bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calvin's Theological Legacy
Authors: Fergusson David 
Published: September 2010

AbstractOften caricatured for its rigidity, harshness and hostility to the arts, Calvinism has suffered from frequent misrepresentation, not least in Scotland. In particular, the identification of Calvin's theology with double predestination and religious intolerance present formidable difficulties for a contemporary appropriation of his work. While adopting a critical approach to key aspects of Calvin's thought, this essay nevertheless seeks to understand and to recover other important features of his life and work including his rhetorical strategy, the concept of divine accommodation, and his approach to church, sacraments and ministry which remains an important ecumenical resource.
Calvin's Influence on the Theology of the English Reformation
Authors: Davie Martin 
Published: September 2010

AbstractThis paper traces the influence of John Calvin on the English Reformation from the time of the breach with Rome under Henry VIII until the great ejection of dissenting puritan clergy from the ministry of the Church of England in 1662. It argues that Calvin's teaching only began to have an impact on the English Reformation during the reign of Elizabeth I and that although his theology had a widespread impact on both individuals and groups within the Church of England it never shaped the Church's official doctrine, liturgy or pattern of ministry, although it seemed likely that this would be the case at the time of the Westminster Assembly in the 1640s. It also raises the question of whether Calvin sought episcopacy from the Church of England in the reign of Edward VI.
Dysfunction of the heme recycling system in heme oxygenase 1–deficient mice: effects on macrophage viability and tissue iron distribution
Authors: Kovtunovych Gennadiy , Eckhaus Michael A. , Ghosh Manik C. , Ollivierre-Wilson Hayden , Rouault Tracey A. 
Published: September 2010

AbstractTo better understand the tissue iron overload and anemia previously reported in a human patient and mice that lack heme oxygenase-1 (HO-1), we studied iron distribution and pathology in HO-1(Hmox1)−/− mice. We found that resident splenic and liver macrophages were mostly absent in HO-1−/− mice. Erythrophagocytosis caused the death of HO-1−/− macrophages in in vitro experiments, supporting the hypothesis that HO-1−/− macrophages died of exposure to heme released on erythrophagocytosis. Rupture of HO-1−/− macrophages in vivo and release of nonmetabolized heme probably caused tissue inflammation. In the spleen, initial splenic enlargement progressed to red pulp fibrosis, atrophy, and functional hyposplenism in older mice, recapitulating the asplenia of an HO-1–deficient patient. We postulate that the failure of tissue macrophages to remove senescent erythrocytes led to intravascular hemolysis and increased expression of the heme and hemoglobin scavenger proteins, hemopexin and haptoglobin. Lack of macrophages expressing the haptoglobin receptor, CD163, diminished the ability of haptoglobin to neutralize circulating hemoglobin, and iron overload occurred in kidney proximal tubules, which were able to catabolize heme with HO-2. Thus, in HO-1−/− mammals, the reduced function and viability of erythrophagocytosing macrophages are the main causes of tissue damage and iron redistribution.
8-Aminoadenosine inhibits Akt/mTOR and Erk signaling in mantle cell lymphoma
Authors: Dennison Jennifer B. , Shanmugam Mala , Ayres Mary L. , Qian Jun , Krett Nancy L. , Medeiros L. Jeffrey , Neelapu Sattva S. , Rosen Steven T. , Gandhi Varsha 
Published: September 2010

Abstract8-Aminoadenosine (8-NH2-Ado), a ribosyl nucleoside analog, in preclinical models of multiple myeloma inhibits phosphorylation of proteins in multiple growth and survival pathways, including Akt. Given that Akt controls the activity of mammalian target of rapamycin (mTOR), we hypothesized that 8-NH2-Ado would be active in mantle cell lymphoma (MCL), a hematological malignancy clinically responsive to mTOR inhibitors. In the current study, the preclinical efficacy of 8-NH2-Ado and its resulting effects on Akt/mTOR and extracellular-signal–regulated kinase signaling were evaluated using 4 MCL cell lines, primary MCL cells, and normal lymphocytes from healthy donors. For all MCL cell lines, 8-NH2-Ado inhibited growth and promoted cell death as shown by reduction of thymidine incorporation, loss of mitochondrial membrane potential, and poly (adenosine diphosphate-ribose) polymerase cleavage. The efficacy of 8-NH2-Ado was highly associated with intracellular accumulation of 8-NH2-adenosine triphosphate (ATP) and loss of endogenous ATP. Formation of 8-NH2-ATP was also associated with inhibition of transcription and translation accompanied by loss of phosphorylated (p-)Akt, p-mTOR, p-Erk1/2, p-phosphoprotein (p)38, p-S6, and p-4E-binding protein 1. While normal lymphocytes accumulated 8-NH2-ATP but maintained their viability with 8-NH2-Ado treatment, primary lymphoma cells accumulated higher concentrations of 8-NH2-ATP, had increased loss of ATP, and underwent apoptosis. We conclude that 8-NH2-Ado is efficacious in preclinical models of MCL and inhibits signaling of Akt/mTOR and Erk pathways.
Inheritance of central neuroanatomy and physiology related to pheromone preference in the male European corn borer
Authors: Kárpáti Zsolt , Olsson Shannon , Hansson Bill S , Dekker Teun 
Published: September 2010

