bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple sequence alignment accuracy and evolutionary distance estimation
Authors: Rosenberg Michael S 
Published: November 2005

Abstract
Background
Sequence alignment is a common tool in bioinformatics and comparative genomics. It is generally assumed that multiple sequence alignment yields better results than pair wise sequence alignment, but this assumption has rarely been tested, and never with the control provided by simulation analysis. This study used sequence simulation to examine the gain in accuracy of adding a third sequence to a pair wise alignment, particularly concentrating on how the phylogenetic position of the additional sequence relative to the first pair changes the accuracy of the initial pair's alignment as well as their estimated evolutionary distance.

Results
The maximal gain in alignment accuracy was found not when the third sequence is directly intermediate between the initial two sequences, but rather when it perfectly subdivides the branch leading from the root of the tree to one of the original sequences (making it half as close to one sequence as the other). Evolutionary distance estimation in the multiple alignment framework, however, is largely unrelated to alignment accuracy and rather is dependent on the position of the third sequence; the closer the branch leading to the third sequence is to the root of the tree, the larger the estimated distance between the first two sequences.

Conclusion
The bias in distance estimation appears to be a direct result of the standard greedy progressive algorithm used by many multiple alignment methods. These results have implications for choosing new taxa and genomes to sequence when resources are limited.
Computational identification of strain-, species- and genus-specific proteins
Authors: Mazumder Raja , Natale Darren A , Murthy Sudhir , Thiagarajan Rathi , Wu Cathy H 
Published: November 2005

Abstract
Background
The identification of unique proteins at different taxonomic levels has both scientific and practical value. Strain-, species- and genus-specific proteins can provide insight into the criteria that define an organism and its relationship with close relatives. Such proteins can also serve as taxon-specific diagnostic targets.

Description
A pipeline using a combination of computational and manual analyses of BLAST results was developed to identify strain-, species-, and genus-specific proteins and to catalog the closest sequenced relative for each protein in a proteome. Proteins encoded by a given strain are preliminarily considered to be unique if BLAST, using a comprehensive protein database, fails to retrieve (with an e-value better than 0.001) any protein not encoded by the query strain, species or genus (for strain-, species- and genus-specific proteins respectively), or if BLAST, using the best hit as the query (reverse BLAST), does not retrieve the initial query protein. Results are manually inspected for homology if the initial query is retrieved in the reverse BLAST but is not the best hit. Sequences unlikely to retrieve homologs using the default BLOSUM62 matrix (usually short sequences) are re-tested using the PAM30 matrix, thereby increasing the number of retrieved homologs and increasing the stringency of the search for unique proteins. The above protocol was used to examine several food- and water-borne pathogens. We find that the reverse BLAST step filters out about 22% of proteins with homologs that would otherwise be considered unique at the genus and species levels. Analysis of the annotations of unique proteins reveals that many are remnants of prophage proteins, or may be involved in virulence. The data generated from this study can be accessed and further evaluated from the CUPID (C ore and U nique P rotein Id entification) system web site (updated semi-annually) at http://pir.georgetown.edu/cupid.

Conclusion
CUPID provides a set of proteins specific to a genus, species or a strain, and identifies the most closely related organism.
Analysis of vertebrate genomes suggests a new model for clade B serpin evolution
Authors: Kaiserman Dion , Bird Phillip I 
Published: November 2005

Abstract

Background
The human genome contains 13 clade B serpin genes at two loci, 6p25 and 18q21. The three genes at 6p25 all conform to a 7-exon gene structure with conserved intron positioning and phasing, however, at 18q21 there are two 7-exon genes and eight genes with an additional exon yielding an 8-exon structure. Currently, it is not known how these two loci evolved, nor which gene structure arose first – did the 8-exon genes gain an exon, or did the 7-exon genes lose one? Here we use the genomes of diverse vertebrate species to plot the emergence of clade B serpin genes and to identify the point at which the two genomic structures arose.

Results
Analysis of the chicken genome indicated the presence of a single clade B serpin gene locus, containing orthologues of both human loci and both genomic structures. The frog genome and the genomes of three fish species presented progressively simpler loci, although only the 7-exon structure could be identified. The Serpinb12 gene contains seven exons in the frog genome, but eight exons in chickens and humans, indicating that the additional exon evolved in this gene.

Conclusion
We propose a new model for clade B serpin evolution from a single 7-exon gene (either Serpinb1 or Serpinb6). An additional exon was gained in the Serpinb12 gene between the tetrapoda and amniota radiations to produce the 8-exon structure. Both structures were then duplicated at a single locus until a chromosomal breakage occurred at some point along the mammalian lineage resulting in the two modern loci.
A truncated Kv1.1 protein in the brain of the megencephalymouse: expression and interaction
Authors: Persson Ann-Sophie , Klement Göran , Almgren Malin , Sahlholm Kristoffer , Nilsson Johanna , Petersson Susanna , Århem Peter , Schalling Martin , Lavebratt Catharina 
Published: November 2005

Abstract

Background
The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice.

