bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunomodulator FTY720 and its phosphorylated derivative activate the Smad signalling cascade and upregulate connective tissue growth factor and collagen type IV expression in renal mesangial cells
Authors: Xin Cuiyan , Ren Shuyu , Eberhardt Wolfgang , Pfeilschifter Josef , Huwiler Andrea 
Published: November 2005

The immunomodulating agent FTY720 is a substrate for the sphingosine kinase and the phosphorylated form is able to bind to sphingosine 1‐phosphate (S1P) receptors. In this study, we show that exposure of renal mesangial cells to phospho‐FTY720 leads to a rapid and transient activation of several protein kinase cascades, including the mitogen‐ and stress‐activated protein kinases. The nonphosphorylated FTY720 also increased MAPK phosphorylation, but with a reduced potency and a more delayed time course. In addition, phospho‐FTY720 and FTY720 are able to increase phosphorylation of Smad proteins which are classical members of the transforming growth factor‐β (TGF‐β) signalling device, thus suggesting a crosstalk between FTY720 and TGF‐β signalling.
Pretreatment with the S1P3 receptor antagonist suramin inhibits FTY720 and phospho‐FTY720‐induced Smad phosphorylation, whereas pertussis toxin pretreatment, which blocks Gi/0 proteins, has no effect on Smad phosphorylation.
Since TGF‐β is a potent profibrotic cytokine in mesangial cells and upregulates the connective tissue growth factor (CTGF) and collagen as important hallmarks in the fibrotic sequelae, we investigated whether FTY720 and phospho‐FTY720 are able to mimic these effects of TGF‐β. Indeed, FTY720 and phospho‐FTY720 markedly upregulate CTGF and collagen type IV protein expressions. In addition, the tissue inhibitor of metalloproteinase‐1 is transcriptionally activated by FTY720, whereas cytokine‐induced matrix metalloproteinase‐9 is down‐regulated by FTY720.
Depletion of the TGF‐β receptor type II by the siRNA transfection technique blocks not only Smad phosphorylation but also CTGF upregulation. Similarly, Smad‐4 depletion by siRNA transfection also abrogates CTGF upregulation induced by FTY720 and phospho‐FTY720.
In summary, our data show that FTY720 and phospho‐FTY720 not only activate the Smad signalling cascade in mesangial cells, but also upregulate the expression of CTGF and collagen. These findings suggest that FTY720 may have additional effects besides the established immunomodulatory action and, importantly, a profibrotic activity has to be considered in future experimental approaches.

British Journal of Pharmacology (2006) 147, 164–174. doi:10.1038/sj.bjp.0706452
Study of the mechanisms involved in the vasorelaxation induced by (−)‐epigallocatechin‐3‐gallate in rat aorta
Authors: Álvarez Ezequiel , Campos‐Toimil Manuel , Justiniano‐Basaran Hélène , Lugnier Claire , Orallo Francisco 
Published: November 2005

This study investigated several mechanisms involved in the vasorelaxant effects of (−)‐epigallocatechin‐3‐gallate (EGCG).EGCG (1 μM–1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 μM), high extracellular KCl (60 mM), or phorbol 12‐myristate 13‐acetate (PMA, 1 μM) in intact rat aortic rings. In a Ca2+‐free solution, EGCG (1 μM–1 mM) relaxed 1 μMPMA‐induced contractions, without previous transient contraction. However, EGCG (1 μM–1 mM) did not affect the 1 μMokadaic acid‐induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 μM), tetraethylammonium (2 mM) or charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions induced by NA (in 1.5 mMCa2+‐containing solution) and Ca2+(in depolarizing Ca2+‐free high KCl 60 mMsolution).In rat aortic smooth muscle cells (RASMC), EGCG (100 μM) reduced increases in cytosolic free Ca2+concentration ([Ca2+]i) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mMCaCl2‐containing solution and by ANG II (100 nM) in the absence of extracellular Ca2+.In RASMC, EGCG (100 μM) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 μM) and high KCl (60 mM) on cAMP and cGMP production.EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50∼17) and on PDE1 (IC50∼25).Our results suggest that the vasorelaxant effects of EGCG in rat aorta are mediated, at least in part, by an inhibition of PDE activity, and the subsequent increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist‐ or high KCl concentration‐induced increases in [Ca2+]i.British Journal of Pharmacology(2006)147, 269–280. doi:10.1038/sj.bjp.0706507
The choice of optimal distance measure in genome-wide datasets
Authors: Glazko Galina , Gordon Alexander , Mushegian Arcady 
Published: November 2005

