bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas
Authors: Ding B. Belinda , Yu J. Jessica , Yu Raymond Y.-L. , Mendez Lourdes M. , Shaknovich Rita , Zhang Yonghui , Cattoretti Giorgio , Ye B. Hilda 
Published: October 2007

Abstract
Diffuse large B-cell lymphoma (DLBCL) consists of at least 2 phenotypic subtypes; that is, the germinal center B-cell–like (GCB-DLBCL) and the activated B-cell–like (ABC-DLBCL) groups. It has been shown that GCB-DLBCL responds favorably to chemotherapy and expresses high levels of BCL6, a transcription repressor known to play a causative role in lymphomagenesis. In comparison, ABC-DLBCL has lower levels of BCL6, constitutively activated nuclear factor-κB, and tends to be refractory to chemotherapy. Here, we report that the STAT3 gene is a transcriptional target of BCL6. As a result, high-level STAT3 expression and activation are preferentially detected in ABC-DLBCL and BCL6-negative normal germinal center B cells. Most importantly, inactivating STAT3 by either AG490 or small interference RNA in ABC-DLBCL cells inhibits cell proliferation and triggers apoptosis. These phenotypes are accompanied by decreased expression of several known STAT3 target genes, including c-Myc, JunB, and Mcl-1, and increased expression of the cell- cycle inhibitor p27. In addition to identifying STAT3 as a novel BCL6 target gene, our results define a second oncogenic pathway, STAT3 activation, which operates in ABC-DLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas.
Short sequence motifs, overrepresented in mammalian conserved non-coding sequences
Authors: Minovitsky Simon , Stegmaier Philip , Kel Alexander , Kondrashov Alexey S , Dubchak Inna 
Published: October 2007

Abstract

Background
A substantial fraction of non-coding DNA sequences of multicellular eukaryotes is under selective constraint. In particular, ~5% of the human genome consists of conserved non-coding sequences (CNSs). CNSs differ from other genomic sequences in their nucleotide composition and must play important functional roles, which mostly remain obscure.

Results
We investigated relative abundances of short sequence motifs in all human CNSs present in the human/mouse whole-genome alignments vs. three background sets of sequences: (i) weakly conserved or unconserved non-coding sequences (non-CNSs); (ii) near-promoter sequences (located between nucleotides -500 and -1500, relative to a start of transcription); and (iii) random sequences with the same nucleotide composition as that of CNSs. When compared to non-CNSs and near-promoter sequences, CNSs possess an excess of AT-rich motifs, often containing runs of identical nucleotides. In contrast, when compared to random sequences, CNSs contain an excess of GC-rich motifs which, however, lack CpG dinucleotides. Thus, abundance of short sequence motifs in human CNSs, taken as a whole, is mostly determined by their overall compositional properties and not by overrepresentation of any specific short motifs. These properties are: (i) high AT-content of CNSs, (ii) a tendency, probably due to context-dependent mutation, of A's and T's to clump, (iii) presence of short GC-rich regions, and (iv) avoidance of CpG contexts, due to their hypermutability. Only a small number of short motifs, overrepresented in all human CNSs are similar to binding sites of transcription factors from the FOX family.

Conclusion
Human CNSs as a whole appear to be too broad a class of sequences to possess strong footprints of any short sequence-specific functions. Such footprints should be studied at the level of functional subclasses of CNSs, such as those which flank genes with a particular pattern of expression. Overall properties of CNSs are affected by patterns in mutation, suggesting that selection which causes their conservation is not always very strong.
Establishment of an early liver fibrosis model by the hydrodynamics-based transfer of TGF-β1 gene
Authors: Yang Kun-Lin , Hung Kuo-Chen , Chang Wen-Teng , Li Eric IC 
Published: October 2007

Abstract

Background
Liver fibrosis represents a significant and severe health care problem and there are no efficient drugs for therapy so far. Preventing the progression of fibrogenesis and revival endogenous repair activities is an important strategy for both current and future therapies. Many studies of liver fibrosis consist of animal testing with various hepatotoxins. Although this method is often used, the model at which cirrhosis or extensive fibrosis becomes irreversible has not been well defined and is not representative of early-stage fibrogenesis. We here report the establishment of a transient and reversible liver fibrosis animal model which may better represent an early and natural fibrotic event. We used a high-speed intravenous injection of naked plasmid DNA of transforming growth factor-β1 (TGF-β1) gene which is under the control of a metallothionein-regulated gene in a pPK9A expression vector into the tail vein (the hydrodynamics-based transfer) and fed the mouse with zinc sulfate (ZnSO4)-containing water simultaneously.

