bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy
Authors: Li Lequn , Godfrey Wayne R. , Porter Stephen B. , Ge Ying , June Carle H. , Blazar Bruce R. , Boussiotis Vassiliki A. 
Published: July 2005

Abstract
CD4+CD25+ regulatory T cells (Tregs) are essential negative regulators of immune responses. Here, we examined the signaling properties of human Tregs, using CD4+CD25+ Treg and CD4+CD25– control (Tcont) cell lines generated from cord blood. Treg cell lines were markedly hyporesponsive to stimulation with dendritic cells and with anti-CD3/CD28–coated beads. Hyporesponsiveness was reversed by exogenous interleukin-2 (IL-2). T-cell receptor (TCR)–CD3/CD28–mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated kinase 1/2 (Erk1/2) was impaired. Tregs were blocked from cell cycle progression due to decrease of cyclin E and cyclin A and increase of p27kip1 (p27kip cyclin dependent kinase inhibitor). IL-2 induced sustained increase of cyclin E and cyclin A and prevented up-regulation of p27kip1. Tregs had high susceptibility to apoptosis that was reversed by IL-2, which correlated with activation of Erk1/2, up-regulation of Bcl-xL (B-cell CLL/lymphoma 2-like nuclear gene encoding mitochondrial protein, transcript variant 2), and phosphorylation of Bad (Bcl2 antagonist of cell death) at Ser112. Thus, Tregs share biochemical characteristics of anergy, including abortive activation of Ras-MEK-Erk, increased activation of Rap1, and increased expression of p27kip1. In addition, our results indicate that TCR–CD3/CD28–mediated and IL-2 receptor–mediated signals converge at the level of MEK-Erk kinases to regulate Treg survival and expansion and suggest that manipulation of the MEK-Erk axis may represent a novel strategy for Treg expansion for immunotherapy.
Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study
Authors: Poli Diana , Carbognani Paolo , Corradi Massimo , Goldoni Matteo , Acampa Olga , Balbi Bruno , Bianchi Luca , Rusca Michele , Mutti Antonio 
Published: July 2005

Abstract

Background
Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery.

Methods
The subjects' breath was collected in a Teflon® bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry.

Results
The levels of the selected VOCs ranged from 10-12 M for styrene to 10-9 M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery.

Conclusion
As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.
Diverse spatial, temporal, and sexual expression of recently duplicated androgen-binding protein genes in Mus musculus
Authors: Laukaitis Christina M , Dlouhy Stephen R , Emes Richard D , Ponting Chris P , Karn Robert C 
Published: July 2005

Abstract

Background
The genes for salivary androgen-binding protein (ABP) subunits have been evolving rapidly in ancestors of the house mouse Mus musculus, as evidenced both by recent and extensive gene duplication and by high ratios of nonsynonymous to synonymous nucleotide substitution rates. This makes ABP an appropriate model system with which to investigate how recent adaptive evolution of paralogous genes results in functional innovation (neofunctionalization).

Results
It was our goal to find evidence for the expression of as many of the Abp paralogues in the mouse genome as possible. We observed expression of six Abpa paralogues and five Abpbg paralogues in ten glands and other organs located predominantly in the head and neck (olfactory lobe of the brain, three salivary glands, lacrimal gland, Harderian gland, vomeronasal organ, and major olfactory epithelium). These Abp paralogues differed dramatically in their specific expression in these different glands and in their sexual dimorphism of expression. We also studied the appearance of expression in both late-stage embryos and postnatal animals prior to puberty and found significantly different timing of the onset of expression among the various paralogues.

