bluuebunny/crossref_metadata_2025_split huggingface dataset:
Golden Pigment Production and Virulence Gene Expression Are Affected by Metabolisms in
Staphylococcus aureus
Authors: Lan Lefu , Cheng Alice , Dunman Paul M. , Missiakas Dominique , He Chuan 
Published: April 2010

ABSTRACT

The pathogenesis of staphylococcal infections is multifactorial. Golden pigment is an eponymous feature of the human pathogen
Staphylococcus aureus
that shields the microbe from oxidation-based clearance, an innate host immune response to infection. Here, we screened a collection of
S. aureus
transposon mutants for pigment production variants. A total of 15 previously unidentified genes were discovered. Notably, disrupting metabolic pathways such as the tricarboxylic acid cycle, purine biosynthesis, and oxidative phosphorylation yields mutants with enhanced pigmentation. The dramatic effect on pigment production seems to correlate with altered expression of virulence determinants. Microarray analysis further indicates that purine biosynthesis impacts the expression of ∼400 genes involved in a broad spectrum of functions including virulence. The purine biosynthesis mutant and oxidative phosphorylation mutant strains exhibit significantly attenuated virulence in a murine abscess model of infection. Inhibition of purine biosynthesis with a known small-molecule inhibitor results in altered virulence gene expression and virulence attenuation during infection. Taken together, these results suggest an intimate link between metabolic processes and virulence gene expression in
S. aureus
. This study also establishes the importance of purine biosynthesis and oxidative phosphorylation for
in vivo
survival.
Muropeptide Rescue in
Bacillus subtilis
Involves Sequential Hydrolysis by β-
N
-Acetylglucosaminidase and
N
-Acetylmuramyl-
l
-Alanine Amidase
Authors: Litzinger Silke , Duckworth Amanda , Nitzsche Katja , Risinger Christian , Wittmann Valentin , Mayer Christoph 
Published: April 2010

ABSTRACT

We identified a pathway in
Bacillus subtilis
that is used for recovery of
N
-acetylglucosamine (GlcNAc)-
N
-acetylmuramic acid (MurNAc) peptides (muropeptides) derived from the peptidoglycan of the cell wall. This pathway is encoded by a cluster of six genes, the first three of which are orthologs of
Escherichia coli
genes involved in
N
-acetylmuramic acid dissimilation and encode a MurNAc-6-phosphate etherase (MurQ), a MurNAc-6-phosphate-specific transcriptional regulator (MurR), and a MurNAc-specific phosphotransferase system (MurP). Here we characterized two other genes of this cluster. The first gene was shown to encode a cell wall-associated β-
N
-acetylglucosaminidase (NagZ, formerly YbbD) that cleaves the terminal nonreducing
N
-acetylglucosamine of muropeptides and also accepts chromogenic or fluorogenic β-
N
-acetylglucosaminides. The second gene was shown to encode an amidase (AmiE, formerly YbbE) that hydrolyzes the
N
-acetylmuramyl-
l
-Ala bond of MurNAc peptides but not this bond of muropeptides. Hence, AmiE requires NagZ, and in conjunction these enzymes liberate MurNAc by sequential hydrolysis of muropeptides. NagZ expression was induced at late exponential phase, and it was 6-fold higher in stationary phase. NagZ is noncovalently associated with lysozyme-degradable particulate material and can be released from it with salt. A
nagZ
mutant accumulates muropeptides in the spent medium and displays a lytic phenotype in late stationary phase. The evidence for a muropeptide catabolic pathway presented here is the first evidence for cell wall recovery in a Gram-positive organism, and this pathway is distinct from the cell wall recycling pathway of
E. coli
and other Gram-negative bacteria.
Identification of Novel Acetyltransferase Activity on the Thermostable Protein ST0452 from
Sulfolobus tokodaii
Strain 7
Authors: Zhang Zilian , Akutsu Jun-ichi , Kawarabayasi Yutaka 
Published: April 2010

