A bimodal association of vitamin D levels and vascular disease in children on dialysis.

In addition to its classical role in calcium-phosphate homeostasis, vitamin D has anti-inflammatory effects that may influence vascular disease. This study examined the impact of vitamin D levels on the vascular phenotype in 61 children who had been on dialysis for >or=3 mo and in 40 age-matched control subjects. All dialysis patients were prescribed daily oral 1-alpha hydroxyvitamin D(3).

Being a pretty good citizen: an analysis and monetary valuation of formal and informal voluntary work by gender and educational attainment.

This paper is set in the context of macrosocial/macroeconomic theories of the organization of both paid and unpaid work. The specific topic investigated is engagement in unpaid voluntary work, an activity which is thought to be important for social cohesion, civil society and citizenship. Research on the sources of social cohesion has focused on organizational membership and voluntary organization activity.

Walking behaviours from the 1965-2003 American Heritage Time Use Study (AHTUS).

Background: The American Heritage Time Use Study (AHTUS) represents a harmonised historical data file of time use by adults, amalgamating surveys collected in 1965-66, 1975-76, 1985, 1992-94, and 2003. The objectives of time-use studies have ranged from evaluating household and other unpaid production of goods and services, to monitoring of media use, to comparing lifestyles of more and less privileged social groups, or to tracking broad shifts in social behaviour. The purpose of this paper is to describe the process and utility of identifying and compiling data from the AHTUS to describe a range of walking behaviours collected using time-use survey methods over almost 40 years in the USA.

GENDER CONVERGENCE IN THE AMERICAN HERITAGE TIME USE STUDY (AHTUS).

We present evidence from a new comprehensive database of harmonized national time-diary data that standardizes information on almost 40 years of daily life in America. The advantages of the diary method over other ways of calculating how time is spent are reviewed, along with its ability to generate more reliable and accurate measures of productive activity than respondent estimates or other alternatives. We then discuss the various procedures used to develop these harmonized data, both to standardize reporting detail and to match with Census Bureau population characteristics.

Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in patients with either Huntington's disease or chronic brain injury.

Following a study of oxidative tryptophan metabolism to kynurenines, we have now analysed the blood of patients with either Huntington's disease or traumatic brain injury for levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin. There were no differences in the baseline levels of these compounds between patients and healthy controls. Tryptophan depletion did not reduce 5-HT levels in either the controls or in the patients with Huntington's disease, but it increased 5-HT levels in patients with brain injury and lowered 5-HIAA in the control and Huntington's disease groups.

Tryptophan metabolism and oxidative stress in patients with chronic brain injury.

The kynurenine pathway generates the excitotoxic N-methyl-d-aspartate receptor agonist, quinolinic acid and the glutamate antagonist, kynurenic acid, as well as free-radical generators. We investigated the status of the pathway following severe brain injury sustained at least 1 year previously in 15 patients compared with controls. At baseline, patients with brain injury showed increased levels of neopterin, erythrocyte sedimentation rate, C-reactive protein and peroxidation products in the blood compared with controls, indicating persistent inflammation and oxidative stress.

Tryptophan metabolism and oxidative stress in patients with Huntington's disease.

Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed that the kynurenine : tryptophan ratio was greater in HD than controls in the baseline state and after tryptophan depletion, indicating increased indoleamine dioxygenase activity in HD.

Tryptophan loading induces oxidative stress.

In previous studies tryptophan loads have been administered to human subjects in order to raise central levels of 5-hydroxytryptamine (5HT) and assess the effects of 5HT on behaviour and mood. However, tryptophan is metabolised primarily along the oxidative kynurenine pathway. In this study a 6 g oral tryptophan load was administered to 15 healthy volunteers and the levels of kynurenines and lipid peroxidation products (indicative of oxidative stress) were measured.

Higher education and civic engagement.

This paper focuses on the relationship between social engagement, particularly civic engagement, and education. It is well known that more highly educated people are more likely to engage in voluntary work in formalized settings. It has been difficult to disentangle the effect of higher education from that of family origin and occupational socialization.

Expression databases--resources for pharmacogenomic R&D.

This review aims to outline the primary biological databases that are being generated to understand fundamental biology, identify new drug targets, and to look at compound profiling in a new light. We will give a brief overview of four of the main areas being studied in molecular biology: genomics, pharmacogenomics, pharmacogenetics and proteomics. Looking initially at each data set and some of its potential applications, we will go on to describe some of the potentially enormous advantages gained by fully integrating these data sets.

Lessons to be learned: a case study approach. Unseasonal severe poisoning of two adults by deadly nightside (Atropa belladonna).

Unseasonal, mid-winter, severe poisoning by deadly nightshade is reported in two adults who simultaneously ate from a pie made of frozen deadly nightshade berries, mistaken at the time of picking for bilberries. Atropine levels are reported in the urine. Physostigmine treatment was ineffective.

Ges, A human GTPase of the Rad/Gem/Kir family, promotes endothelial cell sprouting and cytoskeleton reorganization.

Rad, Gem/Kir, and mRem (RGK) represent a unique GTPase family with largely unknown functions (Reynet, C., and C.R.

Effects of a colostrum replacement product derived from serum on immunoglobulin G absorption by calves.