Conclusion
The multiple changes in the spatial expression profile of these genes resulting in various combinations of expression in glands and other organs in the head and face of the mouse strongly suggest that neofunctionalization of these genes, driven by adaptive evolution, has occurred following duplication. The extensive diversification in expression of this family of proteins provides two lines of evidence for a pheromonal role for ABP: 1) different patterns of Abpa/Abpbg expression in different glands; and 2) sexual dimorphism in the expression of the paralogues in a subset of those glands. These expression patterns differ dramatically among various glands that are located almost exclusively in the head and neck, where the sensory organs are located. Since mice are nocturnal, it is expected that they will make extensive use of olfactory as opposed to visual cues. The glands expressing Abp paralogues produce secretions (lacrimal and salivary) or detect odors (MOE and VNO) and thus it appears highly likely that ABP proteins play a role in olfactory communication.
Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21waf1/cip1 among human bronchogenic carcinomas
Authors: Harr Michael W , Graves Timothy G , Crawford Erin L , Warner Kristy A , Reed Cheryl AM , Willey James C 
Published: July 2005

Abstract

Background
Cell proliferation control depends in part on the carefully ordered regulation of transcription factors. The p53 homolog p73, contributes to this control by directly upregulating the cyclin dependent kinase inhibitor, p21waf1/cip1. E2F1, an inducer of cell proliferation, directly upregulates p73 and in some systems upregulates p21 directly. Because of its central role in controlling cell proliferation, upregulation of p21 has been explored as a modality for treating bronchogenic carcinoma (BC). Improved understanding of p21 transcriptional regulation will facilitate identification of BC tissues that are responsive to p21-directed therapies. Toward this goal, we investigated the role that E2F1 and p73 each play in the transcriptional regulation of p21.

Results
Among BC samples (N = 21) p21 transcript abundance (TA) levels varied over two orders of magnitude with values ranging from 400 to 120,000 (in units of molecules/106 molecules β-actin). The p21 values in many BC were high compared to those observed in normal bronchial epithelial cells (BEC) (N = 18). Among all BC samples, there was no correlation between E2F1 and p21 TA but there was positive correlation between E2F1 and p73α (p < 0.001) TA. Among BC cell lines with inactivated p53 and wild type p73 (N = 7) there was positive correlation between p73α and p21 TA (p < 0.05). Additionally, in a BC cell line in which both p53 and p73 were inactivated (H1155), E2F1 TA level was high (50,000), but p21 TA level was low (470). Transiently expressed exogenous p73α in the BC cell line Calu-1, was associated with a significant (p < 0.05) 90% increase in p21 TA and a 20% reduction in E2F1 TA. siRNA mediated reduction of p73 TA in the N417 BC cell line was associated with a significant reduction in p21 TA level (p < 0.01).

Conclusion
p21 TA levels vary considerably among BC patients which may be attributable to 1) genetic alterations in Rb and p53 and 2) variation in TA levels of upstream transcription factors E2F1 and p73. Here we provide evidence that p73 upregulates p21 TA in BC tissues and upregulated p21 TA may result from E2F1 upregulation of p73 but not from E2F1 directly.
To quell obesity, who should regulate food marketing to children?
Authors: Kelly Ben 
Published: July 2005

Abstract
The global hegemony of the United States in the production and marketing of food, while a marvel of economic success, has contributed to the epidemic of obesity that is particularly afflicting children. So far the U.S. government has declined to regulate the aggressive ways in which food producers market high-energy, low-nutrition foods to young people. That public-health responsibility has been left to an industry-created scheme of self-regulation that is deeply flawed; there is a compelling need for government involvement. The issue is certain to be raised by health advocates at a U.S. Federal Trade Commission meeting in mid-July to discuss the self-regulatory approach, but the outlook for remedies to emerge from the meeting is not encouraging.
From a Meccano set to nano meccano
Authors: Stoddart J. Fraser 
Published: July 2005

Abstract
The hurly-burly life of a scientific nomad is traced through thick and thin from the Athens of the North to the City of Angels with brief and not so brief interludes on the edge of the Canadian Shield, in the Socialist Republic of South Yorkshire, on the Plains of Cheshire beside the Wirral, and in the Midlands in the heartland of Albion.
Total synthesis of zincophorin
Authors: Cossy Janine , Meyer Christophe , Defosseux Magali , Blanchard Nicolas 
Published: July 2005

