bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laryngeal dysplasia: aetiology and molecular biology
Authors: Sadri Maziar , McMahon Jeremy , Parker Andrew 
Published: December 2005

Laryngeal premalignancy is a common clinical concern. While tobacco has long been established as the principal identifiable aetiological factor, the last two decades have seen publications investigating a potential role for gastroesophageal reflux, gastrectomy and human papilloma virus. Furthermore, there have been major advances in our understanding of the molecular biology of cancer and premalignancy. Accompanying this increased understanding, significant efforts have been made to correlate the expression of molecular markers with the clinical course of premalignant laryngeal lesions.This review summarizes current knowledge of the aetiological factors and molecular biology of laryngeal premalignancy. All aetiological factors, including molecular markers, are discussed separately and their possible role in the clinical course of these lesions is discussed.
Effect of nasal septal deviation on total ethmoid cell volume
Authors: Firat Ahmet Kemal , Miman Murat Cem , Firat Yezdan , Karakas Muammer , Ozturan Orhan , Altinok Tayfun 
Published: December 2005

Background: The aim of this study was to evaluate the effect of nasal septal deviation (NSD) on ethmoid cell volume and to determine whether there was any correlation between NSD grade and ethmoid cell volume.Methods: Forty computerized tomography (CT) scans from patients with rhinosinusitis symptoms with NSD were evaluated. Septal deviations were classified into three groups according to the degree of deviation on CT. Ethmoid cell volumes were measured and the relationship between NSD and ethmoid cell volume was investigated.Results: There was a moderate but significant negative correlation between the septal deviation angle and the percentage of the ethmoid cell volumes (p = 0.001, r = −0.5152, r2 = 0.2654). Total ethmoid cell volume on the ipsilateral side compared with the contralateral side was found to decrease as the degree of NSD increased.Conclusions: Nasal septal deviation affects the total ethmoid cell volume of the nasal cavity. The results of our study underline the role of ethmoid cell volume in the compensation mechanism equalizing the nasal cavity airflow changes due to NSD.
Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning
Authors: Ogbi Mourad , Johnson John A. 
Published: December 2005

We have previously identified a phorbol ester-induced PKCϵ (protein kinase Cϵ) interaction with the (∼18 kDa) COIV [CO (cytochrome c oxidase) subunit IV] in NCMs (neonatal cardiac myocytes). Since PKCϵ has been implicated as a key mediator of cardiac PC (preconditioning), we examined whether hypoxic PC could induce PKCϵ–COIV interactions. Similar to our recent study with phorbol esters [Ogbi, Chew, Pohl, Stuchlik, Ogbi and Johnson (2004) Biochem. J. 382, 923–932], we observed a time-dependent increase in the in vitro phosphorylation of an approx. 18 kDa protein in particulate cell fractions isolated from NCMs subjected to 1–60 min of hypoxia. Introduction of a PKCϵ-selective translocation inhibitor into cells attenuated this in vitro phosphorylation. Furthermore, when mitochondria isolated from NCMs exposed to 30 min of hypoxia were subjected to immunoprecipitation analyses using PKCϵ-selective antisera, we observed an 11.1-fold increase in PKCϵ–COIV co-precipitation. In addition, we observed up to 4-fold increases in CO activity after brief NCM hypoxia exposures that were also attenuated by introducing a PKCϵ-selective translocation inhibitor into the cells. Finally, in Western-blot analyses, we observed a &gt;2-fold PC-induced protection of COIV levels after 9 h index hypoxia. Our studies suggest that a PKCϵ–COIV interaction and an enhancement of CO activity occur in NCM hypoxic PC. We therefore propose novel mechanisms of PKCϵ-mediated PC involving enhanced energetics, decreased mitochondrial reactive oxygen species production and the preservation of COIV levels.
Carbohydrate specificity of an insecticidal lectin isolated from the leaves of Glechoma hederacea (ground ivy) towards mammalian glycoconjugates
Authors: Singh Tanuja , Wu June H. , Peumans Willy J. , Rougé Pierre , Van Damme Els J. M. , Alvarez Richard A. , Blixt Ola , Wu Albert M. 
Published: December 2005