ABSTRACT

A 401-residue-long protein, ST0452, has been identified from a thermophilic archaeon,
Sulfolobus tokodaii
strain 7, as a glucose-1-phosphate thymidylyltransferase (Glc-1-P TTase) homolog with a 170-residue-long extra C-terminus portion. Functional analyses of the ST0452 protein have confirmed that the protein possessed dual sugar-1-phosphate nucleotidylyltransferase (sugar-1-P NTase) activities. The 24 repeats of a signature motif sequence which has been found in bacterial acetyltransferases, (L/I/V)-(G/A/E/D)-XX-(S/T/A/V)-X, were detected at the C terminus of the ST0452 protein. This observation prompted our group to investigate the acetyltransferase activity of the ST0452 protein. Detection of the release of coenzyme A (CoA) from acetyl-CoA and the production of UDP-
N
-acetyl-
d
-glucosamine (UDP-GlcNAc) from glucosamine-1-phosphate (GlcN-1-P) and UTP in the presence of the ST0452 protein revealed that this protein possesses the GlcN-1-P-specific acetyltransferase activity. In addition, analyses of substrate specificity showed that acetyltransferase activity of the ST0452 protein is capable of catalyzing the change of galactosamine-1-phosphate (GalN-1-P) to
N
-acetyl-
d
-galactosamine-1-phosphate (GalNAc-1-P) as well as GlcN-1-P and that its sugar-1-P NTase activity is capable of producing UDP-GalNAc from GalNAc-1-P and UTP. This is the first report of a thermostable bifunctional enzyme with GalN-1-P acetyltransferase and GalNAc-1-P uridyltransferase activities. The observation reveals that the bacteria-type UDP-GlcNAc biosynthetic pathway from fructose-6-phospate is utilized in this archaeon and represents a novel biosynthetic pathway for producing UDP-GalNAc from GalN-1-P in this microorganism.
ArcB1, a Homolog of
Escherichia coli
ArcB, Regulates Dimethyl Sulfoxide Reduction in
Shewanella oneidensis
MR-1
Authors: Shroff Namita P. , Charania Moiz A. , Saffarini Daad A. 
Published: April 2010

ABSTRACT

Shewanella oneidensis
is a metal reducer that uses the cyclic AMP receptor protein, CRP, to regulate anaerobic respiration. In addition, ArcA

So

is required for anaerobic growth with dimethyl sulfoxide (DMSO) and plays a role in aerobic respiration. The sensor kinase that activates ArcA

So

in
S. oneidensis
is not known. ArcB1

So

, a homolog of the
Escherichia coli
sensor kinase ArcB

Ec

, was identified and found to be required for DMSO reductase gene expression. In combination with HptA, ArcB1

So

complemented an

E. coli arcB
Ec

mutant. ArcA

So

, ArcB1

So

, and HptA appear to constitute a two-component signal transduction system that regulates DMSO reduction in
S. oneidensis
.
RELATIONS BETWEEN MULTIPLICITY AND DIVISOR CLASS GROUP FOR RATIONAL SURFACE SINGULARITIES
Authors: GURJAR R. V. , WAGH VINAY 
Published: April 2010

In this paper we prove that a rational surface singularity with divisor class group ℤ/(2) is a rational double point. This generalizes a result by Brieskorn: if the divisor class group of a rational singularity is trivial then it is the E8 singularity [3]. We also prove several inequalities involving the integers e, δ, mi, [Formula: see text], where [Formula: see text] is the fundamental cycle. The proof of this result uses ideas from Minkowski's theory of reduction of positive-definite quadratic forms. We also give some interesting counterexamples to some of the related questions in this context.
The Proapoptotic Molecule BLID Interacts with Bcl-XL and Its Downregulation in Breast Cancer Correlates with Poor Disease-Free and Overall Survival
Authors: Broustas Constantinos G. , Ross Jeffrey S. , Yang Qifeng , Sheehan Christine E. , Riggins Rebecca , Noone Anne-Michelle , Haddad Bassem R. , Seillier-Moiseiwitsch Françoise , Kallakury Bhaskar V.S. , Haffty Bruce G. , Clarke Robert , Kasid Usha N. 
Published: April 2010

Abstract
Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.
Experimental Design: The interaction between BLID and Bcl-XL was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalin-fixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (&gt;85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years).
Results: BLID was found to interact with Bcl-XL, and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P &lt; 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P &lt; 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P &lt; 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002).
Conclusion: BLID is a new binding partner of Bcl-XL and a significant prognostic factor in breast cancer. Clin Cancer Res; 16(11); 2939–48. ©2010 AACR.
Inhibition of the PI3K Pathway: Hope We Can Believe in?
Authors: van der Heijden Michiel S. , Bernards René 
Published: April 2010

Abstract
The phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly activated pathways in human cancer and has roles in cell proliferation, apoptosis, protein synthesis, and metabolism. The PI3K pathway can be activated by amplification or activating mutation of upstream receptor tyrosine kinases, and by mutations or deletions downstream in the pathway. Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), has been one of the most successful and most widely used targeted therapies. However, many HER2-positive cancers are not sensitive to HER2-based therapies or become resistant during treatment; downstream activation of the pathway is one of the causes of resistance. Because of the common activation of the PI3K pathway in cancer, compounds targeting proteins downstream in the pathway have been developed in recent years. The mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus have been shown to be beneficial in certain cancer types; many other inhibitors of the PI3K pathway are in various stages of clinical development. Ongoing research should clarify which molecular cancer subtypes are most susceptible to specific compounds and explore combinatorial approaches, ultimately leading to individualized patient treatment. Clin Cancer Res; 16(12); 3094–9. ©2010 AACR.
A Four-Kallikrein Panel Predicts Prostate Cancer in Men with Recent Screening: Data from the European Randomized Study of Screening for Prostate Cancer, Rotterdam
Authors: Vickers Andrew J. , Cronin Angel M. , Roobol Monique J. , Savage Caroline J. , Peltola Mari , Pettersson Kim , Scardino Peter T. , Schröder Fritz H. , Lilja Hans 
Published: April 2010

