bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptotic baseline of the hazard rate function of mixtures
Authors: Li Yulin
Published: September 2005

In this article, we consider the limit behavior of the hazard rate function of mixture distributions, assuming knowledge of the behavior of each individual distribution. We show that the asymptotic baseline function of the hazard rate function is preserved under mixture.
Rigorous lower bounds for extinction probabilities of the contact process
Authors: Sudbury Aidan
Published: September 2005

Positive correlations for extinction probabilities in the contact process are used to obtain rigorous lower bounds.
AUXIN RESPONSE FACTOR1andAUXIN RESPONSE FACTOR2regulate senescence and floral organ abscission inArabidopsis thaliana
Authors: Ellis Christine M. , Nagpal Punita , Young Jeffery C. , Hagen Gretchen , Guilfoyle Thomas J. , Reed Jason W.
Published: September 2005

In plants, both endogenous mechanisms and environmental signals regulate developmental transitions such as seed germination, induction of flowering,leaf senescence and shedding of senescent organs. Auxin response factors(ARFs) are transcription factors that mediate responses to the plant hormone auxin. We have examined Arabidopsis lines carrying T-DNA insertions in AUXIN RESPONSE FACTOR1 (ARF1) and ARF2 genes. We found that ARF2 promotes transitions between multiple stages of Arabidopsis development. arf2 mutant plants exhibited delays in several processes related to plant aging, including initiation of flowering, rosette leaf senescence, floral organ abscission and silique ripening. ARF2 expression was induced in senescing leaves. ARF2 regulated leaf senescence and floral organ abscission independently of the ethylene and cytokinin response pathways. arf1 mutations enhanced many arf2 phenotypes, indicating that ARF1 acts in a partially redundant manner with ARF2. However, unlike arf2mutations, an arf1 mutation increased transcription of Aux/IAA genes in Arabidopsis flowers, supporting previous biochemical studies that indicated that ARF1 is a transcriptional repressor. Two other ARF genes, NPH4/ARF7 and ARF19, were also induced by senescence,and mutations in these genes enhanced arf2 phenotypes. NPH4/ARF7 and ARF19 function as transcriptional activators, suggesting that auxin may control senescence in part by activating gene expression.
Adaptation is not required to explain the long-term response of axons to molecular gradients
Authors: Xu Jun , Rosoff William J. , Urbach Jeffrey S. , Goodhill Geoffrey J.
Published: September 2005

It has been suggested that growth cones navigating through the developing nervous system might display adaptation, so that their response to gradient signals is conserved over wide variations in ligand concentration. Recently however, a new chemotaxis assay that allows the effect of gradient parameters on axonal trajectories to be finely varied has revealed a decline in gradient sensitivity on either side of an optimal concentration. We show that this behavior can be quantitatively reproduced with a computational model of axonal chemotaxis that does not employ explicit adaptation. Two crucial components of this model required to reproduce the observed sensitivity are spatial and temporal averaging. These can be interpreted as corresponding, respectively,to the spatial spread of signaling effects downstream from receptor binding,and to the finite time over which these signaling effects decay. For spatial averaging, the model predicts that an effective range of roughly one-third of the extent of the growth cone is optimal for detecting small gradient signals. For temporal decay, a timescale of about 3 minutes is required for the model to reproduce the experimentally observed sensitivity.
A secreted factor represses cell proliferation inDictyostelium
Authors: Brock Debra A. , Gomer Richard H.
Published: September 2005

Many cells appear to secrete factors called chalones that limit their proliferation, but in most cases the factors have not been identified. We found that growing Dictyostelium cells secrete a 60 kDa protein called AprA for autocrine proliferation repressor. AprA has similarity to putative bacterial proteins of unknown function. Compared with wild-type cells, aprA-null cells proliferate faster, while AprA overexpressing cells proliferate slower. Growing wild-type cells secrete a factor that inhibits the proliferation of wild-type and aprA- cells;this activity is not secreted by aprA- cells. AprA purified by immunoprecipitation also slows the proliferation of wild-type and aprA- cells. Compared with wild type, there is a higher percentage of multinucleate cells in the aprA- population,and when starved, aprA- cells form abnormal structures that contain fewer spores. AprA may thus decrease the number of multinucleate cells and increase spore production. Together, the data suggest that AprA functions as part of a Dictyostelium chalone.
DPP signaling controls development of the lamina glia required for retinal axon targeting in the visual system ofDrosophila
Authors: Yoshida Shoko , Soustelle Laurent , Giangrande Angela , Umetsu Daiki , Murakami Satoshi , Yasugi Tetsuo , Awasaki Takeshi , Ito Kei , Sato Makoto , Tabata Tetsuya
Published: September 2005

