bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sickle Red Cell–Endothelium Interactions
Authors: KAUL DHANANJAY K. , FINNEGAN EILEEN , BARABINO GILDA A. 
Published: August 2008

ABSTRACTPeriodic recurrence of painful vaso‐occlusive crisis is the defining feature of sickle cell disease. Among multiple pathologies associated with this disease, sickle red cell–endothelium interaction has been implicated as a potential initiating mechanism in vaso‐occlusive events. This review focuses on various interrelated mechanisms involved in human sickle red cell adhesion. We discuss in vitro and microcirculatory findings on sickle red cell adhesion, its potential role in vaso‐occlusion, and the current understanding of receptor‐ligand interactions involved in this pathological phenomenon. In addition, we discuss the contribution of other cellular interactions (leukocytes recruitment and leukocyte–red cell interaction) to vaso‐occlusion, as observed in transgenic sickle mouse models. Emphasis is given to recently discovered adhesion molecules that play a predominant role in mediating human sickle red cell adhesion. Finally, we analyze various therapeutic approaches for inhibiting sickle red cell adhesion by targeting adhesion molecules and also consider therapeutic strategies that target stimuli involved in endothelial activation and initiation of adhesion.
Model-based analysis of interferon-β induced signaling pathway
Authors: Smieja Jaroslaw , Jamaluddin Mohammad , Brasier Allan R. , Kimmel Marek 
Published: August 2008

Abstract
Motivation: Interferon-β induced JAK-STAT signaling pathways contribute to mucosal immune recognition and an anti-viral state. Though the main molecular mechanisms constituting these pathways are known, neither the detailed structure of the regulatory network, nor its dynamics has yet been investigated. The objective of this work is to build a mathematical model for the pathway that would serve two purposes: (1) to reproduce experimental results in simulation of both early and late response to Interferon-β stimulation and (2) to explain experimental phenomena generating new hypotheses about regulatory mechanisms that cannot yet be tested experimentally.
Results: Experimentally determined time dependent changes in the major components of this pathway were used to build a mathematical model describing pathway dynamics in the form of ordinary differential equations. The experimental results suggested existence of unknown negative control mechanisms that were tested numerically using the model. Together, experimental and numerical data show that the epithelial JAK-STAT pathway might be subjected to previously unknown dynamic negative control mechanisms: (1) activation of dormant phosphatases and (2) inhibition of nuclear import of IRF1.
Availability: The model, written in Matlab, is available online at www.stat.rice.edu/~jsmieja/IFN
Contact: jaroslaw.smieja@polsl.pl
Supplementary information: Supplementary data are available at Bioinformatics online.
Patterning of Inflorescences and Flowers by the F-Box Protein DOUBLE TOP and the LEAFY Homolog ABERRANT LEAF AND FLOWER of Petunia
Authors: Souer Erik , Rebocho Alexandra B. , Bliek Mattijs , Kusters Elske , de Bruin Robert A.M. , Koes Ronald 
Published: August 2008

AbstractAngiosperms display a wide variety of inflorescence architectures differing in the positions where flowers or branches arise. The expression of floral meristem identity (FMI) genes determines when and where flowers are formed. In Arabidopsis thaliana, this is regulated via transcription of LEAFY (LFY), which encodes a transcription factor that promotes FMI. We found that this is regulated in petunia (Petunia hybrida) via transcription of a distinct gene, DOUBLE TOP (DOT), a homolog of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Mutation of DOT or its tomato (Solanum lycopersicum) homolog ANANTHA abolishes FMI. Ubiquitous expression of DOT or UFO in petunia causes very early flowering and transforms the inflorescence into a solitary flower and leaves into petals. Ectopic expression of DOT or UFO together with LFY or its homolog ABERRANT LEAF AND FLOWER (ALF) in petunia seedlings activates genes required for identity or outgrowth of organ primordia. DOT interacts physically with ALF, suggesting that it activates ALF by a posttranslational mechanism. Our findings suggest a wider role than previously thought for DOT and UFO in the patterning of flowers and indicate that the different roles of LFY and UFO homologs in the spatiotemporal control of floral identity in distinct species result from their divergent expression patterns.
Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: Comparison with isoform G and implications for structure‐based drug discovery
Authors: Lohman Jeremy R. , Olson Andrew C. , Remington S. James 
Published: August 2008

AbstractEnzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as Mycobacterium tuberculosis and Candida albicans. Two isoforms have been identified for malate synthase, the second enzyme in the pathway. Isoform A, found in fungi and plants, comprises ∼530 residues, whereas isoform G, found only in bacteria, is larger by ∼200 residues. Crystal structures of malate synthase isoform G from Escherichia coli and Mycobacterium tuberculosis were previously determined at moderate resolution. Here we describe crystal structures of E. coli malate synthase A (MSA) in the apo form (1.04 Å resolution) and in complex with acetyl‐coenzyme A and a competitive inhibitor, possibly pyruvate or oxalate (1.40 Å resolution). In addition, a crystal structure for Bacillus anthracis MSA at 1.70 Å resolution is reported. The increase in size between isoforms A and G can be attributed primarily to an inserted α/β domain that may have regulatory function. Upon binding of inhibitor or substrate, several active site loops in MSA undergo large conformational changes. However, in the substrate bound form, the active sites of isoforms A and G from E. coli are nearly identical. Considering that inhibitors bind with very similar affinities to both isoforms, MSA is as an excellent platform for high‐resolution structural studies and drug discovery efforts.
Benzothiadiazole affects the leaf proteome in arctic bramble (Rubus arcticus)
Authors: HUKKANEN ANNE , KOKKO HARRI , BUCHALA ANTONY , HÄYRINEN JUKKA , KÄRENLAMPI SIRPA 
Published: August 2008

SUMMARYBenzothiadiazole (BTH) induces resistance to the downy mildew pathogen, Peronospora sparsa, in arctic bramble, but the basis for the BTH‐induced resistance is unknown. Arctic bramble cv. Mespi was treated with BTH to study the changes in leaf proteome and to identify proteins with a putative role in disease resistance. First, BTH induced strong expression of one PR‐1 protein isoform, which was also induced by salicylic acid (SA). The PR‐1 was responsive to BTH and exogenous SA despite a high endogenous SA content (20–25 µg/g fresh weight), which increased to an even higher level after treatment with BTH. Secondly, a total of 792 protein spots were detected in two‐dimensional gel electrophoresis, eight proteins being detected solely in the BTH‐treated plants. BTH caused up‐ or down‐regulation of 72 and 31 proteins, respectively, of which 18 were tentatively identified by mass spectrometry. The up‐regulation of flavanone‐3‐hydroxylase, alanine aminotransferase, 1‐aminocyclopropane‐1‐carboxylate oxidase, PR‐1 and PR‐10 proteins may partly explain the BTH‐induced resistance against P. sparsa. Other proteins with changes in intensity appear to be involved in, for example, energy metabolism and protein processing. The decline in ATP synthase, triosephosphate isomerase, fructose bisphosphate aldolase and glutamine synthetase suggests that BTH causes significant changes in primary metabolism, which provides one possible explanation for the decreased vegetative growth of foliage and rhizome observed in BTH‐treated plants.
Clinical experience with a pumpless extracorporeal lung assist device
Authors: Hammell C. , Forrest M. , Barrett P. 
Published: August 2008

SummaryWe present three patients with respiratory failure in whom conventional mechanical lung ventilation resulted in unacceptably high levels of carbon dioxide, severe acidosis and high vasopressor requirements. A pumpless arteriovenous extracorporeal carbon dioxide removal device (Novalung™) was inserted. Arterial carbon dioxide levels were reduced rapidly with a corresponding increase in pH, reduction in vasopressor requirements and reduction in inspiratory pressures. One patient required the additional use of high frequency oscillatory ventilation. There were no complications associated with use of the device. We conclude that use of extracorporeal carbon dioxide removal devices should be considered at an early stage in the management of respiratory failure refractory to conventional ventilatory techniques.
Linkage disequilibrium and signatures of selection on chromosomes 19 and 29 in beef and dairy cattle
Authors: Prasad A. , Schnabel R. D. , McKay S. D. , Murdoch B. , Stothard P. , Kolbehdari D. , Wang Z. , Taylor J. F. , Moore S. S. 
Published: August 2008

