In vivo treatment of class II MHC-deficient mice with anti-TCR antibody restores the generation of circulating CD4 T cells and optimal architecture of thymic medulla

TCR ligation by the self-peptide-associated MHC molecules is essential for T cell development in the thymus, so that class II MHC-deficient mice do not generate CD4(+)CD8(-) T cells. The present results show that the administration of anti-TCR mAb into class II MHC-deficient mice restores the generation of CD4(+)CD8(-) T cells in vivo. The CD4 T cells were recovered in the thymus, peripheral blood, and the spleen, indicating that the anti-TCR treatment is sufficient for peripheral supply of newly generated CD4 T cells. Unlike peripheral CD4 T cells that disappeared within 5 wk after the treatment, CD4(+)CD8(-) thymocytes remained undiminished even after 5 wk, suggesting that CD4 T cells in the thymus are maintained separately from circulating CD4 T cells and even without class II MHC molecules. It was also found that the mass of medullary region in the thymus, which was reduced in class II MHC-deficient mice, was restored by the anti-TCR administration, suggesting that the medulla for CD4(+)CD8(-) thymocytes is formed independently of the medulla for CD4(-)CD8(+) thymocytes. These results indicate that in vivo anti-TCR treatment in class II MHC-deficient mice restores the generation of circulating CD4 T cells and optimal formation of the medulla in the thymus, suggesting that anti-TCR Ab may be useful for clinical treatment of class II MHC deficiencies.     

O‐Methyltransferases involved in biphenyl and dibenzofuran biosynthesis

Biphenyls and dibenzofurans are the phytoalexins of the Malinae involving apple and pear. Biosynthesis of the defence compounds includes two O‐methylation reactions. cDNAs encoding the O‐methyltransferase (OMT) enzymes were isolated from rowan (Sorbus aucuparia) cell cultures after treatment with an elicitor preparation from the scab‐causing fungus, Venturia inaequalis. The preferred substrate for SaOMT1 was 3,5‐dihydroxybiphenyl, supplied by the first pathway‐specific enzyme, biphenyl synthase (BIS). 3,5‐Dihydroxybiphenyl underwent a single methylation reaction in the presence of S‐adenosyl‐l ‐methionine (SAM). The second enzyme, SaOMT2, exhibited its highest affinity for noraucuparin, however the turnover rate was greater with 5‐hydroxyferulic acid. Both substrates were only methylated at the meta‐positioned hydroxyl group. The substrate specificities of the OMTs and the regiospecificities of their reactions were rationalized by homology modeling and substrate docking. Interaction of the substrates with SAM also took place at a position other than the sulfur group. Expression of SaOMT1, SaOMT2 and SaBIS3 was transiently induced in rowan cell cultures by the addition of the fungal elicitor. While the immediate SaOMT1 products were not detectable in elicitor‐treated cell cultures, noraucuparin and noreriobofuran accumulated transiently, followed by increasing levels of the SaOMT2 products aucuparin and eriobofuran. SaOMT1, SaOMT2 and SaBIS3 were N‐ and C‐terminally fused with the super cyan fluorescent protein and a modified yellow fluorescent protein, respectively. All the fluorescent reporter fusions were localized to the cytoplasm of Nicotiana benthamiana leaf epidermis cells. A revised biosynthetic pathway of biphenyls and dibenzofurans in the Malinae is presented.     

Nitrogen transport in the ectomycorrhiza association: the Hebeloma cylindrosporum-Pinus pinaster model

The function of the ectomycorrhizal mutualism depends on the ability of the fungal symbionts to take up nutrients (particularly nitrogen) available in inorganic and/or organic form in the soil and to translocate them (or their metabolites) to the symbiotic roots. A better understanding of the molecular mechanisms underlying nutrient exchanges between fungus and plant at the symbiotic interface is necessary to fully understand the function of the mycorrhizal symbioses. The present review reports the characterization of several genes putatively involved in nitrogen uptake and transfer in the Hebeloma cylindrosporum-Pinus pinaster ectomycorrhizal association. Study of this model system will further clarify the symbiotic nutrient exchange which plays a major role in plant nutrition as well as in resistance of plants against pathogens, heavy metals, drought stress, etc. Ultimately, ecological balance is maintained and/or improved with the help of symbiotic associations, and therefore, warrant further understanding.     