Abstract
A total synthesis of the naturally occurring ionophore zincophorin has been realized. The key steps are an intramolecular oxymercuration of a cyclopropanemethanol for the elaboration of the tetrahydropyran ring and a Carroll–Claisen rearrangement to control the configuration of the double bond at C20–C21 as well as the stereogenic center at C21.
Syntheses of antiangiogenic or cytotoxic natural products: Fumagillin and bengacarboline
Authors: Bedel O. , Haudrechy A. , Pouilhès A. , Langlois Y. 
Published: July 2005

Abstract
Syntheses of fumagillol, a precursor of antiangiogenic sesquiterpene fumagillin, and of cytotoxic marine alkaloid bengacarboline are described.
Total synthesis and structural elucidation of natural products: (–)-Delactonmycin, (+)-plumerinine, and (–)-parvistemoamide
Authors: Pilli Ronaldo A. , Corrêa Ivan R. , Maldaner Adriano O. , Rosso Giovanni B. 
Published: July 2005

Abstract
Synthetic studies that established the relative configuration of (–)-delactonmycin, a polyketide with inhibitory activity against HIV-1 Rev protein, and our efforts toward the structural elucidation of the alkaloids (+)-plumerinine, isolated from P. rubra, and (–)-parvistemoamide, isolated from S. parviflora, are discussed.
Carbohydrates as versatile platforms in the construction of small compound libraries
Authors: Timmer Mattie S. M. , Verhelst Steven H. L. , Grotenbreg Gijsbert M. , Overhand Mark , Overkleeft Herman S. 
Published: July 2005

Abstract
This paper presents our recent results concerning the use of carbohydrates as cheap, chiral, and enantiopure starting materials in the construction of a variety of densely functionalized molecules. The compatibility of ring-closing metathesis with standard carbohydrate chemistry is demonstrated in the synthesis of new stereoisomers of deoxystreptamine and neamine–important building blocks for the generation of synthetic aminoglycosides with potential antibacterial activity. Ring-closing metathesis is also a key step in the rapid synthesis of new indolizidines and quinolizidines, and in a new solid-phase assisted carbohydrate-based combinatorial scaffold strategy. Further, some of our latest results in the conformational analysis of sugar amino acid-based peptide mimetics and in the development of a novel Ugi-type three-component reaction of sugar-derived azido-aldehydes are discussed.
General and practical approach to the syntheses of linear homoallylic alcohols
Authors: Cheng Hin-Soon , Loh Teck-Peng 
Published: July 2005

Abstract
We have demonstrated that metal-mediated allylation of aldehydes can afford γ-homoallylic alcohols or α-linear homoallylic alcohols by judicious choice of the solvents. A new mechanism has been proposed to account for this new α-selective metal-mediated allylation reaction. On the other hand, the metal-mediated prenylation under the same conditions to obtain α-prenyl alcohols was unsuccessful. Detailed mechanistic studies have resulted in the discovery of a new method to obtain compounds with diverse structures via an oxonium-ene cyclization. Suppressing the oxonium-ene reaction during the reaction has resulted in the formation of α-prenyl alcohols. A highly enantioselective process to obtain α-prenyl product in high optical purity has also been accomplished.
Ring-closing metathesis: A facile construct for alkaloid synthesis
Authors: Martin Stephen F. 
Published: July 2005

Abstract
Ring-closing metathesis has been found to be a highly effective reaction for the synthesis of functionalized, bridged nitrogen heterocycles. The utility of the process has been established in several case studies, including a facile synthesis of the tropane ring system and efficient, enantioselective syntheses of the natural products (–)-peduncularine and (+)-anatoxin-a.
Masked o-benzoquinone strategy in organic synthesis: Short and efficient construction of cis-decalins and linear triquinanes from 2-methoxyphenols
Authors: Liao Chun-Chen 
Published: July 2005

