bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo
Authors: Nishioka Chie , Ikezoe Takayuki , Yang Jing , Miwa Atsushi , Tasaka Taizo , Kuwayama Yoshio , Togitani Kazuto , Koeffler H. Phillip , Yokoyama Akihito 
Published: February 2008

Abstract
Ki11502 is a novel multitargeted receptor tyrosine kinase (RTK) inhibitor with selectivity against platelet-derived growth factor receptor alpha/beta (PDGFRα/β). Ki11502 (0.1-1 nM, 2 days) profoundly caused growth arrest, G0/G1 cell-cycle arrest, and apoptosis associated with down-regulation of Bcl-2 family proteins in the eosinophilic leukemia EOL-1 cells having the activated FIP1-like 1/PDGFRα fusion gene. Ki11502 decreased levels of p-PDGFRα and its downstream signals, including p-Akt, p-ERK, and p-STAT5, in EOL-1 cells. Of note, Ki11502 was also active against imatinib-resistant PDGFRαT674I mutant. In addition, Ki11502 inhibited proliferation of biphenotipic leukemia MV4-11 and acute myelogenous leukemia MOLM13 and freshly isolated leukemia cells having activating mutations in FMS-like tyrosine kinase 3 (FLT3). This occurred in parallel with the drug inhibiting FLT3 and its downstream signal pathways, as measured by fluorescence-activated cell sorting using the phospho-specific antibodies. In addition, Ki11502 totally inhibited proliferation of EOL-1 cells growing as tumor xenografts in SCID mice without any noticeable adverse effects. Taken together, Ki11502 has profound antiproliferative effects on select subsets of leukemia including those possessing imatinib-resistant mutation.
HIF-1–dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak
Authors: Morote-Garcia Julio C. , Rosenberger Peter , Kuhlicke Johannes , Eltzschig Holger K. 
Published: February 2008

Abstract
Extracellular adenosine has been implicated in vascular adaptation to hypoxia. Based on the observation that increases in intracellular adenosine can effectively elevate extracellular adenosine, we studied the contribution of adenosine kinase (AK, intracellular conversion of adenosine to adenosine monophosphate [AMP]) to vascular adenosine responses. Initial in vitro studies of ambient hypoxia revealed prominent repression of endothelial AK transcript (85% ± 2% reduction), protein, and function. Transcription factor binding assays and hypoxia inducible factor 1-α (HIF-1α) loss- and gain-of-function studies suggested a role for HIF-1α in transcriptional repression of AK. Moreover, repression of AK by ambient hypoxia was abolished in conditional HIF-1α mutant mice in vivo. Studies of endothelial barrier function revealed that inhibition or siRNA repression of AK is associated with enhanced adenosine-dependent barrier responses in vitro. Moreover, in vivo studies of vascular barrier function demonstrated that AK inhibition with 5′-iodotubericidin (1 mg/kg prior to hypoxia) significantly attenuated hypoxia-induced vascular leakage in multiple organs and reduced hypoxia-associated increases in lung water. Taken together, our data reveal a critical role of AK in modulating vascular adenosine responses and suggest pharmacologic inhibitors of AK in the treatment of conditions associated with hypoxia-induced vascular leakage (eg, sepsis or acute lung injury).
Interstitial lung diseases in infants and children: Fig. 1—
Authors: Clement A. , Eber E. 
Published: February 2008

Interstitial lung disease (ILD) in infants and children represents a heterogeneous group of respiratory disorders that are mostly chronic and associated with high morbidity and mortality.Typical features of ILD include dyspnoea, the presence of diffuse infiltrates on chest radiographs and abnormal pulmonary function tests with evidence of a restrictive ventilatory defect (in older children) and/or impaired gas exchange.ILD is difficult to diagnose, as no classification scheme is entirely satisfactory. Recently, it has been proposed to categorise paediatric ILD as either primary pulmonary disorders or systemic disorders with pulmonary involvement. However, this classification leaves the difficult problem of which clinical conditions should be included or excluded in infants and children.The present article reviews interstitial lung disease in infants and children, placing emphasis on current concepts of pathophysiological mechanisms and approaches to treatment.
Peroxisome proliferator-activated receptors: a therapeutic target in COPD?: Fig. 1—
Authors: Remels A. H. , Gosker H. R. , Schrauwen P. , Langen R. C. , Schols A. M. 
Published: February 2008

