bluuebunny/crossref_metadata_2025 huggingface dataset:
NAD Glycohydrolase Activities and ADP-Ribose Uptake in Erythrocytes From Normal Subjects and Cancer Patients
Authors: Albeniz Işıl , Demir Özlem , Nurten Rüstem , Bermek Engin
Published: August 2004

Erythrocytes from cancer patients exhibited up to fivefold higher NAD glycohydrolase activities than control erythrocytes from normal subjects and also similarly increased [14C] ADP-ribose uptake values. When [adenosine-14C] NAD was used instead of free [14C] ADP-ribose, the uptake was dependent on ecto-NAD glycohydrolase activity. This was reflected in the inhibition of ADP-ribose uptake from [adenosine-14C] NAD by Cibacron Blue. ADP-ribose uptake in erythrocytes appeared to be complex: upon incubation with free [14C] ADP-ribose, the radiolabel associated with erythrocytes was located in nearly equal parts in cytoplasm and plasma membrane. Part of [14C] ADP-ribose binding to the membrane was covalent, as indicated by its resistance to trichloroacetic acid-treatment. A preincubation with unlabeled ADP-ribose depressed subsequent erythrocyte NAD glycohydrolase activity and binding of [14C] ADP-ribose to erythrocyte membrane; but it failed to inhibit the transfer of labeled ADP-ribose to erythrocyte cytoplasm. On the other hand, incubation with [adenosine-14C] NAD did not result in a similar covalent binding of radiolabel to erythrocyte membrane. In line with this finding, a preincubation with unlabeled NAD was not inhibitory on subsequent NAD glycohydrolase reaction and ADP-ribose binding. ADP-ribose binding and NAD glycohydrolase activities were found also in solubilized erythrocyte membrane proteins and, after size fractionation, mainly in a protein fraction of around 45kDa-molecular weight.
Modulation of Antigenic Phenotype by IL-1β, IFNγ and TGFβ1 on Cultured Human Decidual Stromal Cells
Authors: Ruiz C. , Reyes-Botella C. , García-Martínez O. , Montes M. J.
Published: August 2004

Decidual stromal cells (DSC) constitute the most abundant population in normal human decidua together with leukocytes. Both populations may be involved in the immunological role of the decidua by favoring gestational functions, participating in physiological mechanisms to eliminate the fetus, or providing local defense against infection. Using flow cytometry, we investigated whether different cytokines modulate the expression on cultured DSC of antigen-presenting molecules. The treatment with IFNγ or IL-1β enhanced the expression of CD54. The percentage of expression of HLA-DR was enhanced by IL-1β treatment but was not modified by IFNγ. The expression of CD80 and CD86 was enhanced by IFNγ treatment but was not modified by IL-1β; the expression of CD86 and HLA-DR was reduced by TGFβ1 treatment. The response of DSC and dendritic cells to these cytokines appears to be similar, suggesting a phenotypic and functional relationship between these cell types.
How might marbling begin?
Authors: Harper G. S. , Pethick D. W.
Published: August 2004

Marbling is an important meat quality trait, in that it contributes directly to the value of beef on international markets. The development of marbling is not well understood, though there have been some significant recent discoveries regarding adipogenesis in general. This article describes a working hypothesis around the early events of marbling. It attempts to rationalise findings from several mammalian experimental systems on hyperplastic growth of adipocyte precursor cells.
Objective on-line assessment of marbling: a brief review
Authors: Ferguson D. M.
Published: August 2004

Visual assessment remains the preferred method for evaluation of marbling in abattoirs. However, visual assessments are compromised by the disadvantages inherent in most systems of subjective evaluation. To that end, several objective measurement technologies have been developed and evaluated for on-line measurement of marbling. Several of these technologies are reviewed in this paper. Of the current suite of technologies, video image analysis and the Danish bioelectrical impedance device offer the most promise in terms of measurement accuracy and suitability for on-line use.
Correlates of transsaccadic integration in the primary visual cortex of the monkey
Authors: Khayat Paul S. , Spekreijse Henk , Roelfsema Pieter R.
Published: August 2004

We make several eye movements per second when we explore a visual scene. Each eye movement sweeps the scene's projection across the retina and changes its representation in retinotopic areas of the visual cortex, but we nevertheless perceive a stable world. Here we investigate the neuronal correlates of visual stability in the primary visual cortex. Monkeys were trained to make two saccades along a single curve and to ignore another, distracting curve. Attention enhanced neuronal responses to the entire relevant curve before the first saccade. This response enhancement was rapidly reestablished after the saccade, although the image was shifted across the primary visual cortex. We argue that this fast postsaccadic restoration of the attentional response enhancement contributes to the stability of vision across eye movements, and reduces the impact of saccades on visual cognition.
GATA4 is essential for formation of the proepicardium and regulates cardiogenesis
Authors: Watt Alistair J. , Battle Michele A. , Li Jixuan , Duncan Stephen A.
Published: August 2004

