Microglia, the resident macrophages of the brain, are highly plastic and well known to be pre-activated or ‘primed’ by active inflammatory processes, resulting in amplified responses to a second ...inflammatory insult. Furthermore, the capacity of microglia to develop ‘innate immune memory’ (IIM), that is, long-lasting molecular reprogramming, has recently been demonstrated. Depending on the initial stimulus, IIM can either enhance or suppress microglial responses to a delayed, secondary insult. Moreover, both priming and IIM can affect pathological hallmarks of neurological disease in mouse models, which may be consistent with certain clinical observations in patients. Here, we discuss the remarkable capacity of microglia to process inflammatory signals over short and long timeframes and propose new integrated nomenclature for these processes. We also highlight future research avenues, with implications for human brain disease.
Microglia can adapt their phenotype depending on their history of inflammatory signal exposure, reflecting a status of immune memory. Such changes in microglial responses can significantly impact the progression of neurological disease in mouse models.
The concept of microglial ‘priming’ originally described a permissive state facilitating an exacerbated inflammatory response when an acute inflammatory insult is superimposed onto an ongoing inflammatory process.
Recently, ‘innate immune memory’ in microglia was demonstrated. Here, an initial stimulus alters the microglial response in a way that leads either to a stronger (immune training) or weaker (immune tolerance) reaction to a subsequent inflammatory insult, even after a long latent phase.
We propose an integrated nomenclature that describes ‘immune training’ as induced by ‘priming’ stimuli, and ‘immune tolerance’ as induced by ‘desensitising’ stimuli.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Soft, inflatable segments are the active elements responsible for the actuation of soft machines and robots. Although current designs of fluidic actuators achieve motion with large amplitudes, they ...require large amounts of supplied volume, limiting their speed and compactness. To circumvent these limitations, here we embrace instabilities and show that they can be exploited to amplify the response of the system. By combining experimental and numerical tools we design and construct fluidic actuators in which snap-through instabilities are harnessed to generate large motion, high forces, and fast actuation at constant volume. Our study opens avenues for the design of the next generation of soft actuators and robots in which small amounts of volume are sufficient to achieve significant ranges of motion.
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σ‐Hole Interactions in Catalysis Breugst, Martin; Koenig, Jonas J.
European journal of organic chemistry,
September 14, 2020, Volume:
2020, Issue:
34
Journal Article
Peer reviewed
Open access
Noncovalent interactions like halogen, chalcogen, and pnictogen bonding are known for a very long time. During the last decade, these interactions have found different applications in catalysis. ...These forces are often called σ‐hole interactions which can be explained by the anisotropic distribution of the electron density around these atoms. In this MiniReview, we will present recent applications of halogen, chalcogen, and pnictogen bonding in catalysis and discuss experimental and computational investigations to gain more insights into the underlying mechanisms.
This minireview summarizes the recent applications of halogen, chalcogen, and pnictogen bonding in organocatalysis. In all these cases, a Lewis‐acidic region around an element of group 15–17 (the so‐called σ‐hole) interacts with the electron pair of a suitable Lewis base. Besides a discussion of recent applications, this review focuses on mechanistic investigations and comparisons between the different σ‐hole interactions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Les modes cognitifs actuels du langage s’intéressent en priorité au traitement des informations dans des réseaux distribués avec certaines zones corticales se comportant comme des nœuds pour gérer ...des fonctions spécifiques, reliés via des structures sous-corticales.
Étudier la connectivité de la région temporale basale en fonction de ses articulations avec le langage.
Des stimulations électriques corticales (SEC) à haute fréquence, ayant l’avantage de produire des perturbations transitoires des fonctions cognitives, ont été utilisées chez des patients présentant une épilepsie pharmaco-résistante et explorés par des électrodes profondes dans le cadre du bilan préopératoire afin de délimiter la zone temporale basale du langage (BTLA). Toujours par des SEC mais à basse fréquence, des mesures de connectivité fonctionnelle et effective ont été réalisées par la technique des potentiels évoqués cortico-corticaux.
Les zones apparentant à la BTLA présentent statistiquement plus des connections notamment avec les structures temporales internes. Le gyrus fusiforme est, en parallèle, fortement impliqué dans des réseaux n’appartenant pas à la BTLA.
La mesure de la connectivité effective couplée à la stimulation corticale fonctionnelle dans l’étude du langage et notamment de la BTLA amène une nouvelle dimension dans la compréhension des articulations entre une zone fonctionnelle et ses connections au-delà de sa localisation anatomique. En plus, des patterns de connectivité spécifiques nous permettent d’avancer des hypothèses concernant les relations du langage avec d’autres processus cognitifs, notamment la mémoire.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transforming growth factor (TGF)-β cytokines signal via a complex network of pathways to regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. A high ...percentage of colorectal tumors contain mutations that disrupt TGF-β family member signaling. We review how TGF-β family member signaling is altered during development of colorectal cancer, models of study, interaction of pathways, and potential therapeutic strategies.
Les épilepsies focales structurelles pharmacorésistantes avec crises pariétales représentent seulement 5 % des séries chirurgicales et moins de 10 % dans notre série de patients explorés en SEEG à ...Nancy. Ce sont des épilepsies de diagnostic difficile du fait de leur rareté et d’une symptomatologie riche témoignant d’une implication extrapariétale. Le diagnostic localisateur des crises peut donc être retardé voire conduire à une localisation erronée de la zone épileptogène.