The Drosophila visual system consists of the compound eyes and the optic ganglia in the brain. Among the eight photoreceptor (R) neurons, axons from the R1-R6 neurons stop between two layers of glial cells in the lamina,the most superficial ganglion in the optic lobe. Although it has been suggested that the lamina glia serve as intermediate targets of R axons,little is known about the mechanisms by which these cells develop. We show that DPP signaling plays a key role in this process. dpp is expressed at the margin of the lamina target region, where glial precursors reside. The generation of clones mutant for Medea, the DPP signal transducer, or inhibition of DPP signaling in this region resulted in defects in R neuron projection patterns and in the lamina morphology, which was caused by defects in the differentiation of the lamina glial cells. glial cells missing/glial cells deficient (gcm; also known as glide) is expressed shortly after glia precursors start to differentiate and migrate. Its expression depends on DPP; gcm is reduced or absent in dpp mutants or Medea clones, and ectopic activation of DPP signaling induces ectopic expression of gcmand REPO. In addition, R axon projections and lamina glia development were impaired by the expression of a dominant-negative form of gcm,suggesting that gcm indeed controls the differentiation of lamina glial cells. These results suggest that DPP signaling mediates the maturation of the lamina glia required for the correct R axon projection pattern by controlling the expression of gcm.
Lack of an adrenal cortex inSf1mutant mice is compatible with the generation and differentiation of chromaffin cells
Authors: Gut Philipp , Huber Katrin , Lohr Jennifer , Brühl Barbara , Oberle Stephan , Treier Mathias , Ernsberger Uwe , Kalcheim Chaya , Unsicker Klaus
Published: September 2005

The diversification of neural-crest-derived sympathoadrenal (SA) progenitor cells into sympathetic neurons and neuroendocrine adrenal chromaffin cells was thought to be largely understood. In-vitro studies with isolated SA progenitor cells had suggested that chromaffin cell differentiation depends crucially on glucocorticoids provided by adrenal cortical cells. However, analysis of mice lacking the glucocorticoid receptor gene had revealed that adrenal chromaffin cells develop mostly normally in these mice. Alternative cues from the adrenal cortex that may promote chromaffin cell determination and differentiation have not been identified. We therefore investigated whether the chromaffin cell phenotype can develop in the absence of an adrenal cortex, using mice deficient for the nuclear orphan receptor steroidogenic factor-1 (SF1), which lack adrenal cortical cells and gonads. We show that in Sf1–/– mice typical chromaffin cells assemble correctly in the suprarenal region adjacent to the suprarenal sympathetic ganglion. The cells display most features of chromaffin cells, including the typical large chromaffin granules. Sf1–/–chromaffin cells are numerically reduced by about 50% compared with the wild type at embryonic day (E) 13.5 and E17.5. This phenotype is not accounted for by reduced survival or cell proliferation beyond E12.5. However, already at E12.5 the `adrenal' region in Sf1–/– mice is occupied by fewer PHOX2B+ and TH+ SA cells as well as SOX10+ neural crest cells. Our results suggest that cortical cues are not essential for determining chromaffin cell fate, but may be required for proper migration of SA progenitors to and/or colonization of the adrenal anlage.
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells
Authors: Vallier Ludovic , Alexander Morgan , Pedersen Roger A.
Published: September 2005

Maintenance of pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFβ family members are involved in cell fate decisions of hESCs, including preservation of their pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also maintain long-term expression of pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway maintains pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of pluripotency in mouse and human ESCs.
Molecular motors implicated in the axonal transport of tau and α-synuclein
Authors: Utton Michelle A. , Noble Wendy J. , Hill Josephine E. , Anderton Brian H. , Hanger Diane P.
Published: September 2005

Tau and α-synuclein are both proteins implicated in the pathology of neurodegenerative disease. Here we have investigated the mechanisms of axonal transport of tau and α-synuclein, because failure of axonal transport has been implicated in the development of several neurodegenerative disorders. We found that the transport of both of these proteins depend on an intact microtubule- but not actin-cytoskeleton, and that tau and α-synuclein both move at overall slow rates of transport. We used time-lapse video microscopy to obtain images of live neurons that had been transfected with plasmids expressing proteins tagged with enhanced green fluorescent protein. We found that particulate structures containing tau or α-synuclein travel rapidly when moving along axons but spend the majority of the time paused, and these structures have similar characteristics to those previously observed for neurofilaments. The motile particles containing tau or α-synuclein colocalise with the fast-transporting molecular motor kinesin-1 in neurons. Co-immunoprecipitation experiments demonstrate that tau and α-synuclein are each associated with complexes containing kinesin-1, whereas only α-synuclein appears to interact with dynein-containing complexes. In vitro glutathione S-transferase-binding assays using rat brain homogenate or recombinant protein as bait reveals a direct interaction of kinesin-1 light chains 1 and 2 with tau, but not with α-synuclein. Our findings suggest that the axonal transport of tau occurs via a mechanism utilising fast transport motors, including the kinesin family of proteins, and that α-synuclein transport in neurons may involve both kinesin and dynein motor proteins.
Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity
Authors: Lee Jun Sung , Kim Jong Hyun , Jang Il Ho , Kim Hyeon Soo , Han Jung Min , Kazlauskas Andrius , Yagisawa Hitoshi , Suh Pann-Ghill , Ryu Sung Ho
Published: September 2005