The role of GATA4 during the earliest stages of cardiogenesis has not been defined because
Gata4
knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5
Gata4
–/–
embryos directly from embryonic stem cells. GATA4-null embryos display heart defects characterized by disrupted looping morphogenesis, septation, and a hypoplastic ventricular myocardium. We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6. Moreover, GATA4 expression in the endocardium is dispensable for trabeculae formation. Remarkably, the proepicardium is absent in GATA4-null embryos, blocking formation of the epicardium. Therefore, we propose that the observed myocardial defects may be a secondary consequence of loss of the proepicardium. These findings definitively demonstrate a requirement for GATA4 during early cardiac development and identify an essential factor for generation of the proepicardium.
Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating γ-aminobutyric acid type A receptor membrane trafficking
Authors: Kittler Josef T. , Thomas Philip , Tretter Verena , Bogdanov Yuri D. , Haucke Volker , Smart Trevor G. , Moss Stephen J.
Published: August 2004

γ-Aminobutyric acid type A receptors (GABA
A
Rs) are the major sites of fast synaptic inhibition in the brain. An essential determinant for the efficacy of synaptic inhibition is the regulation of GABA
A
R cell surface stability. Here, we have examined the regulation of GABA
A
R endocytic sorting, a critical regulator of cell surface receptor number. In neurons, rapid constitutive endocytosis of GABA
A
Rs was evident. Internalized receptors were then either rapidly recycled back to the cell surface, or on a slower time scale, targeted for lysosomal degradation. This sorting decision was regulated by a direct interaction of GABA
A
Rs with Huntingtin-associated protein 1 (HAP1). HAP1 modulated synaptic GABA
A
R number by inhibiting receptor degradation and facilitating receptor recycling. Together these observations have identified a role for HAP1 in regulating GABA
A
R sorting, suggesting an important role for this protein in the construction and maintenance of inhibitory synapses.
Structure of adeno-associated virus type 2 Rep40–ADP complex: Insight into nucleotide recognition and catalysis by superfamily 3 helicases
Authors: James J. Anson , Aggarwal Aneel K. , Linden R. Michael , Escalante Carlos R.
Published: August 2004

We have determined the structure of adeno-associated virus type 2 (AAV2) Rep40 to 2.1-Å resolution with ADP bound at the active site. The complex crystallizes as a monomer with one ADP molecule positioned in an unexpectedly open binding site. The nucleotide-binding pocket consists of the P-loop residues interacting with the phosphates and a loop (nucleoside-binding loop) that emanates from the last strand of the central β-sheet and interacts with the sugar and base. As a result of the open nature of the binding site, one face of the adenine ring is completely exposed to the solvent, and consequently the number of protein–nucleotide contacts is scarce as compared with other P-loop nucleotide phosphohydrolases. The conformation of the ADP molecule in its binding site bears a resemblance to those found in only three other families of P-loop ATPases: the ATP-binding cassette transporter family, the bacterial RecA proteins, and the type II topoisomerase family. In all these cases, oligomerization is required to attain a competent nucleotide-binding pocket. We propose that this characteristic is native to superfamily 3 helicases and allows for an additional mechanism of regulation by these multifunctional proteins. Furthermore, it explains the strong tendency by members of this family such as simian virus 40 TAg to oligomerize after binding ATP.
Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the
Ncf1
gene
Authors: Hultqvist Malin , Olofsson Peter , Holmberg Jens , Bäckström B. Thomas , Tordsson Jesper , Holmdahl Rikard
Published: August 2004

The
Ncf1
gene was recently identified as a strong regulator of severe arthritis in rat. This finding was surprising, because the disease-promoting allele mediated a lower level of reactive oxygen species in NADPH oxidase-expressing cells. We have now investigated a splice mutation of the
Ncf1
gene in B10.Q mice, causing a truncated and nonfunctional Ncf1 protein. We found that the mutated Ncf1 led to a more severe and chronic relapsing collagen-induced arthritis. Enhanced IgG and delayed-type hypersensitivity responses against type II collagen were seen, indicating increased activity of autoreactive T cells. Interestingly, female
Ncf1
-mutated mice spontaneously developed severe arthritis during the postpartum period. The arthritis was accompanied by an increased antibody response to type II collagen, with the same fine specificity as in collagen-induced arthritis. The enhancing effect of the mutated Ncf1 could also be shown to be more general in that it enhanced myelin oligodendrocyte glycoprotein protein-induced experimental autoimmune encephalomyelitis, a model for multiple sclerosis. These results show that
Ncf1
, a gene important for oxidative burst, regulates the susceptibility and severity of both arthritis and encephalomyelitis and modulates, directly or indirectly, the level of T cell-dependent autoimmune responses.
Regulation of flowering time in
Arabidopsis
by K homology domain proteins
Authors: Mockler Todd C. , Yu Xuhong , Shalitin Dror , Parikh Dhavan , Michael Todd P. , Liou Jasmine , Huang Jie , Smith Zachery , Alonso Jose M. , Ecker Joseph R. , Chory Joanne , Lin Chentao
Published: August 2004

