Current Trends in Aerogel Use in Heritage Buildings: Case Studies from the Aerogel Architecture Award 2021.

Silica aerogels are high-performance thermal insulation materials that can be used to provide unique solutions in the envelopes of buildings when space is limited. They are most often applied in historic buildings due to thin insulation thicknesses and since they are compatible with historic structures. In 2021, the first Aerogel Architecture Award was held at Empa in Switzerland in order to collect, evaluate and award outstanding uses of this relatively new building material.

Detection of endogenous lipids in chicken feathers distinct from preen gland constituents.

Bird feather lipids are usually attributed to the oily secretion product of the uropygial (preen) gland. We have observed, however, that feathers exhibit a strong reaction with osmium tetroxide (OsO), even after treatment with detergents. This leads us to postulate the existence of endogenous feather lipids distinct from preen gland lipids.

p-ANCAs in autoimmune liver disorders recognise human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ.

Objective: Autoimmune hepatitis and primary sclerosing cholangitis are chronic inflammatory disorders of unknown aetiology, frequently associated with the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) directed against an unknown antigen of myeloid cells.

Methods And Results: Here, it is reported that p-ANCAs in autoimmune liver disorders react with beta-tubulin isotype 5 (TBB-5) as autoantigen as well as with its evolutionary bacterial precursor protein FtsZ. Both proteins were confirmed as antigens of p-ANCAs in autoimmune liver disorders by demonstrating reactivity of ANCA-positive sera with recombinant TBB-5 (72-88%) and FtsZ (64-82%) on immunoblots and antigen-specific abrogation of ANCA immunofluorescence when sera had been preabsorbed with tubulin and FtsZ.

Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3.

The thyroid gland has an exceptionally high selenium content, even during selenium deficiency. At least 11 selenoproteins are expressed, which may be involved in the protection of the gland against the high amounts of H2O2 produced during thyroid hormone biosynthesis. As determined here by in situ hybridization and Northern blotting experiments, glutathione peroxidases (GPx) 1 and 4 and selenoprotein P were moderately expressed, occurring selectively in the follicular cells and in leukocytes of germinal follicles of thyroids affected by Hashimoto's thyroiditis.

Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1.

To address the functions of Rac1 in keratinocytes of the basal epidermal layer and in the outer root sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms revealed that in vivo both proliferation of wound-edge keratinocytes and centripetal migration of the neo-epidermis were impaired.

Laminin-5-deficient human keratinocytes: defective adhesion results in a saltatory and inefficient mode of migration.

Laminin-5 is a major adhesion protein of the skin basement membrane and crucially involved in integrin-mediated cell substrate attachment of keratinocytes, which is important for hemidesmosomal anchorage as well as for keratinocyte migration during epidermal wound healing. To investigate its role in keratinocyte migration, we analyzed laminin-5-deficient cells of patients with a lethal variant of junctional epidermolysis bullosa. Normal migrating keratinocytes adopted monopolar morphology with a distinct front lamella and employed a continuous mode of translocation.

ROCK signaling mediates the adoption of different modes of migration and invasion in human mammary epithelial tumor cells.

For the invasive migration of tumor cells, at least two mechanisms are currently discussed: (1) the mesenchymal mode depending on extracellular proteolysis and (2) the proteolysis-independent amoeboid mode depending on the activity of the Rho kinase ROCK. The ability of tumor cells to switch between different modes of motility has been shown to limit the efficiency of agents aimed to reduce invasion. Here we show by combining 2D and 3D migration assays that human mammary tumor cells exhibited a strongly reduced migration velocity as compared to their normal counterparts indicating that high invasiveness is not necessarily correlated with high migratory capacity in 2D assays.

Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro.

Growing evidence shows that the soluble N-terminal form (sAPPalpha) of the amyloid precursor protein (APP) represents an epidermal growth factor fostering keratinocyte proliferation, migration and adhesion. APP is a member of a protein family including the two mammalian amyloid precursor-like proteins APLP1 and APLP2. In the mammalian epidermis, only APP and APLP2 are expressed.

CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells.

Dendritic cells (DC) change their phenotype and functional properties during maturation. CD83 cell surface expression is induced on mature DC (mDC). In this study, we investigated intracellular CD83 localization and transport in human monocyte-derived DC.

Release of integrin macroaggregates as a mechanism of rear detachment during keratinocyte migration.

Cell-substrate adhesion can be mediated by the relatively short-lived focal complexes and focal adhesions and by the more stable hemidesmosomes. During cell migration both types of cell-substrate adhesions must be disrupted allowing the cell rear to detach. Rear detachment has been described to be accompanied by membrane ripping and the loss of cellular material in a variety of cell types including fibroblasts and chondrocytes, but also in fast moving cells such as keratinocytes.

Cell migration: mechanisms of rear detachment and the formation of migration tracks.

Cell migration is central to many biological and pathological processes, including embryogenesis, tissue repair and regeneration as well as cancer and the inflammatory response. In general, cell migration can be usefully conceptualized as a cyclic process. The initial response of a cell to a migration-promoting agent is to polarize and extend protrusions in the direction of migration.

