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Potent and specific inhibitors of hyaluronidases, a group of enzymes preferentially catalysing the hydrolysis of hyaluronic acid, are not known so far. Such compounds could be useful as pharmacological tools for studying the physiological and pathophysiological role of both hyaluronan and hyaluronidases. The effects of sulphated and non-sulphated structurally different oligosaccharides on bovine testicular hyaluronidase, hyaluronidase from bee venom and hyaluronate lyase from Streptococcus agalactiae (hylB (4755)) were studied with the Morgan-Elson reaction. Several active compounds were identified within a series of sulphated beta-(1,4)-galacto-oligosaccharides. The determined IC (50) values of these sulphated oligosaccharides ranged from 4 microM to 630 microM for all hyaluronan-degrading enzymes. Sulphated oligosaccharides like verbascose, planteose and neomycin showed comparable inhibition on all hyaluronidases, thereby possessing 100 - 500 times the activity of the widely accepted hyaluronidase inhibitor apigenin.

The antiinflammatory effects of ethanol and aqueous extracts from Drosera rotundifolia and from Drosera madagascariensis were compared in vivo in the HET-CAM assay. Both extracts from D. rotundifolia and the ethanol extract from D. madagascariensis showed remarkable efficacy at doses of 500 microg/pellet. The inhibition of the inflammation by the extracts was stronger than that by 50 microg hydrocortisone/pellet. In contrast, there was only a very weak effect observed at a dose of 500 microg/pellet of the water extract from D. madagascariensis. The chemical analyses of the extracts showed that the effect cannot be attributed to naphthoquinones, but might be due to flavonoids. Ellagic acid obviously plays an important role in the antiangiogenic effect of the Drosera extracts.

Sulfated beta-(1-->4)-galacto-oligosaccharides were prepared from an arabino-galacto-rhamno-galacturonan from Lupinus polyphyllus Lindl. by successive partial hydrolysis and SO3-pyridine sulfation in DMF. The resulting oligosaccharide polysulfates were analyzed by analytical GPC and the sulfate content was determined by ion chromatography. DP 5 and higher showed a pronounced antiangiogenic effect with scores of 0.9-1.2 for DP 7-9 using the CAM-assay. An interaction with the fibroblast growth factor FGF-2 was noticed for DP 4-12 depending on the degree of sulfation using the FGF-2-trypsin assay.

A linear 1,4-β-d-galactan has been prepared by partial acid hydrolysis of the major lupin seed polysaccharide on a preparative scale. The galactan has been characterized by acetylation and methylation analysis, by GPC, as well as by its 1H- and 13C-NMR-spectra. Sulfation with increasing amounts of SO3-pyridine yielded a series of galactan sulfates with increasing DS. In all derivatives, the sulfate groups had a similar pattern of distribution, as shown by methylation analysis. Beside unsulfated parts of the molecule, there were also parts with a multiple substitution pattern.

A sulfated emodin glucoside, emodin 8-O-beta-D-glucopyranosyl-6-O-sulfate (1), was isolated from the roots of Rheum emodi in an investigation of the active constituents of this Nepalese medicinal plant, and its structure was determined by spectroscopic and chemical methods. Additionally, two rare auronols, carpusin (2) and maesopsin (3), besides other anthraquinones and phenolics, were isolated and identified. Compounds 2 and 3 showed significant antioxidant activity in the DPPH assay, while chrysophanol, physcion, and emodin and their 8-O-glucosides were found to be inactive.

Suspensions in cylinder machine essentially adapted for providing more uniform webs are formed by adding 0.10 to 1.88 weight percent of a water soluble acrylamide polymer having, molecular in excess of 3, 000, 000 and a percent hydrolysis not in excess of 30 percent to an aqueous suspension containing cellulose fiber.