Phospholipase D (PLD), which catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline, plays key roles in cellular signal transduction by mediating extracellular stimuli including hormones, growth factors, neurotransmitters, cytokines and extracellular matrix molecules. The molecular mechanisms by which domains regulate the activity of PLD - especially the phox homology (PX) domain - have not been fully elucidated. In this study, we have examined the properties of the PX domains of PLD1 and PLD2 in terms of phosphoinositide binding and PLD activity regulation. Interestingly, the PX domain of PLD1, but not that of PLD2, was found to specifically interact with phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3). We found that mutation of the conserved arginine at position 179 of the PLD1 PX domain to lysine or to alanine (R179A or R179K, respectively) disrupts PtdIns(3,4,5)P3 binding. In NIH-3T3 cells, the EGFP-PLD1 PX wild-type domain, but not the two mutants, localized to the plasma membrane after 5-minute treatment with platelet-derived growth factor (PDGF). The enzymatic activity of PLD1 was stimulated by adding PtdIns(3,4,5)P3 in vitro. Treatment with PDGF resulted in the significant increase of PLD1 activity and phosphorylation of the downstream extracellular signal-regulated kinases (ERKs), which was blocked by pre-treatment of HEK 293 cells with phosphoinositide 3-kinase (PI3K) inhibitor after the endogenous PLD2 had been depleted by siRNA specific for PLD2. Nevertheless, both PLD1 mutants (which cannot interact with PtdIns(3,4,5)P3) did not respond to treatment with PDGF. Moreover, PLD1 was activated in HepG2 cells stably expressing the Y40/51 mutant of PDGF receptor that is required for the binding with PI3K. Our results suggest that the PLD1 PX domain enables PLD1 to mediate signal transduction via ERK1/2 by providing a direct binding site for PtdIns(3,4,5)P3 and by activating PLD1.
Sorting nexin-2 is associated with tubular elements of the early endosome, but is not essential for retromer-mediated endosome-to-TGN transport
Authors: Carlton Jez G. , Bujny Miriam V. , Peter Brian J. , Oorschot Viola M. J. , Rutherford Anna , Arkell Rebecca S. , Klumperman Judith , McMahon Harvey T. , Cullen Peter J.
Published: September 2005

Sorting nexins are a large family of phox-homology-domain-containing proteins that have been implicated in the control of endosomal sorting. Sorting nexin-1 is a component of the mammalian retromer complex that regulates retrieval of the cation-independent mannose 6-phosphate receptor from endosomes to the trans-Golgi network. In yeast, retromer is composed of Vps5p (the orthologue of sorting nexin-1), Vps17p (a related sorting nexin) and a cargo selective subcomplex composed of Vps26p, Vps29p and Vps35p. With the exception of Vps17p, mammalian orthologues of all yeast retromer components have been identified. For Vps17p, one potential mammalian orthologue is sorting nexin-2. Here we show that, like sorting nexin-1, sorting nexin-2 binds phosphatidylinositol 3-monophosphate and phosphatidylinositol 3,5-bisphosphate, and possesses a Bin/Amphiphysin/Rvs domain that can sense membrane curvature. However, in contrast to sorting nexin-1, sorting nexin-2 could not induce membrane tubulation in vitro or in vivo. Functionally, we show that endogenous sorting nexin-1 and sorting nexin-2 co-localise on high curvature tubular elements of the 3-phosphoinositide-enriched early endosome, and that suppression of sorting nexin-2 does not perturb the degradative sorting of receptors for epidermal growth factor or transferrin, nor the steady-state distribution of the cation-independent mannose 6-phosphate receptor. However, suppression of sorting nexin-2 results in a subtle alteration in the kinetics of cation-independent mannose 6-phosphate receptor retrieval. These data suggest that although sorting nexin-2 may be a component of the retromer complex, its presence is not essential for the regulation of endosome-to-trans Golgi network retrieval of the cation-independent mannose 6-phosphate receptor.
Cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway
Authors: Maddika Subbareddy , Booy Evan P. , Johar Dina , Gibson Spencer B. , Ghavami Saeid , Los Marek
Published: September 2005

Apoptin, a small proline-rich protein derived from the chicken anaemia virus, induces cell death selectively in cancer cells. The signalling pathways of apoptin-induced, cancer cell-selective apoptosis are not well understood. Here, we demonstrate that apoptin triggers apoptosis by activating the mitochondrial/intrinsic pathway, and that it acts independently of the death receptor/extrinsic pathway. Jurkat cells deficient in either FADD or caspase-8 (which are both necessary for the extrinsic pathway) were equally as sensitive to apoptin as their parental clones. This demonstrates that apoptin is likely to act through the mitochondrial death pathway. Apoptin treatment causes a loss of mitochondrial membrane potential, and release of the mitochondrial proteins cytochrome c and apoptosis-inducing factor. Apoptin-induced cell death is counteracted by the anti-apoptotic Bcl-2 family members, Bcl-2 itself and Bcl-XL, as shown in Jurkat leukaemia cells. In addition, we describe the processing and activation of caspase-3. By contrast, cleavage of caspase-8, which is predominantly triggered by the death receptor pathway, is not observed. Furthermore, apoptin triggers the cytoplasmic translocation of Nur77, and the inhibition of Nur77 expression by siRNA significantly protects MCF7 cells from apoptin-triggered cell death. Thus, our data indicate that the apoptin death signal(s) ultimately converges at the mitochondria, and that it acts independently of the death receptor pathway.
An increase in [Ca2+]i is sufficient but not necessary for driving mitosis in early mouse embryos
Authors: FitzHarris Greg , Larman Mark , Richards Chris , Carroll John
Published: September 2005

