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Hydroxytyrosol decreases LPS- and α-synuclein-induced microglial activation in vitro
No full textNeuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson's disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-кB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder
Plateforme de tests et caractérisations de nano-sondes électromagnétiques résonantes pour le diagnostic dynamique en métrologie fine de processus de la matière molle
No full textLe besoin de développer la nano-instrumentation intégrée de détection, à bas coût à haute sensibilité sur des principes de résonances est un défi majeur et crucial pour les domaines industriels de la cosmétique, de l’agroalimentaire, de la pharmacologie galénique, de la biologie, et du biomédical ; la nécessité étant d’assurer les diagnostiques à réaliser en termes d’analyses, de contrôle qualité et de sécurité des substances, des aliments, des médicaments en solutions, des lotions actives, des crèmes, des mousses... L’ensemble de ces états de la matière en chimie et physique se nomme la matière molle et ses changements les transitions d’états, de phases ou de consistances… A titre d’exemple non exhaustif dans le domaine de la pharmacologie
galénique, certaines solutions fluides avec principes actifs incorporés en suspension seront actives tant que les éléments ne sédimentent pas ; caractéristique qui induirait une qualité moindre de la solution médicamenteuse ou bien une forme de péremption. Sur ce principe d’interaction matière-lumière résonante sur puce intégrée, des mesures fines sur la nouvelle plateforme et le suivi dynamique des dits produits et substances ont permis de
détecter des transitions de phases (gel/fluide/mixe émulsion/poudre solide), de mesurer des vitesses de sédimentation et même des phénomènes et mécanismes comme le séchage, la floculation, les effets Marangoni, ou encore les effets spontanées d’émulsion encore incompris [1-3]
Revisiting the Hallmarks of Aging to Identify Markers of Biological Age.
No full textThe Geroscience aims at a better understanding of the biological processes of aging, to prevent and/or delay the onset of chronic diseases and disability as well as to reduce the severity of these adverse clinical outcomes. Geroscience thus open up new perspectives of care to live a healthy aging, that is to say without dependency. To date, life expectancy in healthy aging is not increasing as fast as lifespan. The identification of biomarkers of aging is critical to predict adverse outcomes during aging, to implement interventions to reduce them, and to monitor the response to these interventions. In this narrative review, we gathered information about biomarkers of aging under the perspective of Geroscience. Based on the current literature, for each hallmark of biological aging, we proposed a putative biomarker of healthy aging, chosen for their association with mortality, age-related chronic diseases, frailty and/or functional loss. We also discussed how they could be validated as useful predictive biomarkers
Diversité génomique de porcs issus d’un croisement Large-White x Piétrain
No full textUn des bénéfices attendus du croisement entre lignées, pratique répandue dans la filière porcine, peut être l’accroissement de variabilité génétique, notamment dans un contexte de création de populations synthétiques. Cette augmentation de la variabilité, liée à l’état hétérozygote des individus, reste difficile à préciser lorsque seule l’information généalogique est disponible. Il est dorénavant possible de caractériser la variabilité génétique présente dans les populations porcines à une échelle génomique via l’analyse de données de génotypage. Une des approches possibles est la détection de régions homozygotes le long du génome, qui permet de quantifier la consanguinité génomique chez un individu. La quantification de ces régions homozygotes pouvant être réalisée à l’échelle du génome ou du chromosome, elle permet de caractériser à la fois la consanguinité génomique globale d’un individu ou une consanguinité locale en des zones plus ciblées du génome. Nous proposons dans cette étude d’utiliser l’information génomique afin d’estimer la consanguinité via la détection de régions homozygotes présentes dans les génomes de reproducteurs de races pures Large White et Piétrain et de leurs produits croisés. L’ensemble des individus a été génotypé sur la puce porcine IlluminaSNP60. Comme attendu, un nombre moins important de segments homozygotes est détecté chez les animaux croisés par rapport aux deux populations parentales. De plus, la longueur totale de ces segments est plus faible chez les animaux croisés. Même si ces observations peuvent être interprétées comme une diminution de la consanguinité, la conservation de segments homozygotes chez les descendants croisés signifie que certains haplotypes sont partagés entre les populations parentales.One of the expected benefits of crossbreeding, a common practice in the pig industry, may be the increase in genetic variability, especially in a context of creation of synthetic populations. This increase in variability, related to the heterozygous status of individuals, remains difficult to specify when only genealogical information is available. It is now possible to characterize genetic variability in pig populations at a genome scale by analyzing genotypic data. One possible approach is to detect homozygous regions along the genome to quantify genomic consanguinity in an individual. These homozygous regions can be quantified at the genome or chromosome scale. It is then possible to characterize both overall genomic consanguinity of an individual or a local one in specific areas of the genome. In this study, we used genomic information to estimate inbreeding by detecting homozygous regions in the genomes of purebred Large White dams and Pietrain sires and their crossbred offspring. All individuals were genotyped using the IlluminaSNP60 porcine chip. As expected, fewer homozygous segments were detected in crossbr ed animals than in their parental populations. In addition, the total length of these segments was lower in crossbr ed animals. These observations can be interpreted as a decrease in consanguinity; however, the conservation of homozygous segments in crossbred offspring means that some haplotypes were shared between parental populations
Milk Microbiota: What Are We Exactly Talking About?