Results
We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi) glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons.

Conclusion
The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth.
Substance P selectively decreases paired pulse depression in the rat hippocampal slice
Authors: Wease Kerrie N , Davies Stephen N 
Published: November 2005

Abstract

Background
Although being widespread in the hippocampus, the role tachykinins play in synaptic transmission is unclear. The effect of substance P on field potentials evoked by stimulation of the Schaffer collateral-commissural fibres and recorded from the CA1 region of the rat hippocampal slice were studied.

Results
Perfusion of substance P (8 μM) had no effect on the fEPSP or population spike. Substance P did however cause a selective reduction in the paired pulse depression of population spikes evoked by paired stimulation at interpulse intervals of 20–80 msec. A comparison of the actions of other tachykinin receptor agonists gave an order of potency of substance P > [β-Ala8]-neurokinin A (4–10) > senktide. The effect of substance P was reduced by the neurokinin-1 receptor antagonist SR140333, but not by the neurokinin-2 or neurokinin-3 receptor antagonists, MDL 29,913 or [Trp7, β-Ala8]-neurokinin A (4–10).

Conclusion
The order of potency of the agonists, and the effects of the antagonists, both indicate that the effect of substance P on paired pulse depression is mediated by neurokinin-1 receptors.
Comparative assessment of three different indices of multimorbidity for studies on health-related quality of life
Authors: Fortin Martin , Hudon Catherine , Dubois Marie-France , Almirall José , Lapointe Lise , Soubhi Hassan 
Published: November 2005

Abstract

Background
Measures of multimorbidity are often applied to source data, populations or outcomes outside the scope of their original developmental work. As the development of a multimorbidity measure is influenced by the population and outcome used, these influences should be taken into account when selecting a multimorbidity index. The aim of this study was to compare the strength of the association of health-related quality of life (HRQOL) with three multimorbidity indices: the Cumulative Illness Rating Scale (CIRS), the Charlson index (Charlson) and the Functional Comorbidity Index (FCI). The first two indices were not developed in light of HRQOL.

Methods
We used data on chronic diseases and on the SF-36 questionnaire assessing HRQOL of 238 adult primary care patients who participated in a previous study. We extracted all the diagnoses for every patient from chart review to score the CIRS, the FCI and the Charlson. Data for potential confounders (age, sex, self-perceived economic status and self-perceived social support) were also collected. We calculated the Pearson correlation coefficients (r) of the SF-36 scores with the three measures of multimorbidity, as well as the coefficient of determination, R2, while controlling for confounders.

Results
The r values for the CIRS (range: -0.55 to -0.18) were always higher than those for the FCI (-0.47 to -0.10) and Charlson (-0.31 to -0.04) indices. The CIRS explained the highest percent of variation in all scores of the SF-36, except for the Mental Component Summary Score where the variation was not significant. Variations explained by the FCI were significant in all scores of SF-36 measuring physical health and in two scales evaluating mental health. Variations explained by the Charlson were significant in only three scores measuring physical health.

Conclusion
The CIRS is a better choice as a measure of multimorbidity than the FCI and the Charlson when HRQOL is the outcome of interest. However, the FCI may provide a good option to evaluate the physical aspect of HRQOL for the ease in its administration and scoring. The Charlson index may not be recommended as a measure of multimorbidity in studies related to either physical or mental aspects of HRQOL.
Recent developments in targeting access to high cost medicines in Australia
Authors: Lu Christine Y , Ritchie Jan , Williams Kenneth M , Day Richard O 
Published: November 2005

Abstract

Background
In Australia, the Pharmaceutical Benefits Scheme (PBS) has developed a set of arrangements to control access to high-cost medicines to ensure their use is cost-effective. These medicines include the tumour necrosis factor-alpha inhibitors (TNFIs) for the treatment of rheumatoid arthritis. The aim of this first phase of a qualitative study was to explore basic views on the restricted access to TNFIs in order to confirm where further investigation should take place in the next phase.

Methods
Semi-structured interviews were conducted in 2004 with a member of the four relevant stakeholder groups. Participants were asked their opinions about features of the establishment, process and effects of the system of restricted access to TNFIs. Views on the collaboration between stakeholder groups in the decision-making process were also collected.

Results
The principle of 'controlled access' to TNFIs was supported in general. There were concerns regarding some of the specific eligibility criteria. Wider and more transparent stakeholder consultation was judged desirable. Some flexibility around prescribing of TNFIs by physicians, and regular review of the arrangements were proposed. These themes will inform the next phase of the study.