Abstract
Motivation: Many types of genomic data are naturally represented as binary vectors. Numerous tasks in computational biology can be cast as analysis of relationships between these vectors, and the first step is, frequently, to compute their pairwise distance matrix. Many distance measures have been proposed in the literature, but there is no theory justifying the choice of distance measure.
Results: We examine the approaches to measuring distances between binary vectors and study the characteristic properties of various distance measures and their performance in several tasks of genome analysis. Most distance measures between binary vectors turn out to belong to a single parametric family, namely generalized average-based distance with different exponents. We show that descriptive statistics of distance distribution, such as skewness and kurtosis, can guide the appropriate choice of the exponent. On the contrary, the more familiar distance properties, such as metric and additivity, appear to have much less effect on the performance of distances.
Availability: R code GADIST and Supplementary material are available at
Contact: gvg@stowers-institute.org
Mining sequence annotation databanks for association patterns
Authors: Artamonova Irena I. , Frishman Goar , Gelfand Mikhail S. , Frishman Dmitrij 
Published: November 2005

Abstract
Motivation: Millions of protein sequences currently being deposited to sequence databanks will never be annotated manually. Similarity-based annotation generated by automatic software pipelines unavoidably contains spurious assignments due to the imperfection of bioinformatics methods. Examples of such annotation errors include over- and underpredictions caused by the use of fixed recognition thresholds and incorrect annotations caused by transitivity based information transfer to unrelated proteins or transfer of errors already accumulated in databases. One of the most difficult and timely challenges in bioinformatics is the development of intelligent systems aimed at improving the quality of automatically generated annotation. A possible approach to this problem is to detect anomalies in annotation items based on association rule mining.
Results: We present the first large-scale analysis of association rules derived from two large protein annotation databases—Swiss-Prot and PEDANT—and reveal novel, previously unknown tendencies of rule strength distributions. Most of the rules are either very strong or very weak, with rules in the medium strength range being relatively infrequent. Based on dynamics of error correction in subsequent Swiss-Prot releases and on our own manual analysis we demonstrate that exceptions from strong rules are, indeed, significantly enriched in annotation errors and can be used to automatically flag them. We identify different strength dependencies of rules derived from different fields in Swiss-Prot. A compositional breakdown of association rules generated from PEDANT in terms of their constituent items indicates that most of the errors that can be corrected are related to gene functional roles. Swiss-Prot errors are usually caused by under-annotation owing to its conservative approach, whereas automatically generated PEDANT annotation suffers from over-annotation.
Availability: All data generated in this study are available for download and browsing at .
Contact: d.frishman@wzw.tum.de
Supplementary information:
Myokymia in Axonal Disorders
Authors: Kelkar Praful , Kimura Jun 
Published: November 2005

Abstract

Myokymic discharges are spontaneous bursts of individual motor units occurring rhythmically or semirhythmically. Myokymia is typically seen in demyelinating disorders. We present 5 patients with myokymia in axonal disorders, including a case of myokymia after Botox injection, which has not been reported previously.
Parotid Gland Injections of Botulinum Toxin A Are Effective in Treating Sialorrhea in Amyotrophic Lateral Sclerosis
Authors: Scott Kevin R , Kothari Milind J , Venkatesh Y Swami , Murphy Tamara , Simmons Zachary 
Published: November 2005

Abstract

Objective:
The objective of this study was to determine the safety and efficacy of botulinum toxin A in ameliorating refractory sialorrhea and improving quality of life in patients with amyotrophic lateral sclerosis.

Materials and Methods:
Six patients with bulbar ALS received bilateral parotid gland injections of botulinum toxin A.

Results:
No adverse effects occurred. Tissue use decreased in 5 of 7 patients at a dose of 10 units and in 3 of 4 patients at a dose of 20 units. Self-reported quality of life did not change in most.