Preliminary studies indicated that the potent insecticidal lectin, Gleheda, from the leaves of Glechoma hederacea (ground ivy) preferentially agglutinates human erythrocytes carrying the Tn (GalNAcα1-Ser/Thr) antigen. However, no details have been reported yet with respect to the fine specificity of the lectin. To corroborate the molecular basis of the insecticidal activity and physiological function of Gleheda, it is necessary to identify the recognition factors that are involved in the Gleheda–glycotope interaction. In the present study, the requirement of high-density multivalent carbohydrate structural units for Gleheda binding and a fine-affinity profile were evaluated using ELLSA (enzyme-linked lectinosorbent assay) with our extended glycan/ligand collections, a glycan array and molecular modelling. From the results, we concluded that a high-density of exposed multivalent Tn-containing glycoproteins (natural armadillo and asialo ovine salivary glycoproteins) were the most potent factors for Gleheda binding. They were, on a nanogram basis, 6.5×105, 1.5×104 and 3.1×103 times more active than univalent Gal (galactose), GalNAc (N-acetylgalactosamine) and Tn respectively. Among mono- and oligo-saccharides examined, simple clustered Tn (molecular mass &lt;3000 Da) from ovine salivary glycoprotein was the best, being 37.5 and 1.7×103 times better than GalNAc and Gal respectively. GalNAc glycosides were significantly more active than Gal glycosides, indicating that the N-acetamido group at C-2 plays an important role in Gleheda binding. The results of glycan array support the conclusions drawn with respect to the specificity of Gleheda based on the ELLSA assays. These findings combined with the results of the molecular modelling and docking indicate the occurrence of a primary GalNAcα1-binding site in the Gleheda monomer. However, the extraordinary binding feature of Gleheda for glycoproteins demonstrates the importance of affinity enhancement by high-density multivalent glycotopes in the ligand–lectin interactions in biological processes.
Overproduction of cardiac S-adenosylmethionine decarboxylase in transgenic mice
Authors: Nisenberg Oleg , Pegg Anthony E. , Welsh Patricia A. , Keefer Kerry , Shantz Lisa M. 
Published: December 2005

The present study was designed to provide a better understanding of the role played by AdoMetDC (S-adenosylmethionine decarboxylase), the key rate-controlling enzyme in the synthesis of spermidine and spermine, in controlling polyamine levels and the importance of polyamines in cardiac physiology. The αMHC (α-myosin heavy chain) promoter was used to generate transgenic mice with cardiac-specific expression of AdoMetDC. A founder line (αMHC/AdoMetDC) was established with a &gt;100-fold increase in AdoMetDC activity in the heart. Transgene expression was maximal by 1 week of age and remained constant into adulthood. However, the changes in polyamine levels were most pronounced during the first week of age, with a 2-fold decrease in putrescine and spermidine and a 2-fold increase in spermine. At later times, spermine returned to near control levels, whereas putrescine and spermidine levels remained lower, suggesting that compensatory mechanisms exist to limit spermine accumulation. The αMHC/AdoMetDC mice did not display an overt cardiac phenotype, but there was an increased cardiac hypertrophy after β-adrenergic stimulation with isoprenaline (‘isoproterenol’), as well as a small increase in spermine content. Crosses of the αMHC/AdoMetDC with αMHC/ornithine decarboxylase mice that have a &gt;1000-fold increase in cardiac ornithine decarboxylase were lethal in utero, presumably due to increase in spermine to toxic levels. These findings suggest that cardiac spermine levels are highly regulated to avoid polyamine-induced toxicity and that homoeostatic mechanisms can maintain non-toxic levels even when one enzyme of the biosynthetic pathway is greatly elevated but are unable to do so when two biosynthetic enzymes are increased.
The orphan transporter v7-3 (slc6a15) is a Na+-dependent neutral amino acid transporter (B0AT2)
Authors: Bröer Angelika , Tietze Nadine , Kowalczuk Sonja , Chubb Sarah , Munzinger Michael , Bak Lasse K. , Bröer Stefan 
Published: December 2005