Extrapulmonary pathology significantly impairs clinical outcome in chronic obstructive pulmonary disease (COPD).The peroxisome proliferator-activated receptors (PPARs) are implicated in the regulation of several hallmarks of systemic COPD pathology, including cachexia, decreased oxidative muscle metabolism, oxidative stress and systemic inflammation.Recently, expression of PPARs and related cofactors was shown to be reduced in peripheral skeletal muscle of patients with moderate-to-severe COPD and muscle weakness.The current authors hypothesise that impaired peroxisome proliferator-activated receptor signalling may underlie some of the muscular disturbances in chronic obstructive pulmonary disease. Proposed mechanisms will be outlined in the present article, as well as the therapeutic potential of peroxisome proliferator-activated receptor modulation in the treatment of skeletal muscle dysfunction.
Possible mechanisms underlying the development of cachexia in COPD
Authors: Wagner P. D. 
Published: February 2008

About 25% of patients with chronic obstructive pulmonary disease (COPD) will develop cachexia (fat-free body mass index <17 kg·m−2(males) or <14 kg·m−2(females)). This is associated with ∼50% reduction in median survival.The pathogenetic mechanism has been variously suggested to result from the following: 1) energy imbalance; 2) disuse atrophy; 3) tissue hypoxia from arterial hypoxaemia; 4) systemic inflammation; and 5) anabolic hormonal insufficiency. Genetic polymorphisms implicate inflammatory cytokines, especially interleukin (IL)-1β, but IL-6 and tumour necrosis factor (TNF)-α do not show polymorphisms in these patients. Early reports of elevated TNF-α levels suggested a role for inflammation, but recent studies have not shown elevated levels of either IL-6 or TNF-α. Therapeutic trials of nutritional support, hormonal supplementation, anti-TNF-α immunotherapy, ghrelin and antioxidants have been conducted, but only a few have shown any benefits in muscle structure and function.Considerably more mechanistic knowledge is needed before therapeutic recommendations can be made. At this time, it is not possible to attribute cachexia in COPD unequivocally to inflammation or any other cause, and much more research is needed.To date, studies have been predominantly cross-sectional, with measurements made only after cachexia has developed. Future research should target prospective observation, studying patients as cachexia progresses, since once cachexia is established, inflammatory cytokine levels may not be abnormal.
Anxiety and depression in end-stage COPD
Authors: Hill K. , Geist R. , Goldstein R. S. , Lacasse Y. 
Published: February 2008

Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), estimates of their prevalence vary considerably. This probably reflects the variety of scales and methods used to measure such symptoms. Regardless of whether anxiety and depression are considered separately or as a single construct, their impact on COPD patients is important.A heightened experience of dyspnoea is likely to be a contributing factor to anxiety. Feelings of depression may be precipitated by the loss and grief associated with the disability of COPD. Smoking has been associated with nicotine addiction, and the factors that contribute to smoking may also predispose to anxiety and depressive disorders.Randomised controlled trials indicate that exercise training and carefully selected pharmacological therapy are often effective in ameliorating anxiety and depression. Most medical illnesses are influenced by the psychological responses and coping mechanisms that patients use. However, anxiety and depression are associated with dyspnoea, fatigue and altered sleep, all of which also occur in COPD.An understanding of the psychological history and coping mechanisms of patients and the role of anxiety and depressive reactions to illness may enable clinicians to reduce these symptoms and improve quality of life among patients with chronic obstructive pulmonary disease.
Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection
Authors: Mikerov Anatoly N , Gan Xiaozhuang , Umstead Todd M , Miller Laura , Chinchilli Vernon M , Phelps David S , Floros Joanna 
Published: February 2008

AbstractBackgroundSex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected withKlebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice.MethodsMale and female C57BL/6 mice were exposed to O3or to filtered air (FA) (control) and then infected intratracheally withK. pneumoniaebacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogenin vivowas investigated after 1 h.Results1) Both male and female mice exposed to O3are significantly more susceptible toK. pneumoniaeinfection than mice treated with FA; 2) although females appeared to be more resistant toK. pneumoniaethan males, O3exposure significantly increased the susceptibility of females toK. pneumoniaeinfection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice.ConclusionO3exposure reduces the ability of mice to surviveK. pneumoniaeinfection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.
Term-tissue specific models for prediction of gene ontology biological processes using transcriptional profiles of aging in drosophila melanogaster
Authors: Zhang Wensheng , Zou Sige , Song Jiuzhou 
Published: February 2008

