255 research outputs found

    Patterns of Development and Nitrogen Reserves Mobilization during Regrowth of Defoliated Clover

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    Contribution of nitrogen reserves to regrowth following defoliation was studied in white clover plants (Trifolium repens) according to the morphological pattern of differentiation of the aerial parts during the same period. Low temperature and short day lengths were used as a pre-treatment in order to increase branching and enhance new sites of leaf production during a further 25 d period of regrowth. Pre-treated plants exhibited a large reduction in leaf area largely counterbalanced with a high increase in leaf pool size during the first 10 d of regrowth. The mobilization of nitrogen reserves during regrowth of defoliated clover was intimately linked to the pattern of differentiation of the newly developed organs. It thus appeared that regrowth of pretreated plants was less supported by endogenous N during the first 10 d as compared to control plants continously grown in standard conditions. It is assumed that regrowth of dwarf plants is less dependent upon the mobilization rate of soluble proteins previously accumulated in roots and uncut stolons

    Modelling Nitrogen Uptake in Winter Oilseed Rape by Using Influx Kinetics of Nitrate Transport Systems

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    A mechanistic model was proposed in order to predict nitrogen uptake by a culture of oilseed rape (Brassica napus L.), using independently measured characteristics of plants growing in hydroponic or under field conditions. Uptake kinetics of the different components (Constitutive and Inducible) of the Low and High Affinity Transport Systems of nitrate (CLATS, ILATS, CHATS and IHATS, respectively) were determined by 15NO3- labelling in controlled conditions. The use of kinetic equations of transport systems and the experimental field data from the INRA-Châlons rape databank allowed to model NO3- uptake during the plant growth cycle. The study of different factors such as root temperature, day/night cycle and ontogenetic stages on NO3- uptake rate has been undertaken in order to improve the model prediction. Model outputs show that the high affinity transport system (HATS) accounted for about 90 % of total NO3- uptake (20 and 70 % for CHATS and IHATS without fertilization, respectively). The low affinity transport system (LATS) accounted for a minor proportion of total N uptake, and its activity was restricted to the early phase of the growth cycle. However, N autumnal fertilization increased the duration of its contribution (from 67 to 100 days) to total N uptake

    Neuropathic complications after 157 procedures of continuous popliteal nerve block for hallux valgus surgery. A retrospective study

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    SummaryBackgroundContinuous peripheral nerve block (CPNB), in particular at the popliteal fossa, is widely used in orthopedic surgery, allowing good postoperative analgesia. Possible neuropathic complications, however, remain poorly known.ObjectiveTo review the characteristics of peripheral neuropathy (PN) after sciatic CPNB at the popliteal fossa, estimating prevalence, severity, evolution and possible risk factors, especially those relating to the procedure.MethodsRetrospective study of PN associated with popliteal fossa CPNB for hallux valgus surgery, between November 1st, 2005 and November 1st, 2009. All procedures were analyzed (type of anesthesia, approach, nerve location technique, number of procedures by operator) with, for each case of PN, analysis of clinical and electromyographic data.ResultsOne hundred and fifty seven sciatic CPNBs were performed (92% women; mean age, 55 years). The approach was lateral (n=62), posterior (n=74) or unknown (n=21). Ultrasound guidance was combined to neurostimulation for 69 patients (44%). Three women (prevalence=1.91%), aged 19, 24 and 65 years respectively, developed associated common superficial peroneal and sural nerve injury (2), axonal on electromyography, with motor (n=1) and/or sensory (n=3) residual dysfunction.DiscussionThe higher prevalence found in the present study than in the literature (0 to 0.5%) raises questions of methodological bias or technical problems. The common peroneal and sural nerves seem to be exposed, unlike the tibial. Several mechanisms can be suggested: anesthetic neurotoxicity, direct mechanical lesion, or tourniquet-related ischemia and conduction block. Further studies are necessary to determine the ideal anesthetic procedure.ConclusionPatients should be informed of the potential risk, however rare, even during mild surgery. The best possible technique should be implemented, with reinforced surveillance.Level of evidenceLevel IV retrospective study

    Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

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    Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB

    On three-dimensional misorientation spaces.

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    Determining the local orientation of crystals in engineering and geological materials has become routine with the advent of modern crystallographic mapping techniques. These techniques enable many thousands of orientation measurements to be made, directing attention towards how such orientation data are best studied. Here, we provide a guide to the visualization of misorientation data in three-dimensional vector spaces, reduced by crystal symmetry, to reveal crystallographic orientation relationships. Domains for all point group symmetries are presented and an analysis methodology is developed and applied to identify crystallographic relationships, indicated by clusters in the misorientation space, in examples from materials science and geology. This analysis aids the determination of active deformation mechanisms and evaluation of cluster centres and spread enables more accurate description of transformation processes supporting arguments regarding provenance

    Stereospecific Lasofoxifene Derivatives Reveal the Interplay between Estrogen Receptor Alpha Stability and Antagonistic Activity in <i>ESR1</i> Mutant Breast Cancer Cells

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    Chemical manipulation of estrogen receptor alpha ligand binding domain structural mobility tunes receptor lifetime and influences breast cancer therapeutic activities. Selective estrogen receptor modulators (SERMs) extend ERα cellular lifetime/accumulation. They are antagonists in the breast but agonists in the uterine epithelium and/or in bone. Selective estrogen receptor degraders/downregulators (SERDs) reduce ERα cellular lifetime/accumulation and are pure antagonists. Activating somatic ESR1 mutations Y537S and D538G enable resistance to first-line endocrine therapies. SERDs have shown significant activities in ESR1 mutant setting while few SERMs have been studied. To understand whether chemical manipulation of ERα cellular lifetime and accumulation influences antagonistic activity, we studied a series of methylpyrollidine lasofoxifene derivatives that maintained the drug’s antagonistic activities while uniquely tuning ERα cellular accumulation. These molecules were examined alongside a panel of antiestrogens in live cell assays of ERα cellular accumulation, lifetime, SUMOylation, and transcriptional antagonism. High-resolution x-ray crystal structures of WT and Y537S ERα ligand binding domain in complex with the methylated lasofoxifene derivatives or representative SERMs and SERDs show that molecules that favor a highly buried helix 12 antagonist conformation achieve the greatest transcriptional suppression activities in breast cancer cells harboring WT/Y537S ESR1. Together these results show that chemical reduction of ERα cellular lifetime is not necessarily the most crucial parameter for transcriptional antagonism in ESR1 mutated breast cancer cells. Importantly, our studies show how small chemical differences within a scaffold series can provide compounds with similar antagonistic activities, but with greatly different effects of the cellular lifetime of the ERα, which is crucial for achieving desired SERM or SERD profiles. SIGNIFICANCE This study shows that antiestrogens that enforce a wild-type-like estrogen receptor alpha antagonist conformation demonstrate improved therapeutic activities in hormone-resistant breast cancer cells harboring activating Y537S ESR1 mutant
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