Nanostructure and Optical Property Tailoring of Zinc Tin Nitride Thin Films through Phenomenological Decoupling: A Pathway to Enhanced Control.

This work addresses the need for precise control of thin film sputtering processes to enable thin film material tailoring on the example of zinc tin nitride (ZTN) thin films deposited via microwave plasma-assisted high power reactive magnetron sputtering (MAR-HiPIMS). The applied in situ diagnostic techniques (Langmuir probe and energy-resolved time-of-flight mass spectrometry) supported monitoring changes in the deposition environment with respect to microwave (MW) power. During MAR-HiPIMS, the presence of nitride ions in the gas phase (ZnN+, ZnN2+, SnN+, SnN2+) was detected. This indicates that the MW plasma facilitated their production, as opposed to pure R-HiPIMS. Additionally, MW plasma caused post-ionisation of sputtered atoms and reduced the overall energy-per-charge range of incoming charged species. By varying the MW power and substrate biasing, films with comparable chemical compositions (approximately Zn0.92Sn1.08N2) but different structures, ranging from polycrystalline to preferentially textured, were successfully produced. The application of density functional theory (DFT) further enabled the relationship between the lattice parameters and the optical properties of ZTN to be explored, where the material's optical anisotropy nature was determined. It was found that despite considerable differences in crystallinity, the changes induced in the lattice parameters were subangstrom, causing only minor changes in the final optical properties of ZTN.

Unlocking the Potential of CuAgZr Metallic Glasses: A Comprehensive Exploration with Combinatorial Synthesis, High-Throughput Characterization, and Machine Learning.

In this work, the CuAgZr metallic glasses (MGs) are investigated, a promising material for biomedical applications due to their high strength, corrosion resistance, and antibacterial activity. Using an integrated approach of combinatorial synthesis, high-throughput characterization, and machine learning (ML), the mechanical properties of CuAgZr MGs are efficiently explored. The investigation find that post-deposition oxidation in inter-columnar regions with looser packing causes high oxygen content in Cu-rich regions, significantly affecting the alloys' mechanical behavior. The study also reveals that nanoscale structural features greatly impact plastic yielding and flow in the alloys. ML algorithms are tested, and the multi-layer perceptron algorithm produced satisfactory predictions for the alloys' hardness of untested alloys, providing valuable clues for future research. The work demonstrates the potential of using combinatorial synthesis, high-throughput characterization, and ML  techniques to facilitate the development of new MGs with improved strength and economic feasibility.

Imipramine administration induces changes in the phosphorylation of FAK and PYK2 and modulates signaling pathways related to their activity.

BACKGROUND: Antidepressants can modify neuronal functioning by affecting many levels of signal transduction pathways that are involved in neuroplasticity. We investigated whether the phosphorylation status of focal adhesion kinase (FAK/PTK2) and its homolog, PYK2/PTK2B, and their complex with the downstream effectors (Src kinase, p130Cas, and paxillin) are affected by administration of the antidepressant drug, imipramine. The treatment influence on the levels of ERK1/2 kinases and their phosphorylated forms (pERK1/2) or the Gαq, Gα11 and Gα12 proteins were also assessed. METHODS: Rats were injected with imipramine (10 mg/kg, twice daily) for 21 days. The levels of proteins investigated in their prefrontal cortices were measured by Western blotting. RESULTS: Imipramine induced contrasting changes in the phosphorylation of FAK and PYK2 at Tyr397 and Tyr402, respectively. The decreased FAK phosphorylation and increased PYK2 phosphorylation were reflected by changes in the levels of their complex with Src and p130Cas, which was observed predominantly after chronic imipramine treatment. Similarly only chronic imipramine decreased the Gαq expression while Gα11 and Gα12 proteins were untouched. Acute and chronic treatment with imipramine elevated ERK1 and ERK2 total protein levels, whereas only the pERK1 was significantly affected by the drug. CONCLUSION: The enhanced activation of PYK2 observed here could function as compensation for FAK inhibition. GENERAL SIGNIFICANCE: These data demonstrate that treatment with imipramine, which is a routine in counteracting depressive disorders, enhances the phosphorylation of PYK2, a non-receptor kinase instrumental in promoting synaptic plasticity. This effect documents as yet not considered target in the mechanism of imipramine action.

Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice.

Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell-specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells' apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.

Alterations in the expression of the Atp7a gene in the early postnatal development of the mosaic mutant mice (Atp7a mo-ms) - An animal model for Menkes disease.

Copper is a trace element that is essential for the normal growth and development of all living organisms. In mammals, the ATP7A Cu-transporting ATPase is a key protein that is required for the maintenance of copper homeostasis. In both humans and mice, the ATP7A protein is coded by the X-linked ATP7A/Atp7a gene. Disturbances in copper metabolism caused by mutations in the ATP7A/Atp7a gene lead to severe metabolic syndromes Menkes disease in humans and the lethal mottled phenotype in mice. Mosaic is one of numerous mottled mutations and may serve as a model for a severe Menkes disease variant. In Menkes patients, mutations in the ATP7A gene often result in a decreased level of the normal ATP7A protein. The aim of this study was to analyse the expression of the Atp7a gene in mosaic mutants in early postnatal development, a critical period for starting copper supplementation therapy in both Menkes patients and mutant mice. Using real-time quantitative RT-PCR, we analysed the expression of the Atp7a gene in the brain, kidney and liver of newborn (P0.5) and suckling (P14) mice. Our results indicate that in mosaic P0.5 mutants, the Atp7a mRNA level is decreased in all analysed organs in comparison with wild-type animals. In two week-old mutants, a significant decrease was observed only in the kidney. In contrast, their hepatic level of Atp7a tended to be higher than in wild-type mice. We speculate that disturbance in the expression of the Atp7a gene and, consequently, change in the copper concentration of the organs, may contribute to the early fatal outcome of mosaic males.

Developmental changes in the expression of the Atp7a gene in the liver of mice during the postnatal period.

In all living organisms trace element metabolism and transport are closely regulated at the genetic level. Copper is one of the essential microelements required for normal growth and development. The main organ in mammals involved in copper metabolism is the liver. It is known that copper metabolism in the liver is controlled by ATP7B, a P-type ATP-ase encoded by the Atp7b gene. However, little is known about the expression and function of the second important P-type ATP-ase, ATP7A encoded by the Atp7a gene. In this study we investigated the expression of the Atp7a gene in the liver during postnatal development in mice. We analyzed expression of Atp7a gene in the livers from neonatal (P.05), young (P14) and adult (P240) mice using RT-PCR and real-time PCR method. We found a transcript of the Atp7a gene in the liver of all investigated animals. Moreover, we found that the expression of the Atp7a gene in the liver in mice is age-dependent and decreases during postnatal development. Interestingly, the Atp7a expression in adult mice is very low in comparison with neonatal and young animals. Western blot analysis revealed that Atp7a is expressed not only at mRNA level but also at the protein level in the liver of all investigated animals. The expression of Atp7a gene and ATP7A protein was also confirmed in primary hepatocytes from adult mouse. Demonstration of the hepatic Atp7a gene expression may shed light on new aspects of copper metabolism in the liver in mammals.

Effect of cocaine on responsiveness of alpha(1)-adrenergic receptors in rat cerebral cortex: modulation by GABA-mimetic drugs.

We investigated the effects of single doses of cocaine (10 mg/kg, ip) and the gamma-aminobutyric acid (GABA)-mimetics tiagabine (10 mg/kg, ip) and vigabatrin (150 mg/kg, ip) injected separately or concomitantly with cocaine, on the responsiveness of cerebral cortical alpha(1)-adrenergic receptors. The accumulation of noradrenaline-stimulated inositol phosphates was estimated in vitro at 2 and 24 h after the drug injection. Cocaine significantly enhanced alpha(1)-adrenergic receptor responsiveness to noradrenaline. Neither tiagabine nor vigabatrin influenced the accumulation of inositol phosphates. Finally, the cocaine-evoked augmentation of alpha(1)-adrenoceptor responsiveness was counteracted by tiagabine but not by vigabatrin. This effect may represent a characteristic feature of tiagabine, not necessarily shared by other GABA-mimetic drugs.