Results
Using our hydrodynamics-based gene transfer model we found that upon induction by ZnSO4, the serum TGF-β1 level in Balb/c mice and Sp1 transcription factor binding activity peaked at 48 h and declined thereafter to a normal level on the 5th day. In addition, mRNA and protein levels of TGF-β1 in the liver were also upregulated at 48 h. Furthermore, induction of TGF-β1 increased the α-smooth muscle actin (α-SMA), p-Smad2/3, hydroxyproline and collagen 1A2 (Col 1A2) levels in the liver, suggesting a significant liver fibrosis.

Conclusion
Our results show that TGF-β1 in pPK9a-transferred mice liver with ZnSO4 feeding can achieve a high expression level with significant fibrosis. However, since TGF-β1 induction is transient in our model, the fibrotic level does not reach a large scale (panlobular fibrosis) as seen in the CCl4-treated liver. Our model hence represents a dynamic and reversible liver fibrosis and could be a useful tool for studying early molecular mechanism of fibrogenesis or screening of antifibrotic drugs for clinical use.
Estimating the role of casual contact from the community in transmission of Bordetella pertussis to young infants
Authors: Wendelboe Aaron M , Hudgens Michael G , Poole Charles , Van Rie Annelies 
Published: October 2007

AbstractThe proportion of infant pertussis cases due to transmission from casual contact in the community has not been estimated since before the introduction of pertussis vaccines in the 1950s. This study aimed to estimate the proportion of pertussis transmission due to casual contact using demographic and clinical data from a study of 95 infant pertussis cases and their close contacts enrolled at 14 hospitals in France, Germany, Canada, and the U.S. between February 2003 and September 2004. A complete case analysis was conducted as well as multiple imputation (MI) to account for missing data for participants and close contacts who did not participate. By considering all possible close contacts, the MI analysis estimated 66% of source cases were close contacts, implying the minimum attributable proportion of infant cases due to transmission from casual contact with community members was 34% (95% CI = 24%, 44%). Estimates from the complete case analysis were comparable but less precise. Results were sensitive to changes in the operational definition of a source case, which broadened the range of MI point estimates of transmission from casual community contact to 20%–47%. We conclude that casual contact appears to be responsible for a substantial proportion of pertussis transmission to young infants.Medical subject headings (MeSH): multiple imputation, pertussis, transmission, casual contact, sensitivity analysis, missing data, community.
Purification of infectious human herpesvirus 6A virions and association of host cell proteins
Authors: Hammarstedt Maria , Ahlqvist Jenny , Jacobson Steven , Garoff Henrik , Fogdell-Hahn Anna 
Published: October 2007

AbstractBackgroundViruses that are incorporating host cell proteins might trigger autoimmune diseases. It is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6A (HHV-6A) in multiple sclerosis (MS).ResultsWe have established a method for rapid and morphology preserving purification of HHV-6A virions, which in combination with parallel analyses with background control material released from mock-infected cells facilitates qualitative and quantitative investigations of the protein content of HHV-6A virions. In our iodixanol gradient purified preparation, we detected high levels of viral DNA by real-time PCR and viral proteins by metabolic labelling, silver staining and western blots. In contrast, the background level of cellular contamination was low in the purified samples as demonstrated by the silver staining and metabolic labelling analyses. Western blot analyses showed that the cellular complement protein CD46, the receptor for HHV-6A, is associated with the purified and infectious virions. Also, the cellular proteins clathrin, ezrin and Tsg101 are associated with intact HHV-6A virions.ConclusionCellular proteins are associated with HHV-6A virions. The relevance of the association in disease and especially in autoimmunity will be further investigated.
The impact of the introduction of critical care outreach services in England: a multicentre interrupted time-series analysis
Authors: Gao Haiyan , Harrison David A , Parry Gareth J , Daly Kathleen , Subbe Christian P , Rowan Kathy 
Published: October 2007