The transition from vegetative growth to reproductive development in
Arabidopsis
is regulated by multiple floral induction pathways, including the photoperiodic, the autonomous, the vernalization, and the hormonal pathways. These pathways converge to regulate the expression of a small set of genes critical for floral initiation and different signal transduction pathways can interact to govern the time to flower. One important regulator of floral initiation is the MADS-box transcription factor FLC, which acts as a negative regulator of flowering in response to both endogenous and environmental signals. In this report, we describe a study of the flowering-time gene,
FLK
[flowering locus K homology (KH) domain] that encodes a putative RNA-binding protein with three KH domains. The
flk
mutations cause delayed flowering without a significant effect on the photoperiodic or vernalization responses. FLK functions primarily as a repressor of
FLC
expression, although it also modestly affects expression of genes associated with the photoperiodic pathway. In addition to
FLK
, the expression of two other KH domain genes are modestly affected by the
flk
mutation, suggesting a possible involvement of more than one KH domain protein in the regulation of flowering time in
Arabidopsis
.
Derivation of midbrain dopamine neurons from human embryonic stem cells
Authors: Perrier Anselme L. , Tabar Viviane , Barberi Tiziano , Rubio Maria E. , Bruses Juan , Topf Norbert , Harrison Neil L. , Studer Lorenz
Published: August 2004

Human embryonic stem (hES) cells are defined by their extensive self-renewal capacity and their potential to differentiate into any cell type of the human body. The challenge in using hES cells for developmental biology and regenerative medicine has been to direct the wide differentiation potential toward the derivation of a specific cell fate. Within the nervous system, hES cells have been shown to differentiate
in vitro
into neural progenitor cells, neurons, and astrocytes. However, to our knowledge, the selective derivation of any given neuron subtype has not yet been demonstrated. Here, we describe conditions to direct hES cells into neurons of midbrain dopaminergic identity. Neuroectodermal differentiation was triggered on stromal feeder cells followed by regional specification by means of the sequential application of defined patterning molecules that direct
in vivo
midbrain development. Progression toward a midbrain dopamine (DA) neuron fate was monitored by the sequential expression of key transcription factors, including Pax2, Pax5, and engrailed-1 (En1), measurements of DA release, the presence of tetrodotoxin-sensitive action potentials, and the electron-microscopic visualization of tyrosinehydroxylase-positive synaptic terminals. High-yield DA neuron derivation was confirmed from three independent hES and two monkey embryonic stem cell lines. The availability of unlimited numbers of midbrain DA neurons is a first step toward exploring the potential of hES cells in preclinical models of Parkinson's disease. This experimental system also provides a powerful tool to probe the molecular mechanisms that control the development and function of human midbrain DA neurons.
Staphylococcus aureus
virulence genes identified by
bursa aurealis
mutagenesis and nematode killing
Authors: Bae Taeok , Banger Alison K. , Wallace Adam , Glass Elizabeth M. , Åslund Fredrik , Schneewind Olaf , Missiakas Dominique M.
Published: August 2004

Staphylococcus aureus
is the leading cause of wound and hospital-acquired infections worldwide. The emergence of
S. aureus
strains with resistance to multiple antibiotics requires the identification of bacterial virulence genes and the development of novel therapeutic strategies. Herein,
bursa aurealis
, a mariner-based transposon, was used for random mutagenesis and for the isolation of 10,325
S. aureus
variants with defined insertion sites. By screening for loss-of-function mutants in a
Caenorhabditis elegans
killing assay, 71
S. aureus
virulence genes were identified. Some of these genes are also required for
S. aureus
abscess formation in a murine infection model.
Evidence for conformational coupling between two calcium channels
Authors: Paolini C. , Fessenden James D. , Pessah Isaac N. , Franzini-Armstrong C.
Published: August 2004

Ryanodine receptor 1 (RyR1, the sarcoplasmic reticulum Ca
2+
release channel) and α
1S
dihydropyridine receptor (DHPR, the surface membrane voltage sensor) of skeletal muscle belong to separate membrane systems but are functionally and structurally linked. Four α
1S
DHPRs associated with the four identical subunits of a RyR form a tetrad. We treated skeletal muscle cell lines with ryanodine, at concentrations that block RyRs, and determined whether this treatment affects the distance between DHPRs in the tetrad. We find a substantial (≈2-nm) shift in the α
1S
DHPR positions, indicating that ryanodine induces large conformational changes in the RyR1 cytoplasmic domain and that the α
1S
DHPR-RyR complex acts as a unit.
Retroelements and the human genome: New perspectives on an old relation
Authors: Bannert Norbert , Kurth Reinhard
Published: August 2004

Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.
Carbon dioxide mediates Mn(II)-catalyzed decomposition of hydrogen peroxide and peroxidation reactions
Authors: Liochev Stefan I. , Fridovich Irwin
Published: August 2004

Mn(II) can catalyze the decomposition of H
2
O
2
and, in the presence of H
2
O
2
, can catalyze the oxidation of NADH. Strikingly, these processes depend on the simultaneous presence of both CO
2
and

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. This explains the exponential dependence of the rates on [

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], previously noted by other workers. These processes are inhibited by Mn-superoxide dismutase, establishing the generation of

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and its role as an essential reactant. A scheme of reactions, consistent with the known properties of this system, is proposed. The large rate enhancements provided by

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+ CO
2
, and the abundance of both of these species
in vivo
, suggest that similar reactions have relevance to the oxidative stress imposed by

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and H
2
O
2
.
Binding affinity of lactose permease is not altered by the H
+
electrochemical gradient
Authors: Guan Lan , Kaback H. Ronald
Published: August 2004

The x-ray structure of lactose permease of
Escherichia coli
(LacY) exhibits a single sugar-binding site at the apex of a hydrophilic cavity open to the cytoplasm, and it has been postulated that the binding site has alternating access to either side of the membrane during turnover. Here, the affinity of LacY for ligand in right-side-out or inside-out membrane vesicles is measured in the absence or presence of an H
+
electrochemical gradient (

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) by utilizing ligand protection against alkylation. Right-side-out or inside-out membrane vesicles containing LacY with a single cysteine residue at position 148 exhibit
K
D
values for lactose or β-
d
-galactopyranosyl 1-thio-β-
d
-galactopyranoside of ≈1.0 mM or 40 μM, respectively, and no systematic change is observed in the presence of

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under conditions in which there is little or no accumulation of ligand. The results are consistent with a mechanism in which the major effect of

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on sugar accumulation is caused by an increased rate of deprotonation on the inner face of the membrane, leading to an increase in the rate of return of the unloaded symporter to the outer face of the membrane.
Regional glucose metabolism and glutamatergic neurotransmission in rat brainin vivo
Authors: de Graaf Robin A. , Mason Graeme F. , Patel Anant B. , Rothman Douglas L. , Behar Kevin L.
Published: August 2004

Multivolume1H-[13C] NMR spectroscopy in combination with i.v. [1,6-13C2]glucose infusion was used to detect regional glucose metabolism and glutamatergic neurotransmission in the halothane-anesthetized rat brain at 7 T. The regional information was decomposed into pure cerebral gray matter, white matter, and subcortical structures by means of tissue segmentation based on quantitative T1relaxation mapping. The13C turnover curves of [4-13C]glutamate, [4-13C]glutamine, and [3-13C]glutamate + glutamine were fitted with a two-compartment neuronal-astroglial metabolic model. The neuronal tricarboxylic acid cycle fluxes in cerebral gray matter, white matter, and subcortex were 0.79 ± 0.15, 0.20 ± 0.11, and 0.42 ± 0.09 μmol/min per g, respectively. The glutamate-glutamine neurotransmitter cycle fluxes in cerebral gray matter, white matter, and subcortex were 0.31 ± 0.07, 0.02 ± 0.04, and 0.18 ± 0.12 μmol/min per g, respectively. The exchange rate between the mitochondrial and cytosolic metabolite pools was fast relative to the neuronal tricarboxylic acid cycle flux for all cerebral tissue types.
Variation in
GRM3
affects cognition, prefrontal glutamate, and risk for schizophrenia
Authors: Egan Michael F. , Straub Richard E. , Goldberg Terry E. , Yakub Imtiaz , Callicott Joseph H. , Hariri Ahmad R. , Mattay Venkata S. , Bertolino Alessandro , Hyde Thomas M. , Shannon-Weickert Cynthia , Akil Mayada , Crook Jeremy , Vakkalanka Radha Krishna , Balkissoon Rishi , Gibbs Richard A. , Kleinman Joel E. , Weinberger Daniel R.
Published: August 2004

