On a daily basis, people are exposed to a multitude of health‐hazardous airborne particulate matter with notable deposition in the fragile alveolar region of the lungs. Hence, there is a great need ...for identification and prediction of material‐associated diseases, currently hindered due to the lack of in‐depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modeling, it is determined herein that the long‐lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows prediction of the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modeling, potentially relating outcomes to material properties for a large number of materials, and thus boosting safe‐by‐design‐based material development. Because of its profound implications for animal‐free predictive toxicology, this work paves the way to a more efficient and hazard‐free introduction of numerous new advanced materials into our lives.
The prediction of material‐associated diseases is currently hindered by the lack of understanding of underlying mechanisms. Counteracting of nanomaterial quarantining and nanomaterial cycling are identified as the main modes of cellular response in a living nanomaterial‐exposed lung epithelium. This enables animal‐free prediction of material‐induced chronic inflammation using only in vitro measurements and in silico modeling.
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•Get fluorescent glyco-BODIPYs by the combination of a Heck-like cross coupling and a Knoevenagel condensation.•The glycosidase stable BODIPY-mannose acts as efficient DC-SIGN ...targeting probes in vitro.•BODIPY-mannose: a high performant tool in fluorescence and STED microscopy.•The functional and modular glyco-probe can be further functionalized with bioactive compounds.•Significant perspectives on tracking lectin-mediated cell uptake in diverse biological settings.
Lectins are involved in a wide range of carbohydrate mediated recognition processes. Therefore, the availability of highly performant fluorescent tools tailored for lectin targeting and able to efficiently track events related to such key targets is in high demand. We report here on the synthesis of the glyco-BODIPYs 1 and 2, based on the efficient combination of a Heck-like cross coupling and a Knoevenagel condensation, which revealed efficient in addressing lectins. In particular, glyco-BODIPY 1 has two glycosidase stable C-mannose residues, which act as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) targeting modules. By using live-cell fluorescence microscopy, we proved that BODIPY-mannose 1 was efficiently taken up by immune cells expressing DC-SIGN receptors. Super-resolution stimulated emission depletion (STED) microscopy further revealed that the internalized 1 localized in membranes of endosomes, proving that 1 is a reliable tool also in STED applications. Of note, glyco-BODIPY 1 contains an aryl-azido group, which allows further functionalization of the glycoprobe with bioactive molecules, thus paving the way for the use of 1 for tracking lectin-mediated cell internalization in diverse biological settings.
The prediction of diseases associated with nanomaterials is currently hampered by an incomplete understanding of the underlying mechanisms. Newly discovered nanomaterial quarantining and ...counteracting nanomaterial cycling fill that gap allowing Tilen Koklič, Tobias Stoeger, Janez Štrancar, and co‐workers to incorporate these main modes of cellular response into a mechanistic model and predict in vivo inflammation solely on animal‐free in vitro tests, as described in article number 2003913.
Osnovno različico pripadnostnega kostumiranja moških so sestavljali visoki škornji, dolge spodnje hlače, irhaste ali krojno irhastim sorodne podkolenske hlače, srajca, telovnik, ovratna ruta in ...klobuk ter dodatki.Zanimiva srebrna verižica s tolarji iz Preddvora je ohranjena v Gorenjskem muzeju v Kranju pod inventarno številko E1512. Gre za verižico za uro, na kateri visijo trije tolarji. Muzeju je bila izročena leta 1961, in sicer mu jo je izročil Franc Strniša iz Preddvora 36.
Ženske so pečo na glavo polagale na različne načine, odvisno od njihovega družbenega položaja, od obdobja, v katerem so živele, od letnega časa, od tega, ali so jo nosile za pražnjo ali vsakdanjo ...priložnost ipd. »Peče so dale k lepim oblekam gor. Tete so ble na ohcet s pečo. Pa kakšen govor so naredle. So mele tut solo ples. Tete so postlo postlale. Pečo so imele prekrižano zadaj in potem zavezano na vrh glave. Je bil kt en petelinček. »Ta po figana« je bila s tako veliko rožo. Lahko je bla pa tut mejhna roža.« (Terenski zapiski, 7. 11. 2011)Peča je v 19. stoletju sodila med vsakdanje in pražnje žensko pokrivalo, v petelinčkovo vezavo – na Beli pri Preddvoru so tako zavezano pečo imenovali »ta pofigana« – pa se je razvila v okviru kostumiranja za posebne priložnosti.»Ene so mele pečo. Peče so imel bl bogat, razkošn. Mrbit jo j naša teta tut mela. Tiste, ki so se kej ukvarjale s kšnmu petjam, so jo mele. Vse ta velke kmetice so jih tut mele. Za na ohcet so dale peče. To so ble ta lepe – so jim rekl, de so ta lepe, če so pršli s pečo.« (Terenski zapiski, 7. 11. 2011)
S poustvarjanjem plesnega in glasbenega izročila, s poustvarjanjem šeg in navad ter ob tem z razvijanju dojemanja lastne oblačilne dediščine ob vsesplošnem pomenu kulturnega delovanja razvijamo ...občutek pripadnosti lokalni skupnosti, iz katere prihajamo – v pričujočem primeru skupnosti Preddvorčanov –, potem pa tudi občutek pripadnosti širši skupnosti – skupnosti Gorenjcev in Slovencev – posredno tudi skupnosti Evropejcev.
Pripadnostne kostume so oblačili ob različnih priložnostih, pogosto predvsem pri tistih, ki so bile povezane Cerkvijo. »Narodno nošo so oblekli, če je bil na primer pogreb duhovnika ali pogreb ...kakšnga bl pomembnga človeka . Če je bil praznik so oblekli nošo. So bili tak prazniki, k se je spodobl, de si obleku nošo. Pa nova maša. K je bla procesija za mal šmarn v Velesovem, so šli zmerej tja tudi ljudje u v narodni noši.« (Terenski zapiski, 6. 11. 2011)
Peča je žensko pokrivalo kvadratne oblike oziroma pogosteje pravokotne oblike, ki se zaradi neenakomernega krčenja blaga, do česar prihaja pri pranju, kvadratu skuša približati. Izdelana je iz belega ...lanenega blaga, kasneje pogosteje iz bombažnega. Lahko je bila neokrašena, a zaradi dragocenosti so se do danes ohranile predvsem različice, ki so okrašene z vezenino in obrobljene s čipkami. Nosile so jo ženske vseh družbenih plasti vsaj od poznega srednjega veka dalje.