bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines
Authors: Ahonen Cory L. , Wasiuk Anna , Fuse Shinichiro , Turk Mary Jo , Ernstoff Marc S. , Suriawinata Arief A. , Gorham James D. , Kedl Ross M. , Usherwood Edward J. , Noelle Randolph J. 
Published: January 2008

Abstract
Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor–tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8+ T cells, potent tumor-specific CD8+ memory, CD8+ T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8+ T cells to FoxP3+ cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans.
Repression via the GATA box is essential for tissue-specific erythropoietin gene expression
Authors: Obara Naoshi , Suzuki Norio , Kim Kibom , Nagasawa Toshiro , Imagawa Shigehiko , Yamamoto Masayuki 
Published: January 2008

AbstractIn response to anemia, erythropoietin (Epo) gene transcription is markedly induced in the kidney and liver. To elucidate how Epo gene expression is regulated in vivo, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of a 180-kb mouse Epo gene locus. GFP expression was induced by anemia or hypoxia specifically in peritubular interstitial cells of the kidney and hepatocytes surrounding the central vein. Surprisingly, renal Epo-producing cells had a neuronlike morphology and expressed neuronal marker genes. Furthermore, the regulatory mechanisms of Epo gene expression were explored using transgenes containing mutations in the GATA motif of the promoter region. A single nucleotide mutation in this motif resulted in constitutive ectopic expression of transgenic GFP in renal distal tubules, collecting ducts, and certain populations of epithelial cells in other tissues. Since both GATA-2 and GATA-3 bind to the GATA box in distal tubular cells, both factors are likely to repress constitutively ectopic Epo gene expression in these cells. Thus, GATA-based repression is essential for the inducible and cell type–specific expression of the Epo gene.
Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation
Authors: Zhang Cheng Cheng , Kaba Megan , Iizuka Satoru , Huynh HoangDinh , Lodish Harvey F. 
Published: January 2008

Abstract
Hematopoietic stem cells (HSCs) are the basis of bone marrow transplantation and are attractive target cells for hematopoietic gene therapy, but these important clinical applications have been severely hampered by difficulties in ex vivo expansion of HSCs. In particular, the use of cord blood for adult transplantation is greatly limited by the number of HSCs. Previously we identified angiopoietin-like proteins and IGF-binding protein 2 (IGFBP2) as new hormones that, together with other factors, can expand mouse bone marrow HSCs in culture. Here, we measure the activity of multipotent human severe combined immunodeficient (SCID)–repopulating cells (SRCs) by transplantation into the nonobese diabetic SCID (NOD/SCID) mice; secondary transplantation was performed to evaluate the self-renewal potential of SRCs. A serum-free medium containing SCF, TPO, and FGF-1 or Flt3-L cannot significantly support expansion of the SRCs present in human cord blood CD133+ cells. Addition of either angiopoietin-like 5 or IGF-binding protein 2 to the cultures led to a sizable expansion of HSC numbers, as assayed by NOD/SCID transplantation. A serum-free culture containing SCF, TPO, FGF-1, angiopoietin-like 5, and IGFBP2 supports an approximately 20-fold net expansion of repopulating human cord blood HSCs, a number potentially applicable to several clinical processes including HSC transplantation.
Broadly sampled multigene trees of eukaryotes
Authors: Yoon Hwan Su , Grant Jessica , Tekle Yonas I , Wu Min , Chaon Benjamin C , Cole Jeffrey C , Logsdon John M , Patterson David J , Bhattacharya Debashish , Katz Laura A 
Published: January 2008

Abstract

Background
Our understanding of the eukaryotic tree of life and the tremendous diversity of microbial eukaryotes is in flux as additional genes and diverse taxa are sampled for molecular analyses. Despite instability in many analyses, there is an increasing trend to classify eukaryotic diversity into six major supergroups: the 'Amoebozoa', 'Chromalveolata', 'Excavata', 'Opisthokonta', 'Plantae', and 'Rhizaria'. Previous molecular analyses have often suffered from either a broad taxon sampling using only single-gene data or have used multigene data with a limited sample of taxa. This study has two major aims: (1) to place taxa represented by 72 sequences, 61 of which have not been characterized previously, onto a well-sampled multigene genealogy, and (2) to evaluate the support for the six putative supergroups using two taxon-rich data sets and a variety of phylogenetic approaches.

