is a Transcriptional Regulator of Virulence-Associated Genes
Authors: Song Lihua , Carlson John H. , Whitmire William M. , Kari Laszlo , Virtaneva Kimmo , Sturdevant Daniel E. , Watkins Heather , Zhou Bing , Sturdevant Gail L. , Porcella Stephen F. , McClarty Grant , Caldwell Harlan D. 
Published: January 2013

ABSTRACTChlamydia trachomatiscauses chronic inflammatory diseases of the eye and genital tract and has global medical importance. The chlamydial plasmid plays an important role in the pathophysiology of these diseases, as plasmid-deficient organisms are highly attenuated. The cryptic plasmid carries noncoding RNAs and eight conserved open reading frames (ORFs). To understand plasmid gene function, we generated plasmid shuttle vectors with deletions in each of the eight ORFs. The individual deletion mutants were used to transform chlamydiae and the transformants were characterized phenotypically and at the transcriptional level. We show thatpgp1, -2, -6, and -8are essential for plasmid maintenance, while the other ORFs can be deleted and the plasmid stably maintained. We further show that apgp4knockout mutant exhibits anin vitrophenotype similar to its isogenic plasmidless strain, in terms of abnormal inclusion morphology and lack of glycogen accumulation. Microarray and qRT-PCR analysis revealed that Pgp4 is a transcriptional regulator of plasmid-encodedpgp3and multiple chromosomal genes, including the glycogen synthase geneglgA, that are likely important in chlamydial virulence. Our findings have major implications for understanding the plasmid's role in chlamydial pathogenesis at the molecular level.
The Paint Pots, Kootenay National Park, Canada — a natural acid spring analogue for Mars
Authors: Grasby Stephen E. , Richards Barry C. , Sharp Christine E. , Brady Allyson L. , Jones Gareth M. , Dunfield Peter F. 
Published: January 2013

The Paint Pots are a natural Fe–SO4acid spring system along the Kicking Horse Rim, a major geological feature that has controlled fluid flow and mineralization over geologic time. The very low pH (∼3) and extremely high trace metal concentrations of the springs are anomalous and greatly exceed health limits (Zn = 35.8 mg/L, Pb = 0.461 mg/L, As = 82.7 ppb). Sulphur isotopes (δ34S and δ18O in sulphate equal to +11.4 and –12.1 ‰, respectively) are consistent with sulphide oxidation. Mass balance calculations indicate that the springs must have derived their acidity and metal content from natural weathering of a pyrite-rich ore deposit in the vicinity. Several ore deposit types occur along the Kicking Horse Rim, with the Mississippi Valley Type (MVT) style being the most consistent with the source of the spring waters. At the spring outlet, Fe-rich waters oxidize, forming large cone features of Fe–O precipitates, predominantly goethite. A diverse microbial community has been identified in the site that is distinct from those found at acid mine drainage sites. At one site, there was a high proportion of the bacterial candidate division WPS-2, the first time that this group has been detected as the predominant phylum in a community. Compared with anthropogenically influenced acid mine drainage sites that have been studied to date as Mars analogues, the unique uncultured organisms found in the Paint Pots provide a distinct analogue site that can offer insights into the diversity of extremophilic organisms in more natural environments.
Improving performance per watt of asymmetric multi-core processors via online program phase classification and adaptive core morphing
Authors: Rodrigues Rance , Annamalai Arunachalam , Koren Israel , Kundu Sandip 
Published: January 2013

Asymmetric multi-core processors (AMPs) have been shown to outperform symmetric ones in terms of performance and performance/watt. Improved performance and power efficiency are achieved when the program threads are matched to their most suitable cores. Since the computational needs of a program may change during its execution, the best thread to core assignment will likely change with time. We have, therefore, developed an online program phase classification scheme that allows the swapping of threads when the current needs of the threads justify a change in the assignment.
The architectural differences among the cores in an AMP can never match the diversity that exists among different programs and even between different phases of the same program. Consider, for example, a program (or a program phase) that has a high instruction-level parallelism (ILP) and will exhibit high power efficiency if executed on a powerful core. We can not, however, include such powerful cores in the designed AMP, since they will remain underutilized most of the time, and they are not power efficient when the programs do not exhibit a high degree of ILP. Thus, we must expect to see program phases where the designed cores will be unable to support the ILP that the program can exhibit. We, therefore, propose in this article a dynamic morphing scheme. This scheme will allow a core to gain control of a functional unit that is ordinarily under the control of a neighboring core during periods of intense computation with high ILP. This way, we dynamically adjust the hardware resources to the current needs of the application.
Our results show that combining online phase classification and dynamic core morphing can significantly improve the performance/watt of most multithreaded workloads.
Online thermal control methods for multiprocessor systems
Authors: Zanini Francesco , Atienza David , Jones Colin N. , Benini Luca , De Micheli Giovanni 
Published: January 2013

