The effect of bile, bile acids and detergents on calcium absorption in the chick

1. Bile from rachitic or normal chicks causes an immediate increase in the intestinal absorption of soluble calcium in rachitic and vitamin D(3)-treated chicks as tested in vivo by intestinal-loop and oral-dosing methods. 2. This effect is apparently solely due to the taurine-conjugated bile acids present in the bile and is independent of the action of vitamin D. 3. Chick bile and bile acids can increase the solubility and the absorption of calcium presented as sparingly soluble calcium hydrogen phosphate. 4. In addition, bile is necessary to some extent at least for the intestinal absorption of vitamin D(3) in the chick and this would indirectly enhance the absorption of calcium. 5. Thus bile is capable of a threefold action in the absorption of calcium in the chick. It is suggested that the direct action on sparingly soluble forms of calcium is of considerable physiological importance since most of the calcium in the normal bird's diet would be in this form. 6. Bile acids enhance the absorption of calcium in all regions of the small intestine of the chick. 7. Of a range of bile acids and detergents tested for enhancement of calcium absorption, various taurine-conjugated bile acids and sodium lauryl sulphate, an anionic detergent, are effective. A non-ionic detergent (Tween 80) and a cationic detergent (Zephiran) are without effect. 8. The ability of a substance to increase directly the intestinal absorption of soluble calcium appears to depend to some extent on an anionic detergent action, i.e. the ability to form a salt or complex soluble to some extent in both aqueous and lipid phases. 9. In chicks the immediate deposition of calcium ((45)Ca) in the bones closely reflects any increase in plasma calcium radioactivity regardless of the cause of the increase and regardless of the vitamin D(3) status. Although sodium lauryl sulphate can increase markedly the calcium absorption from the gut and the immediate deposition in the bones it has no significant effect on rickets. 10. Some of the implications of these findings are discussed.     

Expression of CA IX in dysplasia adjacent to surgical resection margins of oral squamous cell carcinoma

Carbonic anhydrase (CA) IX is a hypoxia marker located almost exclusively in tumor cells. We analyzed the expression of this marker in dysplastic lesions adjacent to the surgical resection margin in patients with oral squamous cell carcinoma. We investigated 70 archived tumors, 36 of which showed dysplasia adjacent to the surgical margin. We used tissue microarray technology to perform an immunohistochemical study of CA IX expression. We found 12 (33.3%) cases of mild dysplasia (10 negative, 2 positive for CA IX), five (13.9%) cases of moderate dysplasia (3 negative, 2 positive for CA IX), 1 (2.8%) case of severe dysplasia (negative for CA IX) and 18 (50%) cases of carcinoma in situ (10 negative, 8 positive for CA IX). In cases of intense expression of CA IX in the tumor, the same distribution of positive and negative cases was observed in all degrees of dysplasia (mild, moderate, severe), although cases of carcinoma in situ tended to be CA IX positive.     

Mutations in the Arabidopsis Peroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal β-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved “EAA motif” of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data.     

Remission in psoriatic arthritis: is it possible and how can it be predicted?

Introduction

Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Methods

Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.

Results

A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).

Conclusions

DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.     

Earthworm invasion into previously earthworm-free temperate and boreal forests

Earthworms are keystone detritivores that can influence primary producers by changing seedbed conditions, soil characteristics, flow of water, nutrients and carbon, and plant–herbivore interactions. The invasion of European earthworms into previously earthworm-free temperate and boreal forests of North America dominated by Acer, Quercus, Betula, Pinus and Populus has provided ample opportunity to observe how earthworms engineer ecosystems. Impacts vary with soil parent material, land use history, and assemblage of invading earthworm species. Earthworms reduce the thickness of organic layers, increase the bulk density of soils and incorporate litter and humus materials into deeper horizons of the soil profile, thereby affecting the whole soil food web and the above ground plant community. Mixing of organic and mineral materials turns mor into mull humus which significantly changes the distribution and community composition of the soil microflora and seedbed conditions for vascular plants. In some forests earthworm invasion leads to reduced availability and increased leaching of N and P in soil horizons where most fine roots are concentrated. Earthworms can contribute to a forest decline syndrome, and forest herbs in the genera Aralia, Botrychium, Osmorhiza, Trillium, Uvularia, and Viola are reduced in abundance during earthworm invasion. The degree of plant recovery after invasion varies greatly among sites and depends on complex interactions with soil processes and herbivores. These changes are likely to alter competitive relationships among plant species, possibly facilitating invasion of exotic plant species such as Rhamnus cathartica into North American forests, leading to as yet unknown changes in successional trajectory.     

Chewing the fat: beta-oxidation in signalling and development

Peroxisomal beta-oxidation is involved not only in fatty acid catabolism and lipid housekeeping but also in metabolism of hormones and amino acids in plants. Recent research in model species has led to new insights into the roles of this pathway in signalling and development, in particular regarding the involvement of beta-oxidation in jasmonic acid biosynthesis. Analysis of associated processes, such as the glyoxylate cycle and redox metabolism has also highlighted the importance of integration of beta-oxidation with cytosolic and mitochondrial metabolism. Mutations that disrupt beta-oxidation can have extremely pleiotropic effects, indicating important and varied roles for this pathway throughout the plant life cycle and making this an exciting topic for future research.