Calves are born hypogammaglobulinemic and rely on immunoglobulin (Ig) from colostrum to obtain passive immunity. Previous research has indicated that colostrum supplements derived from milk are less effective than is maternal colostrum in providing adequate IgG to neonatal calves. Our objective was to determine the absorption of IgG by newborn calves fed a USDA food-grade colostrum supplement derived from bovine serum or fed pooled maternal colostrum.

Characterization of human and rat brain myristoyl-CoA:protein N-myristoyltransferase: evidence for an alternative splice variant of the enzyme.

Using 5'-rapid amplification of cDNA ends, we have identified an extended 5'-end of mRNA coding for human myristoyl-CoA:protein N-myristoyltransferase (NMT). PCR using primers based on this new 5'-sequence and reverse primers within the currently accepted coding sequence of the enzyme resulted in the identification of a novel splice variant of NMT. In vitro translation of these cDNAs resulted in the production of proteins with apparent molecular masses of 63 kDa and 48 kDa.

Activation of the extracellular signal-regulated kinase pathway is differentially required for TCR-stimulated production of six cytokines in primary T lymphocytes.

The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate methods to interfere with TCR activation of the ERK cascade.

Crystal structure of the anti-fungal target N-myristoyl transferase.

N-myristoyl transferase (NMT) catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins, and is found only in eukaryotic cells. The enzyme in this study is the 451 amino acid protein produced by Candida albicans, a yeast responsible for the majority of systemic infections in immuno-compromised humans. NMT activity is essential for vegetative growth, and the structure was determined in order to assist in the discovery of a selective inhibitor of NMT which could be developed as an anti-fungal drug.

Activated T cells from draining lymph nodes and an effector site differ in their responses to TCR stimulation.

We previously showed that T cells from the mediastinal lymph nodes (MLN) and lung parenchyma of influenza virus-infected mice were functionally remarkably different. Here we demonstrate that the differences in cytokine production are due to differences in the frequencies of T cells within the activated pool able to produce cytokines after TCR stimulation. FACS analysis of T cells from MLN and lung tissue demonstrated that T cells expressing any of the activation markers tested (LFA-1, CD25, CD44, CD45RB, CD49d, CD62L) always expressed high levels of CD44 and LFA-1.

Interaction between ATM protein and c-Abl in response to DNA damage.

The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT), designated ATM (for 'AT mutated'), is a member of a family of phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle control, meiotic recombination, telomere length monitoring and DNA-damage response. Previous results have demonstrated that AT cells are hypersensitive to ionizing radiation and are defective at the G1/S checkpoint after radiation damage. Because cells lacking the protein tyrosine kinase c-Abl are also defective in radiation-induced G1 arrest, we investigated the possibility that ATM might interact with c-Abl in response to radiation damage.

Yeast-enhanced green fluorescent protein (yEGFP): a reporter of gene expression in Candida albicans.

The green fluorescent protein (GFP) of Aequorea victoria has been developed here as a reporter for gene expression and protein localization in Candida albicans. When wild-type (wt) GFP was expressed in C. albicans, it was not possible to detect fluorescence or a translation product for the wt protein.

Analysis of the promoter region of the human VEGF-related factor gene.

We have characterised the promoters of the human and murine VRF (vascular endothelial growth factor (VEGF) related factor) gene. A series of deletions were made of a 553-bp region 5' of the VRF initiation codon and were used in a luciferase reporter gene assay to determine the minimal promoter of the VRF gene. The region between base pairs -443 and -195 was sufficient to mediate transcription in lymphocytes and the region between -550 and -443 enhanced this promoter activity.

Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation.

The enzyme N-myristoyl transferase transfers the 14 carbon fatty acid myristate to an N-terminal glycine residue in a small subset of cytoplasmic proteins. Many myristoyl proteins are components of cellular signalling pathways, some of which play important roles during embryonic development, for example protein kinase A. Thus, the function of N-myristoyl transferase is probably essential for embryogenesis and it is of some interest to study the enzyme in an organism with well understood developmental biology.

Differential activation of T cell cytokine production by the extracellular signal-regulated kinase (ERK) signaling pathway.

Stimulation of T cells via the T cell receptor (TCR) activates a number of signaling pathways that are potentially involved in the elicitation of physiological responses, such as the production of cytokines. The extracellular signal-regulated kinases (ERK) are a group of molecules activated in response to TCR ligation, whose role in T cell cytokine production is controversial. In this study, we have asked whether ERK activation is coupled to the production of a number of T cell-derived cytokines, and whether particular cytokines are differentially affected by ERK activation.

Identification of the 70kD heat shock cognate protein (Hsc70) and alpha-actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes.

T cell antigen receptor (TCR) ligation results in the tyrosine phosphorylation of numerous intracellular protein substrates, and the identification of these substrates has been a major undertaking by several groups. We have used pervanadate treatment to artificially increase cellular phosphotyrosine levels and immobilized anti-phosphotyrosine monoclonal antibodies to partially purify tyrosine phosphorylated proteins in quantities suitable for amino acid sequencing. This strategy was used to identify three phosphotyrosine containing proteins, with relative molecular masses of 105, 81, and 76 kD by amino acid sequencing.