No full textThe development of powerful sequencing techniques has allowed, albeit with some biases, the identification and inventory of complex microbial communities that inhabit different body sites or body fluids, some of which were previously considered sterile. Notably, milk is now considered to host a complex microbial community with great diversity. Milk microbiota is now well documented in various hosts. Based on the growing literature on this microbial community, we address here the question of what milk microbiota is. We summarize and compare the microbial composition of milk in humans and in ruminants and address the existence of a putative core milk microbiota. We discuss the factors that contribute to shape the milk microbiota or affect its composition, including host and environmental factors as well as methodological factors, such as the sampling and sequencing techniques, which likely introduce distortion in milk microbiota analysis. The roles that milk microbiota are likely to play in the mother and offspring physiology and health are presented together with recent data on the hypothesis of an enteromammary pathway. At last, this fascinating field raises a series of questions, which are listed and commented here and which open new research avenues
A multiscale approach to detect selection in nonmodel tree species: Widespread adaptation despite population decline in Taxus baccata L
No full textDetecting the molecular basis of local adaptation and identifying selective drivers is still challenging in nonmodel species. The use of purely population genetic approaches is limited by some characteristics of genetic systems, such as pleiotropy and polygenic control, and parallel evidence from phenotypic‐based experimental comparisons is required. In long‐lived organisms, the detection of selective pressures might also be precluded by evolutionary lag times in response to the environment. Here, we used the English yew to showcase an example of a multiscale integrative approach in a nonmodel species with limited plant and genomic resources. We combined information from two independent sources, phenotypes in a common environment and genomic data in natural populations, to investigate the signature of selection. Growth differences among populations in a common environment, and phenological patterns of both shoot elongation and male strobili maturation, were associated with climate clines, providing evidence for local adaptation and guiding us in the selection of populations for genomic analyses. We used information on over 25,000 SNPs from c. 1,200 genes to infer the demographic history and to test for molecular signatures of selection at different levels: SNP, gene, and biological pathway. Our results confirmed an overall demographic history of population decline, but we also found evidence for putative local adaptation at the molecular level. We identified or confirmed several candidate genes for positive and negative selection in forest trees, including the pseudo‐response regulator 7 (PRR7), an essential component of the circadian clock in plants. In addition, we successfully tested an approach to detect polygenic adaptation in biological pathways, allowing us to identify the flavonoid biosynthesis pathway as a candidate stress‐response pathway that deserves further attention in other plants. Finally, our study contributes to the emerging view that explaining contemporary standing genetic variation requires considering adaptation to past climates, especially for long‐lived trees
Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis
No full textIn Europe, badgers (Meles meles) are recognized as major tuberculosis (TB) reservoir hosts with the potential to transmit infection to associated cattle herds. Recent studies in Spain have demonstrated that vaccination with a heat-inactivated Mycobacterium bovis vaccine (HIMB) successfully protects captive wild boar and red deer against progressive disease. The aim of this study was to evaluate the efficacy of two oral vaccines against TB in a badger model: the live-attenuated M. bovis bacillus Calmette-Guérin BCG vaccine (Danish strain) and a HIMB vaccine. Twenty-four badgers were separated in three treatment groups: oral vaccinated with live BCG (108 CFU, n = 5), oral vaccinated with HIMB (107 CFU, n = 7), and unvaccinated controls (n = 12). All badgers were experimentally infected with M. bovis (103 CFU) by the endobronchial route targeting the right middle lung lobe. Throughout the study, clinical, immunological, pathological, and bacteriological parameters of infection were measured. Both vaccines conferred protection against experimental TB in badger, as measured by a reduction of the severity and lesion volumes. Based on these data, HIMB vaccination appears to be a promising TB oral vaccine candidate for badgers in endemic countries
Diafiltration of skimmed milk using polymeric spiral-wound microfiltration membrane: impact of solvent and diavolume ratio on the efficiency of protein separation
No full textMicrofiltration, MF is largely used in dairy industry to separate casein micelles from whey
proteins. The weak performances of polymeric membranes compared to ceramic membranes
are a restriction for their implementation in industry. Adding a diafiltration step is promising
to improve polymeric MF performances, however most of the works have focused on the
hydraulic performances and few have investigated the repercussion of diafiltration on protein
separation. This work aims at investigating the impact of both the nature of solvent and the
diavolume ratio on the MF efficiency.