Abstract

Background
The European corn borer (ECB), Ostrinia nubilalis, is a textbook example of pheromone polymorphism. Males of the two strains (Z and E) prefer opposite ratios of the two pheromone components, Z11- and E11-tetradecenyl acetate, with a sex-linked factor underlying this difference in preference. The male antennal lobes of the two strains contain a pheromone sensitive macroglomerular complex (MGC) that is identical in morphology, but reversed in functional topology. However, hybrids prefer intermediate ratios. How a topological arrangement of two glomeruli can accommodate for an intermediate preference was unclear. Therefore we studied the neurophysiology of hybrids and paternal backcrosses to see which factors correlated with male behavior.

Results
Projection neuron (PN) recordings and stainings in hybrids and backcrosses show a dominance of the E-type MGC topology, notwithstanding their intermediate preference. Apparently, the topological arrangement of glomeruli does not directly dictate preference. However, two other factors did correlated very well with preference. First, volumetric measurements of MGC glomeruli demonstrate that, whereas in the parental strains the medial MGC glomerulus is more than 2 times larger than the lateral, in hybrids they are intermediate between the parents, i.e. equally sized. Paternal backcrosses showed that the volume ratio is sex-linked and co-dominant. Second, we measured the summed potential difference of the antennae in response to pheromone stimulation using electroantennogram recordings (EAG). Z-strain antennae responded 2.5 times stronger to Z11 than to E11-14:OAc, whereas in E-strain antennae the ratio was approximately equal. Hybrid responses were intermediate to the parents, and also here the antennal response of the paternal backcrosses followed a pattern similar to the behavioral phenotype. We found no differences in frequency and types of projection and local interneurons encountered between the two strains and their hybrids.

Conclusions
Male pheromone preference in the ECB strains serves as a strong prezygotic reproductive isolation mechanism, and has contributed to population divergence in the field. Our results demonstrate that male pheromone preference is not directly affected by the topological arrangement of olfactory glomeruli itself, but that male preference may instead be mediated by an antennal factor, which causes the MGC glomeruli to be differentially sized. We postulate that this factor affects readout of blend information from the MGC. The results are an illustration of how pheromone preference may be 'spelled out' in the ALs, and how evolution may modulate this.
Probing the pan-genome of Listeria monocytogenes: new insights into intraspecific niche expansion and genomic diversification
Authors: Deng Xiangyu , Phillippy Adam M , Li Zengxin , Salzberg Steven L , Zhang Wei 
Published: September 2010

AbstractBackgroundBacterial pathogens often show significant intraspecific variations in ecological fitness, host preference and pathogenic potential to cause infectious disease. The species ofListeria monocytogenes, a facultative intracellular pathogen and the causative agent of human listeriosis, consists of at least three distinct genetic lineages. Two of these lineages predominantly cause human sporadic and epidemic infections, whereas the third lineage has never been implicated in human disease outbreaks despite its overall conservation of many known virulence factors.ResultsHere we compare the genomes of 26L. monocytogenesstrains representing the three lineages based on bothin silicocomparative genomic analysis and high-density, pan-genomic DNA array hybridizations. We uncover 86 genes and 8 small regulatory RNAs that likely makeL. monocytogeneslineages differ in carbohydrate utilization and stress resistance during their residence in natural habitats and passage through the host gastrointestinal tract. We also identify 2,330 to 2,456 core genes that define this species along with an open pan-genome pool that contains more than 4,052 genes. Phylogenomic reconstructions based on 3,560 homologous groups allowed robust estimation of phylogenetic relatedness amongL. monocytogenesstrains.ConclusionsOur pan-genome approach enables accurate co-analysis of DNA sequence and hybridization array data for both core gene estimation and phylogenomics. Application of our method to the pan-genome ofL. monocytogenessheds new insights into the intraspecific niche expansion and evolution of this important foodborne pathogen.
Global regulation of gene expression in response to cysteine availability in Clostridium perfringens
Authors: André Gaelle , Haudecoeur Elise , Monot Marc , Ohtani Kaori , Shimizu Tohru , Dupuy Bruno , Martin-Verstraete Isabelle 
Published: September 2010