Transporters of the SLC6 (solute carrier 6) family play an important role in the removal of neurotransmitters in brain tissue and in amino acid transport in epithelial cells. In the present study, we demonstrate that mouse v7-3 (slc6a15) encodes a transporter for neutral amino acids. The transporter is functionally and sequence related to B0AT1 (slc6a19) and was hence named B0AT2. Leucine, isoleucine, valine, proline and methionine were recognized by the transporter, with values of K0.5 (half-saturation constant) ranging from 40 to 200 μM. Alanine, glutamine and phenylalanine were low-affinity substrates of the transporter, with K0.5 values in the millimolar range. Transport of neutral amino acids via B0AT2 was Na+-dependent, Cl−-independent and electrogenic. Superfusion of mouse B0AT2-expressing oocytes with amino acid substrates generated robust inward currents. Na+-activation kinetics of proline transport and uptake under voltage clamp suggested a 1:1 Na+/amino acid co-transport stoichiometry. Susbtrate and co-substrate influenced each other's K0.5 values, suggesting that they share the same binding site. A mouse B0AT2-like transport activity was detected in synaptosomes and cultured neurons. A potential role of B0AT2 in transporting neurotransmitter precursors and neuromodulators is proposed.
Interaction with phospholipids modulates α-synuclein nitration and lipid–protein adduct formation
Authors: Trostchansky Andrés , Lind Summer , Hodara Roberto , Oe Tomoyuki , Blair Ian A. , Ischiropoulos Harry , Rubbo Homero , Souza José M. 
Published: December 2005

Intracellular aggregates of α-syn (α-synuclein) represent pathoanatomical hallmarks of neurodegenerative disorders (synucleinopathies). The molecular mechanisms underlying α-syn aggregation into filamentous inclusions may involve oxidation and nitration of the protein. Whereas the effects of oxidants and nitrating species on soluble α-syn have been studied in detail, the effect of these reactive species on α-syn associated with lipids is still unknown. In the present paper, we report that α-syn bound to small unilamellar liposomes composed of phosphatidylcholine/phosphatidic acid is resistant to oxidation and nitration when compared with soluble α-syn. Additionally, increasing concentrations of unsaturated fatty acids diminished the oxidation and nitration of α-syn upon exposure to fluxes of peroxynitrite (8–20 μM·min−1). To investigate the effect of oxidized lipids on α-syn, the protein was incubated with the bifunctional electrophile 4-HNE [4-hydroxy-2(E)-nonenal]. MS analysis showed the formation of three major products corresponding to the native protein and α-syn plus one or two 4-HNE molecules. Trypsin digestion of the modified protein followed by peptide ‘finger-printing’ revealed that 4-HNE modified the peptide E46GVVHGVATVAEK58. Further analysis of the peptides with liquid chromatography–tandem MS identified the modified residue as His50. The data indicate that the association of α-syn with biological membranes protects the protein from oxidation and nitration and thus diminishes the formation of protein molecules capable of forming aggregates. However, products of lipid peroxidation can also modify α-syn, generating novel protein adducts that could serve as biomarkers for documenting oxidative processes in human as well as animal and cellular models of α-syn aggregation and pathology.
KESTREL: a powerful method for identifying the physiological substrates of protein kinases
Authors: Cohen Philip , Knebel Axel 
Published: December 2005

The identification of all the substrates of every protein kinase is one of the major challenges of post-genomic research. Here we review a powerful method for tackling this problem that we have developed over the last 5 years. The method has so far been used to identify novel substrates for eight different protein kinases, demonstrating that it is of general utility. Importantly, the method can be used to identify distinct physiological substrates of protein kinases, such as PKB (protein kinase B) and SGK (serum- and glucocorticoid-induced kinase), that are closely related in structure and have similar specificity determinants.
Reduced glomerular filtration rate in pre-dialysis non-diabetic chronic kidney disease patients is associated with impaired baroreceptor sensitivity and reduced vascular compliance
Authors: Lacy Peter , Carr Susan J. , O'Brien David , Fentum Barbara , Williams Bryan , Paul Sanjoy K. , Robinson Thompson G. 
Published: December 2005