Abstract
The inter- and intramolecular Diels–Alder reactions of masked o-benzoquinones generated in situ from the oxidation of easily accessible 2-methoxyphenols with diacetoxyiodobenzene or bis(trifluoroacetoxy)iodobenzene provided cycloadducts in excellent regio- and stereoselectivity and good yields. A general approach to the synthesis of highly substituted cis-decalins and triquinanes with complete stereocontrol from the cycloadducts has been developed. The applicability of our methodology is demonstrated by the total syntheses of several natural products.
Diastereoselective alkylation of cyclo-β-dipeptides en route to enantiopure β-amino acids
Authors: Juaristi Eusebio , Aviña Judit 
Published: July 2005

Abstract
The cyclization of various β-amino acids with PhP(O)Cl2 affords cyclo-β-dipeptides, whose boat conformation is probably responsible for the high diastereoselectivity observed in the alkylation reactions of their lithium enolate derivatives.
Chiral designer phase-transfer catalysts for practical asymmetric synthesis
Authors: Maruoka Keiji 
Published: July 2005

Abstract
A series of C
2-symmetric, spiro-type chiral quaternary ammonium bromides have been designed as new, purely synthetic chiral phase-transfer catalysts, and readily prepared from commercially available optically pure (R)- or (S)-1,1'-bi-2-naphthol as a basic chiral unit. The structures of the assembled N-spiro chiral quaternary ammonium bromides were unequivocally determined by single-crystal X-ray diffraction analysis. The reactivity and selectivity of these chiral ammonium bromides as chiral phase-transfer catalysts have been evaluated in the asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild liquid–liquid phase-transfer conditions, and the optimization of the reaction variables (solvent, base, and temperature) has also been conducted. Furthermore, the scope and limitations of other asymmetric transformations have been thoroughly investigated with a variety of substrates, in which the advantage of the unique N-spiro structure of our chiral phase-transfer catalysts and dramatic effect of the steric as well as the electronic properties of the aromatic substituents on the 3,3'-position of one binaphthyl moiety have been particularly emphasized.
Effect of l-Carnitine on Acetyl-CoA Content and Activity of Blood Platelets in Healthy and Diabetic Persons
Authors: Michno Anna , Raszeja-Specht Anna , Jankowska-Kulawy Agnieszka , Pawełczyk Tadeusz , Szutowicz Andrzej 
Published: July 2005

AbstractBackground: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether l-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals.Methods: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of l-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed.Results: Fasting glucose, fructosamine, and hemoglobin A1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%–62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. l-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, l-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation.Conclusions: Excessive platelet activity in persons with diabetes may result from increased acetyl-CoA, which apparently increases synthesis of lipid activators of platelet function. l-Carnitine may aggravate platelet hyperactivity in diabetic persons by increasing the provision of surplus acetyl-CoA to the cytoplasmic compartment.
Identification and Quantification of 8 Sulfonylureas with Clinical Toxicology Interest by Liquid Chromatography–Ion-Trap Tandem Mass Spectrometry and Library Searching
Authors: Hoizey Guillaume , Lamiable Denis , Trenque Thierry , Robinet Arnaud , Binet Laurent , Kaltenbach Matthieu L , Havet Sandrine , Millart Hervé 
Published: July 2005

