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Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.
Get PDFBACKGROUND
Blood-brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood. One suggested candidate to impact BBB function is the transient receptor potential vanilloid-type 4 ion channel (TRPV4), but its specific role in MS pathogenesis remains unclear. Here, we investigated the role of TRPV4 in BBB dysfunction in MS.
MAIN TEXT
In human post-mortem MS brain tissue, we observed a region-specific increase in endothelial TRPV4 expression around mixed active/inactive lesions, which coincided with perivascular microglia enrichment in the same area. Using in vitro models, we identified that microglia-derived tumor necrosis factor-α (TNFα) induced brain endothelial TRPV4 expression. Also, we found that TRPV4 levels influenced brain endothelial barrier formation via expression of the brain endothelial tight junction molecule claudin-5. In contrast, during an inflammatory insult, TRPV4 promoted a pathological endothelial molecular signature, as evidenced by enhanced expression of inflammatory mediators and cell adhesion molecules. Moreover, TRPV4 activity mediated T cell extravasation across the brain endothelium.
CONCLUSION
Collectively, our findings suggest a novel role for endothelial TRPV4 in MS, in which enhanced expression contributes to MS pathogenesis by driving BBB dysfunction and immune cell migration
The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia.
No full textAutomated Discovery of Anomalous Features in Ultralarge Planetary Remote-Sensing Datasets Using Variational Autoencoders
Get PDFThe NASA Lunar Reconnaissance Orbiter (LRO) has returned petabytes of lunar high spatial resolution surface imagery over the past decade, impractical for humans to fully review manually. Here, we develop an automated method using a deep generative visual model that rapidly retrieves scientifically interesting examples of LRO surface imagery representing the first planetary image anomaly detector. We give quantitative experimental evidence that our method preferentially retrieves anomalous samples such as notable geological features and known human landing and spacecraft crash sites. Our method addresses a major capability gap in planetary science and presents a novel way to unlock insights hidden in ever-increasing remote-sensing data archives, with numerous applications to other science domains
Current progress in quantifying and monitoring instream large wood supply and transfer in rivers
No full textLarge wood drives both the form and function of gravel-bed rivers draining forested basins. Previously overlooked benefits of wood in rivers are now widely recognized. Together with flow and sediment regimes, the wood regime controls rivers' physical and ecological integrity. Yet large quantities of wood transported during floods can pose additional hazards, potentially damaging infrastructures like bridges or dams and exacerbating flooding. However, unlike the water and sediment regimes intensively studied over the past decades, the instream wood regime or budgeting has been only recently defined and thus is still rarely quantified. The instream wood budget describes the cascading processes from supply or recruitment, entrainment, and transport to deposition, storage and decay (i.e., fragmentation or decomposition). These processes show high spatial and temporal variability but can be characterized by magnitude, frequency, timing, duration and mode. Instream wood budgeting is challenging, primarily because of the lack of observations, monitoring stations, and standardized protocols to acquire data. This contribution reviews the most recent advances to quantify the different instream wood budget components, notably the wood supply, and transfer. Case studies showing applications of biogeochemistry, videography, artificial intelligence, numerical modelling or tracking illustrate the current progress. Because critical challenges remain, we identify and describe some of them and discuss how the wood in riverine sciences may develop in the future
THE VISION OF GOD IN LATE ANTIQUE AUTHORS. Review of Mirrors of the Divine: Late Ancient Christianity and the Vision of God, by E. R. Cain
No full textVon der Leitung zur Gesamtkoordination. Ein Gespräch mit Michelle Akanji und Juliane Hahn über das Theaterhaus Gessnerallee
No full textDer Beitrag fragt nach veränderten Leitungsverständnissen in Produktionshäusern der freien Szene in der Schweiz und fokussiert die Leitungsperiode von Michelle Akanji und Juliane Hahn am Theaterhaus Gessnerallee in Zürich
Distinguishing Oceans of Water from Magma on Mini-Neptune K2-18b