An increase in intracellular Ca2+ concentration ([Ca2+]i) has been shown to drive sea-urchin embryos and some fibroblasts through nuclear-envelope breakdown (NEBD) and the metaphase-to-anaphase transition. Mitotic Ca2+ transients can be pan-cellular global events or localized to the perinuclear region. It is not known whether Ca2+ is a universal regulator of mitosis or whether its role is confined to specific cell types. To test the hypothesis that Ca2+ is a universal regulator of mitosis, we have investigated the role of Ca2+ in mitosis in one-cell mouse embryos. Fertilized embryos generate Ca2+ transients during the first mitotic division. Imposing a Ca2+ transient by photorelease of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] resulted in acceleration of mitosis entry, suggesting that a [Ca2+]i increase is capable of triggering mitosis. Mitotic Ca2+ transients were inhibited using three independent approaches: injection of intracellular Ca2+ buffers; downregulation of Ins(1,4,5)P3 receptors; and removal of extracellular Ca2+. None of the interventions had any effects on the timing of NEBD or cytokinesis. The possibility that NEBD is driven by localized perinuclear Ca2+ transients was examined using two-photon microscopy but no Ca2+-dependent increases in fluorescence were found to precede NEBD. Finally, the second mitotic division took place in the absence of any detectable [Ca2+]i increase. Thus, although an induced [Ca2+]i increase can accelerate mitosis entry, neither cytosolic nor perinuclear [Ca2+] increases appear to be necessary for progression through mitosis in mouse embryos.
Contribution of 16S rRNA nucleotides forming the 30S subunit A and P sites to translation inEscherichia coli
Authors: ABDI NIMO M. , FREDRICK KURT
Published: September 2005

Many contacts between the ribosome and its principal substrates, tRNA and mRNA, involve universally conserved rRNA nucleotides, implying their functional importance in translation. Here, we measure the in vivo translation activity conferred by substitution of each 16S rRNA base believed to contribute to the A or P site. We find that the 30S P site is generally more tolerant of mutation than the 30S A site. In the A site, A1493C or any substitution of G530 or A1492 results in complete loss of translation activity, while A1493U and A1493G decrease translation activity by >20-fold. Among the P-site nucleotides, A1339 is most critical; any mutation of A1339 confers a >18-fold decrease in translation activity. Regarding all other P-site bases, ribosomes harboring at least one substitution retain considerable activity, >10% that of control ribosomes. Moreover, several sets of multiple substitutions within the 30S P site fail to inactivate the ribosome. The robust nature of the 30S P site indicates that its interaction with the codon–anticodon helix is less stringent than that of the 30S A site. In addition, we show that G1338A suppresses phenotypes conferred by m2G966A and several multiple P-site substitutions, suggesting that adenine at position 1338 can stabilize tRNA interaction in the P site.
Dramatically improved RNA in situ hybridization signals using LNA-modified probes
Authors: THOMSEN RUNE , NIELSEN PETER STEIN , JENSEN TORBEN HEICK
Published: September 2005

In situ detection of RNA by hybridization with complementary probes is a powerful technique. Probe design is a critical parameter in successful target detection. We have evaluated the efficiency of fluorescent DNA oligonucleotides modified to contain locked nucleic acid (LNA) residues. This increases the thermal stability of hybrids formed with RNA. The LNA-based probes detect specific RNAs in fixed yeast cells with an efficiency far better than conventional DNA oligonucleotide probes of the same sequence. Using this probe design, we were also able to detect poly(A)+ RNA accumulation within the nucleus/ nucleolus of wild-type cells. LNA-based probes should be readily applicable to a diverse array of cells and tissue samples.
A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing
Authors: REHWINKEL JAN , BEHM-ANSMANT ISABELLE , GATFIELD DAVID , IZAURRALDE ELISA
Published: September 2005