À partir des corrélations anatomo-électrocliniques en SEEG, déterminer les signes critiques associés à la décharge critique pariétale initiale et à la propagation pariétale et extrapariétale.
Étude de deux patients implantés en SEEG présentant une épilepsie pariétale pharmacorésistante. Analyse de l’activité paroxystique enregistrée et de la clinique lors de la crise enregistrée en simultanée en vidéo.
La première patiente présente une symptomatologie sensitive unilatérale associée à une décharge limitée au cortex post-central. Le second patient présente une activité motrice dystonique et hyperkinétique concomitante d’une décharge pariétale avec une propagation lente intrapariétale (26 s) puis secondairement une propagation extrapariétale asymétrique (frontal ipsilatéral), contrairement aux crises frontales qui se caractérisent par une propagation bilatérale rapide.
Ces deux observations permettent de mettre évidence un pattern électroclinique orientant vers le lobe pariétal aussi bien au niveau des signes que de la dynamique. Ces conclusions sont à confirmer sur une série de patient plus importante.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A biodegradable fertilizer made of blends of starch and chitosan is proposed.•A dripping technique involving ionotropic crosslinking is used.•Starch content and crosslinking time highly affect the ...macrobeads characteristics.
The present study examines the agrochemical application of macrospheres prepared with chitosan and chitosan-starch blends by an easy dripping technique, using a sodium tripolyphosphate aqueous solution as the crosslinking agent. These biopolymers form hydrogels that could be a viable alternative method to obtain controlled-release fertilizers (CRFs). Three different concentrations (ranging from 20 to 100wt/wt% of chitosan) and two crosslinking times (2 or 4h) were used. The resulting polymeric matrices were examined by scanning electron microscopy coupled with energy dispersive X-ray, X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, thermogravimetric analysis and differential scanning calorimetry. Ionotropic gelation and neutralization induced the formation of the macrospheres. The crosslinking time and the composition of the polymeric hydrogel controlled the crosslinking degree, the swelling behavior and the fertilizer loading capability. Potassium nitrate-loaded beads were shown to be useful as a controlled-release fertilizer. After 14days of continuous release into distilled water, the cumulative concentration in the release medium reached between 70 and 93% of the initially loaded salt, depending on the matrix used. The prepared beads showed properties that make them suitable for use in the agrochemical industry as CRFs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Molecular self-assembly with nucleic acids can be used to fabricate discrete objects with defined sizes and arbitrary shapes. It relies on building blocks that are commensurate to those of biological ...macromolecular machines and should therefore be capable of delivering the atomic-scale placement accuracy known today only from natural and designed proteins. However, research in the field has predominantly focused on producing increasingly large and complex, but more coarsely defined, objects and placing them in an orderly manner on solid substrates. So far, few objects afford a design accuracy better than 5 nm, and the subnanometre scale has been reached only within the unit cells of designed DNA crystals. Here, we report a molecular positioning device made from a hinged DNA origami object in which the angle between the two structural units can be controlled with adjuster helices. To test the positioning capabilities of the device, we used photophysical and crosslinking assays that report the coordinate of interest directly with atomic resolution. Using this combination of placement and analysis, we rationally adjusted the average distance between fluorescent molecules and reactive groups from 1.5 to 9 nm in 123 discrete displacement steps. The smallest displacement step possible was 0.04 nm, which is slightly less than the Bohr radius. The fluctuation amplitudes in the distance coordinate were also small (±0.5 nm), and within a factor of two to three of the amplitudes found in protein structures.
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Species distribution models (SDMs) have rapidly evolved into one of the most widely used tools to answer a broad range of ecological questions, from the effects of climate change to challenges for ...species management. Current SDMs and their predictions under anthropogenic climate change are, however, often based on free‐air or synoptic temperature conditions with a coarse resolution, and thus fail to capture apparent temperature (cf. microclimate) experienced by living organisms within their habitats. Yet microclimate operates as soon as a habitat can be characterized by a vertical component (e.g. forests, mountains, or cities) or by horizontal variation in surface cover. The mismatch between how we usually express climate (cf. coarse‐grained free‐air conditions) and the apparent microclimatic conditions that living organisms experience has only recently been acknowledged in SDMs, yet several studies have already made considerable progress in tackling this problem from different angles. In this review, we summarize the currently available methods to obtain meaningful microclimatic data for use in distribution modelling. We discuss the issue of extent and resolution, and propose an integrated framework using a selection of appropriately‐placed sensors in combination with both the detailed measurements of the habitat 3D structure, for example derived from digital elevation models or airborne laser scanning, and the long‐term records of free‐air conditions from weather stations. As such, we can obtain microclimatic data with a relevant spatiotemporal resolution and extent to dynamically model current and future species distributions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although consistently implicated, the exact role of interferon (IFN) signaling in Alzheimer’s disease remains largely unexplored. Roy et al. now demonstrate that type I IFNs may drive cognitive ...dysfunction through acting not only on microglia but, surprisingly, also on neurons.
Although consistently implicated, the exact role of interferon (IFN) signaling in Alzheimer’s disease remains largely unexplored. Roy et al. now demonstrate that type I IFNs may drive cognitive dysfunction through acting not only on microglia but, surprisingly, also on neurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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