bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dehydroepiandrosterone administration modulates endothelial and neutrophil adhesion molecule expression in vitro
Authors: Barkhausen Tanja , Westphal Britt-Mailin , Pütz Claudia , Krettek Christian , van Griensven Martijn 
Published: July 2006

Abstract
Introduction
The steroid hormone dehydroepiandrosterone (DHEA) exerts protecting effects in the treatment of traumatic and septic complications in several animal models. This effect goes along with reduced amounts of infiltrating immune cells in organs such as lung and liver. However, the underlying mechanisms of DHEA action are still not known. Adhesion molecules are important for the extravasation of neutrophils into organs where they may exhibit detrimental effects. Therefore, we investigated the in vitro effect of DHEA on the expression pattern of adhesion molecules of human endothelial cells and neutrophils.

Methods
Endothelial cells derived from human umbilical cord were subjected to an lipopolysaccharide (LPS) challenge. DHEA was administered in two different concentrations, 10-5 M and 10-8 M, as a single stimulus or in combination with LPS challenge. After two, four and 24 hours, fluorescence activated cell sorter (FACS) analysis for vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-selectin was performed. Neutrophils were freshly isolated from blood of 10 male healthy volunteers, stimulated the same way as endothelial cells and analyzed for surface expression of L-selectin, CD11b and CD18.

Results
In the present study, we were able to demonstrate effects of DHEA on the expression of every adhesion molecule investigated. DHEA exhibits opposite effects to those seen upon LPS exposure. Furthermore, these effects are both time and concentration dependent as most DHEA specific effects could be detected in the physiological concentration of 10-8 M.

Conclusion
Thus, we conclude that one mechanism by which DHEA may exert its protection in animal models is via the differential regulation of adhesion molecule expression.
Serum procalcitonin level and leukocyte antisedimentation rate as early predictors of respiratory dysfunction after oesophageal tumour resection
Authors: Bogar Lajos , Molnar Zsolt , Tarsoly Piroska , Kenyeres Peter , Marton Sandor 
Published: July 2006

Abstract
Introduction
Postoperative care after oesophageal tumour resection holds a high risk of respiratory complications. We therefore aimed to determine the value of systemic inflammatory markers in predicting arterial hypoxaemia as the earliest sign of developing lung injury after oesophageal tumour resection.

Methods
In a prospective observational study, 33 consecutive patients were observed for three days (T1–T3) after admission (T0) to an intensive care unit following oesophageal tumour resection. The daily highest values of the heart rate, axillary temperature, leukocyte count and PaCO2 were recorded. Serum C-reactive protein and procalcitonin concentrations and the leukocyte antisedimentation rate (LAR) were determined at T1 and T2. Respiratory function was monitored 6-hourly measurement of the PaO2/FIO2 ratio, and the lowest value was recorded at T3. Patients were categorised as normoxaemic or hypoxaemic using the cutoff value of 300 mmHg for PaO2/FIO2.

Results
Seventeen out of 33 patients were classified as hypoxaemic and 16 patients as normoxaemic at T3. Increases of temperature at T0 and of the procalcitonin and LAR values at T2 were predictive of hypoxaemia at T3 (P < 0.05, P < 0.01 and P < 0.001, respectively). The area under the receiver-operating characteristic curve was 0.65 for the temperature at T0, which was significantly lower than that for the procalcitonin level at T2 (0.83; 95% confidence interval, 0.69–0.97; P < 0.01) and that for LAR at T2 (0.89; 95% confidence interval, 0.77–1.00; P < 0.001).

Conclusion
These results suggest that an elevated LAR (>15%) and an elevated procalcitonin concentration (>2.5 ng/ml) measured on the second postoperative day can predict next-day arterial hypoxaemia (PaO2/FIO2 < 300 mmHg) after oesophageal tumour resection.
Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis
Authors: Garnacho-Montero Jose , Aldabo-Pallas Teresa , Garnacho-Montero Carmen , Cayuela Aurelio , Jiménez Rocio , Barroso Sonia , Ortiz-Leyba Carlos 
Published: July 2006

Abstract
Introduction
Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients.

Method
The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-α 308 promoter polymorphism; the polymorphism in the first intron of the TNF-β gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission.

Results
A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy.

Conclusion
This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.
Design principles of molecular networks revealed by global comparisons and composite motifs
Authors: Yu Haiyuan , Xia Yu , Trifonov Valery , Gerstein Mark 
Published: July 2006

Abstract
Background
Molecular networks are of current interest, particularly with the publication of many large-scale datasets. Previous analyses have focused on topologic structures of individual networks.

