Synthesis, characterization, mechanical and magnetic characteristics of Gd3+ /PO4 3 - substituted zircon for application in hard tissue replacements.

The study reports on the use of sol-gel technique to yield zircon type [Zr(1-0.1-x) GdxTi0.1 ] [(SiO4 )1-x (PO4 )x ] solid solution. Titanium has been used as a mineralizer to trigger zircon formation while equimolar concentrations of Gd3+ and PO4 3- were added to determine their accommodation limits in the zircon structure. The crystallization of t-ZrO2 as a dominant phase alongside the crystallization of m-ZrO2 and zircon were detected at 1200°C while their further annealing revealed the formation of zircon as a major phase at 1300°C. Heat treatment at 1400°C revealed the formation of zircon-type solid solution [Zr(1-0.1-x) Gdx Ti0.1 ][(SiO4 )1-x (PO4 )x ] comprising the accommodation of 10 mol.% of Gd3+ /PO4 3- at the zircon lattice. Beyond 10 mol.% of Gd3+ /PO4 3- , the crystallization of GdPO4 as a secondary phase is noticed. Structural analysis revealed the expansion of zircon lattice due to the simultaneous occupancy of Gd3+ /PO4 3- for the corresponding Zr4+ /SiO4 4- sites. The mechanical strength of single-phase zircon solid solution was higher in comparison to that of multiphase materials, namely in the presence of GdPO4 formed as a secondary phase in samples with added equimolar Gd3+ /PO4 3- contents beyond 10 mol.%. Nevertheless, the paramagnetic behavior of the samples demonstrated a steady surge as a function of enhanced Gd3+ content.

Enhancing the zircon yield through the addition of calcium phosphates into ZrO2-SiO2 binary systems: synthesis and structural, morphological, mechanical and in vitro analysis.

The crystallization of ZrSiO4 is generally accomplished by the addition of mineralizers into ZrO2-SiO2 binary oxides. The current investigation aimed to investigate the effect of adding calcium phosphates into ZrO2-SiO2 binary oxides on the yield of ZrSiO4. The concentration of calcium phosphate additions were varied to obtain ZrSiO4 that fetches improved mechanical and biological properties for application in hard tissue replacements. The findings highlight the significant role of Ca2+ and P5+ in triggering the ZrSiO4 formation via their accommodation at the Zr4+ and Si4+ sites. Especially, calcium phosphate additions trigger the t- → m-ZrO2 transition beyond 1000 °C, which consequently reacts with SiO2 to promote ZrSiO4 formation. Calcium phosphates are accommodated at the lattice sites of ZrSiO4 with a maximum limit of 20 mol%, beyond which the crystallization of ß-Ca3(PO4)2 is noticed. The optimum amount of 20 mol% of calcium phosphates displayed a better strength than that of all the investigated specimens. More than 80% of cell viability in MG-63 cells was invariably determined in all the calcium phosphate-added ZrSiO4 systems.

Structure, Activity and Function of the Protein Arginine Methyltransferase 6.

Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections.

The ribosomal protein eL21 interacts with the protein lysine methyltransferase SMYD2 and regulates its steady state levels.

The protein lysine methyltransferase, SMYD2 is involved in diverse cellular events by regulating protein functions through lysine methylation. Though several substrate proteins of SMYD2 are well-studied, only a limited number of its interaction partners have been identified and characterized. Here, we performed a yeast two-hybrid screening of SMYD2 and found that the ribosomal protein, eL21 could interact with SMYD2. SMYD2-eL21 interaction in the human cells was confirmed by immunoprecipitation methods. In vitro pull-down assays revealed that SMYD2 interacts with eL21 directly through its SET and MYND domain. Computational mapping, followed by experimental studies identified that Lys81 and Lys83 residues of eL21 are important for the SMYD2-eL21 interaction. Evolutionary analysis showed that these residues might have co-evolved with the emergence of SMYD2. We found that eL21 regulates the steady state levels of SMYD2 by promoting its transcription and inhibiting its proteasomal degradation. Importantly, SMYD2-eL21 interaction plays an important role in regulating cell proliferation and its dysregulation might lead to tumorigenesis. Our findings highlight a novel extra-ribosomal function of eL21 on regulating SMYD2 levels and imply that ribosomal proteins might regulate wide range of cellular functions through protein-protein interactions in addition to their core function in translation.

The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions.

Protein arginine methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues in various proteins affecting diverse cellular processes such as transcriptional regulation, splicing, DNA repair, differentiation, and cell cycle. Elevated levels of PRMT5 are observed in several types of cancers and are associated with poor clinical outcomes, making PRMT5 an important diagnostic marker and/or therapeutic target for cancers. Here, using yeast two-hybrid screening, followed by immunoprecipitation and pull-down assays, we identify a previously uncharacterized protein, FAM47E, as an interaction partner of PRMT5. We report that FAM47E regulates steady-state levels of PRMT5 by affecting its stability through inhibition of its proteasomal degradation. Importantly, FAM47E enhances the chromatin association and histone methylation activity of PRMT5. The PRMT5-FAM47E interaction affects the regulation of PRMT5 target genes expression and colony-forming capacity of the cells. Taken together, we identify FAM47E as a protein regulator of PRMT5, which promotes the functions of this versatile enzyme. These findings imply that disruption of PRMT5-FAM47E interaction by small molecules might be an alternative strategy to attenuate the oncogenic function(s) of PRMT5.