Results
The inferred trees reveal strong support for many clades that also have defining ultrastructural or molecular characters. In contrast, we find limited to no support for most of the putative supergroups as only the 'Opisthokonta' receive strong support in our analyses. The supergroup 'Amoebozoa' has only moderate support, whereas the 'Chromalveolata', 'Excavata', 'Plantae', and 'Rhizaria' receive very limited or no support.

Conclusion
Our analytical approach substantiates the power of increased taxon sampling in placing diverse eukaryotic lineages within well-supported clades. At the same time, this study indicates that the six supergroup hypothesis of higher-level eukaryotic classification is likely premature. The use of a taxon-rich data set with 105 lineages, which still includes only a small fraction of the diversity of microbial eukaryotes, fails to resolve deeper phylogenetic relationships and reveals no support for four of the six proposed supergroups. Our analyses provide a point of departure for future taxon- and gene-rich analyses of the eukaryotic tree of life, which will be critical for resolving their phylogenetic interrelationships.
Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells
Authors: Brozek Wolfgang , Bises Giovanna , Fabjani Gerhild , Cross Heide S , Peterlik Meinrad 
Published: January 2008

AbstractBackgroundMany cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect ofIL-6modulators, i.e. IL-1β, prostaglandin E2, 17β-estradiol, and 1,25-dihydroxyvitamin D3, on expression and synthesis of the cytokine at different stages of tumour progression.MethodsWe utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in theIL-6gene promoter.ResultsIL-6mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10-7M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in theIL-6promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of theIL-6gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-mycproto-oncogene expression. These effects were inhibited by 10-8M 1,25-dihydroxyvitamin D3.ConclusionIn human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE2, 1,25-dihydroxyvitamin D3, and 17β-estradiol. However, IL-6 is highly abundant in undifferentiated tumour cells and is effectively stimulated by IL-1β. In case of overexpression of anIL-6gene variant with extreme sensitivity to IL-1β, massive release of the cytokine from undifferentiated tumour cells may accelerate progression towards malignancy by paracrine action on more differentiated tumour cells with a still functioning proliferative IL-6 signalling pathway.
Loss of Endocan tumorigenic properties after alternative splicing of exon 2
Authors: Depontieu Florence , Grigoriu Bogdan-Dragos , Scherpereel Arnaud , Adam Estelle , Delehedde Maryse , Gosset Philippe , Lassalle Philippe 
Published: January 2008

AbstractBackgroundEndocan was originally described as a dermatan sulfate proteoglycan found freely circulating in the blood. Endocan expression confers tumorigenic properties to epithelial cell lines or accelerate the growth of already tumorigenic cells. This molecule is the product of a single gene composed of 3 exons. Previous data showed that endocan mRNA is subject to alternative splicing with possible generation of two protein products. In the present study we identified, and functionally characterized, the alternative spliced product of the endocan gene: the exon 2-deleted endocan, called endocanΔ2.MethodsStable, endocanΔ2-overexpressing cell lines were generated to investigate the biological activities of this new alternatively spliced product of endocan gene. Tumorigenesis was studied by inoculating endocan and endocanΔ2 expressing cell lines subcutaneously in SCID mice. Biochemical properties of endocan and endocanΔ2 were studied after production of recombinant proteins in various cell lines of human and murine origin.ResultsOur results showed that the exon 2 deletion impairs synthesis of the glycan chain, known to be involved in the pro-tumoral effect of endocan. EndocanΔ2 did not promote tumor formation by 293 cells implanted in the skin of severe combined immunodeficient (SCID) mice.ConclusionOur results emphasize the key role of the polypeptide sequence encoded by the exon 2 of endocan gene in tumorigenesis, and suggest that this sequence could be a target for future therapies against cancer.
Establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in Taiwan
Authors: Wu Tsung-Shu Joseph , Shih Fuh-Yuan Frank , Yen Muh-Yong , Wu Jiunn-Shyan Julian , Lu Shiou-Wen , Chang Kevin Chi-Ming , Hsiung Chao , Chou Jr-How , Chu Yu-Tseng , Chang Hang , Chiu Chan-Hsien , Tsui Fu-Chiang Richard , Wagner Michael M , Su Ih-Jen , King Chwan-Chuen 
Published: January 2008

