A putative Type III Polyketide synthase (PKSIII) encoding gene was identified from a marine yeast,
strain Mo29 (UBOCC-A-208024) (formerly named as
sp.) isolated from deep-sea hydrothermal vents. This ...gene is part of a distinct phylogenetic branch compared to all known terrestrial fungal sequences. This new gene encodes a C-terminus extension of 74 amino acids compared to other known PKSIII proteins like
. Full-length and reduced versions of this PKSIII were successfully cloned and overexpressed in a bacterial host,
BL21 (DE3). Both proteins showed the same activity, suggesting that additional amino acid residues at the C-terminus are probably not required for biochemical functions. We demonstrated by LC-ESI-MS/MS that these two recombinant PKSIII proteins could only produce tri- and tetraketide pyrones and alkylresorcinols using only long fatty acid chain from C8 to C16 acyl-CoAs as starter units, in presence of malonyl-CoA. In addition, we showed that some of these molecules exhibit cytotoxic activities against several cancer cell lines.
In support of the InSight mission in which two instruments (the SEIS seismometer and the
HP
3
heat flow probe) will interact directly with the regolith on the surface of Mars, a series of mechanical ...tests were conducted on three different regolith simulants to better understand the observations of the physical and mechanical parameters that will be derived from InSight. The mechanical data obtained were also compared to data on terrestrial sands. The density of the regolith strongly influences its mechanical properties, as determined from the data on terrestrial sands. The elastoplastic compression volume changes were investigated through oedometer tests that also provided estimates of possible changes in density with depth. The results of direct shear tests provided values of friction angles that were compared with that of a terrestrial sand, and an extrapolation to lower density provided a friction angle compatible with that estimated from previous observations on the surface of Mars. The importance of the contracting/dilating shear volume changes of sands on the dynamic penetration of the mole was determined, with penetration facilitated by the
∼
1.3
Mg/m
3
density estimated at the landing site. Seismic velocities, measured by means of piezoelectric bender elements in triaxial specimens submitted to various isotropic confining stresses, show the importance of the confining stress, with lesser influence of density changes under compression. A power law relation of velocity as a function of confining stress with an exponent of 0.3 was identified from the tests, allowing an estimate of the surface seismic velocity of 150 m/s. The effect on the seismic velocity of a 10% proportion of rock in the regolith was also studied. These data will be compared with in situ data measured by InSight after landing.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
À partir d’octobre 2017, #MeToo devient un phénomène mondial, en diffusant internationalement le slogan que Tarana Burke, militante new-yorkaise contre les violences sexuelles, avait lancé dix ans ...plus tôt. Une multitude de victimes témoignent sur divers supports numériques et médiatiques, reformulant et intensifiant des luttes féministes en cours contre les violences sexistes. À l’initiative d’une nouvelle génération de chercheuses et chercheurs francophones sur les violences de genre, ce premier ouvrage académique en France sur #MeToo cherche à comprendre l’événement. Il propose une approche empirique de ce mouvement mondial. Il décrypte d’abord l’événement #MeToo dans sa matérialité, ses contextes de réception et d’appropriation et s’efforce de montrer comment l’usage des réseaux socionumériques permet d’articuler de nouvelles formes de militantisme ou de renforcer des pratiques militantes existantes en ligne et hors ligne. Il inscrit ensuite #MeToo dans une histoire des luttes féministes de plus long terme et s’efforce de questionner son unité à travers l’étude de ses résonances contrastées dans différents milieux professionnels.
Gardner's (1956, https://doi.org/10.2136/sssaj1956.03615995002000030006x) transient method of measuring the hydraulic conductivity function of unsaturated media has been largely used, together with ...the improved graphical method proposed by Kunze and Kirkham (1962, https://doi.org/10.2136/sssaj1962.03615995002600050006x) to account for the impedance effect resulting from using a low hydraulic conductivity ceramic disk in porous plate testing. These methods are nowadays seldom used, since they have been replaced by numerical back analysis and methods for parameter optimization. Based on tests carried out on a specific device allowing to determine the water retention and transport properties of water in a coarse granular media at low suctions (up to 50 kPa), it was found necessary to account (i) for impedance effects and (ii) for the effects of nonconstant suction increments, as is often the case when using the hanging column technique. A new method is proposed to account for impedance effects, based on an analytical solution of the equations governing water transfer. The validity of this method is tested by considering experimental data from three distinct materials: a coarse green roof volcanic substrate, poorly graded sand, and undisturbed silty clay. Compared to the graphical method Kunze and Kirkham's method, it is less operator‐dependent and hence more objective. It is also simpler than numerical back analysis methods, since it does not require any use of numerical code or parameter optimization algorithm, providing a more direct and reliable access to the hydraulic conductivity. An analytical solution is also proposed to solve the problem resulting from the application of a nonconstant suction increment.