In eukaryotic cells degradation of bulk mRNA in the 5′ to 3′ direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5′ to 3′ exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies or GW-bodies (because of the accumulation of the GW182 antigen). Proteins acting in other post-transcriptional processes have also been localized to P-bodies. These include SMG5, SMG7, and UPF1, which function in nonsense-mediated mRNA decay (NMD), and the Argonaute proteins that are essential for RNA interference (RNAi) and the micro-RNA (miRNA) pathway. In addition, XRN1 is required for degradation of mRNAs targeted by NMD and RNAi. To investigate a possible interplay between P-bodies and these post-transcriptional processes we depleted P-body or essential pathway components fromDrosophilacells and analyzed the effects of these depletions on the expression of reporter constructs, allowing us to monitor specifically NMD, RNAi, or miRNA function. We show that the RNA-binding protein GW182 and the DCP1:DCP2 decapping complex are required for miRNA-mediated gene silencing, uncovering a crucial role for P-body components in the miRNA pathway. Our analysis also revealed that inhibition of one pathway by depletion of its key effectors does not prevent the functioning of the other pathways, suggesting a lack of interdependence inDrosophila.
Evolution and the Study of Human Behaviour: A Primer for the Scientist—Practitioner
Authors: Daws Alisdair G. , Boyd Candice P.
Published: September 2005

The theory of evolution has transformed biology from a largely descriptive science to a causal one. However, few psychologists have a thorough understanding of evolution. As a result, psychologists tend not to consider evolutionary explanations for the phenomena they investigate, or they present flawed evolutionary arguments that violate fundamental principles of evolutionary theory. The primary objective of this article is to outline the basic principles of evolution as they relate to the study of behaviour in general. The article then goes on to demonstrate the application of evolutionary theory to the study of human behaviour in particular, and concludes with a discussion of problems that can occur when evolutionary theory is applied incorrectly.
The Effectiveness of Group Triple P and the Impact of the Four Telephone Contacts
Authors: Gallart Sonia C. , Matthey Stephen
Published: September 2005

The aim of this study was to determine the efficacy of the four telephone contact sessions that are prescribed as an integral component of the Group Triple P parenting program, and to compare the efficacy of Group Triple P to a waitlist control group. Parents of children aged 2 to 8 years were randomly assigned to one of three conditions: the usual Group Triple P program, consisting of four group sessions and four telephone calls (n = 16); a modified Group Triple P condition, consisting of just the four group sessions (n = 17); or a waitlist control condition (n = 16). Pre- and post-intervention assessments were conducted using the Eyberg Child Behavior Inventory (ECBI), the Depression Anxiety Stress Scales (DASS) and the Parenting Scale (PS). Statistically and clinically significant main effects were found for attending either the full Triple P or the modified Triple P program on both the DASS and the ECBI, but not on the participant's perception of their parenting style (PS). We conclude that (a) the four telephone sessions are not an essential component for the initial effectiveness of the Group Triple P program (though further research needs to explore whether they impact on maintenance of gains), and (b) that Group Triple P is effective in bringing about change, as measured using these self-report instruments.
Selective Information-Processing in Depressed Children and Adolescents: Is There a Difference in Processing of Self-Referent and Other-Referent Information?
Authors: Timbremont Benedikte , Braet Caroline
Published: September 2005

In this study, selective memory-processing of self-referent and other-referent information in depressed children was examined. A control group (N = 50) and a depressed group (N = 22) were given two intentional self-referent encoding tasks, in which participants were presented with positive and negative adjectives. In the first experiment, participants were given self-referent and structural instructions. The second experiment included a self-referent instruction and an other-referent instruction. The encoding tasks were followed by a recall task. The results of the first experiment supported the selective processing hypothesis for self-referent information in depressed children and adolescents. However, the recall ratios of positive and negative information after focusing on self and others in the second experiment revealed that depressed children diverted their attention away from negative self-referent information and displayed memory-processing similar to nondepressed children.
The Application of Cognitive—Behaviour Therapy in Altering Illness Representations of Systemic Lupus Erythematosus
Authors: Goodman Donna , Morrissey Shirley , Graham Deborah , Bossingham David
Published: September 2005

There is evidence to suggest that illness representations are associated with chronic illness outcomes. Accordingly, several authors have recommended that interventions aimed at improving illness outcomes should include an illness-representations component. While a few researchers have attempted to develop such interventions for chronic illness and chronic pain, no such intervention has been developed for individuals with systemic lupus erythematosus (SLE), a chronic auto-immune illness which results in a variety of negative physical and psychological symptoms. This article reports on a pilot program that investigated the feasibility of a cognitive and behavioural—based intervention for treating SLE which included an illness-representations-change component. The effectiveness of the intervention compared to usual treatment for SLE was evaluated. Also investigated was whether changed illness representations had a beneficial effect on physical health and psychological wellbeing. It was found that the intervention did change participants' treatment control and emotional representations, and that perceived stress was reduced following the intervention. The importance of these findings is discussed, two rival hypotheses for the findings obtained are explored and directions for future research are suggested.
Cognitive Change During Treatment of Compulsive Checking
Authors: Overton Sarah M. , Menzies Ross G.
Published: September 2005