Small uncontrolled studies of dialysis-dependent CKD (chronic kidney disease) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newer non-invasive techniques in pre-dialysis patients with increasing degrees of uraemia. In the present study, 55 non-dialysis-dependent non-diabetic CKD patients with mean GFR (glomerular filtration rate) of 27 ml·min−1·m−2 were studied. All patients underwent a 10-min period of electrocardiographic and non-invasive blood pressure monitoring. Cardiac BRS (baroreceptor sensitivity) was calculated from the combined α-index. PWV (pulse wave velocity) measurement and determination of arterial wave reflexion by applanation tonometry was performed in all patients. Mean (S.D.) cardiac BRS was 10.8 (7.1) ms/mmHg and mean (S.D.) PWV was 8.6 (1.7) m/s. Reduced GFR was correlated with increased PWV and decreased cardiac BRS. On logistic regression analysis with adjustment for clinical significant risk factors, severely impaired renal function (assessed by GFR &lt;15 ml·min−1·m−2) was associated with increased large artery stiffness [odds ratio for PWV=3.14 (95% confidence intervals, 1.03–9.53); P=0.04] and increased cardiovascular autonomic dysfunction [odds ratio for BRS=0.87 (95% confidence intervals, 0.75–1.80); P=0.06]. In conclusion, non-dialysis dependent non-diabetic CKD patients with decreasing GFR have reduced cardiac BRS and increased large artery stiffness. This may have important prognostic and therapeutic consequences for the management of vascular disease in a pre-dialysis population.
Learned society business models and open access: overview of a recent JISC‐funded study
Authors: Waltham Mary 
Published: December 2005

ABSTRACTA summary of the findings of a study which included an in‐depth exploration of journal business and pricing models of nine learned societies in the context of their requirements and of the open access (OA) business model. Detailed information on current trends in revenue costs and surplus is included. The article considers whether and how OA can be adopted by the representative sample of STM publishers.
A simple method to predict protein-binding from aligned sequences—application to MHC superfamily and β2-microglobulin
Authors: Duprat Elodie , Lefranc Marie-Paule , Gascuel Olivier 
Published: December 2005

Abstract
Motivation: The MHC superfamily (MhcSF) consists of immune system MHC class I (MHC-I) proteins, along with proteins with a MHC-I-like structure that are involved in a large variety of biological processes. β2-Microglobulin (B2M) non-covalent binding to MHC-I proteins is required for their surface expression and function, whereas MHC-I-like proteins interact, or not, with B2M. This study was designed to predict B2M binding (or non-binding) of newly identified MhcSF proteins, in order to decipher their function, understand the molecular recognition mechanisms and identify deleterious mutations. IMGT standardization of MhcSF protein domains provides a unique numbering of the multiple alignment positions, and conditions to develop such predictive tool.
Method: We combine a simple-Bayes classifier with IMGT unique numbering. Our method involves two steps: (1) selection of discriminant binary features, which associate an alignment position with an amino acid group; and (2) learning of the classifier by estimating the frequencies of selected features, conditionally to the B2M binding property.
Results: Our dataset contains aligned sequences of 806 allelic forms of 47 MhcSF proteins, corresponding to 9 receptor types and 4 mammalian species. Eighteen discriminant features are selected, belonging to B2M contact sites, or stabilizing the molecular structure required for this contact. Three leave-one-out procedures are used to assess classifier performance, which corresponds to B2M binding prediction for: (1) new proteins, (2) species not represented in the dataset and (3) new receptor types. The prediction accuracy is high, i.e. 98, 94 and 70%, respectively. Application of our classifier to lower vertebrate MHC-I proteins indicates that these proteins bind to B2M and should then be expressed on the cellular surface by a process similar to that of mammalian MHC-I proteins. These results demonstrate the usefulness and accuracy of our (simple) approach, which should apply to other function or interaction prediction problems.
Availability: Data and MhcSF multiple alignments are available on the IMGT website ().
Contact: gascuel@lirmm.fr, duprat@ligm.igh.cnrs.fr, lefranc@ligm.igh.cnrs.fr
Supplementary information: Supplementary material is downloadable at .
Differential gene expression detection and sample classification using penalized linear regression models
Authors: Wu Baolin 
Published: December 2005