Application of [ (14)C]-progesterone to the leaves of NERIUM OLEANDER L. (Apocynaceae) resulted in the formation of [ (14)C]-digitoxigenin and [ (14)C]-oleandrigenin glycosides; the labelled aglycones were obtained after hydrolysis from the cardenolide extract. Both radioactive cardenolide aglycones were further transformed by the leaves of NERIUM OLEANDER L. to the corresponding 3- O-beta-glucosides digitoxigenin glucoside and oleandrigenin glucoside. It could be shown that both cardenolide glucosides are genuine constituents of the cardenolide fraction of NERIUM OLEANDER L. leaves. The structures of these newly identified compounds were verified by (1)H-NMR and FAB (+) mass spectroscopy and by enzymatic cleavage of the glycosidic bond with a beta-glucosidase from HELIX POMATIA.

In this work, a multi-scale model established from the concept of periodic homogenization is utilized to predict the cyclic and time-dependent response of thermoplastic-based woven composites. The macroscopic behaviour of the composite is determined from finite element simulations of the representative unit cell of the periodic microstructure, where the local non-linear constitutive laws of the components are directly integrated, namely, the matrix and the yarns. The thermoplastic matrix is described by a phenomenological multi-mechanisms constitutive model accounting for viscoelasticity, viscoplasticity and ductile damage. For the yarns, a hybrid micromechanical–phenomenological constitutive model accounting for anisotropic damage and anelasticity induced by the presence of a diffuse micro-crack network is utilized. The capabilities of the overall multi-scale model are validated by comparing the numerical predictions with experimental data. Further illustrative examples are also provided, where the composite undergoes time-dependent deformations under uni-axial and non-proportional multi-axial loading paths. The multi-scale model is also employed to analyze the influence of the local deformation processes on the macroscopic response of the composite. This paper is part of the COPERSIM project managed by IRT Jules Verne (French Institute in Research and Technology in Advanced Manufacturing Technologies for Composite, Metallic and Hybrid Structures). The authors wish to associate the industrial and academic partners of this project, respectively, Arts et Metiers Institute of Technology, Solvay, Plastic Omnium, PSA and Renault.

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks. Copyright © 2020 The Author(s) on behalf of the American Society for Nutrition.

Forest production efficiency (FPE) metric describes how efficiently the assimilated carbon is partitioned into plants organs (biomass production, BP) or—more generally—for the production of organic matter (net primary production, NPP). We present a global analysis of the relationship of FPE to stand-age and climate, based on a large compilation of data on gross primary production and either BP or NPP. FPE is important for both forest production and atmospheric carbon dioxide uptake. We find that FPE increases with absolute latitude, precipitation and (all else equal) with temperature. Earlier findings—FPE declining with age—are also supported by this analysis. However, the temperature effect is opposite to what would be expected based on the short-term physiological response of respiration rates to temperature, implying a top-down regulation of carbon loss, perhaps reflecting the higher carbon costs of nutrient acquisition in colder climates. Current ecosystem models do not reproduce this phenomenon. They consistently predict lower FPE in warmer climates, and are therefore likely to overestimate carbon losses in a warming climate., Many models assume a universal carbon use efficiency across forest biomes, in contrast to assumptions of other process-based models. Here the authors analyse forest production efficiency across a wide range of climates to show a positive relationship with annual temperature and precipitation, indicating that ecosystem models are overestimating forest carbon losses under warming.

International audience; Pentameric ligand-gated ion channels (pLGICs) constitute a widespread class of ion channels, present in archaea, bacteria, and eukaryotes. Upon binding of their agonists in the extracellular domain, the transmembrane pore opens, allowing ions to go through, via a gating mechanism that can be modulated by a number of drugs. Even though high-resolution structural information on pLGICs has increased in a spectacular way in recent years, both in bacterial and in eukaryotic systems, the structure of the open channel conformation of some intensively studied receptors whose structures are known in a nonactive (closed) form, such as Erwinia chrysanthemi pLGIC (ELIC), is still lacking. Here we describe a gammaproteobacterial pLGIC from an endo-symbiont of Tevnia jerichonana (sTeLIC), whose sequence is closely related to the pLGIC from ELIC with 28% identity. We provide an X-ray crystallographic structure at 2.3 Å in an active conformation, where the pore is found to be more open than any current conformation found for pLGICs. In addition, two charged restriction rings are present in the vestibule. Functional characterization shows sTeLIC to be a cationic channel activated at alkaline pH. It is inhibited by divalent cations, but not by quaternary ammonium ions, such as tetramethylammonium. Additionally, we found that sTeLIC is allosterically potentiated by aromatic amino acids Phe and Trp, as well as their derivatives, such as 4-bromo-cinnamate, whose cocrystal structure reveals a vestibular binding site equivalent to, but more deeply buried than, the one already described for benzodiazepines in ELIC.

