bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Devil's Advocate: Secular Arguments Diminish both Implicit and Explicit Religious Belief
Authors: Shariff Azim F. , Cohen Adam B. , Norenzayan Ara 
Published: September 2008

AbstractThe religion-science debate has heated up in recent years, with polemical
arguments on both side decrying the other. Given that the dominant view is
of religiousness as a relatively fixed personality trait, all of this furor
seems excessive. Interested in just how malleable religiousness is, we
exposed half of our participants to an argument against the existence of God
by Richard Dawkins. Those exposed to Dawkins' arguments showed lower
self-reported religiousness, as well as less implicit association between
religion and truth. These results demonstrate the flexibility of trait
religiousness.
Recent Revisions to Commercial Agency Law in the United Arab Emirates
Authors: Stovall Howard 
Published: September 2008

AbstractThe United Arab Emirates—despite its general reputation for free trade and limited government regulation of business—has had (for over two decades) the most onerous 'dealer protection' law in the Middle East.Very recently, however, pro-competition (or anti-monopoly) sentiment within certain UAE government circles resulted in enactment of a new federal law and two UAE Ministry of Economy resolutions that collectively reflect a weakening of those dealer protections. For example, Minister of Economy Sheikha Lubna Al Qasimi observed:The new amendments will certainly boost the competitive economic climate in the UAE…. This law was promulgated out of the desire to enhance and maintain stability in prices and ensure that agencies are not manipulated to increase prices.The following summary highlights some of the more significant aspects of current UAE commercial agency law, including a look at those recent amendments. (I have prepared an English translation of the UAE Commercial Agency Law, including the 2006 amendments, listed as Appendix 1 at the end of this article.)
Arbitration in Yemen
Authors: Kambeck Jens 
Published: September 2008

AbstractThe Human Development Index (HDI, 2005) ranked Yemen 151st out of 177 countries. Although it is one of the poorest countries in world, the population of 21.4 million people is the highest in all Arab countries and it is expected to double within the next 20 years. This makes it an interesting and growing market—and one in which international companies are presently investigating opportunities. The Yemeni legal system, although having improved in recent years, is still not capable of making and executing fair legal decisions, by international standards. In this environment, national and international trade requires alternatives for legal decision-making. In response to this, two arbitration centres are currently operating in Yemen and offer businesspeople an alternative to court based adjudication. As Yemen attempts to become a member of the WTO and tries to create a investment-friendly atmosphere, arbitration can be a very important alternative for providing legal certainty as the court system continues to develop towards international standards.
Blue Rubber Bleb Nevus Syndrome
Authors: Having Karen , Bullock Stephani 
Published: September 2008

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by the presence of cutaneous and gastrointestinal (GI) hemangiomas. These BRBNS-associated hemangiomas, possibly numbering into the hundreds, may also be identified in multiple visceral locations. Although the presence of benign cutaneous lesions is of small concern, GI lesions are cause for bleeding. Heavy visceral organ involvement can lead to intravascular coagulation, consumptive coagulathopy, and organ failure. Therefore, GI-related complaints, anemia, the visual identification of a cutaneous blue-colored lesion located on the upper extremity or trunk, and multiple visceral hemangiomas involving a large portion of the organ may indicate the presence of BRBNS. It is important that this unusual combination of patient signs, symptoms, and sonographic findings be presented to the interpreting physician to facilitate inclusion of this rare condition as a possible differential diagnosis to be considered.
A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T cells and participates to cytotoxic granule secretion
Authors: Ménasché Gaël , Ménager Mickaël M. , Lefebvre Juliette M. , Deutsch Einat , Athman Rafika , Lambert Nathalie , Mahlaoui Nizar , Court Magali , Garin Jérôme , Fischer Alain , de Saint Basile Geneviève 
Published: September 2008

Abstract
Cytotoxic T lymphocytes (CTLs) and natural killer cells help control infections and tumors via a killing activity that is mediated by the release of cytotoxic granules. Granule secretion at the synapse formed between the CTL and the target cell leads to apoptosis of the latter. This process involves polarization of the CTL's secretory machinery and cytotoxic granules. The small GTPase Rab27a and the hMunc13-4 protein have been shown to be required for both granule maturation and granule docking and priming at the immunologic synapse. Using a tandem affinity purification technique, we identified a previously unknown hematopoietic form of Slp2a (Slp2a-hem) and determined that it is a specific effector of the active form of Rab27a. This interaction occurs in vivo in primary CTLs. We have shown that (1) Rab27a recruits Slp2a-hem on vesicular structures in peripheral CTLs and (2) following CTL-target cell conjugate formation, the Slp2a-hem/Rab27a complex colocalizes with perforin-containing granules at the immunologic synapse, where it binds to the plasma membrane through its C2 domains. The overexpression of a dominant-negative form of Slp2a-hem markedly impaired exocytosis of cytotoxic granules—indicating that Slp2a is required for cytotoxic granule docking at the immunologic synapse.
Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors
Authors: Brody Joshua D. , Goldstein Matthew J. , Czerwinski Debra K. , Levy Ronald 
Published: September 2008