Results
Here, we present a global comparison of four basic molecular networks: regulatory, co-expression, interaction, and metabolic. In terms of overall topologic correlation - whether nearby proteins in one network are close in another - we find that the four are quite similar. However, focusing on the occurrence of local features, we introduce the concept of composite hubs, namely hubs shared by more than one network. We find that the three 'action' networks (metabolic, co-expression, and interaction) share the same scaffolding of hubs, whereas the regulatory network uses distinctly different regulator hubs. Finally, we examine the inter-relationship between the regulatory network and the three action networks, focusing on three composite motifs - triangles, trusses, and bridges - involving different degrees of regulation of gene pairs. Our analysis shows that interaction and co-expression networks have short-range relationships, with directly interacting and co-expressed proteins sharing regulators. However, the metabolic network contains many long-distance relationships: far-away enzymes in a pathway often have time-delayed expression relationships, which are well coordinated by bridges connecting their regulators.

Conclusion
We demonstrate how basic molecular networks are distinct yet connected and well coordinated. Many of our conclusions can be mapped onto structured social networks, providing intuitive comparisons. In particular, the long-distance regulation in metabolic networks agrees with its counterpart in social networks (namely, assembly lines). Conversely, the segregation of regulator hubs from other hubs diverges from social intuitions (as managers often are centers of interactions).
Shuffling of cis-regulatory elements is a pervasive feature of the vertebrate lineage
Authors: Sanges Remo , Kalmar Eva , Claudiani Pamela , D'Amato Maria , Muller Ferenc , Stupka Elia 
Published: July 2006

Abstract
Background
All vertebrates share a remarkable degree of similarity in their development as well as in the basic functions of their cells. Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development.

Results
We used a unique combination of tools to obtain regional global-local alignments of orthologous loci. This approach takes into account shuffling of regulatory regions that are likely to occur over evolutionary distances greater than those separating mammalian genomes. This approach revealed one order of magnitude more vertebrate conserved elements than was previously reported in over 2,000 genes, including a high number of genes found in the membrane and extracellular regions. Our analysis revealed that 72% of the elements identified have undergone shuffling. We tested the ability of the elements identified to enhance transcription in zebrafish embryos and compared their activity with a set of control fragments. We found that more than 80% of the elements tested were able to enhance transcription significantly, prevalently in a tissue-restricted manner corresponding to the expression domain of the neighboring gene.

Conclusion
Our work elucidates the importance of shuffling in the detection of cis-regulatory elements. It also elucidates how similarities across the vertebrate lineage, which go well beyond development, can be explained not only within the realm of coding genes but also in that of the sequences that ultimately govern their expression.
What makes species unique? The contribution of proteins with obscure features
Authors: Gollery Martin , Harper Jeff , Cushman John , Mittler Taliah , Girke Thomas , Zhu Jian-Kang , Bailey-Serres Julia , Mittler Ron 
Published: July 2006

Abstract
Background
Proteins with obscure features (POFs), which lack currently defined motifs or domains, represent between 18% and 38% of a typical eukaryotic proteome. To evaluate the contribution of this class of proteins to the diversity of eukaryotes, we performed a comparative analysis of the predicted proteomes derived from 10 different sequenced genomes, including budding and fission yeast, worm, fly, mosquito, Arabidopsis, rice, mouse, rat, and human.

Results
Only 1,650 protein groups were found to be conserved among these proteomes (BLAST E-value threshold of 10-6). Of these, only three were designated as POFs. Surprisingly, we found that, on average, 60% of the POFs identified in these 10 proteomes (44,236 in total) were species specific. In contrast, only 7.5% of the proteins with defined features (PDFs) were species specific (17,554 in total). As a group, POFs appear similar to PDFs in their relative contribution to biological functions, as indicated by their expression, participation in protein-protein interactions and association with mutant phenotypes. However, POF have more predicted disordered structure than PDFs, implying that they may exhibit preferential involvement in species-specific regulatory and signaling networks.