Abstract
Introduction
Critical care outreach services (CCOS) have been widely introduced in England with little rigorous evaluation. We undertook a multicentre interrupted time-series analysis of the impact of CCOS, as characterised by the case mix, outcome and activity of admissions to adult, general critical care units in England.

Methods
Data from the Case Mix Programme Database (CMPD) were linked with the results of a survey on the evolution of CCOS in England. Over 350,000 admissions to 172 units between 1996 and 2004 were extracted from the CMPD. The start date of CCOS, activities performed, coverage and staffing were identified from survey data and other sources. Individual patient-level data in the CMPD were collapsed into a monthly time series for each unit (panel data). Population-averaged panel-data models were fitted using a generalised estimating equation approach. Various potential outcomes reflecting possible objectives of the CCOS were investigated in three subgroups of admissions: all admissions to the unit, admissions from the ward, and unit survivors discharged to the ward. The primary comparison was between periods when a formal CCOS was and was not present. Secondary analyses considered specific CCOS activities, coverage and staffing.

Results
In all, 108 units were included in the analysis, of which 79 had formal CCOS starting between 1996 and 2004. For admissions from the ward, CCOS were associated with significant decreases in the proportion of admissions receiving cardiopulmonary resuscitation before admission (odds ratio 0.84, 95% confidence interval 0.73 to 0.96), admission out of hours (odds ratio 0.91, 0.84 to 0.97) and mean Intensive Care National Audit & Research Centre physiology score (decrease in mean 1.22, 0.31 to 2.12). There was no significant change in unit mortality (odds ratio 0.97, 0.87 to 1.08) and no significant, sustained effects on outcomes for unit survivors discharged alive to the ward.

Conclusion
The observational nature of the study limits its ability to infer causality. Although associations were observed with characteristics of patients admitted to critical care units, there was no clear evidence that CCOS have a big impact on the outcomes of these patients, or for characteristics of what should form the optimal CCOS.
Common gene expression strategies revealed by genome-wide analysis in yeast
Authors: García-Martínez José , González-Candelas Fernando , Pérez-Ortín José E 
Published: October 2007

Abstract
Background
Gene expression is a two-step synthesis process that ends with the necessary amount of each protein required to perform its function. Since the protein is the final product, the main focus of gene regulation should be centered on it. However, because mRNA is an intermediate step and the amounts of both mRNA and protein are controlled by their synthesis and degradation rates, the desired amount of protein can be achieved following different strategies.

Results
In this paper we present the first comprehensive analysis of the relationships among the six variables that characterize gene expression in a living organism: transcription and translation rates, mRNA and protein amounts, and mRNA and protein stabilities. We have used previously published data from exponentially growing Saccharomyces cerevisiae cells. We show that there is a general tendency to harmonize the levels of mRNA and protein by coordinating their synthesis rates and that functionally related genes tend to have similar values for the six variables.

Conclusion
We propose that yeast cells use common expression strategies for genes acting in the same physiological pathways. This trend is more evident for genes coding for large and stable protein complexes, such as ribosomes or the proteasome. Hence, each functional group can be defined by a 'six variable profile' that illustrates the common strategy followed by the genes included in it. Genes encoding subunits of protein complexes show a tendency to have relatively unstable mRNAs and a less balanced profile for mRNA than for protein, suggesting a stronger regulation at the transcriptional level.
Comparative genomic analysis of fungal genomes reveals intron-rich ancestors
Authors: Stajich Jason E , Dietrich Fred S , Roy Scott W 
Published: October 2007

Abstract
Background
Eukaryotic protein-coding genes are interrupted by spliceosomal introns, which are removed from transcripts before protein translation. Many facets of spliceosomal intron evolution, including age, mechanisms of origins, the role of natural selection, and the causes of the vast differences in intron number between eukaryotic species, remain debated. Genome sequencing and comparative analysis has made possible whole genome analysis of intron evolution to address these questions.