Abstract
Ex vivo–expanded tumor-infiltrating lymphocytes infused into lymphodepleted recipients has clear antitumor efficacy. More practical sources of such antitumor lymphocytes would broaden the application of this approach. Previously, we described an in situ vaccination combining chemotherapy with intratumoral injection of CpG-enriched oligonucleotides, which induced T-cell immunity against established lymphoma. An ongoing clinical trial of this maneuver has demonstrated clinical responses in lymphoma patients. Here, we use this vaccine maneuver to generate immune cells for transfer into irradiated, syngeneic recipients. Transferred tumor-specific T-effector (Teff) cells preferentially expanded, increasing the Teff/T-regulatory (Treg) ratio in these “immunotransplantation” recipients and curing large and metastatic tumors. Donor T cells were necessary for tumor protection, and CD8 T-cell immune responses were enhanced by posttransplantation booster vaccination. Hematopoietic stem cell transplantation is a standard therapy for lymphoma. Therefore, in situ tumor vaccination followed by immunotransplantation of harvested tumor-specific T cells could be directly tested in clinical trials to treat otherwise resistant malignancies.
In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1
Authors: Río Paula , Meza Néstor W. , González-Murillo África , Navarro Susana , Álvarez Lara , Surrallés Jordi , Castella Maria , Guenechea Guillermo , Segovia José C. , Hanenberg Helmut , Bueren Juan A. 
Published: September 2008

AbstractFanconi anemia (FA) is an inherited recessive DNA repair disorder mainly characterized by bone marrow failure and cancer predisposition. Studies in mosaic FA patients have shown that reversion of one inherited germ-line mutation resulting in a functional allele in one or a few hematopoietic stem cells (HSCs) can lead to the proliferation advantage of corrected cells, thus over time normalizing the hematologic status of the patient. In contrast to these observations, it is still unclear whether ex vivo genetic correction of FA HSCs also provides a similar proliferation advantage to FA HSCs. Using an FA mouse model with a marked hematopoietic phenotype, the FA-D1 (Brca2Δ27/Δ27) mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results in the progressive expansion of genetically corrected clones in mild-conditioned FA-D1 recipients. Consistent with these data, hematopoietic progenitors from FA recipients progressively became mitomycin C resistant and their chromosomal instability was reverted. No evidence of myelodysplasia, leukemias, or abnormal clonal repopulation was observed at multiple time points in primary or secondary recipients. Our results demonstrate that ectopic expression of BRCA2 confers a beneficial in vivo proliferation advantage to FA-D1 HSCs that enables the full hematopoietic repopulation of FA recipients with genetically corrected cells.
Trisomy 21 enhances human fetal erythro-megakaryocytic development
Authors: Chou Stella T. , Opalinska Joanna B. , Yao Yu , Fernandes Myriam A. , Kalota Anna , Brooks John S. J. , Choi John K. , Gewirtz Alan M. , Danet-Desnoyers Gwenn-ael , Nemiroff Richard L. , Weiss Mitchell J. 
Published: September 2008

Abstract
Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. While altered GATA1 inhibits erythro-megakaryocytic development, less is known about how trisomy 21 impacts blood formation, particularly in the human fetus where TMD and AMKL originate. We used in vitro and mouse transplantation assays to study hematopoiesis in trisomy 21 fetal livers with normal GATA1 alleles. Remarkably, trisomy 21 progenitors exhibited enhanced production of erythroid and megakaryocytic cells that proliferated excessively. Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes.
Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo
Authors: Anderson Leah J. , Longnecker Richard 
Published: September 2008

Abstract
Expression of latent membrane protein 2 (LMP2A) during B-cell development leads to global alterations in gene transcription similar to those seen in Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of LMP2A in Epstein-Barr virus–associated HL, this implicates a role for LMP2A in the pathogenesis of HL. We have shown that LMP2A constitutively activates the Notch1 pathway to autoregulate the LMP2A promoter. To determine whether constitutive activation of the Notch pathway is important for LMP2A-mediated alterations in B-cell development in vivo, TgE-LMP2A–transgenic mice were intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase. B cells from TgE Notch1lox/lox-CD19+/Cre mice have an increase in immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow compared with TgE Notch1lox/lox mice, indicating the LMP2A signal for developmental aberrations is impaired in the absence of Notch1. Real-time reverse-transcribed polymerase chain reaction analysis reveals that LMP2A requires the Notch1 pathway to alter levels of B cell–specific transcription factors, E2A and EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells.
Mesenchymal stromal cell–derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction
Authors: Rafei Moutih , Hsieh Jeremy , Fortier Simon , Li MengYang , Yuan Shala , Birman Elena , Forner Kathy , Boivin Marie-Noelle , Doody Karen , Tremblay Michel , Annabi Borhane , Galipeau Jacques 
Published: September 2008