Conclusion
Because the majority of eukaryotic POFs are not well conserved, and by definition do not have defined domains or motifs upon which to formulate a functional working hypothesis, understanding their biochemical and biological functions will require species-specific investigations.
yrGATE: a web-based gene-structure annotation tool for the identification and dissemination of eukaryotic genes
Authors: Wilkerson Matthew D , Schlueter Shannon D , Brendel Volker 
Published: July 2006

AbstractYour Gene structure Annotation Tool for Eukaryotes (yrGATE) provides an Annotation Tool and Community Utilities for worldwide web-based community genome and gene annotation. Annotators can evaluate gene structure evidence derived from multiple sources to create gene structure annotations. Administrators regulate the acceptance of annotations into published gene sets. yrGATE is designed to facilitate rapid and accurate annotation of emerging genomes as well as to confirm, refine, or correct currently published annotations. yrGATE is highly portable and supports different standard input and output formats. The yrGATE software and usage cases are available at http://www.plantgdb.org/prj/yrGATE.
The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains
Authors: Iyer Lakshminarayan M , Burroughs A Maxwell , Aravind L 
Published: July 2006

Abstract
Background
Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear.

Results
We systematically analyzed prokaryotic Ub-related β-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages.

Conclusion
These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes.
A method for high-throughput gene expression signature analysis
Authors: Peck David , Crawford Emily D , Ross Kenneth N , Stegmaier Kimberly , Golub Todd R , Lamb Justin 
Published: July 2006

AbstractGenome-wide transcriptional profiling has shown that different biologic states (for instance, disease and response to pharmacologic manipulation) can be recognized by the expression pattern of relatively small numbers of genes. However, the lack of a practical and cost-effective technology for detection of these gene expression 'signatures' in large numbers of samples has severely limited their exploitation in important medical and pharmaceutical discovery applications. Here, we describe a solution based on the combination of ligation-mediated amplification with an optically addressed microsphere and flow cytometric detection system.
A strategy for extracting and analyzing large-scale quantitative epistatic interaction data
Authors: Collins Sean R , Schuldiner Maya , Krogan Nevan J , Weissman Jonathan S 
Published: July 2006

AbstractRecently, approaches have been developed for high-throughput identification of synthetic sick/lethal gene pairs. However, these are only a specific example of the broader phenomenon of epistasis, wherein the presence of one mutation modulates the phenotype of another. We present analysis techniques for generating high-confidence quantitative epistasis scores from measurements made using synthetic genetic array and epistatic miniarray profile (E-MAP) technology, as well as several tools for higher-level analysis of the resulting data that are greatly enhanced by the quantitative score and detection of alleviating interactions.
Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria
Authors: Ben Nasr Abdelhakim , Haithcoat Judith , Masterson Joseph E , Gunn John S , Eaves-Pyles Tonyia , Klimpel Gary R 
Published: July 2006

Abstract
Francisella tularensis is one of the most infectious human pathogens known. Although much has been learned about the immune response of mice using an attenuated live vaccine strain (LVS) derived from F. tularensis subspecies holarctica (Type B), little is known about the responses of human monocyte-derived immature dendritic cells (DC). Here, we show that optimal phagocytosis of LVS by DC is dependent on serum opsonization. We demonstrate that complement factor C3-derived opsonins and the major complement receptors expressed by DC, the integrins CR3 (CD11b/CD18) and CR4 (CD11c/CD18), play a critical role in this adhesion-mediated phagocytosis. LVS induced proinflammatory cytokine production and up-regulation of costimulatory surface proteins (CD40, CD86, and MHC Class II) on DC but resisted killing. Once taken up, LVS grew intracellularly, resulting in DC death. DC maturation and cytokine production were induced by direct contact/phagocytosis of LVS or interaction with soluble products of the bacteria, and enhanced activation was seen when LVS was pretreated with serum. Sonicated LVS and supernatants from LVS cultures were potent activators of DC, but LVS LPS failed to activate DC maturation or cytokine production. Serum-treated LVS rapidly induced (within 6 h) a number of cytokines including IL-10, a potent suppressor of macrophage functions and down-regulator of Th1-like responses and the Th1 response inducer IL-12. These results suggest that the simultaneous production of an activating (IL-12, IL-1β, and TNF-α) and a suppressing (IL-10) cytokine profile could contribute to the immunopathogenesis of tularemia.
Reciprocal Regulation of a Glucocorticoid Receptor-Steroidogenic Factor-1 Transcription Complex on the Dax-1 Promoter by Glucocorticoids and Adrenocorticotropic Hormone in the Adrenal Cortex
Authors: Gummow Brian M. , Scheys Joshua O. , Cancelli Victoria R. , Hammer Gary D. 
Published: July 2006

