Electrical molecular switch addressed by chemical stimuli.

We demonstrate that the conductance switching of benzo-bis(imidazole) molecules upon protonation depends on the lateral functional groups. The protonated H-substituted molecule shows a higher conductance than the neutral one (Gpro > Gneu), while the opposite (Gneu > Gpro) is observed for a molecule laterally functionalized by amino-phenyl groups. These results are demonstrated at various scale lengths: self-assembled monolayers, tiny nanodot-molecule junctions and single molecules. From ab initio theoretical calculations, we conclude that for the H-substituted molecule, the result Gpro > Gneu is correctly explained by a reduction of the LUMO-HOMO gap, while for the amino-phenyl functionnalized molecule, the result Gneu > Gpro is consistent with a shift of the HOMO, which reduces the density of states at the Fermi energy.

Temporomandibular joint involvement in childhood arthritis: comparison of ultrasonography-assessed capsular width and MRI-assessed synovitis.

OBJECTIVES: Ultrasonography is an effective, low-cost, low-threshold and convenient diagnostic tool in childhood arthritis, but its value in temporomandibular joint (TMJ) involvement is not clear. The purpose of our study was to explore the reliability of ultrasonography to assess TMJ inflammation using contrast-enhanced MRI as reference standard, in order to deduce cut-off values for TMJ capsular width to detect enhanced synovial thickening (synovitis). METHODS: 124 ultrasonography and MRI examinations in 55 patients [mean age 12.4 ± 3.5 years (±standard deviation)], the majority obtained within 1 day, were scored for subcondylar and condylar capsular width (ultrasonography images) and amount of synovitis (MR images). The correlations of these findings were calculated. A receiver operating characteristic (ROC) curve analysis, with MRI findings as reference standard, was obtained. RESULTS: The correlation between ultrasonography-assessed capsular width and MRI-assessed amount of synovitis was moderate both at the subcondylar and condylar level [Spearman's rho (ρ): 0.483; p < 0.001 and 0.347; p < 0.001 respectively]. The ROC curve indicated the best discriminatory ability at the subcondylar level with an area under the curve of 0.77 (95% confidence interval 0.69-0.85) and a cut-off value of 1.2 mm (sensitivity 72%, specificity 70%) for the capsular width. CONCLUSIONS: A moderate correlation between ultrasonography-assessed capsular width and MRI-assessed synovitis was found in childhood arthritis with the best discriminatory ability at the subcondylar level. This indicates that ultrasonography may be a valuable diagnostic tool in the initial assessment of TMJ inflammation.

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis.

BACKGROUND: MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. OBJECTIVE: To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. MATERIALS AND METHODS: This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. RESULTS: The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. CONCLUSION: Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis.

Patterns of gene recombination shape var gene repertoires in Plasmodium falciparum: comparisons of geographically diverse isolates.

BACKGROUND: Var genes encode a family of virulence factors known as PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) which are responsible for both antigenic variation and cytoadherence of infected erythrocytes. Although these molecules play a central role in malaria pathogenesis, the mechanisms generating variant antigen diversification are poorly understood. To investigate var gene evolution, we compared the variant antigen repertoires from three geographically diverse parasite isolates: the 3D7 genome reference isolate; the recently sequenced HB3 isolate; and the IT4/25/5 (IT4) parasite isolate which retains the capacity to cytoadhere in vitro and in vivo. RESULTS: These comparisons revealed that only two var genes (var1csa and var2csa) are conserved in all three isolates and one var gene (Type 3 var) has homologs in IT4 and 3D7. While the remaining 50 plus genes in each isolate are highly divergent most can be classified into the three previously defined major groups (A, B, and C) on the basis of 5' flanking sequence and chromosome location. Repertoire-wide sequence comparisons suggest that the conserved homologs are evolving separately from other var genes and that genes in group A have diverged from other groups. CONCLUSION: These findings support the existence of a var gene recombination hierarchy that restricts recombination possibilities and has a central role in the functional and immunological adaptation of var genes.

