Studies of in vivo chlorophyll a (chl a ) fluorescence per cell, measured with a flow cytometer, and the pigment composition of cultured phytoplanktonic cells suggested that the xanthophyll cycle plays a role in the prevention of photoinhibitory damage to the photosynthetic apparatus.

The accumulation of sugars in grape berries requires the co-ordinate expression of sucrose transporters, invertases, and monosaccharide transporters. A monosaccharide transporter homologue (VvHT1, Vitis vinifera hexose transporter 1) has previously been isolated from grape berries at the veraison stage, and its expression was shown to be regulated by sugars and abscisic acid. The present work investigates the function and localization of VvHT1. Heterologous expression in yeast indicates that VvHT1 encodes a monosaccharide transporter with maximal activity at acidic pH (pH 4.5) and high affinity for glucose (K(m)=70 muM). Fructose, mannose, sorbitol, and mannitol are not transported by VvHT1. In situ hybridization shows that VvHT1 transcripts are primarily found in the phloem region of the conducting bundles. Immunofluorescence and immunogold labelling experiments localized VvHT1 in the plasma membrane of the sieve element/companion cell interface and of the flesh cells. The expression and functional properties of VvHT1 suggests that it retrieves the monosaccharides needed to provide the energy necessary for cell division and cell growth at an early stage of berry development.

AIMSThis study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokineticpharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA). METHODSAdalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model. The relationship between adalimumab concentration and C-reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated. RESULTSThirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd/F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day −1 (17%); first-order absorption rate (ka) = 0.28 day; CRP input (kin) = 22.0 mg l −1 day −1 (65%); adalimumab concentration leading to a 50% decrease in kin (C50) = 3.6 mg l −1 (88%); baseline DAS28 (DAS0) = 5.5 mg l −1 (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50) = 11.0 mg l −1 (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Infliximab pharmacokinetics in ankylosing spondylitis has been described but using sparce data.• A previous work suggests that infliximab concentrations influence clinical response in ankylosing spondylitis, but the infliximab concentration-effect relationship is not known in this disease.• Methotrexate was shown to influence infliximab pharmacokinetics in rheumatoid arthritis. WHAT THIS STUDY ADDS• This study is the first to describe infliximab pharmacokinetics in ankylosing arthritis using rich data.• The infliximab concentration explains only a small part of interindividual variability in the response of ankylosing arthritis patients.• Contrary to what is observed in rheumatoid arthritis, methotrexate influences neither infliximab pharmacokinetics nor concentration-response relationship in ankylosing spondylitis. AIMSInfliximab, an anti-tumour necrosis factor a monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration-effect relationship in axial ankylosing spondylitis (AAS) patients. METHODSTwenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg -1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve. RESULTSA total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day -1 (22%) and intercompartment clearance = 2.3 l day -1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability. CONCLUSIONSUsing the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.

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Five hundred and six EST-derived markers, 313 SSR markers and 26 BAC end-derived or SCAR markers were anchored by PCR on a subset of a Cabernet Sauvignon BAC library representing six genome equivalents pooled in three dimensions. In parallel, the 12,351 EST clusters of the grapevine UniGene set (build #11) from NCBI were used to design 12,125 primers pairs and perform electronic PCR on 67,543 nonredundant BAC-end sequences. This in silico experiment yielded 1,140 positive results concerning 638 different markers, among which 602 had not been already anchored by PCR. The data obtained will provide an easier access to the regulatory sequences surrounding important genes (represented by ESTs). In total, 1,731 islands of BAC clones (set of overlapping BAC clones containing at least one common marker) were obtained and 226 of them contained at least one genetically mapped anchor. These assigned islands are very useful because they will link the genetic map and the future fingerprint-based physical map and because they allowed us to indirectly place 93 ESTs on the genetic map. The islands containing two or more mapped SSR markers were also used to assess the quality of the integrated genetic map of the grapevine genome.