Abstract
Purpose: We have developed a statistical prediction model for prostate cancer based on four kallikrein markers in blood: total, free, and intact prostate-specific antigen (PSA), and kallikrein-related peptidase 2 (hK2). Although this model accurately predicts the result of biopsy in unscreened men, its properties for men with a history of PSA screening have not been fully characterized.
Experimental Design: A total of 1,501 previously screened men with elevated PSA underwent initial biopsy during rounds 2 and 3 of the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 388 cancers diagnosed. Biomarker levels were measured in serum samples taken before biopsy. The prediction model developed on the unscreened cohort was then applied and predictions compared with biopsy outcome.
Results: The previously developed four-kallikrein prediction model had much higher predictive accuracy than PSA and age alone (area under the curve of 0.711 versus 0.585, and 0.713 versus 0.557 with and without digital rectal exam, respectively; both P &lt; 0.001). Similar statistically significant enhancements were seen for high-grade cancer. Applying the model with a cutoff of 20% cancer risk as the criterion for biopsy would reduce the biopsy rate by 362 for every 1,000 men with elevated PSA. Although diagnosis would be delayed for 47 cancers, these would be predominately low-stage and low-grade (83% Gleason 6 T1c).
Conclusions: A panel of four kallikreins can help predict the result of initial biopsy in previously screened men with elevated PSA. Use of a statistical model based on the panel would substantially decrease rates of unnecessary biopsy. Clin Cancer Res; 16(12); 3232–9. ©2010 AACR.
Profits Without Honour? Economics, Theology and the Current Global Recession
Authors: Bradstock Andrew 
Published: April 2010

AbstractThis article argues that the global economic crisis which began in 2008 creates opportunity for a wide-ranging debate about how internal and international markets operate; a debate to which theology would have much to contribute. While on the one hand it is important to look at the factors behind the crisis with a view to preventing its repetition, of greater worth would be a conversation—involving all stakeholders—about the values that should underpin economic activity once the crisis has passed. This will involve asking questions about the fundamental purpose of market activity—is it simply to achieve ‘growth’ in GDP terms or, additionally, outcomes like ‘happiness’ and ‘well-being’—and exploring how markets can operate to strengthen societies and enable all to enjoy ‘fullness of life’.
Plurality and Peace: Inter-Religious Dialogue in a Creative Perspective
Authors: Illman Ruth 
Published: April 2010

AbstractWithin the research on inter-religious relations, dialogue is by tradition treated primarily as an intellectual challenge for political and religious leaders. The aim of this article is to show that this challenge is ethical and practical rather than merely theoretical in nature and to offer analytical reflections on the foundations of dignity in difference. The article focuses on Judaism, Christianity and Islam, treating dialogue and difference as complex questions of interpersonal relatedness. The article analyses creative forms of dialogue as an alternative to traditional rationally defined dialogue efforts. As an example, the groundbreaking work of the Spanish musician Jordi Savall is followed closely through an empirical analysis of his efforts to bring people of different faiths together in music—a ‘dialogue of souls’ engaging people deeply as unique, actively responsible, thinking and feeling individuals who manage to combine plurality and peace into a public theology.
Alzheimer’s and the Dementia of God
Authors: Kevern Peter 
Published: April 2010

AbstractRecent developments in the theory and practice of care for persons with dementia have reopened questions, traditionally explored by theologians, to do with the nature of personal identity and its dialectical relationship to social recognition. This new perspective on classical theological questions serves as a potential theological resource in contemporary western society, where God appears to have withdrawn from the prevailing public discourses. In this article, I explore the analogical potential of imagery of a ‘dementing God’, as a way to describe the contemporary experience of western Christians, to develop appropriate responses to the current climate in public theology and to continue to talk of God in public, while respecting Bonhoeffer’s desire to celebrate a secular world in which humanity may ‘come of age’.
Christianity’s Role in the Modernization and Revitalization of Korean Society in the Twentieth-Century
Authors: Kim Kirsteen 
Published: April 2010

