Monitoring demyelination and remyelination by magnetization transfer imaging in the mouse brain at 9.4 T

OBJECTIVE: The aim of this study was to assess quantitatively structural changes in myelin content occurring during demyelination and remyelination by magnetization transfer imaging (MTI). MATERIALS AND METHODS: In a reversible model of demyelination with no axonal loss, mice intoxicated by cuprizone were studied by MTI in vivo at 9.4 T. MRI data were compared to histopathological examinations. RESULTS: Data revealed that the magnetization transfer ratio (MTR) decreased significantly during demyelination and increased during remyelination with strong correlation to the myelin content (r = 0.79, P = 0.01). CONCLUSIONS: This study demonstrated that MTR is a sensitive and reproducible quantitative marker to assess myelin loss and repair. This may lead to in vivo monitoring of therapeutic strategies promoting remyelination.     

Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses

Increasing the contrast between atheromatous plaque components is a major issue in cardiovascular MRI research. It would allow one to identify unstable plaque by differentiating the lipid core associated with vulnerability, from the fibrous cap, considered as a factor of stability. T₂ and diffusion-weighted imaging have already provided satisfying results. Magnetization transfer (MT) between restricted protons H_r and free-water protons H_f could achieve a different contrast related to collagen and lipoprotein macromolecules present in the fibrous cap and lipid core, respectively. The purpose of this work was to evaluate in vitro the MT effect produced by adapted T₂-selective 1-3-3-1 binomial pulses on isolated samples of atheromatous arteries at 3 T. A method based on simulation was used in order to improve the MT specificity: it is shown that 50% 1-3-3-1 pulses (the percentage indicating the level of H_r saturation) allow an estimation of T_2r, the H_r T₂. Using this technique, magnetization transfer was observed for the first time in atherosclerotic plaque components, an effect more pronounced for the fibrous cap and media than for the lipid core and advantitia. The T_2r estimation gave values ranging from 20 to 25 μs for the four samples. This preliminary study provides a basis for establishing an MT imaging sequence of atheromatous arteries, by using 50% 1-3-3-1 pulses calibrated for saturating protons with a 20 μs T₂. This MT protocol should be further compared to T₂ and diffusion-weighted imaging.     

Sex Bias in Differentiated Thyroid Cancer

Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient’s behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.     

Influence of the Recycling Process on the Fire‐Retardant Properties of PP/EPR Blends

The fire‐retardant properties of a recycled poly(propylene)‐based material were investigated and compared to the non‐recycled formulation. An intrinsic intumescent system and zinc borate were used to flame‐retard these polymers. By mass loss calorimetry, the best results were obtained with 20 wt.‐% of additives. Synergisms between AP765 and ZB were observed in the non‐recycled blends but not in the recycled ones. Solid‐state NMR showed that chemical reactions during the decomposition process were leading to the formation of borophosphates, reinforcing the efficiency of the intumescent char. From a ‘physical’ point of view, it was shown that the fire retardant properties of the materials are related to the formation speed of the intumescent structure and not on the char thickness.

     

Pyruvate Dehydrogenase Kinase Inhibition by Dichloroacetate in Melanoma Cells Unveils Metabolic Vulnerabilities

Melanoma is characterized by high glucose uptake, partially mediated through elevated pyruvate dehydrogenase kinase (PDK), making PDK a potential treatment target in melanoma. We aimed to reduce glucose uptake in melanoma cell lines through PDK inhibitors dichloroacetate (DCA) and AZD7545 and through PDK knockdown, to inhibit cell growth and potentially unveil metabolic co-vulnerabilities resulting from PDK inhibition. MeWo cells were most sensitive to DCA, while SK-MEL-2 was the least sensitive, with IC₅₀ values ranging from 13.3 to 27.0 mM. DCA strongly reduced PDH phosphorylation and increased the oxygen consumption rate:extracellular acidification rate (OCR:ECAR) ratio up to 6-fold. Knockdown of single PDK isoforms had similar effects on PDH phosphorylation and OCR:ECAR ratio as DCA but did not influence sensitivity to DCA. Growth inhibition by DCA was synergistic with the glutaminase inhibitor CB-839 (2- to 5-fold sensitization) and with diclofenac, known to inhibit monocarboxylate transporters (MCTs) (3- to 8-fold sensitization). CB-839 did not affect the OCR:ECAR response to DCA, whereas diclofenac strongly inhibited ECAR and further increased the OCR:ECAR ratio. We conclude that in melanoma cell lines, DCA reduces proliferation through reprogramming of cellular metabolism and synergizes with other metabolically targeted drugs.     