Functional interdependence of the DBLbeta domain and c2 region for binding of the Plasmodium falciparum variant antigen to ICAM-1.

Cytoadherence of Plasmodium falciparum-infected erythrocytes is associated with severe malaria and is primarily mediated through binding of the variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) to specific host ligands. Infected erythrocyte binding to Intercellular Adhesion Molecule 1 (ICAM-1) has been implicated as having a role in cerebral malaria, a major cause of death from P. falciparum infection. We have examined ICAM-1-binding PfEMP1 proteins in the cytoadhesive P. falciparum strain IT4/25/5 in order to extend our understanding of binding. For A4tres, the ICAM-1 binding region was previously shown to reside within contiguous DBL2beta and c2 domains. We determined the gene sequence encoding IT-ICAM var, and showed that ICAM-1 binding in this protein also maps to DBL2betac2 domains that have 48% amino acid identity to A4tres. By truncation and chimera analysis, most of the DBL2beta and the first half of the c2 region were required for A4tres binding to ICAM-1, suggesting this tandem should be considered a structural-functional combination for ICAM-1 binding. Of interest, a chimera formed between two different ICAM-1 binding domains did not bind ICAM-1, suggesting a functional interdependence between DBL2beta and c2 from the same protein. As gene recombination and gene conversion are important mechanisms for generating diversity in the PfEMP1 protein family, this finding implies an extra level of constraint on the functional evolution of binding traits. Knowledge about the PfEMP1::ICAM-1 interaction may allow the development of interventions to prevent binding and disease.

Ethylene glycol and amino acid derivatives of 5-aminolevulinic acid as new photosensitizing precursors of protoporphyrin IX in cells.

Protoporphyrin IX (PpIX) is used as a photosensitizing agent in photodynamic detection and therapy (PDT) of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these products was investigated using cultures of human and rat cell lines of carcinoma and endothelial origins. The cytotoxicity of these compounds in the absence of light was also controlled. The results have shown that ethylenglycol esters can induce high levels of PpIX and are useful at concentrations below their cytotoxicity threshold. From the ALA-amino acid derivatives which were evaluated, the highest PpIX production was obtained using ALA derivatives of neutral amino acids, as compared to acidic or basic amino acids.

Electron spin resonance detection of nitric oxide generation in major organs from LPS-treated rats.

The increased production of nitric oxide (NO) has been implicated as the basis for myocardial dysfunction and the lack of response to vasoconstrictors during endotoxin shock induced by lipopolysaccharide (LPS). Our objective was to evaluate and compare NO production in major organs of rats treated with LPS, 1 or 14 mg/kg. A NO spin-trapping technique using electron spin resonance (ESR) spectroscopy has been used to study NO production in the liver, the kidney, the aorta, and the heart. The method was based on the trapping of NO by a metal-chelator complex consisting of N-methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable [(MGD)2-Fe2+-NO] complex, giving rise to a characteristic triplet ESR spectrum with g = 2.04 and aN = 12.65 G: Iron was quantified in the different organs to study the [(MGD)2-Fe2+] complex distribution. Six hours after intravenous injection of 1 or 14 mg/kg of LPS, we observed large increases in the [(MGD)2-Fe2+-NO] adduct signal in the liver, the kidney, and in the aorta, strongly suggesting an increased production of NO in these organs. The [(MGD)2-Fe2+-NO] adduct was also detected in the heart, 6 h after injection of LPS. Moreover, we observed dose-dependent increases in [(MGD)2-Fe2+-NO] adduct in the heart, whereas no changes were observed in the other organs. Concurrently, the [(MGD)2-Fe2+-NO] adduct was not detected in the blood from rats treated with LPS, although circulating nitrosylhemoglobin, nitrite, and nitrate levels increased. The spin-trapping technique allowed us to monitor organ-specific formation of NO after LPS administration and for the first time demonstrated direct NO production in aorta and heart of LPS-treated animals.