AbstractDifferential gene expression detection and sample classification using microarray data have received much research interest recently. Owing to the large number of genes p and small number of samples n (p ≫ n), microarray data analysis poses big challenges for statistical analysis. An obvious problem owing to the ‘large p small n’ is over-fitting. Just by chance, we are likely to find some non-differentially expressed genes that can classify the samples very well. The idea of shrinkage is to regularize the model parameters to reduce the effects of noise and produce reliable inferences. Shrinkage has been successfully applied in the microarray data analysis. The SAM statistics proposed by Tusher et al. and the ‘nearest shrunken centroid’ proposed by Tibshirani et al. are ad hoc shrinkage methods. Both methods are simple, intuitive and prove to be useful in empirical studies.Recently Wu proposed the penalized t/F-statistics with shrinkage by formally using the ℒ1 penalized linear regression models for two-class microarray data, showing good performance. In this paper we systematically discussed the use of penalized regression models for analyzing microarray data. We generalize the two-class penalized t/F-statistics proposed by Wu to multi-class microarray data. We formally derive the ad hoc shrunken centroid used by Tibshirani et al. using the ℒ1 penalized regression models. And we show that the penalized linear regression models provide a rigorous and unified statistical framework for sample classification and differential gene expression detection.Availability: For the computer programs, detailed analysis results and R functions for the proposed methods, please seeContact: baolin@biostat.umn.eduSupplementary information:
Improved pairwise alignments of proteins in the Twilight Zone using local structure predictions
Authors: Huang Yao-ming , Bystroff Christopher 
Published: December 2005

Abstract
Motivation: In recent years, advances have been made in the ability of computational methods to discriminate between homologous and non-homologous proteins in the ‘twilight zone’ of sequence similarity, where the percent sequence identity is a poor indicator of homology. To make these predictions more valuable to the protein modeler, they must be accompanied by accurate alignments. Pairwise sequence alignments are inferences of orthologous relationships between sequence positions. Evolutionary distance is traditionally modeled using global amino acid substitution matrices. But real differences in the likelihood of substitutions may exist for different structural contexts within proteins, since structural context contributes to the selective pressure.
Results: HMMSUM (HMMSTR-based substitution matrices) is a new model for structural context-based amino acid substitution probabilities consisting of a set of 281 matrices, each for a different sequence–structure context. HMMSUM does not require the structure of the protein to be known. Instead, predictions of local structure are made using HMMSTR, a hidden Markov model for local structure. Alignments using the HMMSUM matrices compare favorably to alignments carried out using the BLOSUM matrices or structure-based substitution matrices SDM and HSDM when validated against remote homolog alignments from BAliBASE. HMMSUM has been implemented using local Dynamic Programming and with the Bayesian Adaptive alignment method.
Availability: Matrices, source codes and programs are available at .
Contact: bystrc@rpi.edu, huangy2@rpi.edu
Priming of CD4+ T cells and development of CD4+ T cell memory; lessons for malaria
Authors: STEPHENS R. , LANGHORNE J. 
Published: December 2005

SUMMARY CD4 T cells play a central role in the immune response to malaria. They are required to help B cells produce the antibody that is essential for parasite clearance. They also produce cytokines that amplify the phagocytic and parasitocidal response of the innate immune system, as well as dampening this response later on to limit immunopathology. Therefore, understanding the mechanisms by which T helper cells are activated and the requirements for development of specific, and effective, T cell memory and immunity is essential in the quest for a malaria vaccine. In this paper on the CD4 session of the Immunology of Malaria Infections meeting, we summarize discussions of CD4 cell priming and memory in malaria and in vaccination and outline critical future lines of investigation. B. Stockinger and M.K. Jenkins proposed cutting edge experimental systems to study basic T cell biology in malaria. Critical parameters in T cell activation include the cell types involved, the route of infection and the timing and location and cell types involved in antigen presentation. A new generation of vaccines that induce CD4 T cell activation and memory are being developed with new adjuvants. Studies of T cell memory focus on differentiation and factors involved in maintenance of antigen specific T cells and control of the size of that population. To improve detection of T cell memory in the field, efforts will have to be made to distinguish antigen‐specific responses from cytokine driven responses.