International audience; Peroxide sensing is essential for bacterial survival during aerobic metabolism and host infection. Peroxide stress regulators (PerRs) are homodimeric transcriptional repressors with each monomer typically containing both structural and regulatory metal-binding sites. PerR binding to gene promoters is controlled by the presence of iron in the regulatory site, and iron-catalyzed oxidation of PerR by H2O2 leads to the dissociation of PerR from DNA. In addition to a regulatory metal, most PerRs require a structural metal for proper dimeric assembly. We present here a structural and functional characterization of the PerR from the pathogenic spirochete Leptospira interrogans, a rare example of PerR lacking a structural metal-binding site. In vivo studies showed that the leptospiral PerR belongs to the peroxide stimulon in pathogenic species and is involved in controlling resistance to peroxide. Moreover, a perR mutant had decreased fitness in other host-related stress conditions, including at 37 °C or in the presence of superoxide anion. In vitro, leptospiral PerR could bind to the perR promoter region in a metal-dependent manner. The crystal structure of the leptospiral PerR revealed an asymmetric homodimer, with one monomer displaying complete regulatory metal coordination in the characteristic caliper-like DNA-binding conformation and the second monomer exhibiting disrupted regulatory metal coordination in an open non-DNA-binding conformation. This structure showed that leptospiral PerR assembles into a dimer in which a metal-induced conformational switch can occur independently in the two monomers. Our study demonstrates that structural metal binding is not compulsory for PerR dimeric assembly and for regulating peroxide stress.

A complèter : pagination et WOS; International audience; Large wood (LW, or pieces of dead wood longer than 1 m and thicker than 10 cm in diameter) is a key element in forested streams, but its abundance has decreased worldwide as a result of snagging and clearing of riparian forests. Therefore, many restoration projects introduce LW into stream channels to enhance geomorphology, biotic communities, and ecosystem functioning. Because LW enhances the retention of organic matter and sediments, its restoration can reduce siltation in receiving reservoirs, although so far little information on this subject is available. We studied the effects of restoring the natural loading of LW in four streams in the Aiako Harria Natural Park (the Basque Country, Spain) in pool abundance, channel form, and storage of organic matter and sediments. In all reaches log jams induced the formation of new geomorphic features and changes in physical habitat, especially an increase in the number and size of pools and in the formation of gravel bars and organic deposits. The storage of organic matter increased 5- to 88-fold and streambed level rose 7 ± 4 to 21 ± 4 cm on average, resulting in the storage of 35.2 ± 19.7 to 711 ± 375 m3 (733–1400 m3 ha− 1 y− 1) of sediment per reach. Extrapolation of these results to the entire drainage basin suggests that basinwide restoration of LW loading would enhance the retention potential of stream channels by 66,817 ± 27,804 m3 (1075 m3 ha− 1 y− 1) of sediment and by 361 t (5.32 T ha− 1 y− 1) of organic matter, which represents 60% of the estimated annual inputs of sediments to the downstream Añarbe Reservoir and almost twice as much as the annual input of organic matter to the entire river network. Therefore, basinwide restoration of LW loading is a potentially important tool to manage catchments that feed reservoirs, where retention of sediments and organic matter can be considered important ecosystem services as they reduce reservoir siltation.