GRM3
,
a metabotropic glutamate receptor-modulating synaptic glutamate, is a promising schizophrenia candidate gene. In a family-based association study, a common
GRM3
haplotype was strongly associated with schizophrenia (
P
= 0.0001). Within this haplotype, the A allele of single-nucleotide polymorphism (SNP) 4 (hCV11245618) in intron 2 was slightly overtransmitted to probands (
P
= 0.02). We studied the effects of this SNP on neurobiological traits related to risk for schizophrenia and glutamate neurotransmission. The SNP4 A allele was associated with poorer performance on several cognitive tests of prefrontal and hippocampal function. The physiological basis of this effect was assessed with functional MRI, which showed relatively deleterious activation patterns in both cortical regions in control subjects homozygous for the SNP4 A allele. We next looked at SNP4's effects on two indirect measures of prefrontal glutamate neurotransmission. Prefrontal
N
-acetylaspartate, an
in vivo
MRI measure related to synaptic activity and closely correlated with tissue glutamate, was lower in SNP4 AA homozygotes. In postmortem human prefrontal cortex, AA homozygotes had lower mRNA levels of the glial glutamate transporter EAAT2, a protein regulated by
GRM3
that critically modulates synaptic glutamate. Effects of SNP4 on prefrontal GRM3 mRNA and protein levels were marginal. Resequencing revealed no missense or splice-site SNPs, suggesting that the intronic SNP4 or related haplotypes may exert subtle regulatory effects on GRM3 transcription. These convergent data point to a specific molecular pathway by which GRM3 genotype alters glutamate neurotransmission, prefrontal and hippocampal physiology and cognition, and thereby increased risk for schizophrenia.
Changes in knowledge and attitudes of folate, and use of dietary supplements among women of reproductive age in Norway 1998 - 2000
Authors: Daltveit Anne Kjersti , Vollset Stein Emil , Lande Britt , Oien Henriette
Published: August 2004

Aims: From March 1998, Norwegian nutrition authorities have recommended that women consume a folic acid supplement before and early in pregnancy to prevent neural tube defects. The authors wished to establish Norwegian data on knowledge of, use of, and attitudes to folic acid supplement and dietary supplements before and after implementing national information campaigns on folate and pregnancy. Methods: Telephone surveys were carried out in late 1998 and in late 2000 among, respectively, 1,146 and 1,218 Norwegian women of reproductive age. Results: Overall, 50% of the women in 1998 and 60% of the women in 2000 had heard about folate, 33% and 46% knew about its role in pregnancy, and 9.5% and 21% knew that it may prevent a congenital malformation. Only 4.0% and 8.5% of the women, respectively, knew that the critical period for folic acid supplement to reduce the risk of neural tube defect is before and early in pregnancy. Knowledge and increase in knowledge between the two surveys were highest among women close to pregnancy (woman planning pregnancy, pregnant women, or women who had given birth within the last 12 months), and among women with high education. Among the 54 women in 1998 and the 55 women in 2000 whose last birth was within the previous year, use of a folic acid supplement before or early in the last pregnancy was reported by 10% (95% confidence interval (CI) 5 - 21%) and by 47% (95% CI 35 - 60%), respectively. Among women close to pregnancy, 76% in 1998 and 87% in 2000 stated that they would use a folic acid supplement in a future pregnancy. Conclusions: Knowledge and use of folate among Norwegian women increased from 1998 to 2000. Future information strategies on folate and pregnancy should in particular aim at increasing women's knowledge on the critical period for folic acid supplementation, as well as reducing socio-demographic differences in use and knowledge of folate.
The cumulative effect of smoking at age 50, 60, and 70 on functional ability at age 75
Authors: Støvring Nina , Avlund Kirsten , Schultz-Larsen Kirsten , Schroll Marianne
Published: August 2004

Aims: As elderly people form a steadily growing part of the population in most parts of the world we are in need of knowledge of the influence of modifiable lifestyle factors on functional ability late in life. This study aims to examine the cumulative impact of smoking from age 50 to 70 on functional ability at age 75. Methods: 387 men and women born in 1914 and living in seven municipalities in the western part of the County of Copenhagen were followed for 25 years with examinations in 1964, 1974, 1984, and 1989. Associations between smoking and functional ability were examined using multiple logistic regression analyses with cumulative smoking as determinant and physical activity, sex, basic school education, and household composition as possible confounders. Results: There is an adverse relation between smoking and functional ability regardless of the time of examination or the ways of accumulating the smoking habits over the examinations. Cumulated former smokers have a larger risk of having reduced functional ability at age 75 (OR: 1.35 (1.13 - 1.61)) compared with never smokers. The odds ratios of reduced functional ability were 2.46 (1.44 - 4.17) among cumulated smokers of 1 - 14 grams of tobacco/day and 3.32 (1.63 - 6.72) among smokers of more than 14 grams of tobacco/ day. Conclusions: The findings in this study stress the importance of continuing and strengthening efforts to reduce the prevalence of smokers in the population. Furthermore the results indicate that even after the 50th birthday it is possible to gain a healthier old age by abstaining from smoking.
DisProt: a database of protein disorder
Authors: Vucetic Slobodan , Obradovic Zoran , Vacic Vladimir , Radivojac Predrag , Peng Kang , Iakoucheva Lilia M. , Cortese Marc S. , Lawson J. David , Brown Celeste J. , Sikes Jason G. , Newton Crystal D. , Dunker A. Keith
Published: August 2004

Summary: The Database of Protein Disorder (DisProt) is a curated database that provides structure and function information about proteins that lack a fixed three-dimensional (3D) structure under putatively native conditions, either in their entirety or in part. Starting from the central premise that intrinsic disorder is an important structural class of protein and in order to meet the increasing interest thereof, DisProt is aimed at becoming a central repository of disorder-related information. For each disordered protein, the database includes the name of the protein, various aliases, accession codes, amino acid sequence, location of the disordered region(s), and methods used for structural (disorder) characterization. If applicable, most entries also list the biological function(s) of each disordered region, how each region of disorder is used for function, as well as provide links to PubMed abstracts and major protein databases.