AbstractBackgroundPredictive classification on the base of gene expression profiles appeared recently as an attractive strategy for identifying the biological functions of genes. Gene Ontology (GO) provides a valuable source of knowledge for model training and validation. The increasing collection of microarray data represents a valuable source for generating functional hypotheses of uncharacterized genes.ResultsThis study focused on using support vector machines (SVM) to predict GO biological processes from individual or multiple-tissue transcriptional profiles of aging in Drosophila melanogaster. Ten-fold cross validation was implemented to evaluate the prediction. One-tail Fisher's exact test was conducted on each cross validation and multiple testing was addressed using BH FDR procedure. The results showed that, of the 148 pursued GO biological processes, fifteen terms each had at least one model with FDR-adjusted p-value (Adj.p) <0.05 and six had the values between 0.05 and 0.25. Furthermore, all these models had the prediction sensitivity (SN) over 30% and specificity (SP) over 80%.ConclusionWe proposed the concept of term-tissue specific models indicating the fact that the major part of the optimized prediction models was trained from individual tissue data. Furthermore, we observed that the memberships of the genes involved in all the three pursued children biological processes on mitochondrial electron transport could be predicted from the transcriptional profiles of aging (Adj.p < 0.01). This finding may be important in biology because the genes of mitochondria play a critical role in the longevity of C. elegans and D. melanogaster.
Genome-wide identification of quantitative trait loci in a cross between Hampshire and Landrace II: Meat quality traits
Authors: Markljung Ellen , Braunschweig Martin H , Karlskov-Mortensen Peter , Bruun Camilla S , Sawera Milena , Cho In-Cheol , Hedebro-Velander Ingela , Josell Åsa , Lundström Kerstin , von Seth Gertrud , Jørgensen Claus B , Fredholm Merete , Andersson Leif 
Published: February 2008

Abstract

Background
Meat quality traits are important in pig breeding programs, but they are difficult to include in a traditional selection program. Marker assisted selection (MAS) of meat quality traits is therefore of interest in breeding programs and a Quantitative Trait Locus (QTL) analysis is the key to identifying markers that can be used in MAS. In this study, Landrace and Hampshire intercross and backcross families were used to investigate meat quality traits. Hampshire pigs are commonly used as the sire line in commercial pig breeding. This is the first time a pedigree including Hampshire pigs has been used for a QTL analysis of meat quality traits.

Results
In total, we analyzed 39 meat quality traits and identified eight genome-wide significant QTL peaks in four regions: one on chromosome 3, two on chromosome 6 and one on chromosome 16. At least two of the QTLs do not appear to have been detected in previous studies. On chromosome 6 we identified QTLs for water content in M. longissimus dorsi (LD), drip loss in LD and post mortem pH decline in LD. On chromosomes 3 and 16 we identified previously undetected QTLs for protein content in LD and for freezing and cooking loss respectively.

Conclusion
We identified at least two new meat quality trait QTLs at the genome-wide significance level. We detected two QTLs on chromosome 6 that possibly coincide with QTLs detected in other studies. We were also able to exclude the C1843T mutation in the ryanodine receptor (RYR1) as a causative mutation for one of the chromosome 6 QTLs in this cross.
Detection and validation of single feature polymorphisms in cowpea (Vigna unguiculata L. Walp) using a soybean genome array
Authors: Das Sayan , Bhat Prasanna R , Sudhakar Chinta , Ehlers Jeffrey D , Wanamaker Steve , Roberts Philip A , Cui Xinping , Close Timothy J 
Published: February 2008

Abstract

Background
Cowpea (Vigna unguiculata L. Walp) is an important food and fodder legume of the semiarid tropics and subtropics worldwide, especially in sub-Saharan Africa. High density genetic linkage maps are needed for marker assisted breeding but are not available for cowpea. A single feature polymorphism (SFP) is a microarray-based marker which can be used for high throughput genotyping and high density mapping.

Results
Here we report detection and validation of SFPs in cowpea using a readily available soybean (Glycine max) genome array. Robustified projection pursuit (RPP) was used for statistical analysis using RNA as a surrogate for DNA. Using a 15% outlying score cut-off, 1058 potential SFPs were enumerated between two parents of a recombinant inbred line (RIL) population segregating for several important traits including drought tolerance, Fusarium and brown blotch resistance, grain size and photoperiod sensitivity. Sequencing of 25 putative polymorphism-containing amplicons yielded a SFP probe set validation rate of 68%.

Conclusion
We conclude that the Affymetrix soybean genome array is a satisfactory platform for identification of some 1000's of SFPs for cowpea. This study provides an example of extension of genomic resources from a well supported species to an orphan crop. Presumably, other legume systems are similarly tractable to SFP marker development using existing legume array resources.
An integrated genetic and physical map of homoeologous chromosomes 12 and 26 in Upland cotton (G. hirsutum L.)
Authors: Xu Zhanyou , Kohel Russell J , Song Guoli , Cho Jaemin , Yu Jing , Yu Shuxun , Tomkins Jeffrey , Yu John Z 
Published: February 2008

Abstract

Background
Upland cotton (G. hirsutum L.) is the leading fiber crop worldwide. Genetic improvement of fiber quality and yield is facilitated by a variety of genomics tools. An integrated genetic and physical map is needed to better characterize quantitative trait loci and to allow for the positional cloning of valuable genes. However, developing integrated genomic tools for complex allotetraploid genomes, like that of cotton, is highly experimental. In this report, we describe an effective approach for developing an integrated physical framework that allows for the distinguishing between subgenomes in cotton.