Pilot-scale MF using polymeric membrane (Synder, 800 kDa) was carried out on thermized
skimmed milk at 12 °C with a volume reduction ratio, VRR from 2.5 to 3.2 and a
transmembrane pressure of 0.7 bar. Continuous diafiltration was performed using reverse
osmosis water (ROW) or milk ultrafiltrate (PUF). Permeation flux and β-lactoglobulin
transmission were evaluated.
During PUF-diafiltration of VRR-2.8-retentate, permeation flux is stable and β-
lactoglobulin transmission declines by 26 % after 4.8 diavolumes. During ROW-diafiltration,
permeation flux increases linearly until 2.9 diavolumes, then reaching an upper value.
Simultaneously β-lactoglobulin transmission follows a parabolic curve with a maximum
increase of 68 % for VRR-3.2-retentate and 10 % for VRR-2.5-retentate. According to Darcy’s
law, the reduction of permeate viscosity during ROW-diafiltration leads to the improvement of
permeation flux. This behavor is accentuated by the fouling layer relaxation consequent to the
diminution of the ionic strength. In case of high repulsive forces in the concentration layer (low
ionic strength), the transmission of negatively charged whey proteins is however restricted.
The decrease of protein concentration during diafiltration may also limit whey protein
transmission for high diavolume ratios.
Diafiltration using ROW is recommended to increase transmission of whey proteins.
However, volume of solvent has to be adapted to the VRR reached prior diafiltration to enable
an optimum transmissio
Combining optical and radar satellite image time series to map natural vegetation: savannas as an example
No full textUp-to-date land cover maps are important for biodiversity monitoring as they are central to habitat and ecosystem distribution assessments. Satellite remote sensing is a key technology for generating these maps. Until recently, land cover mapping has been limited to static approaches, which have primarily led to the production of either global maps at coarse spatial resolutions or geographically restricted maps at high spatial resolutions. The recent availability of optical (Sentinel-2) and radar (Sentinel-1) satellite image time series (SITS) which provide access to high spatial and very high temporal resolutions, is a game changer, offering opportunities to map land cover using both temporal and spatial information. These data moreover open interesting perspectives for land cover mapping based on data combination approach. However, the usefulness of combining dense time series (more than 30 images per year) and data combination approaches to map natural vegetation has so far not been assessed. To address this gap, this contribution tests the idea that the combined consideration of optical and radar data combination and time series analyses can significantly improve natural vegetation mapping in the Pendjari National Park, a Sahelian savanna protected area in Benin. Results highlight that the combination of Sentinel-1 and Sentinel-2 SITS performs as well as Sentinel-2 SITS alone in terms of classification accuracy. Land cover maps are however qualitatively better when considering the data combination approach. Our results also clearly show that the use of dense/hypertemporal optical time series significantly improves classification outcomes compared to using multitemporal only a few images per year) or monotemporal data. Altogether, this work thus demonstrates the ability of dense SITS to improve discrimination of natural vegetation types using information on their phenology, leading to more detailed and more reliable maps for environmental management
Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1
No full textImmune checkpoint inhibitors (ICIs) have dramatically modified the prognosis of several advanced cancers, however many patients still do not respond to treatment. Optimal results might be obtained by targeting cancer cell metabolism to modulate the immunosuppressive tumor microenvironment. Here, we identify sphingosine kinase-1 (SK1) as a key regulator of anti-tumor immunity. Increased expression of SK1 in tumor cells is significantly associated with shorter survival in metastatic melanoma patients treated with anti-PD-1. Targeting SK1
markedly enhances the responses to ICI in murine models of melanoma, breast and colon cancer. Mechanistically, SK1 silencing decreases the expression of various immunosuppressive factors in the tumor microenvironment to limit regulatory T cell (Treg) infiltration. Accordingly, a SK1-dependent immunosuppressive signature is also observed in human melanoma biopsies. Altogether, this study identifies SK1 as a checkpoint lipid kinase that
could be targeted to enhance immunotherapy