Abstract

Background
Cysteine has a crucial role in cellular physiology and its synthesis is tightly controlled due to its reactivity. However, little is known about the sulfur metabolism and its regulation in clostridia compared with other firmicutes. In Clostridium perfringens, the two-component system, VirR/VirS, controls the expression of the ubiG operon involved in methionine to cysteine conversion in addition to the expression of several toxin genes. The existence of links between the C. perfringens virulence regulon and sulfur metabolism prompted us to analyze this metabolism in more detail.

Results
We first performed a tentative reconstruction of sulfur metabolism in C. perfringens and correlated these data with the growth of strain 13 in the presence of various sulfur sources. Surprisingly, C. perfringens can convert cysteine to methionine by an atypical still uncharacterized pathway. We further compared the expression profiles of strain 13 after growth in the presence of cystine or homocysteine that corresponds to conditions of cysteine depletion. Among the 177 genes differentially expressed, we found genes involved in sulfur metabolism and controlled by premature termination of transcription via a cysteine specific T-box system (cysK-cysE, cysP1 and cysP2) or an S-box riboswitch (metK and metT). We also showed that the ubiG operon was submitted to a triple regulation by cysteine availability via a T-box system, by the VirR/VirS system via the VR-RNA and by the VirX regulatory RNA.
In addition, we found that expression of pfoA (theta-toxin), nagL (one of the five genes encoding hyaluronidases) and genes involved in the maintenance of cell redox status was differentially expressed in response to cysteine availability. Finally, we showed that the expression of genes involved in [Fe-S] clusters biogenesis and of the ldh gene encoding the lactate dehydrogenase was induced during cysteine limitation.

Conclusion
Several key functions for the cellular physiology of this anaerobic bacterium were controlled in response to cysteine availability. While most of the genes involved in sulfur metabolism are regulated by premature termination of transcription, other still uncharacterized mechanisms of regulation participated in the induction of gene expression during cysteine starvation.
The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events
Authors: Galasso Gennaro , Santulli Gaetano , Piscione Federico , De Rosa Roberta , Trimarco Valentina , Piccolo Raffaele , Cassese Salvatore , Iaccarino Guido , Trimarco Bruno , Chiariello Massimo 
Published: September 2010

Abstract

Background
The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.

Methods
We studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.

Results
The frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).

Conclusions
Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.
Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression
Authors: Zhang Dake , Ma Sufang , Zhang Xin , Zhao Hanqing , Ding Huiguo , Zeng Changqing 
Published: September 2010

Abstract

Background
Mutations in the basic core promoter (BCP) and its adjacent precore (preC) region in HBV genome are common in chronic hepatitis B patients. However, the patterns of mutation combinations in these two regions during chronic infection are less understood. This study focused on single base mutations in BCP and preC region and the multi-mutation patterns observed in chronic HBV infection patients.

Methods
Total 192 blood samples of chronic HBV infection patients were included. Direct PCR sequencing on the target region of HBV genome was successfully conducted in 157 samples. The rest 35 samples were analyzed by clone sequencing. Only the nucleotide substitutions with their frequencies no less than 10% were included in multi-mutation analysis with the exception for the polymorphic sites between genotypes B and C.

Results
Five high frequency mutations (≥10%) were found in BCP and preC region. Thirteen types of multi-mutations in one fragment were observed, among which 3 types were common combinations (≥5%). The top three multi-mutations were A1762T/G1764A (36%), A1762T/G1764A/G1896A (11%) and T1753(A/C)/A1762T/G1764A/G1896A (8%). Patients with multi-mutations in viral genomes (≥3) were more likely to have liver cirrhosis or hepatocellular carcinoma (OR = 3.1, 95% CI: 1.6-6.0, P = 0.001). G1896A mutation seemed to be involved in liver disease progression independent of the patient age (OR = 3.6, 95% CI: 1.5-8.6; P = 0.004). In addition, patients with more viral mutations detected (≥3) were more likely to be HBeAg negative (OR = 2.7, 95% CI: 1.1-6.4; P = 0.027). Moreover, G1776A mutation was shown to contribute to HBeAg negativity in our study (OR = 8.6, 95% CI: 1.2-44.9; P = 0.01).