Conclusions:
Parotid gland injections of botulinum toxin appear safe and may be helpful in some patients with ALS for the treatment of sialorrhea.
Subclinical Sensory Involvement in Monomelic Amyotrophy
Authors: Liao Jenny P , Waclawik Andrew J , Lotz Barend P 
Published: November 2005

Abstract

An 18-year-old woman presented with weakness and atrophy in her hand without associated sensory symptoms, preceding events, or structural abnormalities on neuroimaging. No sensory deficits were detected on neurologic examination. Electrophysiological studies showed not only the expected motor findings for monomelic amyotrophy (MA) in the affected limb, but also markedly reduced sensory nerve action potentials when compared with the unaffected side. These findings suggest that subclinical sensory involvement can exist in patients with otherwise classic presentations of MA.
Parsimony overcomes statistical inconsistency with the addition of more data from the same gene
Authors: Pickett Kurt M. , Tolman Greg L. , Wheeler Ward C. , Wenzel John W. 
Published: November 2005

AbstractMany authors have demonstrated that the parsimony method of phylogenetic analysis can fail to estimate phylogeny accurately under certain conditions when data follow a model that stipulates homogeneity of the evolutionary process. These demonstrations further show that no matter how much data are added, parsimony will forever exhibit this statistical inconsistency if the additional data have the same distributional properties as the original data. This final component—that the additional data must follow the same distribution as the original data—is crucial to the demonstration. Recent simulations show, however, that if data evolve heterogeneously, parsimony can perform consistently. Here we show, using natural data, that parsimony can overcome inconsistency if new data from the same gene are added to an analysis already exhibiting a condition indistinguishable from inconsistency.© The Willi Hennig Society 2005.
The Pseudomonas syringae phytotoxin coronatine promotes virulence by overcoming salicylic acid‐dependent defences in Arabidopsis thaliana
Authors: BROOKS DAVID M. , BENDER CAROL L. , KUNKEL BARBARA N. 
Published: November 2005

SUMMARYSuccessful pathogen infection likely involves the suppression of general antimicrobial host defences. One Pseudomonas syringae virulence factor proposed to act in this manner is coronatine (COR), a phytotoxin believed to function as an analogue of one or more jasmonates, a family of plant growth regulators. COR biosynthetic (COR−) mutants of P. syringae pv. tomato strain DC3000 exhibit reduced virulence on Arabidopsis thaliana and tomato. In the present study, three genetically and biochemically defined COR− mutants of DC3000 were used to explore potential effects of COR and its precursors, coronafacic acid (CFA) and coronamic acid (CMA), on defence signalling pathways in A. thaliana. Inoculation with wild‐type DC3000 resulted in the accumulation of several jasmonate‐responsive transcripts, whereas infection with a mutant strain that accumulates CFA, which is structurally similar to methyl jasmonate (MeJA), did not. Thus, COR, but not CFA, stimulates jasmonate signalling during P. syringae infection of A. thaliana. The ability of the COR− mutants to grow to high levels in planta was fully restored in A. thaliana lines deficient for salicylic acid (SA) accumulation. Although the COR− mutants grew to high levels in SA‐deficient plants, disease symptoms were reduced in these plants. Collectively, these results indicate that COR is required both for overcoming or suppressing SA‐dependent defences during growth in plant tissue and for normal disease symptom development in A. thaliana.
Review article: the role of antisecretory therapy in the management of non‐variceal upper gastrointestinal bleeding
Authors: TRIADAFILOPOULOS G. 
Published: November 2005