Cognitive variables hypothesised to be mediating obsessive—compulsive behaviour include an overestimation of the probability and consequences of danger, a sense of overinflated personal responsibility for harm to oneself or others, a belief in the overimportance of thoughts, a lack of confidence in memory, an intolerance of uncertainty and a need to control thoughts. In the present study, the relationship between these variables and improvement in OCD symptoms was examined. Fourteen obsessive—compulsives with checking concerns completed a 12-session treatment program of exposure and response prevention (ERP). Before and after treatment, subjects completed the Maudsley Obsessional-Compulsive Inventory (MOCI) and a self-rating of severity (SER), and each week they completed the Yale-Brown Obsessive Compulsive Scale (YBOCS) and answered seven questions that were used to rate their beliefs in the six cognitive domains outlined above. Changes in perception of danger, intolerance of uncertainty and need to control thoughts all correlated significantly with improvement in symptoms. Moreover, significant changes in these variables occurred immediately prior to or concurrent with major symptom improvement, supporting the possibility that they are mediators of the disorder. Changes in ratings of responsibility, overimportance of thoughts and confidence in memory were not related to improvements in compulsive checking on any scale and, in the case of responsibility, ratings actually increased (i.e., worsened) in the week prior to major improvement in symptoms. For most subjects, major reductions in responsibility ratings only took place after symptom reduction. The implications of these findings for the role of these variables in mediating obsessive—compulsive checking are discussed.
Apolipoprotein A5 and triglyceridemia. Focus on the effects of the common variants
Authors: Hubacek Jaroslav A.
Published: September 2005

High plasma levels of triglycerides are an independent risk factor for the development of cardiovascular disease. Apolipoprotein A5 (

It has now been clearly established that distinct polymorphisms in the

The possible roles of
APOE genotypes and dyslipidemias in a sample of the Portuguese population
Authors: Rodrigues Maria Odete , Fonseca Aidil , Matias Dias Carlos , Albergaria Isabel , Martins Gisela , Liseta Alpendre Maria , Martins Maria do Carmo
Published: September 2005

The objective of this work was to study the distribution of apolipoprotein E (
Erythrocyte zinc content in critically ill patients
Authors: Cutinha Darren , Vaja Sashi , Treacher David , Swaminathan R.
Published: September 2005

Abnormalities in thyroid hormone metabolism are common in critically ill patients. However, it is not known if these patients are truly hypothyroid at tissue level. Erythrocyte zinc has been shown to be a tissue marker of thyroid hormone status. In this study we have measured the erythrocyte zinc in critically ill patients.

In this observational study we measured the zinc content of young erythrocytes in blood samples from 33 healthy subjects, 26 hypothyroid patients, four hyperthyroid patients, and 44 patients in the intensive care unit – 22 of these were admitted after a major surgical procedure (surgical group) and the other 22 patients had a variety of conditions (non-surgical group). Erythrocytes were separated according to age by centrifugation. Plasma thyroid hormone concentrations were abnormal in 70% of the critically ill group. Erythrocyte zinc was significantly lower in hyperthyroid patients and higher in hypothyroid patients. In the non-surgical patients, erythrocyte zinc of young cells (median 256μmol/L of cells) was significantly higher than (p<0.01) the corresponding cells in the healthy controls (202μmol/L of cells), whereas in the surgical group it was not different (197μmol/L of cells). We conclude that in non-surgical critically ill patients, erythrocyte zinc content is higher, suggesting that these patients may be hypothyroid at tissue level.
Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease
Authors: Sfiridaki Aikaterini , Miyakis Spiros , Tsirakis George , Alegakis Athanassios , Passam Andreas M. , Kandidaki Ermioni , Margioris Andrew N. , Alexandrakis Michael G.
Published: September 2005

Multiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption.

Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78±91.27 vs. 59.25±33.09 ng/mL, p<0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p<0.001, p<0.03, p<0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p<0.0001, p<0.01, respectively). MMP-9 levels were lower in patients compared with controls (p<0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p<0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p<0.03, p<0.003, p<0.002, p<0.003 and p<0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation.
Analysis of the applicability of artificial neural networks for studying blood plasma: determination of magnesium ion concentration as a case study
Authors: Liparini Alexandre , Carvalho Sandra , Belchior Jadson C.
Published: September 2005

Artificial neural networks are suggested for use in predicting metal ion concentration in human blood plasma. Simulated and available experimental data are used to train the artificial neural network. Particularly, using 850 simulated samples, the network predicted the magnesium-free ion concentration with an average error smaller than 1%. Clinical data recently reported for 20 patients were considered and the artificial neural network predicted the concentration of free magnesium ion with an average error of about 6%. Overall, the approach of using artificial neural networks as an alternative or complementary strategy to deal with the analysis of human blood plasma can be useful for clinical diagnostics, if there is sufficient data to train the artificial neural network.
The effect of long-term storage on measured plasma lactate concentrations and prospective lactate results from a multicenter trial of antiretroviral therapy
Authors: Dubé Michael P. , Kitch Douglas W. , Parker Robert A. , Alston-Smith Beverly L. , Mulligan Kathleen
Published: September 2005