With technological advances, the number of cores integrated on a chip is increasing. This in turn is leading to thermal constraints and thermal design challenges. Temperature gradients and hotspots not only affect the performance of the system but also lead to unreliable circuit operation and affect the lifetime of the chip. Meeting temperature constraints and reducing hotspots are critical for achieving reliable and efficient operation of complex multi-core systems.
In this article, we analyze the use of four of the most promising families of online control techniques for thermal management of multiprocessors system-on-chip (MPSoC). In particular, in our exploration, we aim at achieving an online smooth thermal control action that minimizes the performance loss as well as the computational and hardware overhead of embedding a thermal management system inside the MPSoC. The definition of the optimization problem to tackle in this work considers the thermal profile of the system, its evolution over time, and current time-varying workload requirements. Thus, this problem is formulated as a finite-horizon optimal control problem, and we analyze the control features of different online thermal control approaches. In addition, we implemented the policies on an MPSoC hardware simulation platform and performed experiments on a cycle-accurate model of the eight-core Niagara multi-core architecture using benchmarks ranging from Web-accessing to playing multimedia. Results show different trade-offs among the analyzed techniques regarding the thermal profile, the frequency setting, the power consumption, and the implementation complexity.
Verification work reduction methodology in low-power chip implementation
Authors: Kurimoto Masanori , Yamamoto Takeshi , Nakano Satoshi , Hanami Atsuto , Kondo Hiroyuki 
Published: January 2013

In order to achieve satisfactory verification for complicated low-power demands in green products, we propose a verification work reduction methodology. It consists of three step, namely virtual, direct actual, and actual model simulations. Virtual low-power simulation inserts low-power cells, such as isolators or level shifters, virtually and simulates logical behavior for design under test (DUT) based on user-defined power mode. Direct actual low-power simulation replaces behavior models without non-logical pins for some of modules with actual models with non-logical pins, which are Vdd and Gnd, and simulates DUT in mixed level. Actual low-power simulation simulates DUT by using actual models with non-logical pins for all cells and hard macros. We introduce techniques which classify the type of the bugs on which we focus at each verification step and prevent the concerned bugs from leaking to the latter verification step as much as possible.
We applied our methodology to an actual chip and could reduce the total simulation period until tape-out by 38.8% and the total chip development period by 10%, compared with the conventional methodology.
FOXP3Regulates Sensitivity of Cancer Cells to Irradiation by Transcriptional Repression ofBRCA1
Authors: Li Weiquan , Katoh Hiroto , Wang Lizhong , Yu Xiaochun , Du Zhanwen , Yan Xiaoli , Zheng Pan , Liu Yang 
Published: January 2013

AbstractFOXP3 is an X-linked tumor suppressor gene and a master regulator in T regulatory cell function. This gene has been found to be mutated frequently in breast and prostate cancers and to inhibit tumor cell growth, but its functional significance in DNA repair has not been studied. We found that FOXP3 silencing stimulates homologous recombination-mediated DNA repair and also repair of γ-irradiation-induced DNA damage. Expression profiling and chromatin-immunoprecipitation analyses revealed that FOXP3 regulated the BRCA1-mediated DNA repair program. Among 48 FOXP3-regulated DNA repair genes, BRCA1 and 12 others were direct targets of FOXP3 transcriptional control. Site-specific interaction of FOXP3 with the BRCA1 promoter repressed its transcription. Somatic FOXP3 mutants identified in breast cancer samples had reduced BRCA1 repressor activity, whereas FOXP3 silencing and knock-in of a prostate cancer-derived somatic FOXP3 mutant increased the radioresistance of cancer cells. Together our findings provide a missing link between FOXP3 function and DNA repair programs. Cancer Res; 73(7); 2170–80. ©2012 AACR.
IFN-γ–Mediated Downregulation of LXA4 Is Necessary for the Maintenance of Nonresolving Inflammation and Papilloma Persistence
Authors: Wang Chunhui , Xiao Mingjie , Liu Xiaoman , Ni Chen , Liu Jianhong , Erben Ulrike , Qin Zhihai 
Published: January 2013