Ectopic expression of a grape vine vacuolar NHX antiporter enhances transgenic potato plant tolerance to salinity

Journal of Plant Biochemistry and Biotechnology - Salinity is a crucial environmental constraint that reduces plant productivity. However, plants activate different signaling pathways to overcome...     

Fatty acid-induced atherogenic changes in extracellular matrix proteoglycans

PURPOSE OF REVIEW: Nonesterified fatty acids change the expression and properties of the extracellular matrix proteoglycans of arterial and hepatic cells. We review how this may contribute to arterial disease in insulin resistance and type 2 diabetes. RECENT FINDINGS: Elevated nonesterified fatty acids characterize the dyslipidemia of insulin resistance and type 2 diabetes. In hepatocytes high levels of fatty acids cause changes in proteoglycans leading to a matrix with decreased affinity for VLDL remnants. Furthermore, liver proteoglycans from insulin resistant hyperlipidemic Zucker rats showed alterations also associated with decreased remnant affinity. In arterial smooth muscle cells overexposure to fatty acids augmented expression of matrix proteoglycans for which LDL showed increased affinity. Fatty acids appeared to compromise insulin signaling by protein kinase C activation. The observed fatty acid-induced changes in matrix proteoglycans in liver and arteries can be an important component of the atherogenicity of the dyslipidemia of insulin resistance and type 2 diabetes. SUMMARY: Overexposure to fatty acids can contribute to generate a remnant-rich dyslipidemia and to precondition the arterial intima for lipoprotein deposition via changes in expression of matrix proteoglycans. Normalizing fatty acid should be a key target in treatment of the atherogenic dyslipidemia of insulin resistance.     

Cross-sectional analysis of adverse outcomes in 1,029 pregnancies of Afro-Caribbean women in Trinidad with and without systemic lupus erythematosus

The objective of the study was to examine pregnancy outcomes in women with systemic lupus erythematosus (SLE) and population controls in Trinidad. We performed a cross-sectional analysis of adverse outcomes in pregnancies of Afro-Caribbean women with SLE and without SLE. One hundred and twenty-two female adult cases of SLE and 203 neighbourhood age-matched women without SLE were interviewed concerning details of their reproductive history, and the anticardiolipin antibody (ACL) status was established for women with SLE. A total of 1,029 pregnancies were reported (356 by women with SLE, 673 by women without SLE). In women with ≥ 1 pregnancy the total number of pregnancies was similar in women with a diagnosis of SLE and women without; however, a lower proportion of women with SLE had ever been pregnant compared with women without SLE (80% versus 91%, P = 0.002). In multivariate logistic regression analyses adjusted for maternal age, district of residence, pregnancy order and smoking, SLE pregnancies were more than twice as likely to end in foetal death than non-SLE pregnancies (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2–4.7). This effect was driven by a large increase in the odds of stillbirth (OR, 8.5; 95% CI, 2.5–28.8). The odds of early miscarriage (OR, 1.4; 95% CI, 0.6–3.1) and of mid-trimester miscarriage (OR, 1.9; 95% CI, 0.4–9.5) were higher, but were not statistically significantly different, in SLE pregnancies than in non-SLE pregnancies. The odds of ectopic pregnancy (OR, 7.5; 95% CI, 0.9–62.5) and of preterm birth (OR, 3.4; 95% CI, 1.2–10.0) were higher in SLE pregnancies conceived after diagnosis than in non-SLE pregnancies. There was no evidence of raised levels of IgG or IgM ACL among the majority (93/97 women, 96%) of SLE cases who reported sporadic mid-trimester miscarriage or stillbirth, although there was evidence of high levels of IgM and IgG ACL among women reporting three or more miscarriages and three consecutive miscarriages, and of raised IgG ACL among those experiencing ectopic pregnancy. In conclusion, we found evidence for a large increase in risk of stillbirth in the pregnancies of Afro-Caribbean Trinidadian women with SLE (not accounted for by high ACL status). There was some evidence of an increased risk of preterm delivery and ectopic pregnancy in pregnancies conceived after a diagnosis of maternal SLE.