SummaryThe objective of this study was to quantify the extent of linkage disequilibrium (LD) on bovine chromosomes 19 and 29 and to study the pattern of selection signatures in beef and dairy breeds (Angus and Holstein) of Bos taurus. The extent of LD was estimated for 370 and 186 single nucleotide polymorphism markers on BTA19 and 29 respectively using the square of the correlation coefficient (r2) among alleles at pairs of loci. A comparison of the extent of LD found that the decline of LD followed a similar pattern in both breeds. We observed long‐range LD and found that LD dissipates to background levels at a locus separation of about 20 Mb on both chromosomes. Along each chromosome, patterns of LD were variable in both breeds. We find that a minimum of 30 000 informative and evenly spaced markers would be required for whole‐genome association studies in cattle. In addition, we have identified chromosomal regions that show some evidence of selection for economically important traits in Angus and Holstein cattle. The results of this study are of importance for the design and application of association studies.
Impact of adiponectin and ghrelin on incident glucose intolerance and on weight change
Authors: Bennett Nadia R. , Boyne Michael S. , Cooper Richard S. , Royal‐Thomas Tamika Y. , Bennett Franklyn I. , Luke Amy , Wilks Rainford J. , Forrester Terrence E. 
Published: August 2008

SummaryObjectives  Adiponectin and ghrelin are associated with adiposity and type 2 diabetes in several studies. We sought to prospectively determine the interaction of adiponectin and ghrelin in the development of adiposity and hyperglycaemia.Design  Prospective observational study.Participants  393 community‐dwelling Afro‐Jamaicans (mean age 47 ± 13 years; BMI 27·3 ± 6·3 kg/m2; 63% women) without glucose intolerance at baseline.Measurements  Anthropometry, fasting plasma glucose, 2‐h plasma glucose, insulin resistance (HOMA‐IR), adiponectin and ghrelin concentrations were measured at baseline and 4·1 ± 0·9 years later. Multivariate analyses were used to explore the associations of HOMA‐IR, adiponectin and ghrelin with weight change and glycaemia.Results  The mean weight change was 2·6 ± 5·5 kg. There were 114 incident cases of impaired glucose tolerance (IGT) and 35 cases of diabetes mellitus. Adiponectin was positively correlated with age and female sex (P‐values < 0·01). After adjusting for age and sex, adiponectin and ghrelin were significantly correlated with weight at baseline and follow‐up. However, they were not associated with weight change even after further adjustment for baseline weight. Adiponectin, but not ghrelin, was associated with 2‐h glucose concentrations at follow‐up even after adjusting for age, sex, HOMA‐IR and BMI (P = 0·04). In the fully adjusted logistic regression model, adiponectin predicted incident IGT (OR 0·93; 95% CI: 0·87–0·99) and attenuated the effect of BMI on incident IGT.Conclusions  These longitudinal data show that adiponectin and ghrelin may not be causally involved in the development of obesity. However, adiponectin is independently associated with decreased risk of incident IGT.
Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T‐cell lymphoma
Authors: Marquard L , Gjerdrum L M , Christensen Ib J , Jensen P B , Sehested M , Ralfkiaer E 
Published: August 2008

Aims:  Aberrant histone acetylation has been associated with malignancy and histone deacetylase (HDAC) inhibitors are currently being investigated in numerous clinical trials. So far, the malignancy most sensitive to HDAC inhibitors has been cutaneous T‐cell lymphoma (CTCL). The reason for this sensitivity is unclear and studies on HDAC expression and histone acetylation in CTCL are lacking. The aim of this study was to address this issue.Methods and results:  The immunohistochemical expression of HDAC1, HDAC2, HDAC6, and acetylated H4 was examined in 73 CTCLs and the results related to histological subtypes and overall survival. HDAC1 was most abundantly expressed (P < 0.0001), followed by HDAC2; HDAC6 and H4 acetylation were equally expressed. HDAC2 (P = 0.001) and H4 acetylation (P = 0.03) were significantly more common in aggressive than indolent CTCL subtypes. In contrast, no differences were observed for HDAC1 and HDAC6. In a Cox analysis, elevated HDAC6 was the only parameter showing significant influence on survival (P = 0.04).Conclusions:  High expression of HDAC2 and acetylated H4 is more common in aggressive than indolent CTCL. HDAC6 expression is associated with a favorable outcome independent of the subtype.
Biogeography of the ubiquitous marine bacterium Alteromonas macleodii determined by multilocus sequence analysis
Authors: IVARS‐MARTÍNEZ ELENA , D’AURIA GIUSEPPE , RODRÍGUEZ‐VALERA FRANCISCO , SÁNCHEZ‐PORRO CRISTINA , VENTOSA ANTONIO , JOINT IAN , MÜHLING MARTIN 
Published: August 2008