Abstract
Numerous genes required for adrenocortical steroidogenesis are activated by the nuclear hormone receptor steroidogenic factor 1 (SF-1) (NR5A1). Dax-1 (NR0B1), another nuclear hormone receptor, represses SF-1-dependent activation. Glucocorticoid products of the adrenal cortex provide negative feedback to the production of hypothalamic CRH and pituitary ACTH. We hypothesized that glucocorticoids stimulate an intraadrenal negative feedback loop via activation of Dax-1 expression. Reporter constructs show glucocorticoid-dependent synergy between SF-1 and glucocorticoid receptor (GR) in the activation of Dax-1, which is antagonized by ACTH signaling. We map the functional glucocorticoid response element between –718 and −704 bp, required for activation by GR and synergy with SF-1. Of three SF-1 response elements, only the –128-bp SF-1 response element is required for synergy with GR. Chromatin immunoprecipitation (ChIP) assays demonstrate that dexamethasone treatment increases GR and SF-1 binding to the endogenous murine Dax-1 promoter 10- and 3.5-fold over baseline. Serial ChIP assays reveal that that GR and SF-1 are part of the same complex on the Dax-1 promoter, whereas coimmunoprecipitation assay confirms the presence of a protein complex that contains both GR and SF-1. ACTH stimulation disrupts the formation of this complex by abrogating SF-1 binding to the Dax-1 promoter, while promoting SF-1 binding to the melanocortin-2 receptor (Mc2r) and steroidogenic acute regulatory protein (StAR) promoters. Finally, dexamethasone treatment increases endogenous Dax-1 expression and concordantly decreases StAR expression. ACTH signaling antagonizes the increase in Dax-1 yet strongly activates StAR transcription. These data indicate that GR provides feedback regulation of adrenocortical steroid production through synergistic activation of Dax-1 with SF-1, which is antagonized by ACTH activation of the adrenal cortex.
Aminoboranes as new iminium ion generators in amination reactions
Authors: Suginome Michinori 
Published: July 2006

Abstract
The utilization of aminoborane derivatives in amination reactions such as Strecker-type aminative cyanation, Mannich-type reaction, and reductive amination is described. Bis(dialkylamino)cyanoboranes and bis(dialkylamino)boron enolates underwent the concurrent transfer of the amino group and either the cyano or the enoxy group from the boron to carbonyl carbon atom in their reaction with aldehydes, leading to the formation of α-amino nitriles and β-amino ketones, respectively. Bis(dialkylamino)borane derivatives that lack the additional nucleophilic groups on the boron atoms were found to serve as effective generators of iminium ions from aldehydes. In the presence of these aminoboranes, reactions of aldehydes with ketene silyl acetals or silyl enol ethers take place, giving Mannich-type products, i.e., β-amino esters and ketones, selectively. Using diisopropylamino-substituted boron compounds, which are designed as "universal" iminium ion generators, reactions of free sec-amines, aldehydes, and ketene silyl acetals proceed efficiently, giving β-amino esters in which the amino groups are derived exclusively from the free amines. The use of the universal iminium ion generator is also effective for reductive amination of aldehydes, in which NaBH4 is used as a hydride donor.
Asymmetric synthesis with the robust and versatile 10-substituted 9-borabicyclo[3.3.2]decanes: Homoallylic amines from aldimines
Authors: Hernandez Eliud , Canales Eda , Gonzalez Eduvigis , Soderquist John A. 
Published: July 2006

Abstract
The asymmetric allylboration of N-H aldimines, generated from either N-trimethylsilyl or N-diisobutylalanyl precursors, with B-allyl-9-borabicyclo[3.3.2]decane is described. The desired homoallylic amines are obtained efficiently (60-90 %) and selectively (60-89 % ee). A non-oxidative work-up procedure has also been developed for this new method, which permits the recovery of the air-stable pseudoephedrine (PE) complex (50-70 %), which is conveniently converted back to B-allyl-9-borabicyclo[3.3.2]decane (98 %) with allylmagnesium bromide in ether for its reuse in the asymmetric allylboration process. Additional studies were conducted to better understand these processes and the origin of the observed enantioselectivity.
Synthesis of transition-metal-containing poly(pyrazabole)s
Authors: Matsumoto Fukashi , Chujo Yoshiki 
Published: July 2006

Abstract
Novel organoboron polymers containing transition metals (Ni, Pd, Pt) and pyrazaboles in the main chain were prepared by Cu-catalyzed coupling polymerization. The Ni- and Pt-containing polymers showed MLCT (metal-to-ligand charge transfer) absorption, whereas the Pd-containing polymer did not demonstrate the absorption. Only the Pd-containing polymer exhibited the emission spectrum with a vibronic structure. These differences in the optical properties were studied in detail.