Abstract
Nonresolving inflammation is a hallmark of many types of tumors and the molecular mechanisms maintaining this inflammation are still largely unknown. In a two-stage carcinogenesis model, we observed here that the lack of IFN-γ receptor or neutralization of IFN-γ accelerated spontaneous papilloma regression in mice. The impaired maintenance of local inflammation was associated with reduced IFN-γ and enhanced biosynthesis of proresolution lipid mediator lipoxin A4 (LXA4). Interestingly, blocking LXA4 eliminated the effect of anti-IFN-γ, whereas treatment of mice with a therapeutic dose of LXA4 accelerated papilloma regression in an IFN-γ–independent manner. These results link for the first time a cytokine-dependent maintenance of inflammation with a downregulated production of proresolution lipid mediators. Strategies promoting spontaneous resolution of chronic inflammation by blocking IFN-γ and/or increasing LXA4 may be useful for the treatment of inflammation-associated tumors. Cancer Res; 73(6); 1742–51. ©2012 AACR.
mTOR Complex 2 Is Involved in Regulation of Cbl-Dependent c-FLIP Degradation and Sensitivity of TRAIL-Induced Apoptosis
Authors: Zhao Liqun , Yue Ping , Khuri Fadlo R. , Sun Shi-Yong 
Published: January 2013

Abstract
The mTOR positively regulates cell proliferation and survival through forming 2 complexes with raptor (mTOR complex 1; mTORC1) or rictor (mTOR complex 2; mTORC2). Compared with the mTORC1, relatively little is known about the biologic functions of mTORC2. This study focuses on addressing whether mTORC2 regulates apoptosis, particularly induced by TRAIL (TNFSF10). Using the mTOR kinase inhibitor, PP242, as a research tool, we found that it synergized with TRAIL to augment apoptosis of cancer cells. PP242 reduced the abundance of the short form of c-FLIP (FLIPS, CFLARS) and survivin (BIRC5). Enforced expression of ectopic FLIPS, but not survivin, attenuated augmented apoptosis induced by PP242 plus TRAIL. Thus, it is FLIPS downregulation that contributes to synergistic induction of apoptosis by PP242 plus TRAIL. PP242 decreased FLIPS stability, increased FLIPS ubiquitination, and facilitated FLIPS degradation. Moreover, knockdown of the E3 ligase Cbl (CBL) abolished PP242-induced FLIPS reduction. Thus, PP242 induces Cbl-dependent degradation of FLIPS, leading to FLIPS downregulation. Consistently, knockdown of rictor or mTOR, but not raptor, mimicked PP242 in decreasing FLIPS levels and sensitizing cells to TRAIL. Rictor knockdown decreased FLIPS stability, whereas enforced expression of rictor stabilized FLIPS. Moreover, silencing of Cbl abrogated FLIPS reduction induced by rictor knockdown. Collectively we conclude that it is mTORC2 inhibition that results in FLIPS downregulation and subsequent sensitization of TRAIL-induced apoptosis. Our findings provide the first evidence showing that mTORC2 stabilizes FLIPS, hence connecting mTORC2 signaling to the regulation of death receptor-mediated apoptosis. Cancer Res; 73(6); 1946–57. ©2012 AACR.
Lack of Estrogen Receptor-α Is Associated with Epithelial–Mesenchymal Transition and PI3K Alterations in Endometrial Carcinoma
Authors: Wik Elisabeth , Ræder Maria B. , Krakstad Camilla , Trovik Jone , Birkeland Even , Hoivik Erling A. , Mjos Siv , Werner Henrica M.J. , Mannelqvist Monica , Stefansson Ingunn M. , Oyan Anne M. , Kalland Karl H. , Akslen Lars A. , Salvesen Helga B. 
Published: January 2013

AbstractPurpose: We hypothesized that estrogen receptor-α (ER-α) status in endometrial carcinomas, associated with poor prognosis, is reflected in transcriptional signatures suggesting targets for new therapy.Experimental Design: Endometrial carcinoma samples in a primary investigation cohort (n = 76) and three independent validation cohorts (n = 155/286/111) were analyzed through integrated molecular profiling. Biomarkers were assessed by immunohistochemistry (IHC), DNA oligonucleotide microarray, quantitative PCR (qPCR), single-nucleotide polymorphism (SNP) array, and Sanger sequencing in the cohorts, annotated for comprehensive histopathologic and clinical data, including follow-up.Results: ER-α immunohistochemical staining was strongly associated with mRNA expression of the receptor gene (ESR1) and patient survival (both P &lt; 0.001). ER-α negativity associated with activation of genes involved in Wnt-, Sonic Hedgehog-, and TGF-β signaling in the investigation cohort, indicating epithelial–mesenchymal transition (EMT). The association between low ER-α and EMT was validated in three independent datasets. Furthermore, phosphoinositide 3-kinase (PI3K) and mTOR inhibitors were among the top-ranked drug signatures negatively correlated with the ER-α–negative tumors. Low ER-α was significantly associated with PIK3CA amplifications but not mutations. Also, low ER-α was correlated to high expression of Stathmin, a marker associated with PTEN loss, and a high PI3K activation signature.Conclusion: Lack of ER-α in endometrial cancer is associated with EMT and reduced survival. We present a rationale for investigating ER-α's potential to predict response to PI3K/mTOR inhibitors in clinical trials and also suggest EMT inhibitors to ER-α–negative endometrial carcinomas. Clin Cancer Res; 19(5); 1094–105. ©2012 AACR.
Disparities in Revascularization Rates After Acute Myocardial Infarction Between Aboriginal and Non-Aboriginal People in Australia
Authors: Randall Deborah A. , Jorm Louisa R. , Lujic Sanja , O’Loughlin Aiden J. , Eades Sandra J. , Leyland Alastair H. 
Published: January 2013