AbstractTwenty‐three isolates of the widely distributed marine bacteria Alteromonas macleodii have been analysed by multilocus sequence analysis combined with phylogenetic and multivariate statistical analyses. The strains originated from the Pacific Ocean, Mediterranean Sea, English Channel, Black Sea and Thailand. Using the nucleotide sequences of nine loci for each of the 23 isolates, a robust identification was achieved of different clades within the single species. Strains generally clustered with the depth in the water column from which the isolate originated. Strains also showed more recombination with isolates from the same vicinity, suggesting that genetic exchange plays a role in diversification of planktonic marine prokaryotes. This study thus shows for the first time for a large set of isolates of a species of planktonic marine prokaryotes that multilocus sequence analysis overcomes the problems associated with the analysis of individual marker genes or presence of extensive recombination events. It can thus achieve intraspecific identification to the level of genotypes and, by comparison with relevant environmental data, ecotypes.
The effect of multiple paternity on the genetically effective size of a population
Authors: KARL STEPHEN A. 
Published: August 2008

AbstractWith the availability of highly variable microsatellite loci, many previously elusive aspects of the lives of animals have been revealed. One important finding is that multiple paternity (MP) appears to be somewhat common throughout the metazoa. Frequently, along with the discovery of MP are assertions that it can increase the genetically effective size of the population (NE). I argue that MP is not likely to have a positive effect on NE because it increases the variance in male reproductive success. Published studies suggesting the contrary have implicitly or explicitly included other changes to the breeding system, and these additions are likely responsible for the presumed increase in NE.
Heterozygosity–fitness correlations and their relevance to studies on inbreeding depression in threatened species
Authors: GRUEBER CATHERINE E , WALLIS GRAHAM P , JAMIESON IAN G 
Published: August 2008

AbstractThe majority of reported multilocus heterozygosity–fitness correlations (HFCs) are from large, outbred populations, and their relevance to studies on inbreeding depression in threatened populations is often stressed. The results of such HFC studies conducted on outbred populations may be of limited application to threatened population management, however, as bottlenecked populations exhibit increased incidence of inbreeding, increased linkage disequilibrium, reduced genetic diversity and possible effects of historical inbreeding such as purging. These differences may affect both our ability to detect inbreeding depression in threatened species, and our interpretation of the underlying mechanisms for observed heterozygosity–fitness relationships. The study of HFCs in outbred populations is of interest in itself, but the results may not translate directly to threatened populations that have undergone severe bottlenecks.
Stress‐induced expression of an activated form of AtbZIP17 provides protection from salt stress in Arabidopsis
Authors: LIU JIAN‐XIANG , SRIVASTAVA RENU , HOWELL STEPHEN H. 
Published: August 2008

ABSTRACTMembrane‐associated basic‐leucine zipper (bZIP) transcription factors that reside in the endoplasmic reticulum represent a newly described class of plant stress sensor/transducers. The bZIP factors are anchored in endoplasmic reticulum (ER) membranes with their C‐terminal tails facing the ER lumen and their N terminii, which contain transcriptional components, facing the cytosol. In response to stress, cytosolic components of the transcription factors are released by proteolysis and move to the nucleus where they promote the up‐regulation of stress response genes. One such stress sensor/transducer in Arabidopsis is AtbZIP17, which is activated in response to salt stress. With the aim of enhancing salt tolerance, a constitutively activated form of AtbZIP17, truncated before its membrane‐anchor domain, was introduced into transgenic plants. When placed under the control of a constitutive promoter, the activated form of AtbZIP17 up‐regulated stress response genes under unstressed conditions, but caused a substantial delay in plant development. When the activated form of AtbZIP17 was placed under the control of stress‐inducible promoter, development was normal under unstressed conditions. Under salt stress conditions, the stress‐inducible expression of the activated AtbZIP17 enhanced salt tolerance as demonstrated by chlorophyll bleaching and seedling survival assays.
Adaptive eukaryote‐to‐eukaryote lateral gene transfer: stress‐related genes of algal origin in the closest unicellular relatives of animals
Authors: NEDELCU A. M. , MILES I. H. , FAGIR A. M. , KAROL K. 
Published: August 2008