DspA/E-Triggered Non-Host Resistance against E. amylovora Depends on the Arabidopsis GLYCOLATE OXIDASE 2 Gene

DspA/E is a type three effector injected by the pathogenic bacterium Erwinia amylovora inside plant cells. In non-host Arabidopsis thaliana, DspA/E inhibits seed germination, root growth, de novo protein synthesis and triggers localized cell death. To better understand the mechanisms involved, we performed EMS mutagenesis on a transgenic line, 13-1-2, containing an inducible dspA/E gene. We identified three suppressor mutants, two of which belonged to the same complementation group. Both were resistant to the toxic effects of DspA/E. Metabolome analysis showed that the 13-1-2 line was depleted in metabolites of the TCA cycle and accumulated metabolites associated with cell death and defense. TCA cycle and cell-death associated metabolite levels were respectively increased and reduced in both suppressor mutants compared to the 13-1-2 line. Whole genome sequencing indicated that both suppressor mutants displayed missense mutations in conserved residues of Glycolate oxidase 2 (GOX2), a photorespiratory enzyme that we confirmed to be localized in the peroxisome. Leaf GOX activity increased in leaves infected with E. amylovora in a DspA/E-dependent manner. Moreover, the gox2-2 KO mutant was more sensitive to E. amylovora infection and displayed reduced JA-signaling. Our results point to a role for glycolate oxidase in type II non-host resistance and to the importance of central metabolic functions in controlling growth/defense balance.     

Thermal and fire degradation of recycled and polluted polypropylene‐based materials

In this study, the effect of processing cycles and two pollutants (engine oil (HM) and ethylene glycol (EG)) on the thermal and rheological properties of polypropylene‐based materials (108MF97 and 7510) has been studied. It was investigated if polymers coming from bumper face bar could keep their properties and can be reused after recycling. The different results demonstrate that the two polymers that were polluted and recycled do not show any decrease of their intrinsic properties. Moreover, for one of the two polymers (108MF97), the presence of engine oil enables to increase the thermal stability and reaction to fire. Finally, it appears that the reuse of such polymers is possible. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Adsorption of hydrogen gas and redox processes in clays

In order to assess the adsorption properties of hydrogen gas and reactivity of adsorbed hydrogen, we measured H(2)(g) adsorption on Na synthetic montmorillonite-type clays and Callovo-Oxfordian (COx) clayrock using gas chromatography. Synthetic montmorillonites with increasing structural Fe(III) substitution (0 wt %, 3.2 wt %, and 6.4 wt % Fe) were used. Fe in the synthetic montmorillonites is principally present as structural Fe(III) ions. We studied the concomitant reduction of structural Fe(III) in the clays using (57)Fe M?ssbauer spectrometry. The COx, which mainly contains smectite/illite and calcite minerals, is also studied together with the pure clay fraction of this clayrock. Experiments were performed with dry clay samples which were reacted with hydrogen gas at 90 and 120 °C for 30 to 45 days at a hydrogen partial pressure close to 0.45 bar. Results indicate that up to 0.11 wt % of hydrogen is adsorbed on the clays at 90 °C under 0.45 bar of relative pressure. (57)Fe M?ssbauer spectrometry shows that up to 6% of the total structural Fe(III) initially present in these synthetic clays is reduced upon adsorption of hydrogen gas. No reduction is observed with the COx sample in the present experimental conditions.     

First skin-physiological tests in weightlessness in the ISS space station

Citation: IFSCC Magazine , 11 (2008) (3) 231–238
A prolonged stay in weightlessness induces several medical alterations of the human body and also results in impairment of the skin. The stratum corneum, epidermal barrier as well as other skin compartments are affected in terms of their susceptibility to dryness, desquamation and pruritus. This can lead, for example, to wound healing disorders. Skin physiological tests were performed on the skin of an astronaut during the ASTROLAB-Mission within the Skin Care program initiated by the ESA. The skin was analyzed before, partly during and after the mission. In addition, the tests were repeated after 1 year. During the mission a control skin area was treated with a skincare product. The results showed corneal disturbance caused by environmental conditions, suboptimal skin cleansing and skin care. The observed effects were minimized by application of a skincare product. Measurements of the epidermis showed an accelerated rate of epidermal keratinization; skin elasticity was reduced distinctly and the sonographic examination showed a disaggregation of the cutis with hypoechoic areas. Additional measurements performed a year after the mission indicate that the verified alterations, which in a broader sense seem similar to skin ageing and appear as a time lapse process in weightlessness, are reversible. Further testing of the preventive efficacy of anti-ageing products from a cosmetic point of view would appear to be an appropriate objective for prospective long-term space missions.
Keywords:  Weightlessness, skin changes, hydration, TEWL, SELS (Visioscan^®), elasticity, US-B-scan