Plasma lactate measurements are typically performed in real time, limiting their usefulness in multicenter or longitudinal studies. To determine the stability of lactate specimens, blood was drawn in sodium fluoride/potassium oxalate tubes from 13 volunteers before and after 5min of handgrip exercise to intentionally increase lactate concentrations. Plasma was stored at −70°C. Aliquots were assayed in real time and after 1, 3, 6, 9, 12, 18, and 24months. Real-time lactate concentrations measured at baseline ranged from 0.52 to 2.23mmol/L before and from 2.91 to 11.04mmol/L after handgrip exercise. Using a linear mixed model, the estimated change from baseline at month 24 was 1.67% (95% confidence interval, −0.70% to 4.03%) for pre-exercise samples and 0.39% (95% CI, −1.13% to 1.91%) for post-exercise samples. Stored serial specimens from 232 HIV-infected subjects in a multicenter trial of antiretroviral therapy were also assayed centrally. Among those, median plasma lactate increased from baseline to 64weeks by 0.4mmol/L with zidovudine+lamivudine treatment and by 0.6mmol/L with didanosine+stavudine (each p<0.001 from baseline; p=0.04 for difference between groups over time). When performed as in this study, frozen storage with central batch lactate analysis is appropriate for prospectively collected samples in multicenter trials.
Evaluation of renal function in intensive care: plasma cystatin C vs. creatinine and derived glomerular filtration rate estimates
Authors: Le Bricon Thierry , Leblanc Isabelle , Benlakehal Mourad , Gay-Bellile Cécile , Erlich Danielle , Boudaoud Said
Published: September 2005

Plasma cystatin C, a new marker of glomerular filtration rate (GFR), was prospectively evaluated in surgical intensive care. Cystatin C was measured (immunonephelometry, Dade-Behring) in 10 patients selected to cover a full range of GFR (phase I) and in 28 unselected consecutive patients followed for 5days post-admission (phase II). Results were compared with
Preliminary evaluation of the Iris IQ™ 200 automated urine analyser
Authors: Alves Lia , Ballester Frederic , Camps Jordi , Joven Jorge
Published: September 2005

The IRIS IQ™
The design of TSK‐type fuzzy controllers using a new hybrid learning approach
Authors: Lin Cheng‐Jian , Xu Yong‐Ji
Published: September 2005

In this paper, the TSK‐type fuzzy controllers with a novel hybrid learning approach (TFC‐HLA) are proposed. The proposed hybrid learning approach consists of the self‐clustering algorithm (SCA) and the dynamic‐form symbiotic evolution (DSE). First, the proposed SCA is used to identify a parsimonious internal structure. Secondly, the proposed DSE uses the sequential‐search‐based dynamic evolution method. Better combinations of the chromosomes will be initially generated while better mutation points will be determined to perform dynamic mutation. The advantages of the proposed learning algorithm are that, first, it converges quickly and the obtained fuzzy rules are more precise. Second, the proposed TFC‐HLA controller only requires a few population sizes. Third, the DSE constructs only four fuzzy controllers every generation. The performance of the TFC‐HLA controller compares excellently with other existing models in our control simulations. Copyright © 2005 John Wiley & Sons, Ltd.
Simple Synthesis of Hollow Tin Dioxide Microspheres and Their Application to Lithium‐Ion Battery Anodes
Authors: Han S. , Jang B. , Kim T. , Oh S. M. , Hyeon T.
Published: September 2005

Hollow tin dioxide (SnO2) microspheres were synthesized by the simple heat treatment of a mixture composed of tin(IV) tetrachloride pentahydrate (SnCl4·5H2O) and resorcinol–formaldehyde gel (RF gel). Because hollow structures were formed during the heat treatment, the pre‐formation of template and the adsorption of target precursor on template are unnecessary in the current method, leading to simplified synthetic procedures and facilitating mass production. Field‐emission scanning electron microscopy (FE‐SEM) images showed 1.7–2.5 μm sized hollow spherical particles. Transmission electron microscopy (TEM) images showed that the produced spherical particles are composed of a hollow inner cavity and thin outer shell. When the hollow SnO2 microspheres were used as a lithium‐battery anode, they exhibited extraordinarily high discharge capacities and coulombic efficiency. The reported synthetic procedure is straightforward and inexpensive, and consequently can be readily adopted to produce large quantities of hollow SnO2 microspheres. This straightforward approach can be extended for the synthesis of other hollow microspheres including those obtained from ZrO2 and ZrO2/CeO2 solid solutions.
Light Out‐Coupling Efficiencies of Organic Light‐Emitting Diode Structures and the Effect of Photoluminescence Quantum Yield
Authors: Smith L. H. , Wasey J. A. E. , Samuel I. D. W. , Barnes W. L.
Published: September 2005