AbstractBackgroundWith international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems. A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004. This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making.MethodsBetween June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS. The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005.ResultsTaiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001). It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters. Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities.ConclusionTaiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia. The experiences reported herein can encourage other countries to develop their own surveillance systems. The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration.
Biomolecular network querying: a promising approach in systems biology
Authors: Zhang Shihua , Zhang Xiang-Sun , Chen Luonan 
Published: January 2008

Abstract
The rapid accumulation of various network-related data from multiple species and conditions (e.g. disease versus normal) provides unprecedented opportunities to study the function and evolution of biological systems. Comparison of biomolecular networks between species or conditions is a promising approach to understanding the essential mechanisms used by living organisms. Computationally, the basic goal of this network comparison or 'querying' is to uncover identical or similar subnetworks by mapping the queried network (e.g. a pathway or functional module) to another network or network database. Such comparative analysis may reveal biologically or clinically important pathways or regulatory networks. In particular, we argue that user-friendly tools for network querying will greatly enhance our ability to study the fundamental properties of biomolecular networks at a system-wide level.
Inhibition of hyaluronan export reduces collagen degradation in interleukin-1 treated cartilage
Authors: Deiters Barthold , Prehm Peter 
Published: January 2008

Abstract
Background
Osteoarthrosis is characterized by cartilage erosion, proteolysis of aggrecan and collagen, and disturbed rates of synthesis of aggrecan and hyaluronan by chondrocytes, with hyaluronan over-production being an early reaction. We considered that inhibition of hyaluronan export might prevent subsequent proteoglycan loss and collagen degradation.

Methods
To test this hypothesis, we studied a tissue culture model using bovine cartilages explants activated with IL-1α to induce osteoarthritic reactions using the phosphodiesterase-5 inhibitors tadalafil, zaprinast and vardenafil.

Results
These drugs inhibited hyaluronan export, but they did not inhibit hyaluronan synthase activity. Simultaneously, they inhibited proteoglycan loss and collagen degradation, but not their synthesis. They also reduced the release of gelatinases into the culture media and diffusion of the indicator protein horseradish peroxidase through the cartilage explants. The mechanism of action of these compounds may be through inhibition of hyaluronan exporter multidrug resistance-associated protein 5 (MRP5), because the effective drug concentrations were much higher than required for phosphodiesterase-5 inhibition and intracellular cGMP accumulation.

Conclusion
Inhibition of hyaluronan over-production may be an appropriate target to attenuate IL-1-induced reactions in osteoarthritic cartilage.
Identification of a silicatein(-related) protease in the giant spicules of the deep-sea hexactinellidMonorhaphis chuni
Authors: Müller Werner E. G. , Boreiko Alexandra , Schloßmacher Ute , Wang Xiaohong , Eckert Carsten , Kropf Klaus , Li Jinhe , Schröder Heinz C. 
Published: January 2008

