Formation of Porous ZnO Nanosystems for Potential Use in Sensor Electronics

The semiconducting ZnO is a very promising material for applications in UV light emitters, optical de-tectors, solar cells, piezoelectric transducers, transparent electronics, gas sensors etc. It is known that physical properties, and as a result areas of applications, are strongly determined by morphology and size of the material’s structural elements. Therefore, the development of a technology that allows formation of nanoporous metal oxide structures with a high surface to volume ratio is of great interest nowadays. The aim of this work was to develop technology for selective formation of porous ZnO nanosystems and to de-termine the relationship between morphological characteristics of the layers obtained and their optical and electrical sensor properties with the aim of potential applications in optoelectronics and sensor electronics. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3519

Formation of Porous ZnO Nanosystems for Potential Use in Sensor Electronics

The semiconducting ZnO is a very promising material for applications in UV light emitters, optical de-tectors, solar cells, piezoelectric transducers, transparent electronics, gas sensors etc. It is known that physical properties, and as a result areas of applications, are strongly determined by morphology and size of the material’s structural elements. Therefore, the development of a technology that allows formation of nanoporous metal oxide structures with a high surface to volume ratio is of great interest nowadays. The aim of this work was to develop technology for selective formation of porous ZnO nanosystems and to de-termine the relationship between morphological characteristics of the layers obtained and their optical and electrical sensor properties with the aim of potential applications in optoelectronics and sensor electronics. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3519

S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8(+) T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients

The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping

S100B is a homodimeric zinc-, copper-, and calcium-binding protein of the family of EF-hand S100 proteins. Zn(2+) binding to S100B increases its affinity towards Ca(2+) as well as towards target peptides and proteins. Cu(2+) and Zn(2+) bind presumably to the same site in S100B. We determined the structures of human Zn(2+)- and Ca(2+)-loaded S100B at pH 6.5, pH 9, and pH 10 by X-ray crystallography at 1.5, 1.4, and 1.65Å resolution, respectively. Two Zn(2+) ions are coordinated tetrahedrally at the dimer interface by His and Glu residues from both subunits. The crystal structures revealed that ligand swapping occurs for one of the four ligands in the Zn(2+)-binding sites. Whereas at pH 9, the Zn(2+) ions are coordinated by His15, His25, His 85', and His 90', at pH 6.5 and pH 10, His90' is replaced by Glu89'. The results document that the Zn(2+)-binding sites are flexible to accommodate other metal ions such as Cu(2+). Moreover, we characterized the structural changes upon Zn(2+) binding, which might lead to increased affinity towards Ca(2+) as well as towards target proteins. We observed that in Zn(2+)-Ca(2+)-loaded S100B the C-termini of helix IV adopt a distinct conformation. Zn(2+) binding induces a repositioning of residues Phe87 and Phe88, which are involved in target protein binding. This article is part of a Special Issue entitled: 11th European Symposium on Calcium