Abstract
Background: Identification of sulfonylureas in blood may be useful in the evaluation of hypoglycemic crises of unknown origin. The aim of the present study was to develop a highly selective liquid chromatography–electrospray tandem mass spectrometry (MS-MS) method using an ion-trap detector for rapid screening, identification, and quantification of sulfonylureas in human plasma.
Methods: After standard liquid–liquid extraction with glisoxepide as an internal standard, 8 sulfonylureas (glibenclamide, glipizide, gliclazide, glibornuride, glimepiride, carbutamide, chlorpropamide, and tolbutamide) were eluted from a C18 column within 10 min with an isocratic mobile phase. Drugs were identified and quantified in full-scan MS-MS mode by use of a homemade MS-MS library. We used the assay in 134 cases of hypoglycemic crises of unknown origin.
Results: No ion suppression effect was noted for the analytes at their specific retention-time windows. For all drugs, assay validation showed good linearity (r2 &gt;0.990) and acceptable imprecision and recovery based on commonly used criteria of acceptance. The mean extraction recoveries were 63%–87% for 5 sulfonylureas but &lt;45% for 3 (carbutamide, chlorpropamide, and tolbutamide). Nevertheless, the high sensitivity of the MS instrument made possible detection and quantification of all 8 drugs at subtherapeutic to toxic concentrations with good precision. Sulfonylureas were found in 9 hypoglycemic patients.
Conclusion: The described assay method allows accurate, rapid identification and quantification of 8 sulfonylureas in human plasma and can be used for specific diagnosis of factitious hypoglycemia caused by ingestion of these drugs.
Highly Efficient Sex Chromosome Interchanges Produced By I-CreI Expression in Drosophila
Authors: Maggert Keith A , Golic Kent G 
Published: July 2005

Abstract
The homing endonuclease I-CreI recognizes a site in the gene encoding the 23S rRNA of Chlamydomonas reinhardtii. A very similar sequence is present in the 28S rRNA genes that are located on the X and Y chromosomes of Drosophila melanogaster. In this work we show that I-CreI expression in Drosophila is capable of causing induced DNA damage and eliciting cell cycle arrest. Expression also caused recombination between the X and Y chromosomes in the heterochromatic regions where the rDNA is located, presumably as a result of a high frequency of double-strand breaks in these regions. Approximately 20% of the offspring of males expressing I-CreI showed exceptional inheritance of X- and Y-linked markers, consistent with chromosome exchange at rDNA loci. Cytogenetic analysis confirmed the structures of many of these products. Exchange between the X and Y chromosomes can be induced in males and females to produce derivative-altered Y chromosomes, attached-XY, and attached-X chromosomes. This method has advantages over the traditional use of X rays for generating X-Y interchanges because it is very frequent and it generates predictable products.
Epistatic Interactions Among Herbicide Resistances in Arabidopsis thaliana: The Fitness Cost of Multiresistance
Authors: Roux Fabrice , Camilleri Christine , Giancola Sandra , Brunel Dominique , Reboud Xavier 
Published: July 2005

Abstract
The type of interactions among deleterious mutations is considered to be crucial in numerous areas of evolutionary biology, including the evolution of sex and recombination, the evolution of ploidy, the evolution of selfing, and the conservation of small populations. Because the herbicide resistance genes could be viewed as slightly deleterious mutations in the absence of the pesticide selection pressure, the epistatic interactions among three herbicide resistance genes (acetolactate synthase CSR, cellulose synthase IXR1, and auxin-induced AXR1 target genes) were estimated in both the homozygous and the heterozygous states, giving 27 genotype combinations in the model plant Arabidopsis thaliana. By analyzing eight quantitative traits in a segregating population for the three herbicide resistances in the absence of herbicide, we found that most interactions in both the homozygous and the heterozygous states were best explained by multiplicative effects (each additional resistance gene causes a comparable reduction in fitness) rather than by synergistic effects (each additional resistance gene causes a disproportionate fitness reduction). Dominance coefficients of the herbicide resistance cost ranged from partial dominance to underdominance, with a mean dominance coefficient of 0.07. It was suggested that the csr1-1, ixr1-2, and axr1-3 resistance alleles are nearly fully recessive for the fitness cost. More interestingly, the dominance of a specific resistance gene in the absence of herbicide varied according to, first, the presence of the other resistance genes and, second, the quantitative trait analyzed. These results and their implications for multiresistance evolution are discussed in relation to the maintenance of polymorphism at resistance loci in a heterogeneous environment.