Conclusion
This first phase highlighted a range of issues associated with the PBS arrangements restricting access to TNFIs. Timely review and report of issues and concerns associated with such policy developments that arose in practice are essential. There is a need for a more comprehensive exploration across a wide range of stakeholders with different perspectives that will in turn be helpful in guiding policy and practice around national arrangements to manage access to high-cost medicines.
ASIC3, an Acid-Sensing Ion Channel, is Expressed in Metaboreceptive Sensory Neurons
Authors: Molliver Derek C , Immke David C , Fierro Leonardo , Paré Michel , Rice Frank L , McCleskey Edwin W 
Published: November 2005

Background: ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1) ASIC3 might trigger ischemic pain in heart and muscle; 2) it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. Results: Less than half (40%) of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small (<25 μm) sensory neurons that innervate muscle are more likely to express ASIC3 than those that innervate skin (51% of small muscle afferents vs. 28% of small skin afferents). Over 80% of ASIC3+ muscle afferents co-express CGRP (a vasodilatory peptide). Remarkably few (9%) ASIC3+ cells express P2X3 receptors (an ATP-gated ion channel), whereas 31% express TRPV1 (the noxious heat and capsaicin-activated ion channel also known as VR1). ASIC3+/CGRP+ sensory nerve endings were observed on muscle arterioles, the blood vessels that control vascular resistance; like the cell bodies, the endings are P2X3- and can be TRPV1+. The TrkC+/ASIC3+ cell bodies are uniformly large, possibly consistent with non-nociceptive mechanosensation. They are not proprioceptors because they fail two other tests: ASIC3+ cells do not express parvalbumin and they are absent from the mesencephalic trigeminal nucleus. Conclusion: Our data indicates that: 1) ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2) co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.
Influence of static lumbar flexion on the trunk muscles' response to sudden arm movements
Authors: Lehman Gregory J , Story Stephen , Mabee Robert 
Published: November 2005

Abstract

Background

Viscoelastic creep of lumbar ligaments (prolonged forward bend) has been shown to negatively influence the spine's muscular reflexive behaviour and spinal stability. No studies to date have investigated the influence of spinall viscoelastic creep on the feedforward response of the trunk muscles to sudden arm raises.

Methods

Surface myoelectric activity was collected from the transversus abdominis/internal oblique, the lower erector spinae and the deltoid muscle during sudden ballistic arm raising before and after 10 minutes of prolonged forward bend in 11 healthy participants free of low back injury. The timing of trunk muscle activity relative to the deltoid muscle was calculated for 5 trials before and 5 trials after the creep procedure.

Results

Viscoelastic creep had no influence on the feedforward response of the trunk muscles during sudden arm raises. A feedforward response of the trunk muscles was not seen in every study participant and during every trial.

Conclusion

Passive trunk muscle fatigue does not appear to influence the timing of the stabilizing role of the investigated trunk muscles to sudden arm flexion.
Estrogen Dendrimer Conjugates that Preferentially Activate Extranuclear, Nongenomic Versus Genomic Pathways of Estrogen Action
Authors: Harrington William R. , Kim Sung Hoon , Funk Cory C. , Madak-Erdogan Zeynep , Schiff Rachel , Katzenellenbogen John A. , Katzenellenbogen Benita S. 
Published: November 2005

Abstract
Estrogenic hormones are classically thought to exert their effects by binding to nuclear estrogen receptors and altering target gene transcription, but estrogens can also have nongenomic effects through rapid activation of membrane-initiated kinase cascades. The development of ligands that selectively activate only the nongenomic pathways would provide useful tools to investigate the significance of these pathways. We have prepared large, abiotic, nondegradable poly(amido)amine dendrimer macromolecules that are conjugated to multiple estrogen molecules through chemically robust linkages. Because of their charge and size, these estrogen-dendrimer conjugates (EDCs) remain outside the nucleus. They stimulate ERK, Shc, and Src phosphorylation in MCF-7 breast cancer cells at low concentrations, yet they are very ineffective in stimulating transcription of endogenous estrogen target genes, being approximately 10,000-fold less potent than estradiol in genomic actions. In contrast to estradiol, EDC was not effective in stimulating breast cancer cell proliferation. Because these EDC ligands activate nongenomic activity at concentrations at which they do not alter the transcription of estrogen target genes, they should be useful in studying extranuclear initiated pathways of estrogen action in a variety of target cells.
Western Blotting of Total Lysate of Helicobacter pylori in Cases of Atrophic Body Gastritis
Authors: Mini Roberta , Annibale Bruno , Lahner Edith , Bernardini Giulia , Figura Natale , Santucci Annalisa 
Published: November 2005

