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Abstract The adaptation of vertebrates to different environments was associated with changes in the molecular composition and regulation of epithelia. Whales and dolphins, together forming the clade cetaceans, have lost multiple epithelial keratins during or after their evolutionary transition from life on land to life in water. It is unknown whether the changes in keratins were accompanied by gain or loss of cytoskeletal adapter proteins of the plakin family. Here we investigated whether plakin proteins are conserved in cetaceans and other vertebrates. Comparative analysis of genome sequences showed conservation of dystonin, microtubule actin crosslinking factor 1 (MACF1), plectin, desmoplakin, periplakin and envoplakin in cetaceans. By contrast, EPPK1 (epiplakin) was disrupted by inactivating mutations in all cetaceans investigated. Orthologs of EPPK1 are present in bony and cartilaginous fishes and tetrapods, indicating an evolutionary origin of EPPK1 in a common ancestor of jawed vertebrates (Gnathostomes). In many vertebrates, EPPK1 is flanked by an as-yet uncharacterized gene that encodes protein domains homologous to the carboxy-terminal segment of MACF1. We conclude that epiplakin, unlike other plakins, was lost in cetaceans.

Inhibition of the interaction between the scaffolding protein PSD-95 and the NMDA receptor has been shown to obstruct ischemic stroke-triggered excitotoxic reactions, leading to neuronal death. The peptides NR2B9c and N-dimer are inhibitors of this interaction. Delivery of the peptides to the brain is challenging due to the general low blood–brain barrier (BBB) permeability. NR2B9c and N-dimer have therefore been conjugated to the cell-penetrating peptide (CPP) Tat, to facilitate blood–brain barrier permeation. However, the BBB permeation of Tat-NR2B9c and Tat-N-dimer has not been fully elucidated. We recently demonstrated that the BBB permeation in vitro and in vivo was lowered upon conjugation of NR2B9c or N-dimer to Tat. In the present study, we aimed to further understand the impact of cargo conjugation to Tat with respect to interaction with and permeation across the BBB in vitro and in vivo. The peptides were labeled with the fluorophore TAMRA (T) and demonstrated efficient Tat-mediated uptake into BBB endothelial cells but differed in their degree of plasma membrane interaction and embedding (T-Tat-NR2B9c = T-Tat > T-Tat-N-dimer) as well as in their chemical stability (T-Tat-N-dimer = T-Tat > T-Tat-NR2B9c). The Tat conjugates all displayed a similar degree of self-association and/or plasma protein adsorption. T-Tat-NR2B9c and T-Tat affected the BBB integrity but not the permeation of the paracellular marker C14-mannitol. T-Tat-NR2B9c and T-Tat-N-dimer displayed less efficient permeation across an in vitro model representing the healthy BBB, when compared to T-Tat, and low BBB permeation in healthy rats.

Keratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using live-cell imaging of epithelial cells expressing fluorescently tagged EPPK1 and keratin, we report here an unexpected dynamic behavior of EPPK1 upon stress. EPPK1 was diffusely distributed throughout the cytoplasm and not associated with keratin filaments in living cells under standard culture conditions. However, ER-, oxidative and UV-stress, as well as cell fixation, induced a rapid association of EPPK1 with keratin filaments. This re-localization of EPPK1 was reversible and dependent on the elevation of cytoplasmic Ca2+ levels. Moreover, keratin filament association of EPPK1 led to significantly reduced keratin dynamics. Thus, we propose that EPPK1 stabilizes the keratin network in stress conditions, which involve increased cytoplasmic Ca2+.

We show that a zero-symmetric near-ring $N$ is left regular if and only if $N $ is regular and isomorphic to a subdirect product of integral near-rings, where each component is either an Anshel-Clay near-ring or a trivial integral near-ring. We also show that a zero-symmetric near-ring is regular without nonzero nilpotent elements if and only if the multiplicative semigroup of N is a union of disjoint groups.

Abstract Compositional grading has been widely exploited in highly efficient Cu(In,Ga)Se2, CdTe, GaAs, quantum dot solar cells, and this strategy has the potential to improve the performance of emerging perovskite solar cells. However, realizing and maintaining compositionally graded perovskite absorber from solution processing is challenging. Moreover, the operational stability of graded perovskite solar cells under long‐term heat/light soaking has not been demonstrated. In this study, a facile partial ion‐exchange approach is reported to achieve compositionally graded perovskite absorber layers. Incorporating compositional grading improves charge collection and suppresses interface recombination, enabling to fabricate near‐infrared‐transparent perovskite solar cells with power conversion efficiency of 16.8% in substrate configuration, and demonstrate 22.7% tandem efficiency with 3.3% absolute gain when mechanically stacked on a Cu(In,Ga)Se2 bottom cell. Non‐encapsulated graded perovskite device retains over 93% of its initial efficiency after 1000 h operation at maximum power point at 60 °C under equivalent 1 sun illumination. The results open an avenue in exploring partial ion‐exchange to design graded perovskite solar cells with improved efficiency and stability.

Recent years have shown the importance of tunable semiconductor lasers in optical sensing. We describe the status quo concerning DFB laser diodes between 760 nm and 3,000 nm as well as new developments aiming for up to 80 nm tuning range in this spectral region. Furthermore we report on QCL between 3 µm and 16 µm and present new developments. An overview of the most interesting applications using such devices is given at the end of this paper.

Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/-) mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

Autosomal recessive mutations in the cytolinker protein plectin account for the multisystem disorders epidermolysis bullosa simplex (EBS) associated with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and congenital myasthenia (EBS-CMS). In contrast, a dominant missense mutation leads to the disease EBS-Ogna, manifesting exclusively as skin fragility. We have exploited this trait to study the molecular basis of hemidesmosome failure in EBS-Ogna and to reveal the contribution of plectin to hemidesmosome homeostasis. We generated EBS-Ogna knock-in mice mimicking the human phenotype and show that blistering reflects insufficient protein levels of the hemidesmosome-associated plectin isoform 1a. We found that plectin 1a, in contrast to plectin 1c, the major isoform expressed in epidermal keratinocytes, is proteolytically degraded, supporting the notion that degradation of hemidesmosome-anchored plectin is spatially controlled. Using recombinant proteins, we show that the mutation renders plectin's 190-nm-long coiled-coil rod domain more vulnerable to cleavage by calpains and other proteases activated in the epidermis but not in skeletal muscle. Accordingly, treatment of cultured EBS-Ogna keratinocytes as well as of EBS-Ogna mouse skin with calpain inhibitors resulted in increased plectin 1a protein expression levels. Moreover, we report that plectin's rod domain forms dimeric structures that can further associate laterally into remarkably stable (paracrystalline) polymers. We propose focal self-association of plectin molecules as a novel mechanism contributing to hemidesmosome homeostasis and stabilization.