SummaryNon‐variceal, upper gastrointestinal bleeding accounts for 300,000 hospitalizations annually in the US and the risk of rebleeding and mortality remain high.The aim of this study was to review the incidence and causes of non‐variceal upper gastrointestinal haemorrhage, criteria for early discharge, risk stratification and intravenous vs. oral proton‐pump inhibitor use. Peptic ulcer disease accounts for 45% of all admissions for upper gastrointestinal bleeding.Clinical and endoscopic predictors of adverse outcome have been identified. The Rockall scoring system identifies patients who can be considered for early discharge after endoscopy.Evidence supports the use of intravenous proton‐pump inhibitor therapy for patients with bleeding ulcers associated with high‐risk stigmata. Patients who are clinically stable and in whom upper endoscopy has shown an ulcer with a clean base or a flat pigmented spot have a low risk for rebleeding and may be discharged early on oral proton‐pump inhibitor therapy. Proton‐pump inhibitor treatment reduces ulcer rebleeding but does not affect overall mortality. In the US, most patients with ulcer bleeding have low‐risk stigmata, and thus, can be treated with oral proton‐pump inhibitors and discharged early.
Specific leaf area explains differences in leaf traits between congeneric savanna and forest trees
Authors: HOFFMANN W. A. , FRANCO A. C. , MOREIRA M. Z. , HARIDASAN M. 
Published: November 2005

Summary

Leaf traits are commonly associated with the life history, distribution and resource requirements of a species. To improve our understanding of the ecological and physiological differences between tropical savanna and forest trees, we compared leaf traits of species native to savanna and gallery (riverine) forests in the Cerrado region of central Brazil.
Congeneric species pairs from 14 different taxonomic families were studied, each with a savanna species and a forest species present at the study site. Only individuals growing in savanna conditions under full sun were studied. We measured foliar nutrients, δ13C, δ15N and specific leaf area (SLA: leaf area per unit leaf mass). We used phylogenetically independent contrasts to compare savanna and forest species and to test for correlations among species traits.
Overall, leaves of forest species had 17% higher N concentration, 32% higher P concentration, and 37% higher K concentration, despite growing in similar soils. Concentrations of all three elements were strongly and positively correlated with SLA.
Forest species had 52% greater SLA, on average, than savanna species, which accounts for the higher foliar nutrient concentrations of these species.
Savanna species had higher δ13C values than forest species, indicating higher water‐use efficiency. The SLA was negatively correlated with δ13C, suggesting that SLA may also account for the higher water‐use efficiency of savanna species.
There was no difference in foliar δ15N between savanna and forest species, but foliar δ15N was negatively correlated with soil pH.
These results contribute to recent studies showing that tropical savanna and forest species represent two distinct functional types, with large differences in ecology and physiology, that have important consequences for the dynamics of savanna–forest boundaries.
Can secondary compounds of an invasive plant affect larval amphibians?
Authors: MAERZ J. C. , BROWN C. J. , CHAPIN C. T. , BLOSSEY B. 
Published: November 2005

Summary

There is significant concern over the impacts of plant invasions on habitat quality for native fauna. Recent research suggests that non‐native Purple Loosestrife (Lythrum salicaria) invasions may negatively affect the performance of larval American Toad tadpoles (Bufo americanus), and that compounds leached from L. salicaria leaves play a direct or indirect role in this effect.
We raised individual B. americanus and Gray Treefrog (Hyla versicolor) tadpoles on high‐quality diets in aqueous extracts of senescent leaves from L. salicaria, native Broad‐Leaf Cattail (Typha latifolia), and control water to determine whether loosestrife extracts directly affect anuran tadpole performance.
Even at high artificial food levels, B. americanus survival was significantly lower in L. salicaria extracts compared with T. latifolia extracts and a water control. Food level strongly affected B. americanus development, but tadpoles raised in L. salicaria extract were less developed compared with conspecifics raised in cattail extract or water. Unlike B. americanus, Hyla performance was not affected by exposure to any plant extract compared with the water control.
Our study implicates secondary plant compounds as a mechanism underlying the impact of an invasive plant on some but not all native fauna. We hypothesize that high tannin concentrations of L. salicaria leaves have the potential to create environments that are directly toxic to B. americanus tadpoles. We hypothesize that obligate gill breathers such as B. americanus tadpoles are highly sensitive to gill damage caused by high concentrations of phenolics. Other anuran species such as H. versicolor that develop well‐functioning lungs early may be less affected by high tannin concentrations.
The malathion‐specific resistance gene confers a sperm competition advantage in Tribolium castaneum
Authors: ARNAUD L. , HAUBRUGE E. , GAGE M. J. G. 
Published: November 2005