Background—
This study examined revascularization rates after acute myocardial infarction (AMI) for Aboriginal and non-Aboriginal patients sequentially controlling for admitting hospital and risk factors.

Methods and Results—
Hospital data from the state of New South Wales, Australia (July 2000 through December 2008) were linked to mortality data (July 2000 through December 2009). The study sample were all people aged 25 to 84 years admitted to public hospitals with a diagnosis of AMI (n=59 282). Single level and multilevel Cox regression was used to estimate rates of revascularization within 30 days of admission. A third (32.9%) of Aboriginal AMI patients had a revascularization within 30 days compared with 39.7% non-Aboriginal patients. Aboriginal patients had a revascularization rate 37% lower than non-Aboriginal patients of the same age, sex, year of admission, and AMI type (adjusted hazard ratio, 0.63; 95% confidence interval, 0.57–0.70). Within the same hospital, however, Aboriginal patients had a revascularization rate 18% lower (adjusted hazard ratio, 0.82; 95% confidence interval, 0.74–0.91). Accounting for comorbidities, substance use and private health insurance further explained the disparity (adjusted hazard ratio, 0.96; 95% confidence interval, 0.87–1.07). Hospitals varied markedly in procedure rates, and this variation was associated with hospital size, remoteness, and catheterization laboratory facilities.

Conclusions—
Aboriginal Australians were less likely to have revascularization procedures after AMI than non-Aboriginal Australians, and this was largely explained by lower revascularization rates at the hospital of first admission for all patients admitted to smaller regional and rural hospitals, a higher comorbidity burden for Aboriginal people, and to a lesser extent a lower rate of private health insurance among Aboriginal patients.
Translating <i>natural selection</i>: true concept, but false term?
Authors: HOQUET Thierry 
Published: January 2013

This paper focuses on the translation of the term “natural selection” in some European languages (mostly French and German). It adopts a historical and philosophical perspective on the term “natural selection” to emphasize the power of words in science. Although natural selection is probably Darwin’s most significant contribution to the theory of evolution, the phrase itself has been strangely and largely neglected by historians. This paper tries to understand why Darwin maintained the term in spite of the considerable dispute which it provoked from 1859, when the Origin of Species was first published. Indeed, Darwin thought it useful since it is both a technical term and one that nicely encapsulates an analogy with the practice of breeders. However, what Darwin saw as linguistic and conceptual efficiency entailed great difficulties in translating the term, and also in understanding it—as is clearly evidenced by ever-recurring debates on the “agential” connotations of selection. Besides, processes of translation suggest that the phrase “natural selection” gained a technical value before its sense was fully understood and a general theory of natural selection was well established. The study of the French translation of “natural selection” leads to another important result. I claim that French breeders did not have the word sélection; and if they were actually “choosing” individuals for breeding and leading breeding experiments over several generations, the absence of the term is nonetheless indicative of important differences between the practices in France and in the United Kingdom. The case of Vilmorin’s method of “maddening” [“affolement”] is indicative of those different “philosophies of breeding”: although “affolement” is a choice of mates, it differs from selection as it is not the patient accumulation of minute variations in a definite direction but a perturbation of the organization as a whole.
The distinction between introduction of a new nomen and subsequent use of a previously introduced nomen in zoological nomenclature
Authors: DUBOIS Alain 
Published: January 2013

In order to avoid or at least reduce the number of mistakes and confusions due to the indiscriminate use of imprecise categories and terms which too often occur in publications dealing with zoological nomenclature, a precise terminology is provided for the distinction between different categories of terms designating the erection of new taxa and their subsequent modification, and the introduction of new nomina, their subsequent use or modification, and their replacement by other nomina.