AbstractIn addition to mutation, gene duplication and recombination, the transfer of genetic material between unrelated species is now regarded as a potentially significant player in the shaping of extant genomes and the evolution and diversification of life. Although this is probably true for prokaryotes, the extent of such genetic exchanges in eukaryotes (especially eukaryote‐to‐eukaryote transfers) is more controversial and the selective advantage and evolutionary impact of such events are less documented. A laterally transferred gene could either be added to the gene complement of the recipient or replace the recipient’s homologue; whereas gene replacements can be either adaptive or stochastic, gene additions are most likely adaptive. Here, we report the finding of four stress‐related genes (two ascorbate peroxidase and two metacaspase genes) of algal origin in the closest unicellular relatives of animals, the choanoflagellates. At least three of these sequences represent additions to the choanoflagellate gene complement, which is consistent with these transfers being adaptive. We suggest that these laterally acquired sequences could have provided the primitive choanoflagellates with additional or more efficient means to cope with stress, especially in relation to adapting to freshwater environments and/or sessile or colonial lifestyles.
Risk factors for the development of diabetes mellitus in chronic hepatitis C virus genotype 4 infection
Authors: Chehadeh Wassim , Abdella Nabila , Ben‐Nakhi Abdullah , Al‐Arouj Monira , Al‐Nakib Widad 
Published: August 2008

AbstractBackground and Aim:  A high occurrence of type 2 diabetes (T2D) in patients with chronic hepatitis C virus (HCV) infection has been reported in Kuwait and other countries. However, HCV genotype 4 has been underrepresented in all previous studies. Our aim was to investigate the viral and host risk factors associated with the development of T2D in patients with chronic hepatitis C genotype 4 infection in the absence of liver fibrosis and steatosis.Methods:  The study population consisted of 181 HCV‐positive patients and 170 control HCV‐negative patients with T2D.Results:  The prevalence of HCV‐patients with T2D was 39.8%. There was no significant association of T2D with gender, nationality, obesity, HCV viral load, or antiviral therapy. Older age (≥ 50 years) and family history of diabetes were the only independent risk factor for T2D in HCV patients. However, the median age and the prevalence of obesity in HCV‐positive patients with T2D were significantly lower than those in diabetic HCV‐negative patients. By following‐up HCV‐patients receiving antiviral drugs, a significant decrease of fasting plasma glucose and glycosylated hemoglobin levels was observed in diabetic patients who achieved a sustained viral response (SVR).Conclusions:  The risk factors associated with the development of T2D in the general population cannot alone account for the high prevalence of T2D obtained in chronic HCV genotype 4 infection. In the absence of liver fibrosis and steatosis, the improvement in glycemic control obtained in SVR patients may imply direct involvement of HCV in the development of T2D.
Effects of branched‐chain amino acids–enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma
Authors: Okabayashi Takehiro , Nishimori Isao , Sugimoto Takeki , Maeda Hiromichi , Dabanaka Ken , Onishi Saburo , Kobayashi Michiya , Hanazaki Kazuhiro 
Published: August 2008

AbstractBackground and Aims:  Most patients with hepatocellular carcinoma (HCC) have underlying liver cirrhosis that is frequently associated with a state of protein energy malnutrition. The aim of this study was to evaluate the clinical benefit of perioperative supplementation of a branched‐chain amino acid–enriched nutrient‐mixture for patients undergoing liver resection for HCC.Methods:  A total of 112 patients with HCC who underwent hepatic resection were enrolled in this study. These patients were divided into two groups: 40 patients received perioperative supplementation of branched‐chain amino acid–enriched nutrient‐mixture (AEN group) and 72 patients did not (control group). Laboratory data, postoperative complications, duration of hospitalization, and survival were assessed for each group and compared.Results:  The overall incidence of postoperative complications was lower in the AEN group (17.5%) than in the control group (44.4%) (P = 0.01). Among the postoperative complications, surgical site infection and bile leakage was observed in 5% of patients in the AEN group and in 15.3% and 12.5% of patients in the control group, respectively. Ascites appeared after the surgery in 7.5% of patients in the AEN group and in 16.7% of patients in the control group. The duration of hospitalization was significantly shorter in the AEN group was than in the control group (P < 0.05).Conclusions:  This study strongly suggests that perioperative supplementation of a branched‐chain amino acid–enriched nutrient‐mixture is clinically beneficial in reducing the morbidity associated with postoperative complications and in shortening the duration of hospitalization of patients with chronic liver disease who undergo liver resection for HCC.