Cytoprotective function of sAppalpha in human keratinocytes.

sAPPalpha, the soluble form of the beta-amyloid precursor protein, has been shown to act as a potent epidermal growth factor by stimulating keratinocyte proliferation and migration. In this report we provide evidence for a cytoprotective role of sAPPalpha. As a model we used HaCaT cells and normal human keratinocytes (NHK) cultured in the absence of fetal calf serum and bovine pituitary extract.

Biological roles of APP in the epidermis.

The amyloid precursor protein (APP) was initially detected in cells of the central nervous system where it is considered to be involved in the pathogenesis of Alzheimer's disease. However, APP is also found in peripheral organs with exceptionally strong expression in the mammalian epidermis where it fulfils a variety of distinct biological roles. Full length APP appears to facilitate keratinocyte adhesion due to its ability to interact with the extracellular matrix.

Misfolded BiP is degraded by a proteasome-independent endoplasmic-reticulum-associated degradation pathway.

Misfolded proteins are removed from the ER (endoplasmic reticulum) by retrotranslocation to the cytosol and degradation by the ubiquitin-proteasome system in a process designated ERAD (ER-associated degradation). Analysing the turnover of a misfolded form of the ER-resident chaperone BiP (heavy-chain binding protein) (BiPDeltaA), we found that the degradation of BiPDeltaA did not follow this general ERAD pathway. In transfected cells, BiPDeltaA was degraded, although proteasome-dependent ERAD was inactivated either by proteasome inhibitors or by ATP depletion.

Membrane ruffles in cell migration: indicators of inefficient lamellipodia adhesion and compartments of actin filament reorganization.

During epithelial cell migration, membrane ruffles can be visualized by phase contrast microscopy as dark waves arising at the leading edge of lamellipodia that move centripetally toward the main cell body. Despite the common use of the term membrane ruffles, their structure, molecular composition, and the mechanisms leading to their formation remained largely unknown. We show here that membrane ruffles differ from the underlying cell lamella by more densely packed bundles of actin filaments that are enriched in the actin cross-linkers filamin and ezrin, pointing to a specific bundling process based on these cross-linkers.

Simultaneous cell death and desquamation of the embryonic diffusion barrier during epidermal development.

The periderm is an epithelial layer covering the emerging epidermis in early embryogenesis of vertebrates. In the chicken embryo, an additional cellular layer, the subperiderm, occurs at later embryonic stages underneath the periderm. The questions arose what is the function of both epithelial layers and, as they are transitory structures, by which mechanism are they removed.

Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-release.

The soluble form of the beta-amyloid precursor protein (sAPPalpha) is known to function in the autocrine regulation of epidermal growth and repair. Here we show that its proteolytic release by alpha-secretase in normal human keratinocytes is susceptible to hydroxamic-acid-based zinc metalloproteinase inhibitors and suppressed by these inhibitors by 80%-90%. As various other growth factors participate in regulating epidermal growth we investigated whether the inhibitor-induced sAPPalpha-deficiency would affect keratinocyte proliferation.

Endoplasmic reticulum-localized amyloid beta-peptide is degraded in the cytosol by two distinct degradation pathways.

The paradigm of endoplasmic reticulum (ER)-associated degradation (ERAD) holds that misfolded secretory and membrane proteins are translocated back to the cytosol and degraded by the proteasome in a coupled process. Analyzing the degradation of ER-localized amyloid beta-peptide (Abeta), we found a divergence from this general model. Cell-free reconstitution of the export in biosynthetically loaded ER-derived brain microsomes showed that the export was mediated by the Sec61p complex and required a cytosolic factor but was independent of ATP.

BiP-dependent export of cholera toxin from endoplasmic reticulum-derived microsomes.

Cholera toxin (CT) is transported from the cell surface to the endoplasmic reticulum (ER) from where it is translocated to the cytosol in a process depending on ATP and luminal ER proteins. To test whether the molecular chaperone BiP (heavy chain binding protein), which is an ER-luminal ATPase, was one of the required proteins the export of CT was analyzed using ER-derived CT-loaded microsomes. The resubstitution of extracted export-incompetent microsomes with purified BiP was sufficient to restore the export of CT.

Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation.

Abnormal cleavage of amyloid precursor protein (APP) in the central nervous system has been linked to the development of Alzheimer's disease. Recent work has identified additional roles for APP in peripheral tissue, such as cellular proliferation and motility. APP undergoes proteolytic processing to release a soluble NH(2)-terminal ectodomain fragment (sAPP), an Abeta or p3 peptide, and cytosolic COOH-terminal fragments.

Membrane and raft association of reggie-1/flotillin-2: role of myristoylation, palmitoylation and oligomerization and induction of filopodia by overexpression.

The reggie protein family consists of two proteins, reggie-1 and -2, also called flotillins, which are highly ubiquitous and evolutionarily conserved. Both reggies have been shown to be associated with membrane rafts and are involved in various cellular processes such as T-cell activation, phagocytosis and insulin signalling. However, the exact molecular function of these proteins remains to be determined.

sAPP as a regulator of dendrite motility and melanin release in epidermal melanocytes and melanoma cells.

Numerous factors including ultraviolet (UV) radiation and growth factors regulate the specific function of epidermal melanocytes. A recently discovered epidermal growth factor is sAPP, the soluble N-terminal ectodomain of the beta-amyloid precursor protein (APP). Using whole mount preparations of isolated human epidermis, we detected a small population of basal cells, which expressed exceptionally high levels of APP.