Syndecan transmembrane domain specifically regulates downstream signaling events of the transmembrane receptor cytoplasmic domain

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains un-known. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory ef-fects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, com-prising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corre-sponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.1

A Strategy to Design High-Density Nanoscale Devices utilizing Vapor Deposition of Metal Halide Perovskite Materials

The demand for high memory density has increased due to increasing needs of information storage, such as big data processing and the Internet of Things. Organic-inorganic perovskite materials that show nonvolatile resistive switching memory properties have potential applications as the resistive switching layer for next-generation memory devices, but, for practical applications, these materials should be utilized in high-density data-storage devices. Here, nanoscale memory devices are fabricated by sequential vapor deposition of organolead halide perovskite (OHP) CH3NH3PbI3 layers on wafers perforated with 250 nm via-holes. These devices have bipolar resistive switching properties, and show low-voltage operation, fast switching speed (200 ns), good endurance, and data-retention time > 10(5)s. Moreover, the use of sequential vapor deposition is extended to deposit CH3NH3PbI3 as the memory element in a cross-point array structure. This method to fabricate high-density memory devices could be used for memory cells that occupy large areas, and to overcome the scaling limit of existing methods; it also presents a way to use OHPs to increase memory storage capacity.1125sciescopu

Lead-Free, Air-Stable Hybrid Organic-Inorganic Perovskite Resistive Switching and Multilevel Data Storage

Organolead halide perovskites exhibit excellent optoelectronic and photovoltaic properties such as a wide range of light absorption and tunable band gaps. However, the presence of toxic elements and chemical instability under an ambient atmosphere hindered lead halide perovskites from real device applications because of environmental issues and stability. Here, we demonstrate a resistive switching memory device based on a lead-free bismuth halide perovskite (CH3NH3)3Bi2I9 (MABI). The active layer of the device can be easily prepared by solvent engineering. The nonvolatile memory based on MABI layers has reliable retention properties (∼104 s), endurance (300 cycles), and switching speed (100 ns), as well as environmental stability. Moreover, the control of the compliance current leads to multilevel data storage with four resistance states, which can be applied to high-density memory devices. These results suggest that MABI has potential applications in information storage.114sciescopu

Organic-inorganic hybrid memory devices for high-density memory applications

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Mixed halide perovskite resistive switching memory: controlling operating parameters through halide incorporation

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Impact of Grain Sizes on Programmable Memory Characteristics in Two-Dimensional Organic-Inorganic Hybrid Perovskite Memory

Recently, organic-inorganic hybrid perovskites (OIHPs) have been used in resistive switching memory applications because of current-voltage hysteresis that originated from ion migration in the perovskite film. As the density of the memory devices continues to increase, the size of the devices approaches that of the individual grains of the polycrystalline films. Thus, the effects of the grain boundary and the grain size will become important to investigate the influence on the switching behaviors. Here, we report the effects of grain sizes on the resistive switching property of (C4H9NH3)(2)PbBr4 (BA(2)PbBr(4)) films. The BA(2)PbBr(4) films were formed by using sequential vapor deposition. First, a lead bromide (PbBr2) film was deposited by thermal evaporation, and then the film was exposed to organic vapor to form BA(2)PbBr(4) films. The grain sizes were controlled by changing the transformation temperatures (T-T = 100, 150, and 200 degrees C). When the TT values were 100, 150, and 200 degrees C, the grain sizes of BA(2)PbBr(4) were similar to 180 nm, similar to 1, and similar to 30 mu m, respectively. In the memory device based on BA(2)PbBr(4), the off current decreased from similar to 10(-4) to similar to 10(-8) A as the grain size increased from similar to 180 nm to similar to 30 mu m. This method to synthesize BA(2)PbBr(4) films provides a simple way to control the grain sizes, and understanding of the effects of grain sizes on memory characteristics will provide an insight to improve the reliability of the OIHP-based memory as the electronic devices are scaled down to the sizes of grains.11Nsciescopu

Stability Improvement of Organolead Halide Perovskite Memory Enabled by Passivation

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Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance

In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (or tumor-initiating cells) is characterized by self-renewal, unlimited proliferative potential, expression of multidrug-resistance proteins, active DNA repair capacity, apoptosis resistance, and a considerable developmental plasticity. Due to these properties, cancer stem cells display increased resistance to chemo- and radiotherapy. Recent findings indicate that aberrant functions of proteoglycans and glycosaminoglycans contribute substantially to the cancer stem cell phenotype and therapeutic resistance. In this review, we summarize how the diverse functions of the glycoproteins and carbohydrates facilitate acquisition and maintenance of the cancer stem cell phenotype, and how this knowledge can be exploited to develop novel anti-cancer therapies. For example, the large transmembrane chondroitin sulfate proteoglycan NG2 / CSPG4 marks stem cell populations in brain tumors. Cell surface heparan sulfate proteoglycans of the syndecan and glypican families modulate the stemness-associated Wnt, hedgehog and notch signaling pathways, whereas the interplay of hyaluronan in the stem cell niche with cancer stem cell CD44 determines maintenance of stemness and promotes therapeutic resistance. A better understanding of the molecular mechanisms by which proteoglycans and glycosaminoglycans regulate cancer stem cell function will aid the development of targeted therapeutic approaches which could avoid relapse after an otherwise successful conventional therapy. Chimeric antigen receptor T cells, proteoglycan-primed dendritic cells, proteoglycan-targeted antibody-drug conjugates and inhibitory peptides and glycans have already shown highly promising results in preclinical models.Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Kumar Katakam, Sampath. Münster University Hospital; AlemaniaFil: Greve, Burkhard. Münster University Hospital; AlemaniaFil: Jang, Bohee. Ewha Womans University; Corea del SurFil: Oh, Eok Soo. Ewha Womans University; Corea del SurFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Götte, Martin. Münster University Hospital; Alemani

Substituted Syndecan-2-Derived Mimetic Peptides Show Improved Antitumor Activity over the Parent Syndecan-2-Derived Peptide

We previously showed that a synthetic peptide (S2-P) corresponding to a portion of the human syndecan-2 (SDC2) sequence can bind to the pro-domain of matrix metalloproteinase-7 (MMP-7) to inhibit colon cancer activities. Since S2-P had a relatively weak binding affinity for the MMP-7 pro-domain, we herein modified the amino acid sequence of S2-P to improve the anticancer potential. On the basis of the interaction structure of S2-P and MMP-7, four peptides were generated by replacing amino acids near Tyr 51, which is critical for the interaction. The SDC2-mimetic peptides harboring an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-D) or with an Ala-to-Phe substitution at the N-terminal side of Tyr 51 and an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-FE) showed improved interaction affinities for the MMP-7 pro-domain. Compared to S2-P, S2-FE was better able to inhibit the SDC2–MMP-7 interaction, the cell surface localization of MMP-7, the gelatin degradation activity of MMP-7, and the cancer activities (cell migration, invasion, and colony-forming activity) of human HCT116 colon cancer cells in vitro. In vivo, S2-FE inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a xenograft mouse model. Together, these data suggest that S2-FE could be useful therapeutic anticancer peptides for colon cancer