Conclusions
Patients with advanced liver diseases and with HBeAg negativity more likely have multi-mutations in HBV genomes but with different mutation combination patterns. G1896A mutation appears to be independent of infection history.
Effects of antibacterial mineral leachates on the cellular ultrastructure, morphology, and membrane integrity of Escherichia coli and methicillin-resistant Staphylococcus aureus
Authors: Otto Caitlin C , Cunningham Tanya M , Hansen Michael R , Haydel Shelley E 
Published: September 2010

Abstract

Background
We have previously identified two mineral mixtures, CB07 and BY07, and their respective aqueous leachates that exhibit in vitro antibacterial activity against a broad spectrum of pathogens. The present study assesses cellular ultrastructure and membrane integrity of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli after exposure to CB07 and BY07 aqueous leachates.

Methods
We used scanning and transmission electron microscopy to evaluate E. coli and MRSA ultrastructure and morphology following exposure to antibacterial leachates. Additionally, we employed Bac light LIVE/DEAD staining and flow cytometry to investigate the cellular membrane as a possible target for antibacterial activity.

Results
Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) imaging of E. coli and MRSA revealed intact cells following exposure to antibacterial mineral leachates. TEM images of MRSA showed disruption of the cytoplasmic contents, distorted cell shape, irregular membranes, and distorted septa of dividing cells. TEM images of E. coli exposed to leachates exhibited different patterns of cytoplasmic condensation with respect to the controls and no apparent change in cell envelope structure. Although bactericidal activity of the leachates occurs more rapidly in E. coli than in MRSA, LIVE/DEAD staining demonstrated that the membrane of E. coli remains intact, while the MRSA membrane is permeabilized following exposure to the leachates.

Conclusions
These data suggest that the leachate antibacterial mechanism of action differs for Gram-positive and Gram-negative organisms. Upon antibacterial mineral leachate exposure, structural integrity is retained, however, compromised membrane integrity accounts for bactericidal activity in Gram-positive, but not in Gram-negative cells.
FATS is a transcriptional target of p53 and associated with antitumor activity
Authors: Zhang Xifeng , Zhang Qian , Zhang Jun , Qiu Li , Yan Shuang-shuang , Feng Juling , Sun Yan , Huang Xingxu , Lu Karen H , Li Zheng 
Published: September 2010

Abstract
Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374) through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability.
Phosphorylation of HOX11/TLX1 on Threonine-247 during mitosis modulates expression of cyclin B1
Authors: Chen Edwin , Huang Xiaoyong , Zheng Yanzhen , Li You-Jun , Chesney Alden , Ben-David Yaacov , Yang Eric , Hough Margaret R 
Published: September 2010

Abstract

Background
The HOX11/TLX1 (hereafter referred to as HOX11) homeobox gene was originally identified at a t(10;14)(q24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). We previously reported a predisposition to aberrant spindle assembly checkpoint arrest and heightened incidences of chromosome missegregation in HOX11-overexpressing B lymphocytes following exposure to spindle poisons. The purpose of the current study was to evaluate cell cycle specific expression of HOX11.

Results
Cell cycle specific expression studies revealed a phosphorylated form of HOX11 detectable only in the mitotic fraction of cells after treatment with inhibitors to arrest cells at different stages of the cell cycle. Mutational analyses revealed phosphorylation on threonine-247 (Thr247), a conserved amino acid that defines the HOX11 gene family and is integral for the association with DNA binding elements. The effect of HOX11 phosphorylation on its ability to modulate expression of the downstream target, cyclin B1, was tested. A HOX11 mutant in which Thr247 was substituted with glutamic acid (HOX11 T247E), thereby mimicking a constitutively phosphorylated HOX11 isoform, was unable to bind the cyclin B1 promoter or enhance levels of the cyclin B1 protein. Expression of the wildtype HOX11 was associated with accelerated progression through the G2/M phase of the cell cycle, impaired synchronization in prometaphase and reduced apoptosis whereas expression of the HOX11 T247E mutant restored cell cycle kinetics, the spindle checkpoint and apoptosis.

Conclusions
Our results demonstrate that the transcriptional activity of HOX11 is regulated by phosphorylation of Thr247 in a cell cycle-specific manner and that this phosphorylation modulates the expression of the target gene, cyclin B1. Since it is likely that Thr247 phosphorylation regulates DNA binding activity to multiple HOX11 target sequences, it is conceivable that phosphorylation functions to regulate the expression of HOX11 target genes involved in the control of the mitotic spindle checkpoint.