Results
A physical map has been developed with 220 and 115 BAC contigs for homeologous chromosomes 12 and 26, respectively, covering 73.49 Mb and 34.23 Mb in physical length. Approximately one half of the 220 contigs were anchored to the At subgenome only, while 48 of the 115 contigs were allocated to the Dt subgenome only. Between the two chromosomes, 67 contigs were shared with an estimated overall physical similarity between the two chromosomal homeologs at 40.0 %. A total of 401 fiber unigenes plus 214 non-fiber unigenes were located to chromosome 12 while 207 fiber unigenes plus 183 non-fiber unigenes were allocated to chromosome 26. Anchoring was done through an overgo hybridization approach and all anchored ESTs were functionally annotated via blast analysis.

Conclusion
This integrated genomic map describes the first pair of homoeologous chromosomes of an allotetraploid genome in which BAC contigs were identified and partially separated through the use of chromosome-specific probes and locus-specific genetic markers. The approach used in this study should prove useful in the construction of genome-wide physical maps for polyploid plant genomes including Upland cotton. The identification of Gene-rich islands in the integrated map provides a platform for positional cloning of important genes and the targeted sequencing of specific genomic regions.
Comparative genomic analysis and evolution of the T cell receptor loci in the opossum Monodelphis domestica
Authors: Parra Zuly E , Baker Michelle L , Hathaway Jennifer , Lopez April M , Trujillo Jonathan , Sharp Alana , Miller Robert D 
Published: February 2008

AbstractBackgroundAll jawed-vertebrates have four T cell receptor (TCR) chains: alpha (TRA), beta (TRB), gamma (TRG) and delta (TRD). Marsupials appear unique by having an additional TCR: mu (TRM). The evolutionary origin of TRM and its relationship to other TCR remain obscure, and is confounded by previous results that support TRM being a hybrid between a TCR and immunoglobulin locus. The availability of the first marsupial genome sequence allows investigation of these evolutionary relationships.ResultsThe organization of the conventional TCR loci, encoding the TRA, TRB, TRG and TRD chains, in the opossumMonodelphis domesticaare highly conserved with and of similar complexity to that of eutherians (placental mammals). There is a high degree of conserved synteny in the genomic regions encoding the conventional TCR across mammals and birds. In contrast the chromosomal region containing TRM is not well conserved across mammals. None of the conventional TCR loci contain variable region gene segments with homology to those found in TRM; rather TRM variable genes are most similar to that of immunoglobulin heavy chain genes.ConclusionComplete genomic analyses of the opossum TCR loci continue to support an origin of TRM as a hybrid between a TCR and immunoglobulin locus. None of the conventional TCR loci contain evidence that such a recombination event occurred, rather they demonstrate a high degree of stability across distantly related mammals. TRM, therefore, appears to be derived from receptor genes no longer extant in placental mammals. These analyses provide the first genomic scale structural detail of marsupial TCR genes, a lineage of mammals used as models of early development and human disease.
The presence of the pilus locus is a clonal property among pneumococcal invasive isolates
Authors: Aguiar Sandra I , Serrano Isa , Pinto Francisco R , Melo-Cristino José , Ramirez Mario 
Published: February 2008

AbstractBackgroundPili were recently recognized inStreptococcus pneumoniaeand implicated in the virulence of this bacterium, which led to the proposal of using these antigens in a future pneumococcal vaccine. However, pili were found to be encoded by therlrAislet that was not universally distributed in the species. We examined the distribution of the pilus islet, using the presence of therlrAgene as a marker for the locus, among a collection of invasive isolates recovered in Portugal and analyzed its association with capsular serotypes, clusters defined by the pulsed-field gel electrophoretic profiles (PFGE) and multilocus sequence types.ResultsOnly a minority of the isolates were positive for the presence of therlrAgene (27%). There was a high correspondence between the serotype and the presence or absence ofrlrA(Wallace coefficient, W = 0.778). In particular, there was an association between the presence ofrlrAand the vaccine serotypes 4, 6B, 9V and 14 whereas the gene was significantly absent from other serotypes, namely 1, 7F, 8, 12B and 23F, a group that included a vaccine serotype (23F) and serotype 1 associated with enhanced invasiveness. Even within serotypes, there was variation in the presence of the pilus islet between PFGE clones and a higher Wallace coefficient (W = 0.939) indicates that carriage of the islet is a clonal property of pneumococci. Analysis ofrlrAnegative isolates revealed heterogeneity in the genomic region downstream of therflgene, the region where the islet is found in other isolates, compatible with recent loss of the islet in some lineages.ConclusionThe pilus islet is present in a minority of pneumococcal isolates recovered from human invasive infections and is therefore not an essential virulence factor in these infections. Carriage of the pilus islet is a clonal property of pneumococci that may vary between isolates expressing the same serotype and loss and acquisition of the islet may be ongoing.