AbstractWe demonstrate that the secretome of mesenchymal stromal cells (MSCs) suppresses plasma cell (PC) immunoglobulin (Ig) production, induces plasmablast proliferation, and leads to interleukin-10–mediated blockade in vitro. We found that these effects are the result of MSC-derived CC chemokine ligands CCL2 and CCL7. More specifically, MSCs further processed these CC chemokines by the activity of matrix metalloproteinases (MMPs), leading to the generation of proteolytically processed antagonistic CCL2 variant. Neutralizing CCL2 or inhibiting MMP enzymatic activity abolished the PC-suppressive effect of MSCs. We also observed that MMP-processed CCL2 suppresses signal transducer and activator of transcription 3 (STAT3) activation in PC. As a result, the transcription factor PAX5 is induced, thus explaining the inhibition of Ig synthesis. The absence of inhibitory effects by MSC on the humoral response of CCR2−/− mice to xenoantigen suggests that MMP-cleaved CCL2/CCR2 interaction as well as downstream phosphatase activity is necessary for antagonistic effect. We tested syngeneic MSCs in hemophilic B6 mice with predeveloped antihuman factor VIII (hFVIII) antibodies and demonstrated a robust decrease in hFVIII-specific IgG levels. Thus, MSCs may play a role in modulating Ig production by PCs via MMP processing of CCL2 and may represent an appealing cell therapy approach for pathologic humoral responses.
GBNet: Deciphering regulatory rules in the co-regulated genes using a Gibbs sampler enhanced Bayesian network approach
Authors: Shen Li , Liu Jie , Wang Wei 
Published: September 2008

Abstract

Background
Combinatorial regulation of transcription factors (TFs) is important in determining the complex gene expression patterns particularly in higher organisms. Deciphering regulatory rules between cooperative TFs is a critical step towards understanding the mechanisms of combinatorial regulation.

Results
We present here a Bayesian network approach called GBNet to search for DNA motifs that may be cooperative in transcriptional regulation and the sequence constraints that these motifs may satisfy. We showed that GBNet outperformed the other available methods in the simulated and the yeast data. We also demonstrated the usefulness of GBNet on learning regulatory rules between YY1, a human TF, and its co-factors. Most of the rules learned by GBNet on YY1 and co-factors were supported by literature. In addition, a spacing constraint between YY1 and E2F was also supported by independent TF binding experiments.

Conclusion
We thus conclude that GBNet is a useful tool for deciphering the "grammar" of transcriptional regulation.
SCUD: Saccharomyces Cerevisiae Ubiquitination Database
Authors: Lee Won-Chul , Lee Minho , Jung Jin Woo , Kim Kwang Pyo , Kim Dongsup 
Published: September 2008

Abstract

Background
Ubiquitination is an important post-translational modification involved in diverse biological processes. Therefore, genomewide representation of the ubiquitination system for a species is important.

Description
SCUD is a web-based database for the ubiquitination system in Saccharomyces cerevisiae (Baker's yeast). We first searched for all the known enzymes involved in the ubiquitination process in yeast, including E1, E2, E3, and deubiquitination enzymes. Then, ubiquitinated substrates were collected by literature search. Especially, E3 and deubiquitination enzymes are classified into classes and subclasses by their shared domains and unique functions. As a result, 42 different E3 enzymes were grouped into corresponding classes and subclasses, and 940 ubiquitinated substrates including mutant substrates were identified. All the enzyme and substrate information are interconnected by hyperlinks, which makes it easy to view the enzyme-specific ubiquitination information.

Conclusion
This database aims to represent a comprehensive yeast ubiquitination system, and is easily expandable with the further experimental data. We expect that this database will be useful for the research on the ubiquitination systems of other higher organisms.
SCUD is accessible at http://scud.kaist.ac.kr
Evolution of the holozoan ribosome biogenesis regulon
Authors: Brown Seth J , Cole Michael D , Erives Albert J 
Published: September 2008

Abstract

Background
The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results
Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion
These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.
Structural analysis of FAD synthetase from Corynebacterium ammoniagenes
Authors: Frago Susana , Martínez-Júlvez Marta , Serrano Ana , Medina Milagros 
Published: September 2008

Abstract

Background
The prokaryotic FAD synthetase family – a group of bifunctional enzymes that catalyse riboflavin phosphorylation and FMN adenylylation within a single polypeptide chain- was analysed in terms of sequence and structure.