AbstractThe development of South Korea and its growth to become the world’s eleventh largest economy has been accompanied by the introduction of Christianity and its increase to become the major religious group, to which nearly thirty per cent of the population are affiliated. This article probes the connection between these two spectacular examples of development; economic and religious. By highlighting moments or episodes of Christian contribution to aspects of development in Korean history and linking these to relevant aspects of Korean Christian theology, there is shown to be a constructive, although not always intentional, link between Korean Christianity and national development. The nature of the Christian contribution is seen not primarily in terms of the work ethic it engenders (as argued by Max Weber in the case of European capitalism) but mainly in the realm of aspirations (visions, hope) of a new society and motivation (inspiration, empowerment) to put them into effect. In other words, it was the public theology of Christianity that played a highly significant role in the modernization and revitalization of Korean society in the twentieth century.
The Limits of Supply Chain Responsibility: A Critical Analysis of Corporate Responsibility Instruments
Authors: Mares Radu 
Published: April 2010

AbstractOne challenge in the area of supply chain management has been achieving sustainable compliance with labour rights throughout the entire production chain, including lower tiers of production. This article inquires specifically around sub-contracting, especially what is a brand's or a buyer's responsibility regarding workers' rights beyond its first tier of suppliers. In-depth literature on this issue remains scarce despite buyer's responsibility being at the core of outsourcing, the very area that brought disrepute to Nike and thus moved corporate social responsibility (CSR) in the international limelight 15 years ago. This article reviews 12 prominent CSR instruments and asks: do they provide legitimacy to calls that buyers should be responsible for labour conditions down their supply chains? Where do these responsibilities end as abuses become more remote and take place at lower tiers of the value chain? What are the concepts, the principles that attribute responsibility to the buyer company and what concepts are used to limit these responsibilities? What strategies exist to improve conditions at sub-contractor level? Reading a dozen CSR instruments with a keen eye to sub-contracting reveals a staggering diversity of answers. The responsibility of the core company, particularly the limits of responsibility, move in and out of focus. Questions around buyers' responsibilities remain open, but there is a wealth of concepts and experience to draw upon. Professor Ruggie, a United Nations Special Representative of the Secretary General, could bring clarity in this area of CSR and is invited to reconsider the justification, scope and content of a buyer company's responsibility to protect workers' rights in its value chains.
The Principle of "Effectiveness" in the Recent Jurisprudence of the European Court of Human Rights: Its Different Dimensions and Its Consistency with Public International Law – No Need for the Concept of Treaty Sui Generis
Authors: Rietiker Daniel 
Published: April 2010

AbstractThe recent past has shown an ever-growing fragmentation of the international legal system where lawyers and judges are facing more and more the phenomenon of the same legal question being discussed in different fora. This is particularly the case in the field of human rights that entails the dispersal of responsibilities for interpretation of numerous instruments among various different judicial and quasi-judicial bodies, of both universal and regional nature. In order to secure coherence and legal certainty in the system, it is important to respect a set of principles and rules of general international law, in particular Articles 31–33 of the 1969 Vienna Convention of the Law of Treaties (VCLT). The first goal of this article is to analyse whether the Court applies the rules of the VCLT to the interpretation of the European Convention on Human Rights (ECHR). Secondly, assuming that the VCLT fully applies, it will be analysed whether Article 31(1) VCLT is flexible enough to allow nevertheless some leeway for the development of specificities, especially as a result of the particular nature of the ECHR. Thirdly, it will be shown that the Court has indeed developed a set of specific methods of interpretation, aiming to render the rights enshrined in the ECHR effective. From the author's point of view, they can all be regarded as sub-forms (or partial aspects) of the teleological interpretation. He distinguishes between four dimensions of the principle of "effectiveness".
What are the Objectives of International Criminal Procedure? – Reflections on the Fragmentation of a Legal Regime
Authors: Klamberg Mark 
Published: April 2010

AbstractInternational criminal courts pursue several objectives including retribution, deterrence, creating a historical record and giving a voice to the victims while the rights of the accused are protected. A problem is that these objectives pull in different directions creating tensions and fragmentation in the procedural system. Numerous legal issues, referred to as 'hard cases', entail a choice where the judge has to make a choice between two or several objectives. In the interest of legal certainty solutions should ultimately controlled by the law and not by the discretion of the judge. This article examines whether it is possible to identify a universally acceptable hierarchy of objectives. It is argued that the relevant objectives which determine the outcome of a hard case vary depending on the procedural stage and in each procedural stage there is a structural bias towards one or several objectives. Considering that law exists as a response to several social needs, it appears as unattainable to identify a universal and fixed hierarchy of objectives.
Implementation of the MARPOL Convention in Developing Countries
Authors: Karim Md. Saiful 
Published: April 2010

AbstractOver the years a large set of international conventions have been adopted under the auspices of the International Maritime Organization for prevention of vessel-source marine pollution. However, most of developing countries failed to effectively implement these conventions. Against this backdrop, this article aims to assess the inherent suitability of the MARPOL Convention for implementation in developing countries. It also examines the role of global community for effective implementation of the MARPOL Convention and identifies the legal and institutional bottlenecks in the current implementation regime.