Availability:  www.disprot.org

Contact:  kedunker@iupui.edu
When Tax Collectors Become Collectors for Child Support and Student Loans: Jeopardizing the Revenue Base?
Authors: Ahmed Eliza , Braithwaite Valerie
Published: August 2004

This paper investigates the relationship between making additional payments to the state for student loan (via the Higher Education Contribution Scheme) and child support (via the Child Support Scheme) and compliance with tax law. Data are taken from the Community Hopes, Fears, and Actions Survey based on a random sample of 2040 individuals. Additional payments were found to pose a compliance problem for tax authorities. At the same time, this study demonstrated that perceived deterrence, moral obligation and possible trustworthiness play significant roles in reducing tax evasion. An important finding to emerge from this study is that tax evasion is more likely to accompany additional payments when personal income and belief in trust norms are low. The finding of greater tax evasion among economically marginalized groups has been demonstrated in other contexts, but the adverse effects of becoming irreconcilably socially marginalized from legal authority has tended to be both undervalued and under‐theorized in the taxation compliance literature.
Deceptive Field Experiments of Discrimination: Are they Ethical?
Authors: Riach Peter A. , Rich Judith
Published: August 2004

Field experiments in which bogus pairs of transactors test for discrimination by applying for employment or housing, or by trading in product markets, have been widely‐published during the last decade. However, no detailed justification has been provided for the deception involved. The general lack of veracity in the market‐place, the social harm inflicted by discrimination and the superior accuracy and transparency of this technique justify deceiving the subjects of experiments. Deception of testers, however, may do them harm, contravenes the ethical standards of psychologists and sociologists and is unnecessary, as alternative procedures are available to deal with ‘experimenter effects’.
Levels of Psychological Distress Experienced by Family Carers of Children and Adolescents with Intellectual Disabilities in an Urban Conurbation
Authors: Emerson Eric , Robertson Janet , Wood Justin
Published: August 2004

Background  The aim of the present study was to identify factors associated with the level of psychological distress reported by family carers of children with intellectual disability living in a large urban conurbation.

Method  Information was collected by postal questionnaire (or interview for family carers who did not have English as their first language) from the family carers of 408 children with intellectual disability (31% of all children within the area administratively identified as having an intellectual disability).

Results  Results indicated that 47% of primary carers scored above the threshold for psychological distress on the GHQ and that scoring above the threshold was strongly related to the emotional and behavioural needs of the index child and South‐Asian ethnicity and moderately associated with the severity of the child's delay in communication.

Conclusions  The rates of psychological distress (47% overall, 70% among South‐Asian carers) were markedly higher than that found in previous studies of carers supporting a child with intellectual disabilities. It is suggested that these elevated rates of psychological distress may be mediated by socio‐economic deprivation.
‘Diagnostic Overshadowing’ Amongst Clinicians Working with People with Intellectual Disabilities in the UK
Authors: Mason Jonathan , Scior Katrina
Published: August 2004

Background  Mental health problems are known to be hard to recognize in people with intellectual disabilities. One factor that may contribute to this is the diagnostic overshadowing bias, which describes the tendency of the clinicians to overlook symptoms of mental health problems in this client group and attribute them to being part of ‘having an intellectual disability’. Although a small amount of research has investigated this in the USA, very little has taken place in the UK.

Materials and methods  Two clinical vignettes were produced. Both described identical clinical problems, except that one vignette described a man with an IQ of 58 and impaired social functioning (i.e. an intellectual disability) and one a man with an IQ of 108 and normal social functioning (i.e. non‐intellectually impaired). Psychiatrists (n = 274) and clinical psychologists (n = 412) throughout UK were randomly assigned to either the low IQ or normal IQ condition, and sent a corresponding clinical vignette.

Results  One hundred and thirty‐three psychologists and 90 psychiatrists responded. Diagnostic overshadowing did appear to be present. Clinicians were more likely to recognize a range of symptoms in those with IQs in the normal range than those with intellectual disabilities. Furthermore, psychiatrists appeared more likely to make this error under some circumstances than clinical psychologists.