Results obtained from modeling the light out‐coupling efficiency of an organic light‐emitting diode (OLED) structure containing the recently developed first‐generation fac‐tris(2‐phenylpyridine) iridium‐cored dendrimer (Ir‐G1) as the emissive organic layer are reported. Comparison of the results obtained for this material with those of corresponding structures based upon small‐molecule and polymer emissive materials is made. The calculations of out‐coupling efficiency performed here take account of many factors, including the photoluminescence quantum yield (PLQY) of the emissive materials. Further, how each material system might perform with regard to out‐coupling efficiency when a range of possible PLQYs are considered is shown. The calculations show that the very high efficiency of dendrimer‐based OLEDs can be attributed primarily to their high PLQY.
Single‐Walled Carbon Nanotube Dispersions in Poly(ethylene oxide)
Authors: Chatterjee T. , Yurekli K. , Hadjiev V. G. , Krishnamoorti R.
Published: September 2005

Dispersions of single‐walled carbon nanotubes (SWNTs) in poly(ethylene oxide) (PEO) assisted by a lithium‐based anionic surfactant demonstrate an electrical percolation of 0.03 wt.‐% and a geometrical percolation, inferred from melt rheometry, of 0.09 wt.‐%. Both the melting temperature and the extent of crystallinity of the PEO crystals decrease with increasing SWNT loading. Raman spectroscopy of the nanocomposites indicates a down‐shift of the SWNT G‐modes and suggests that the nanotubes are subjected to tensile stress transfer from the polymer at room temperature.
Microcavity‐Controlled Single‐Molecule Fluorescence
Authors: Steiner Mathias , Schleifenbaum Frank , Stupperich Clemens , Virgilio Failla Antonio , Hartschuh Achim , Meixner Alfred Johann
Published: September 2005

We present for the first time cavity‐controlled fluorescence spectra and decay curves of single dipole emitters interacting at room temperature with the first longitudinal mode of a Fabry–Perot microcavity offering a λ/2‐spacing between its silver mirrors. The spontaneous emission rate of individual dye molecules was found to be enhanced by the Purcell effect by up to three times compared to the rate in free space, in agreement with theoretical predictions. Moreover, our new microcavity design was found to provide long‐term stability and single‐molecule sensitivity under ambient conditions for several months without noticeable reduction of the cavity‐Q value. We consider this as a significant advance for single‐photon sources operating at room temperature.
The Chemistry of Phosphanyl‐ferrocenecarboxylic Ligands (Eur. J. Inorg. Chem. 19/2005)
Authors: S̆tĕpnic̆ka Petr
Published: September 2005

The cover picture shows the structures of ferrocene‐based phosphanyl‐carboxylic acids that have been synthesized, characterized by various physicochemical methods, and further utilized as novel organometallic synthons, ligands in coordination compounds, and components of various catalytic systems over the last ten years that have passed since the discovery of the first representative. Some aspects of the chemistry of these and other related phosphanyl‐ferrocenecarboxylic ligands addressed in the Microreview by P. S̆tĕpnic̆ka on p. 3787 ff. are indicated in the centre of the cover picture, which is arranged in a chessboard‐like manner to emphasize their close, and sometimes causal, relations and complementarity.
In vitro micronucleus scoring by flow cytometry: Differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability
Authors: Avlasevich Svetlana L. , Bryce Steven M. , Cairns Siân E. , Dertinger Stephen D.
Published: September 2005

The in vitro micronucleus test has received considerable attention in recent years for its use in drug safety assessment and toxicological research. The less tedious nature of the assay relative to chromosome aberration analyses is a driving force, and explains why many chemical and drug safety programs have adopted the endpoint. Development of a high‐throughput micronucleus scoring system would further enhance the utility of the assay for lead optimization and other early drug development work. Although several variations of a flow cytometric (FCM) method for scoring cell‐culture‐derived micronuclei (MN) have been described in the literature, they have been unable to distinguish true MN from apoptotic and necrotic chromatin (Nüsse M and Marx K 1997: Mutat Res 392: 109–115). Here, we report advances to this methodology whereby a sequential staining procedure is used to differentially label these types of sub‐2n particles. With the use of ethidium monoazide (EMA), the chromatin of dead and dying cells is labeled. After a photoactivation step that covalently binds EMA to chromatin, cytoplasmic membranes are digested and resulting lysates are incubated with RNase plus a pan‐nucleic acid dye (SYTOX Green). This process provides a suspension of free nuclei and sub‐2n particles that are labeled with either SYTOX or SYTOX and EMA. Preliminary studies with heat‐shocked L5178Y mouse cells demonstrated that EMA stains necrotic and mid‐ through late‐stage apoptotic cells. Importantly, the sequential labeling procedure provided reliable micronucleus enumeration, even when cultures contained high percentages of dead cells. Subsequently, experiments with the following diverse genotoxicants were performed: hydroxyurea, methyl methanesulfonate, benzo[a]pyrene, etoposide, cyclophosphamide, and vinblastine. Additionally, the nongenotoxicants sucrose, tributyltin methoxide, and dexamethasone were tested up to 5 mg/ ml, or to cytotoxic concentrations. FCM data were found to correspond closely with microscopy‐based measurements. Collectively, these data suggest that this sequential EMA/SYTOX staining procedure provides reliable, high‐throughput enumeration of in vitro MN. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.