Results
We analyzed intron positions in 1,161 sets of orthologous genes across 25 eukaryotic species. We find strong support for an intron-rich fungus-animal ancestor, with more than four introns per kilobase, comparable to the highest known modern intron densities. Indeed, the fungus-animal ancestor is estimated to have had more introns than any of the extant fungi in this study. Thus, subsequent fungal evolution has been characterized by widespread and recurrent intron loss occurring in all fungal clades. These results reconcile three previously proposed methods for estimation of ancestral intron number, which previously gave very different estimates of ancestral intron number for eight eukaryotic species, as well as a fourth more recent method. We do not find a clear inverse correspondence between rates of intron loss and gain, contrary to the predictions of selection-based proposals for interspecific differences in intron number.

Conclusion
Our results underscore the high intron density of eukaryotic ancestors and the widespread importance of intron loss through eukaryotic evolution.
Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation
Authors: Schaer Christian A , Vallelian Florence , Imhof Alexander , Schoedon Gabriele , Schaer Dominik J 
Published: October 2007

AbstractMacrophages constitute the major cellular compartment for hemoglobin (Hb) degradation and subsequent recycling of heme-iron to erythropoiesis. Dysregulation of macrophage iron and heme metabolism is a major pathophysiologic determinant of anemia of chronic disease. In this study, we show that the heme transporter heme carrier protein 1 (HCP-1) is expressed in human macrophages. Within early endosomes, HCP-1 colocalizes with endocytosed Hb-haptoglobin (Hp) complexes, which are taken up via the CD163 scavenger receptor pathway. Hb-Hp passes the divalent metal transporter 1B/HCP-1-positive endosomal compartment on its route from the cell surface to lysosomes. HCP-1 mRNA and protein expression are down-regulated by stimulation of macrophages with various TLR agonists and IFN-γ. The profound suppression of HCP-1 expression by inflammatory macrophage activation parallels the regulation of the iron exporter ferroportin. In contrast, dexamethasone enhanced HCP-1 expression significantly. Given the spatial relationship, we propose that the Hb scavenger receptor CD163 and HCP-1 constitute a linked pathway for Hb catabolism and heme-iron recycling in human macrophages.
Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease
Authors: Cabrelle Anna , Dell’Aica Isabella , Melchiori Luca , Carraro Samuela , Brunetta Enrico , Niero Raffaele , Scquizzato Elisa , D’Intino Giulia , Calzà Laura , Garbisa Spiridione , Agostini Carlo 
Published: October 2007

AbstractHyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-γ production, with down-regulation of T-box (T-bet; marker of Th1 gene expression) and up-regulation of GATA-3 (marker gene of Th2) on IL-2/PHA-activated T cells. In parallel, we showed a strong down-regulation of the chemokine receptor CXCR3 expression on activated T cells. The latter effect and the down-modulation of matrix metalloproteinase 9 expression may eventually lead to the inhibition of migratory capability and matrix traversal toward the chemoattractant CXCL10 by activated lymphocytes that we observed in vitro. The effect of Hyp was thus evaluated on an animal model of experimental allergic encephalomyelitis (EAE), a classic, Th1-mediated autoimmune disease of the CNS, and we observed that Hyp attenuates the severity of the disease symptoms significantly. Together, these properties qualify Hyp as a putative, therapeutic molecule for the treatment of autoimmune inflammatory disease sustained by Th1 cells, including EAE.
Magnetic maps in animals: nature's GPS
Authors: Lohmann Kenneth J. , Lohmann Catherine M. F. , Putman Nathan F. 
Published: October 2007