Conclusions  Diagnostic overshadowing may contribute to the difficulties that mental health professionals commonly experience in identifying mental health problems in people with intellectual disabilities. However, the methodology commonly used in this type of research has a number of weaknesses, and would benefit from an alternative approach.
Reconceptualizing the learning transfer conceptual framework: empirical validation of a new systemic model
Authors: Kontoghiorghes Constantine
Published: August 2004

The main purpose of this study was to examine the validity of a new systemic model of learning transfer and thus determine if a more holistic approach to training transfer could better explain the phenomenon. In all, this study confirmed the validity of the new systemic model and suggested that a high performance work system could indeed serve as a catalyst to successful training transfer.
The use of clozapine in adults with intellectual disability
Authors: Thalayasingam S. , Alexander R. T. , Singh I.
Published: August 2004

Background  There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region.

Method  A retrospective file‐review of patients treated in these three settings during the time period March–June 2002 was performed (n = 24). Information was collected using a semistructured proforma.

Results  Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia.

Conclusion  Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side‐effects is needed during therapy.
Pharmacokinetics of tramadol and the metaboliteO‐desmethyltramadol in dogs
Authors: KuKanich B. , Papich M. G.
Published: August 2004

Tramadol is an analgesic and antitussive agent that is metabolized toO‐desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half‐life, volume of distribution, and total body clearance were 0.80 ± 0.12 h, 3.79 ± 0.93 L/kg, and 54.63 ± 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 ± 38% and half‐life 1.71 ± 0.12 h following tramadol 11 mg/kg p.o. M1 had a half‐life of 1.69 ± 0.45 and 2.18 ± 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half‐life, volume of distribution, and clearance of M1 were 0.94 ± 0.09 h, 2.80 ± 0.15 L/kg, and 34.93 ± 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.
The effect of body region on the canine hair cycle as defined by unit area trichogram
Authors: DIAZ SANDRA F. , TORRES SHEILA M. F. , DUNSTAN ROBERT W. , JESSEN CARL R.
Published: August 2004

Abstract  The impact of anatomic location on trichogram analysis of the hair cycle phases was evaluated in 15 clinically normal dogs. The purposes of this study were to determine if the number of hairs in anagen and telogen vary among anatomic sites within a dog and to see whether there is an optimal region to sample hairs for canine trichogram evaluation of the hair cycle phases. In each dog eight sites were sampled. Four (26.7%) of the 15 dogs had no significant differences in the number of hairs in anagen and telogen among the eight body sites examined. Nine (81.8%) of the remaining 11 dogs had only one site that revealed significant differences in the number of hairs in anagen or telogen. In seven (77.8%) of these dogs only the anagen differed significantly, and in two (22.2%) dogs both phases differed significantly. Two (18.2%) dogs revealed two sites with significant differences in the number of hairs in anagen. The number of hairs in anagen and telogen in the shoulder area did not vary significantly in any of the dogs. This observation, coupled with the ease of sampling at this site, indicates that the shoulder is the site of choice when studying variations in ratios of hair cycle phases using unit area trichogram. Our results also suggest that numbers of telogen and anagen hairs from body regions with different hair shaft lengths do not vary significantly, and the occasional inconsistent results noted at some body sites might be due to sample collection technique.
Investigation on the effects of topical therapy with 0.1% tacrolimus ointment (Protopic®) on intradermal skin test reactivity in atopic dogs
Authors: MARSELLA R. , NICKLIN C. F. , SAGLIO S. , LOPEZ J.
Published: August 2004

Abstract  Tacrolimus ointment (TAC) is an effective treatment for atopic dermatitis in humans and dogs. The purposes of the present study were to evaluate the effect of 4 weeks of TAC on intradermal skin testing (IST), and in case of suppression, to investigate if reactivity returned to baseline by 2 or 4 weeks post treatment. Intradermal skin test was performed using saline, histamine, lipopolysaccharide (LPS, 0.4 mg mL−1), house dust (25 PNU mL−1) and house dust mite (1 : 40 000 w/v) at weeks 0, 4, 6 and 8 on nine dogs enrolled in a blinded, crossover, clinical trial, using 0.1% TAC or placebo once daily for 4 weeks. Reactions were evaluated at 15 min, and at 4 and 6 h. Ointment was applied after the 15‐min evaluation on weeks 0 and 4. Data were analysed using the statistical software SAS System for Windows. At week 4, TAC did not affect 15‐min IST, but some reactions in the TAC group were suppressed at 6 h compared to baseline. In the TAC group, 4‐h IST reactivity was reduced 2 weeks after discontinuation but returned to baseline by 4 weeks. In conclusion, TAC has no effect on immediate reactions but decreased some late‐phase reactions. Therefore, no withdrawal is recommended to evaluate only immediate reactions, but a 4‐week withdrawal may be necessary for evaluation of late‐phase reactions.
Hereditary equine regional dermal asthenia (‘hyperelastosis cutis’) in 50 horses: clinical, histological, immunohistological and ultrastructural findings
Authors: WHITE STEPHEN D. , AFFOLTER VERENA K. , BANNASCH DANIKA L. , SCHULTHEISS PATRICIA C. , HAMAR DWAYNE W. , CHAPMAN PHILLIP L. , NAYDAN DIANE , SPIER SHARON J. , ROSYCHUK ROD A. W. , REES CHRISTINE , VENEKLASEN GREGG O. , MARTIN ALONDRA , BEVIER DIANE , JACKSON HILARY A. , BETTENAY SONYA , MATOUSEK JENNIFER , CAMPBELL KAREN L. , IHRKE PETER J.
Published: August 2004