Results
Sequences of nearly 800 prokaryotic species were aligned. Those related with bifunctional FAD synthetase activities showed conservation of several consensus regions and highly conserved residues. A 3D model for the FAD synthetase from Corynebacterium ammoniagenes (CaFADS) was generated. This model confirms that the N-terminal and C-terminal domains are related to nucleotydyltransferases and riboflavin kinases, respectively. Models for the interaction of CaFADS with its substrates were also produced, allowing location of all the protein substrates in their putative binding pockets. These include two independent flavin binding sites for each CaFADS activity.

Conclusion
For the first time, the putative presence of a flavin binding site for the adenylylation activity, independent from that related with the phosphorylation activity, is shown. Additionally, these models suggest the functional relevance of some residues putatively involved in the catalytic processes. Their relevant roles were analysed by site-directed mutagenesis. A role was confirmed for H28, H31, S164 and T165 in the stabilisation of the P groups and the adenine moiety of ATP and, the P of FMN for the adenylylation. Similarly, T208, N210 and E268 appear critical for accommodation of the P groups of ATP and the ribityl end of RF in the active site for the phosphorylation process. Finally, the C-terminal domain was shown to catalyse the phosphorylation process on its own, but no reaction at all was observed with the individually expressed N-terminal domain.
Development of a luciferase-based reporter system to monitor Bifidobacterium breve UCC2003 persistence in mice
Authors: Cronin Michelle , Sleator Roy D , Hill Colin , Fitzgerald Gerald F , van Sinderen Douwe 
Published: September 2008

Abstract

Background
Probiotics such as bifidobacteria have been shown to maintain a healthy intestinal microbial balance and help protect against infections. However, despite these benefits, bifidobacteria still remain poorly understood at the biochemical, physiological and especially the genetic level. Herein we describe, for the first time, the development of a non-invasive luciferase-based reporter system for real-time tracking of Bifidobacterium species in vivo.

Results
The reporter vector pLuxMC1 is based on the recently described theta-type plasmid pBC1 from B. catenatulatum [1] and the luxABCDE operon from pPL2lux [2]. Derivatives of pLuxMC1, harbouring a bifidobacterial promoter (pLuxMC2) as well as a synthetically derived promoter (pLuxMC3) [3] placed upstream of luxABCDE, were constructed and found to stably replicate in B. breve UCC2003. The subsequent analysis of these strains allowed us to assess the functionality of pLuxMC1 both in vitro and in vivo.

Conclusion
Our results demonstrate the potential of pLuxMC1 as a real-time, non-invasive reporter system for Bifidobacterium. It has also allowed us, for the first time, to track the colonisation potential and persistence of this probiotic species in real time. An interesting and significant outcome of the study is the identification of the caecum as a niche environment for B. breve UCC2003 within the mouse gastrointestinal tract (GI) tract.
Association between regular participation in sports and leisure time behaviors in Brazilian adolescents: A cross-sectional study
Authors: Fernandes Rômulo Araújo , Júnior Ismael Forte Freitas , Cardoso Jefferson Rosa , Vaz Ronque Enio Ricardo , Loch Mathias Roberto , de Oliveira Arli Ramos 
Published: September 2008

Abstract

Background
The belief that adolescents engaged in sports increase their overall physical activity level while simultaneously decreasing physical inactivity has been the foundation of many intervention programs in developing countries. The aim of this study was to analyze the association between regular participation in sports and both active behaviors and TV viewing during leisure time.

Methods
A total of 1752 Brazilian adolescents (812 = male and 940 = female) participated in this study. Regular participation in sports, as well as active behaviors (exemplified by walking or cycling) and TV viewing during leisure time were assessed by means of a questionnaire. The chi-square test analyzed the association between sports practice and leisure time behaviors, and the Poisson regression with robust variance indicated the magnitude of these associations.

Results
The prevalence of regular participation in sports was 14.8% (95% confidence interval 13.2% to 16.5%). After adjustment for all confounders, participation in sports was associated with, at the highest frequency, cycling (PR = 2.55 [1.80–3.60]) and walking (PR = 2.69 [1.98–3.64]) during leisure time. However, there was not an association between the participation in sports and frequency of TV viewing (PR = 1.28 [0.81–2.02]).

Conclusion
This study presented data indicating that the regular participation in sports is positively associated with a higher frequency of physically active behaviors during leisure time. However, the results did not support the hypothesis that the engagement in sports necessarily decreases leisure time spent in TV viewing.