SUMMARY
Diverse animals detect the Earth's magnetic field and use it as a cue in orientation and navigation. Most research on magnetoreception has focused on the directional or `compass' information that can be extracted from the Earth's field. Because the field varies predictably across the surface of the globe, however, it also provides a potential source of positional or `map'information, which some animals use to steer themselves along migratory pathways or to navigate toward specific target areas. The use of magnetic positional information has been demonstrated in several diverse animals including sea turtles, spiny lobsters, newts and birds, suggesting that such systems are phylogenetically widespread and can function over a wide range of spatial scales. These `magnetic maps' have not yet been fully characterized. They may be organized in several fundamentally different ways, some of which bear little resemblance to human maps, and they may also be used in conjunction with unconventional navigational strategies.
Light scattering by selected zooplankton from the Gulf of Aqaba
Authors: Gagnon Y. L. , Shashar N. , Warrant E. J. , Johnsen S. J. 
Published: October 2007

SUMMARYLight scattering by zooplankton was investigated as a major factor undermining transparency camouflage in these pelagic animals. Zooplankton of differing transparencies – including the hyperiid amphipod Anchylomera blossevillei, an unknown gammarid amphipod species, the brine shrimp Artemia salina, the euphausiid shrimp Euphausia diomedeae, the isopod Gnathia sp., the copepods Pontella karachiensis, Rhincalanus sp. and Sapphirina sp., the chaetognath Sagitta elegans and an enteropneust tornaria larva– were illuminated dorsally with white light (400–700 nm). Spectral measurements of direct transmittance as well as relative scattered radiances at angles of 30°, 90°, 150° and 180° from the light source were taken. The animals sampled had transparencies between 1.5% and 75%. For all species, the highest recorded relative scattered radiance was at 30°, with radiances reaching 38% of the incident radiance for the amphipod A. blossevillei. Scattering patterns were also found to be species-specific for most animals. Relative scattered radiances were used to estimate sighting distances at different depths. These calculations predict that all of the examined zooplankton are brighter than the background radiance when viewed horizontally, or from diagonally above or below at shallow depths. Thus, in contrast to greater depths, the best strategy for detecting transparent zooplankton in the epipelagic environment may be to search for them from above while looking diagonally downwards, looking horizontally or looking from below diagonally upwards. Looking directly upwards proved to be more beneficial than the other viewing angles only when the viewed animal was at depths greater than 40 m.
Assessment of sperm chemokinesis with exposure to jelly coats of sea urchin eggs and resact: a microfluidic experiment and numerical study
Authors: Inamdar Munish V. , Kim Taeyong , Chung Yao-Kuang , Was Alex M. , Xiang Xinran , Wang Chia-Wei , Takayama Shuichi , Lastoskie Christian M. , Thomas Florence I. M. , Sastry Ann Marie 
Published: October 2007

SUMMARYSpecific peptides contained within the extracellular layer, or jelly coat,of a sea urchin egg have been hypothesized to play an important role in fertilization, though separate accounting of the effects of chemoattraction,chemokinesis, sperm agglomeration and the other possible roles of the jelly coat have not been reported. In the present study, we used a microfluidic device that allowed determination of the differences in the diffusion coefficients of sperm of the purple sea urchin Arbacia punctulatasubjected to two chemoattractants, namely the jelly coat and resact. Our objectives were twofold: (1) to experimentally determine and compare the diffusion coefficients of Arbacia punctulata spermatozoa in seawater,jelly coat solution and resact solution; and (2) to determine the effect of sea urchin sperm diffusion coefficient and egg size on the sperm–egg collision frequency using stochastic simulations. Numerical values of the diffusion coefficients obtained by diffusing the spermatozoa in seawater,resact solution and jelly coat solution were used to quantify the chemotactic effect. This allowed direct incorporation of known enlargements of the egg,and altered sperm diffusion coefficients in the presence of chemoattractant,in the stochastic simulations. Simulation results showed that increase in diffusion coefficient values and egg diameter values increased the collision frequency. From the simulation results, we concluded that type of sperm, egg diameter and diffusion coefficient are significant factors in egg fertilization. Increasing the motility of sperm appears to be the prominent role of the jelly coat.