Get PDFMildly irradiated mini-Neptunes have densities potentially consistent with them hosting substantial liquid-water oceans ("Hycean" planets). The presence of CO2 and simultaneous absence of ammonia (NH3) in their atmospheres has been proposed as a fingerprint of such worlds. JWST observations of K2-18b, the archetypal Hycean, have found the presence of CO2 and the depletion of NH3 to 4 μm region, where CO2 and CO features dominate: magma ocean models suggest a systematically lower CO2/CO ratio than estimated from free-chemistry retrieval, indicating that deeper observations of this spectral region may be able to distinguish between oceans of liquid water and magma on mini-Neptunes
Palaeoenvironmental reconstruction of Loch Duart (NW Scotland, UK) since the Last Glacial Maximum: implications from a multiproxy approach
Get PDFA sediment core from the salt marsh fringing Loch Duart, NW Scotland, UK, containing Lateglacial to Holocene sediments, was analysed using a multi‐element geochemical approach to elucidate the relative sea level (RSL) and palaeoenvironmental changes associated with the deglaciation of the British and Irish Ice Sheet. Elemental and isotopic measurements of rhenium, osmium, carbon and nitrogen, X‐ray fluorescence scanning, radiocarbon dating, and foraminiferal analysis produced a suite of data that complements the existing biostratigraphic framework. This suite of bio‐, litho‐ and chemostratigraphic analyses permits discussion of RSL changes that reflect the interplay between post‐glacial eustatic rise and glacio‐isostatic adjustment. The osmium‐isotope (187Os/188Os) data, coupled with a new age–depth model, depict an RSL fall between 16.8 and 14.1 ka cal BP at an average rate of 2 mm a−1. Falling RSL culminates in basin isolation and is followed by subsequent marine inundation from 11.6 ka cal BP. This RSL record preserves the local interaction between glacial isostatic adjustment and glacio‐eustatic sea‐level change, a relationship that is reflected in the sediment's 187Os/188Os signature. This is the first known application of the osmium isotope system in an isolation basin that is shown to be a viable proxy for RSL change, a technique that could be applied to glacially influenced isolation basins globally
Extreme springs in Switzerland since 1763 in climate and phenological indices
Get PDFHistorical sources report manifold on hazardous past climate and weather events that had considerable impacts on society. Studying changes in the occurrence or mechanisms behind such events is, however, hampered by a lack of spatially and temporally complete weather data. In particular, the spring season has received less attention in comparison to summer and winter but is nevertheless relevant, since weather conditions in spring can delay vegetation and create substantial damage due to late-frost events. For Switzerland, we created a daily high-resolution (1 × 1 km2) reconstruction of temperature and precipitation fields from 1763 to 1960 that forms, together with present-day meteorological fields, a 258-year-long gridded data set. With this data set, we study changes in long-term climate and historical weather events based on climate and phenological indices focusing on the spring season.
Climate and phenological indices show few changes in the mean during the first 200 years compared to the most recent period from 1991 to 2020, where climate change signals clearly emerged in many indices. We evaluate the climate and phenological indices for three cases of extreme spring weather conditions: an unusually warm spring, two late-frost events, and three cold springs. Warm springs are much more frequent in the 21st century, but a very warm and early spring also occurred in 1862. Spring temperatures, however, do not agree on how anomalously warm the spring was when comparing the Swiss temperature reconstruction with reanalyses that extend back to 1868. The three springs of 1785, 1837, and 1853 were particularly cold, with historical sources reporting, for example, prolonged lake freezing and abundant snowfall. Whereas the springs of 1837 and 1853 were characterized by cold and wet conditions, in the spring of 1785 wet days were below average, and frost days reached an all-time maximum, in particular in the Swiss Plateau, indicating inversion conditions. Such conditions are in line with a high occurrence of northeasterly and high-pressure weather types and historical sources describing Bise conditions, a regional wind in the Alpine area related to inversions. Studying such historical events is valuable, since similar atmospheric conditions can lead to cold springs affecting vegetation growth and agricultural production
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