Summary

Genes for insecticide resistance are usually traded against other fitness traits. However, in Tribolium castaneum, the opposite effect occurs under malathion‐specific resistance: susceptible individuals show reduced reproductive success compared with resistant lines.
To determine the mechanisms within this unusual relationship, we explored male fertilization success after sperm competition between homozygotes of two isogenic lines that were only either resistant or susceptible to malathion. We also measured key male reproductive traits known to influence sperm competition and reproductive success.
Malathion‐resistant males were superior sperm competitors than susceptible ones, which explains the rapid proliferation of the resistant genotype. This reproductive advantage was associated with increased ejaculate sperm number and sperm length for males carrying the resistance gene. Conversely, susceptible males have absolutely and relatively larger testis size.
Resistance to malathion is conferred by an increase in activity of a qualitatively variant detoxifying carboxylesterase enzyme compared to the ‘original’ enzyme composition in susceptible populations. Carboxylesterases also play important and conserved roles in sperm development, maturation and possibly fertilization in different taxa.
Our findings reveal a potential pleiotropic link between a single gene that codes for both insecticide resistance and influences key male reproductive traits through the regulation of carboxylesterase production.
Increase in the constitutive innate humoral immune system in Leach's Storm‐Petrel (Oceanodroma leucorhoa) chicks is negatively correlated with growth rate
Authors: MAUCK R. A. , MATSON K. D. , PHILIPSBORN J. , RICKLEFS R. E. 
Published: November 2005

Summary

Using a simple technique for assessing constitutive innate immune function recently adapted for use in wild populations, we characterize changes in avian immune system development by repeated measurements of individuals over the period of nestling growth in a wild population of Leach's Storm‐Petrels (Oceanodroma leucorhoa).
We measured levels of natural antibodies (NAb) during the early, middle and late phases of storm‐petrel development and related these levels and NAb rate of change to mass and wing length growth. We used natural variation in nestling growth to assess the influence of nutritional status on the development of innate immunity.
NAb levels increased over the first 50 days of chick development; however, rate of increase was inversely proportional to wing growth.
Initial titre levels were inversely proportional to rate of change in NAb levels over the first 50 days of immune development. This suggests that individuals with low initial NAb levels accelerate immune development to reach adult levels, whereas individuals with high initial levels do not.
As in previous studies, our results demonstrate an inverse relationship between growth rate and development of components of the avian immune system. While such a relationship is consistent with the idea that immune function development involves trade‐offs, the processes involved are more complex than simple energy allocation.
Critical analysis of root : shoot ratios in terrestrial biomes
Authors: MOKANY KAREL , RAISON R. JOHN , PROKUSHKIN ANATOLY S. 
Published: November 2005

AbstractOne of the most common descriptors of the relationship between root and shoot biomass is the root : shoot ratio, which has become a core method for estimating root biomass from the more easily measured shoot biomass. Previous reviews have examined root : shoot ratio data, but have only considered particular vegetation types and have not always critically reviewed the data used. Reliable root : shoot ratios are needed for a wide range of vegetation types in order to improve the accuracy of root biomass estimates, including those required for estimating the effects of land management and land use change in National Greenhouse Gas Inventories.This study reviewed root : shoot ratios in terrestrial biomes. A key facet of our analysis was a critical methodological review, through which unreliable data were identified and omitted on the basis of specific criteria. Of the 786 root : shoot ratio observations collated, 62% were omitted because of inadequate or unverifiable root sampling methods. When only the reliable data were examined, root : shoot ratios were found to be negatively related to shoot biomass, mean annual precipitation, mean annual temperature, forest stand age, and forest stand height.Although a single allometric equation derived in this study reliably predicted root biomass from shoot biomass for forests and woodlands, in general, the use of vegetation‐specific root : shoot ratios were found to be a more accurate method for predicting root biomass. When the root : shoot ratio data collated here were applied to an analysis of the global carbon budget, there was a 50% increase in estimated global root carbon stock, and a 12% increase in estimated total carbon stock of terrestrial vegetation. The use of the vegetation‐specific root : shoot ratios presented in this study is likely to substantially improve the accuracy of root biomass estimates for purposes such as carbon accounting and for studies of ecosystem dynamics.