SUMMARYSilicateins, members of the cathepsin L family, are enzymes that have been shown to be involved in the biosynthesis/condensation of biosilica in spicules from Demospongiae (phylum Porifera), e.g. Tethya aurantium and Suberites domuncula. The class Hexactinellida also forms spicules from this inorganic material. This class of sponges includes species that form the largest biogenic silica structures on earth. The giant basal spicules from the hexactinellids Monorhaphis chuni and Monorhaphis intermedia can reach lengths of up to 3 m and diameters of 10 mm. The giant spicules as well as the tauactines consist of a biosilica shell that surrounds the axial canal, which harbours the axial filament, in regular concentric, lamellar layers, suggesting an appositional growth of the spicules. The lamellae contain 27 kDa proteins, which undergo post-translational modification (phosphorylation), while total spicule extracts contain additional 70 kDa proteins. The 27 kDa proteins cross-reacted with anti-silicatein antibodies. The extracts of spicules from the hexactinellid Monorhaphis displayed proteolytic activity like the silicateins from the demosponge S. domuncula. Since the proteolytic activity in spicule extracts from both classes of sponge could be sensitively inhibited by E-64 (a specific cysteine proteinase inhibitor), we used a labelled E-64 sample as a probe to identify the protein that bound to this inhibitor on a blot. The experiments revealed that the labelled E-64 selectively recognized the 27 kDa protein. Our data strongly suggest that silicatein(-related) molecules are also present in Hexactinellida. These new results are considered to also be of impact for applied biotechnological studies.
Fluid and osmolyte recovery in the common pond snailLymnaea stagnalisfollowing full-body withdrawal
Authors: Ebanks Sue C. , Grosell Martin 
Published: January 2008

SUMMARYThe common pond snail Lymnaea stagnalis sacrifices 40–60% of its extracellular fluid (ECF) including solutes to the surrounding environment to fully retract into its shell. Our objectives were to determine recovery time following such ECF loss and characterize mechanisms involved in recovering Na+, the primary cationic osmolyte in this snail. Pallial fluid was initially collected post-stimulation and again after a second stimulation on sub-groups of those snails 2 h to 10 weeks after initial sampling. Samples were analyzed for pH, osmotic pressure, and individual solute concentrations. Lost volume was recovered within 8 h with no significant changes in pH or total CO2. Significant decreases in osmotic pressure, [Na+] (43% loss), and [Cl–]recovered in 48 h as a result of enhanced uptake from the water. Copper and total extracellular proteins took 5 weeks to recover. Measurements of Na+ transport kinetics completed before and immediately after fluid loss revealed a near threefold increase in both affinity and capacity of the Na+ uptake system. Sodium uptake was independent of ambient Cl– and HCO3– in both control and fluid-depleted snails. Amiloride significantly reduced recovery-phase Na+ uptake rates but did not influence baseline Na+flux. Recovery uptake was significantly reduced by amiloride,ethylisopropylamiloride, bafilomycin and ethoxzolamide indicating dependency upon Na+/H+ exchange, H+ pump activity and H+ from carbonic anhydrase-catalyzed CO2 hydration. Thus enhanced uptake during recovery is likely via electrogenic Na+/H+ exchange and/or possibly a cation channel.
Hematological changes associated with egg production: estrogen dependence and repeatability
Authors: Wagner Emily C. , Prevolsek Jaime S. , Wynne-Edwards Katherine E. , Williams Tony D. 
Published: January 2008

SUMMARYThe `cost of reproduction' (i.e. the trade-off between current reproduction and future fecundity and/or survival) is a central concept in life history theory, yet we still know very little about the physiological mechanisms underlying such costs. Recently it has been recognized that reproduction itself or the regulatory (hormonal) mechanisms underlying reproduction might result in `costs' (cf. resource-allocation based mechanisms). As one example,it has been suggested that the decrease in hematocrit observed during egg production in birds might be due to antagonistic pleiotropic effects of estrogens. This could generate costs of reproduction by reducing oxygen-carrying capacity during subsequent aerobically demanding stages such as chick-provisioning. Here we show that the reduction in hematocrit during egg-laying is dependent on receptor-mediated actions of endogenous estrogens:blocking estrogen receptors using the anti-estrogen tamoxifen reduces the decrease in hematocrit during egg production in female zebra finches(Taeniopygia guttata) such that hematocrit at the 1-egg stage is not significantly different than pre-breeding, baseline values. We also show that both pre-breeding hematocrit and the decrease in hematocrit associated with egg production are repeatable, and that females with the highest pre-breeding hematocrit values tend to show the largest decreases in hematocrit during egg production. We suggest that hematological changes during egg production are a good candidate mechanism for a regulatory-network based trade-off involving antagonistic pleiotropic effects of estrogens, which otherwise have essential reproductive functions.