International audience; Adding catalyst could improve the yields and qualities of bio-gas and bio-oil, and realize the oriented production. Results showed that the catalytic gas-production capacities of CaO were higher than those of Fe2O3, and the bio-gas yield at 800°C reached a maximum of 35.1%. Because the polar cracking active sites of CaO reduced the activation energy of the pyrolysis reaction and resulted in high catalytic cracking efficiencies. In addition, the quality of bio-oil produced by CaO was superior to that by Fe2O3, although the bio-oil yield of CaO was relatively weak. The light bio-fuel oriented catalytic pyrolysis could be realized when adding different catalysts. At 800°C, CaO was 45% higher than Fe2O3 in aspect of H2 production while Fe2O3 was 103% higher than CaO in aspect of CH4 production. Therefore, CaO was more suitable for H2 production and Fe2O3 was more suitable for CH4 production.

International audience; Among various chronic disorders, cancer and diabetes mellitus are the most common disorders. This study was designed to evaluate the effectiveness of hydroalcoholic extract of Phoenix dactylifera L. leaves (HEPdL) in animal models of type II diabetes in vitro/in vivo and in a human melanoma-derived cell line (IGR-39). A liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis was also performed to determine the amount of phenolic and flavonoid compounds in this plant. The physicochemical results by LC–MS/MS analysis of HEPdL showed the presence of 10 phenolic compounds. The in vitro study showed that the extract exhibited a more specific and potent inhibitor of α-glucosidase than α-amylase with an IC50 value of 20 ± 1 μg/mL and 30 ± 0.8 μg/mL, respectively. More importantly, the in vivo study of the postprandial hyperglycemia activity with (20 mg/kg) of HEPdL showed a decrease in plasma glucose levels after 60 min in resemblance to the glucor (acarbose) (50 mg/kg) effect. The oral administration of HEPdL (20 mg/kg) in alloxan-induced diabetic mices for 28 days showed a more significant anti-diabetic activity than that of the drug (50 mg/kg). Moreover, cytotoxicity effects of HEPdL in IGR-39 cancer cell lines were tested by MTT assay. This extract was effective in inhibiting cancer cells growth (IGR-39) at dose 35 and 75 μg/mL. These results confirm ethnopharmacological significance of the plant and could be taken further for the development of an effective pharmaceutical drug against diabetes and cancer

International audience; In recent years there has been enormous interest in researching oxidative stress. Reactive oxygen species (ROS) are derived from the metabolism of oxygen as by-products of cell respiration, and are continuously produced in all aerobic organisms. Oxidative stress occurs as a consequence of an imbalance between ROS production and the available antioxidant defence against them. Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer’s and autoimmune diseases are mediated by oxidative stress. Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress. This manuscript describes the main mitochondrial sources of ROS and the antioxidant defences involved to prevent oxidative damage in all the mitochondrial compartments. It also deals with discussions concerning the cytotoxic effect of heat stress, mitochondrial heat-induced alterations, as well as heat shock protein (HSP) expression as a defence mechanism.

International audience; The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. Anew therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-α) activator, fenofibrate, protects against cerebral injury by anti-oxidant and antiinflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-α-deficient mice, suggesting that PPAR-α activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-α could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-α activators could preventively decrease the severity of stroke in humans.

International audience; We have investigated the effect of the insertion of a triblock peptide (hydrophobic−hydrophilic−hydrophobic) in a nonionic lamellar phase composed of C12E4, decane, and water, stabilized by bilayer thermal fluctuations. Circular dichroism shows the peptide to be unordered in water, whereas its hydrophilic part is rigid and organized in an α-helix in the presence of surfactant bilayers. Surface tension measurements prove that the peptide is located at the hydrophobic−hydrophilic interface. Together with spectrofluorometry, these experiments suggest that the peptide lies on the bilayer surface. The Caillé parameter, η, of the lamellar phase, obtained by SAXS experiments, decreases with peptide concentration. This decrease has been interpreted as an increase of the bilayer effective thickness induced by the peptide and is well fitted by a recent model. The bilayer bending rigidity κ increases linearly with peptide concentration, up to two times the rigidity of a bare bilayer with mole ratio of peptide to surfactant as low as 5.2 × 10-4. The smectic compressibility modulus, B̄, decreases, implying that the peptide presence softens interactions between bilayers.