Abstract Data on fifty horses with hereditary equine regional dermal asthenia (HERDA; ‘hyperelastosis cutis’) were collected on clinical, histopathological, ultrastructural and immunohistological findings. All horses were Quarter horses or of Quarter horse ancestry. Pedigree evaluation strongly supported an autosomal recessive mode of inheritance. The most common lesions were seromas/haematomas, open wounds, sloughing skin, and loose, easily tented skin that did not return to its initial position. Definitive diagnosis could not be made via histopathology, although the presence of tightly grouped thin and shortened collagen fibres arranged in clusters in the deep dermis was suggestive of the disease. Trichrome, acid orcein‐Giemsa and immunohistochemical stains for collagens I and III showed no consistent abnormalities compared to control horses; an increase in elastic fibres was not a consistent finding. Electron microscopy showed no abnormalities in the periodicity of the collagen bundles; neither orientation nor variation of cross‐section diameter of the collagen fibrils differentiated control from affected horses. The diagnosis of HERDA relies on clinical presentation, but may be supported by suggestive (although not pathognomonic) histopathological lesions.
Duty of care in the emergency department
Authors: Wand Timothy
Published: August 2004

ABSTRACT:  This paper explores issues that relate to the management of deliberate self‐harm in the emergency department (ED) from a New South Wales perspective. A scenario that is typical to the ED is presented to illustrate the dilemma that nurses face and the implications for clinical practice. Confusion and concern regarding the treatment and detention of this type of patient in the ED can often result in the inappropriate use of the Mental Health Act. It is preferable for clinicians to be aware of the treatment options they have under duty of care rather than relying on the unfounded reassurance provided by scheduling a patient under the Mental Health Act. Communication and negotiation skills are highlighted as attributes that clinicians must develop and enhance to effectively manage difficult presentations to the ED.
Initial results of remediation activities to restore hypereutrophic Villerest Reservoir (Roanne, France)
Authors: Jugnia Louis‐B. , Debroas D. , Romagoux J‐C. , Dévaux J.
Published: August 2004

We examined the impacts of remediation activities aimed at improving the water quality of hypereutrophic Villerest Reservoir, in which Microcystis aeruginosa dominated during the summer. We also compared nutrients and chlorophyll a data from this study with the results of a previous study on the reservoir. Between the two studies, the nitrogen and phosphorus loads into the reservoir from the main tributary decreased by 70% and 80%, respectively. Within the reservoir, the quantities of ammonia‐nitrogen were similar in the two studies, and the total nitrogen was significantly higher in this study compared to the initial study. Both the phosphate‐phosphorus and total phosphorus concentrations decreased significantly between the two studies. However, the statistically significant decrease in phosphate‐phosphorus and total phosphorus did not always lead to a significant decrease in chlorophyll a concentrations. The nitrogen/phosphorus mass ratio during the present study remained well above five, the critical value below which summer blooms of Microcystis aeruginosa were observed in Villerest Reservoir. These study results indicated that the remediation activities being used to improve the water quality of Villerest Reservoir were off to a good start.
Stimulus duration in working memory is represented by neuronal activity in the monkey prefrontal cortex
Authors: Sakurai Yoshio , Takahashi Susumu , Inoue Masato
Published: August 2004

Humans are capable of memorizing several attributes of a presented stimulus as well as its duration of presentation. However, the neuronal representation of stimulus duration in memory remains unknown. This study investigated activities of single neurons in the prefrontal cortex of monkeys while they were performing a behavioral task in which working memory for stimulus duration was needed. Here we describe specific neurons whose discharge rates reflect encoding or retention of the duration of the presentation of stimuli to be remembered. We also describe other specific neurons whose activities reflect encoding or retention of fixed duration, similar but unrelated to the stimulus duration presented in each trial. Some of these specific neurons showed the same duration‐related discharges even while the monkeys were performing a different task, in which working memory for stimulus duration was no longer needed. From these results, we suggest that neurons in the prefrontal cortex play roles in encoding and retention of temporal information in working memory and that some of those neurons are dedicated to representation of temporal information attributed to stimuli even when the temporal information is unnecessary for correct performance.