Key Points
Gardner developed the first analytical method for determining the hydraulic conductivity function based on transient outflow data
Kunze and Kirkham developed a graphical method to account for impedance effects, that is nowadays replaced by numerical back analysis
The new proposed analytical method appears to be more reliable than Kunze and Kirkahm's method and simpler than numerical back analysis
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Symptom occurrence at the first ingestion suggests that food allergy may result from earlier sensitization via non-oral routes. We aimed to characterize the cellular populations recruited at various ...mucosal and immune sites after experimental sensitization though different routes. BALB/cJ mice were exposed to a major allergenic food (peanut) mixed with cholera toxin via the intra-gastric (i.g.), respiratory, cutaneous, or intra-peritoneal (i.p.) route. We assessed sensitization and elicitation of the allergic reaction and frequencies of T cells, innate lymphoid cells (ILC), and inflammatory and dendritic cells (DC) in broncho-alveolar lavages (BAL), lungs, skin, intestine, and various lymph nodes. All cellular data were analyzed through non-supervised and supervised uni/multivariate analysis. All exposure routes, except cutaneous, induced sensitization, but intestinal allergy was induced only in i.g.- and i.p.-exposed mice. Multivariate analysis of all cellular constituents did not discriminate i.g. from control mice. Conversely, respiratory-sensitized mice constituted a distinct cluster, characterized by high local inflammation and immune cells recruitment. Those mice also evidenced changes in ILC frequencies at distant site (intestine). Despite absence of sensitization, cutaneous-exposed mice evidenced comparable changes, albeit less intense. Our study highlights that the initial route of sensitization to a food allergen influences the nature of the immune responses at various mucosal sites. Interconnections of mucosal immune systems may participate in the complexity of clinical manifestations as well as in the atopic march.
► The swelling behavior was found to be hydration path and hydration process dependent. ► The new constant-volume cell gives good results of swelling pressure. ► Wetting under volume-constrained ...condition decreased the size of the dominant inter-aggregate pores.
This paper presents an experimental study on the swelling pressure of heavily compacted crushed Callovo-Oxfordian (COx) claystone at a dry unit mass
ρ
d
=
2.0
Mg/m
3 using four different methods: constant-volume, swell-reload, zero-swell and adjusted constant-volume method. Results show that the swelling pressure varies in the range of 1–5
MPa and depends significantly on the test method. From the constant-volume tests, it is observed that the swelling behavior during wetting is a function of the suction and depends on both the hydration paths and wetting conditions (e.g. vapor-wetting or liquid-wetting). The swelling pressure decreases significantly with saturation time. To identify the microstructure changes of specimens before and after wetting, mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) tests were performed. It is observed that, after wetting, the large inter-aggregate pores observed in the as-compacted specimen are no longer apparent; the whole pattern is characterized by a general swell of hydrated clay particles, rendering the soil more homogenous. Results from MIP indicated that wetting caused a significant reduction of the entrance diameter of the dominant inter-aggregate pores from 2.1 to 0.5
μm whereas intra-aggregate pores were not significantly influenced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high ...fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with 1,1,1-
C
-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457.
Based on tests carried out on a specific device allowing to determine the water retention and transport properties of granular media at low suctions, an alternative approach to Kunze and Kirkham’s ...method of accounting for the impedance effects due to the high air entry value ceramic disk when using Gardner’s method is proposed. Impedance effects are accounted for by proposing analytical solutions to the equations governing water transfers occurring within the specimen and the ceramic disk. By using some experimental data obtained on a volcanic granular substrate used for urban green roofs, the method is successfully compared to Kunze and Kikham’s graphical method. Its advantages are to be simpler of use and not operator dependent. A detailed examination of the performance of our method compared to those of Gardner and Kunze and Kirkham is carried out based on experimental data, that confirm its validity.
To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liées à ...l'Age (POLA) Study.
Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125 microm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort.
After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR=0.07; 95% CI: 0.01-0.58; P for trend=0.005), nuclear cataract (OR=0.23; 95% CI: 0.08-0.68; P for trend=0.003) and any cataract (OR=0.53; 95% CI: 0.31-0.89; P for trend=0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR=0.21; 95% CI: 0.05-0.79; P for trend=0.01), and tended to be associated with plasma lutein (OR=0.31; 95% CI: 0.09-1.07; P for trend=0.04), whereas cataract showed no such associations. Among other carotenoids, only beta-carotene showed a significant negative association with nuclear cataract, but not ARM.
These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.
Diffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance ...of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines.
We analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting. To investigate the biological role of BDNF/TrkB/p75(NTR) axis, effects of neurotrophin signalling inhibition were determined on tumour cell survival and vascular endothelial growth factor (VEGF) secretion. The pharmacological pan-Trk inhibitor K252a was used for in vitro and in vivo studies.
A BDNF/TrkB axis was expressed in all biopsies, which was independent of the germinal centre B-cell (GCB)/non-GCB profile. p75(NTR), TrkB, and BDNF tumour scores were significantly correlated and high NGF expression was significantly associated with MUM1/IRF4, and the non-GCB subtype. Diffuse large B-cell lymphoma cell lines co-expressed neurotrophins and their receptors. The full-length TrkB receptor was found in all cell lines, which was also phosphorylated at Tyr-817. p75(NTR) was associated to Trk and not to its cell death co-receptor sortilin. In vitro, inhibition of neurotrophin signalling induced cell apoptosis. K252a caused cell apoptosis, decreased VEGF secretion, and potentiated rituximab effect, notably in less rituximab-sensitive cells. In vivo, K252a significantly reduced tumour growth and potentiated the effects of rituximab in a GCB-DLBCL xenograft model.
This work argues for a pro-survival role of endogenous neurotrophins in DLBCLs and inhibition of Trk signalling might be a potential treatment strategy for rituximab resistant subgroups.
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