Abstract
Background: Atrophic body gastritis is considered the first important step in the histogenesis of gastric carcinoma, a multistep process starting from chronic gastritis and progressing through chronic atrophic gastritis, intestinal metaplasia, and dysplasia. Helicobacter pylori is involved in the induction of atrophic body gastritis, but documentation of H. pylori infection is difficult because of the progressive disappearance of the bacterium. Our study aimed to detect past H. pylori infection in patients with atrophic body gastritis.
Methods: We used Western blot analyses of whole bacterial protein lysate of 2 different strains to probe sera from 143 patients. All sera were analyzed by ELISA (Bio-Rad), and results of gastric histology were available for all patients.
Results: Among 111 patient sera previously classified as negative for H. pylori infection by ELISA, 106 (95.5%) were positive when assayed by immunoblotting.
Conclusions: Commercial diagnostic reagent sets may fail to detect H. pylori infection. Western blotting of whole bacterial protein extracts could provide the basis of a noninvasive serology tool able to assess previous infection with H. pylori in patients with atrophic body gastritis.
Feasibility Study of New Calibrators for Thyroid-Stimulating Hormone (TSH) Immunoprocedures Based on Remodeling of Recombinant TSH to Mimic Glycoforms Circulating in Patients with Thyroid Disorders
Authors: Donadio Sandrine , Pascual Aurélie , Thijssen Jos HH , Ronin Catherine 
Published: November 2005

AbstractBackground: Differences between the glycosylation patterns of a pituitary thyroid-stimulating hormone calibrator (pitTSH) and serum samples have been shown to be responsible for nonidentical epitope expression and for introducing discrepancies in TSH measurements. We studied the feasibility of developing new candidate reference materials by remodeling recombinant TSH (recTSH) to generate potential mimics of serum TSH.Methods: Terminal sialylation and/or inner fucosylation of recTSH were remodeled by a combination of enzyme treatments followed (or not) by lentil lectin-Sepharose affinity chromatography. The resulting TSH preparations were screened for epitope similarity in 23 immunoassays mapping 3 antigenic clusters common to the pitTSH 2nd International Reference Preparation (IRP) and the recTSH 1st IRP and then challenged against a pool of 63 patients with increased serum TSH (&gt;60 mIU/L).Results: pitTSH was poorly correlated with serum TSH, with a mean (SD) slope of 2.124 (0.001), in contrast to recTSH [slope, 1.178 (0.056)]. Comparison of variably sialylated preparations with recTSH gave slopes of 0.860 (0.057) for desialylated TSH, 1.064 (0.057) for α2,3/6-oversialylated recTSH, and 0.953 (0.033) for α2,6-resialylated recTSH, indicating that TSH forms enriched in sialic acid closely resemble serum TSH. Further testing against serum TSH showed satisfactory agreement with both TSH preparations containing α2,6-sialic acid [slopes, 1.064 (0.057) and 0.953 (0.033)], particularly in the absence of nonfucosylated forms [0.985 (0.044)].Conclusions: Glyco-engineered recTSH preparations enriched in sialic acid and inner fucose are promising candidates for future reference materials. These preparations may have advantages over existing preparations used for standardizing TSH measurements.
Evaluation of the Evidence for Rehabilitation Following Acquired Brain Injury
Authors: Turner-Stokes Lynne 
Published: November 2005

AbstractThis article represents a summary of the George Burniston Oration of the Australian Faculty of Rehabilitation Medicine, which was given as a keynote address at the 6th World Congress on Brain Injury, Melbourne, May 2005. The paper concerns evaluation of the evidence for effectiveness of rehabilitation following acquired brain injury (ABI). It explores the current evidence available, and discusses a number of different review strategies which may be used to overcome the challenges of assimilating research evidence in this context.
Behavioural and Psychiatric Symptoms in Patients With Neurodegenerative Diseases
Authors: Lomax Claire , Brown Richard G. , Chaudhuri K. Ray , Howard Robert J. 
Published: November 2005

AbstractNeuropsychiatric symptoms are common features in patients with neurodegenerative diseases, and have important clinical implications for both patients and caregivers. This study used the Neuropsychiatric Inventory (NPI) to measure symptomatology in 120 patients drawn from five disease groups: Parkinson's disease (PD), Alzheimer's disease (AD), dementia associated with Lewy bodies (DLB), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Ninety per cent of the patient group reported experiencing at least one symptom, with the most prevalent symptoms being depression and apathy. However, a differential pattern of symptomatology was reported across the disease groups, a finding which has diagnostic and treatment implications. Furthermore, this provides additional evidence that a broad cortical–subcortical distinction cannot be supported.