The current proteomic landscape of the porcine liver.

The main objective of the study was to create a reproducible protein map of the liver in healthy growing piglets. The analysis was performed on liver homogenates obtained from 8 castrated male piglets (PIC x Penerlan P76) at the 50 days. Two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry allowed to determine the proteomic profile of the liver. Liver proteins were separated at pH 4 - 7, followed by 12% SDS-PAGE. As a result, 470 ± 44 spots were present on the 2-D maps, of which 265 were successfully identified, representing products of 142 unique genes. Of these, 26 gene products have not been previously observed on the protein maps of porcine liver. Gene ontology analysis showed that the most of identified gene products belonged to the known metabolic pathways: protein processing in endoplasmic reticulum, arginine and proline metabolism, microbial metabolism in diverse environments, carbon metabolism, Epstein-Barr virus infection, propionate metabolism, biosynthesis of amino acids, proteasome. These results can undoubtedly serve as a useful and prospective prerequisite for the future analysis of the liver proteome changes in different physiological and pathophysiological conditions.

An update on medium- and low-abundant blood plasma proteome of horse.

The main objectives of the study were to: (1) deeply analyse the serum protein composition of Equus caballus, (2) assess the effectiveness of the high-abundant protein depletion and improve the concentration of medium- and low-abundant proteins. The analysis were performed on the blood plasma of three healthy part-Arabian mares. The implementation of two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation - time of flight mass spectrometry allowed us to establish a horse plasma proteome map. Serum proteins were resolved at pH 4 to 7, followed by 12% SDS-PAGE. As a result 136 spots were successfully identified, representing the products of 46 unique genes. Of these, 22 gene products have not been previously identified in horse serum/plasma samples using proteomic tools. Gene ontology analysis showed that almost 30% of all identified gene products belong to the coagulation and complement cascades. These results can undoubtedly serve as a useful and prospective prerequisite for the future analysis of horse plasma proteome changes in different physiological and pathophysiological conditions. The use of the medium- and low-abundant protein enrichment tool increased their abundance and allowed us to identify a higher number of protein gene products. The highest depletion efficiency was observed for the most abundant plasma proteins, that is albumin, IgG heavy chains and serotransferrin.

Alkali metal impact on structural and phonon properties of Er3+ and Tm3+ co-doped MY(WO4)2 (M = Li, Na, K) nanocrystals.

The Pechini and microwave-assisted hydrothermal syntheses of nanocrystalline Er3+ and Tm3+ co-doped MY(WO4)2, where M = Li, Na, K, double tungstates are reported. The obtained samples were characterized using standard X-ray powder diffraction (XRD) technique, Rietveld method, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and IR spectroscopy. The smallest crystallites (about 13 nm) could be obtained for the sodium samples synthesized by both the Pechini (for the resin calcined at 550 °C) and hydrothermal methods (synthesis at 230 °C). The average particle size of nanocrystalline powders increases with increasing temperature. It was found that nanocrystals retain the bulk structure with tetragonal and monoclinic symmetry for the sodium and potassium analogues, respectively. In contrast to this behaviour, LiY(WO4)2 undergoes a size-induced structural transformation from monoclinic (space group P2/n) to tetragonal (space group I41/a) symmetry. IR spectra of the synthesized sodium and potassium compounds are very similar to their bulk counterparts. IR spectra of the lithium analogues show, however, abrupt changes when the calcination temperature increases to 850 °C or higher. This behaviour is consistent with the size-induced phase transition in this compound.

Polarized Raman and IR spectra of oriented Cd(0.9577)Gd(0.0282)□(0.0141)MoO4 and Cd(0.9346)Dy(0.0436)□(0.0218)MoO4 single crystals where □ denotes the cationic vacancies.

Polarized Fourier Transform IR and Raman spectra of Cd0.9577Gd0.0282□0.0141MoO4 and Cd0.9346Dy0.0436□0.0218MoO4 oriented single crystals have been recorded and analyzed using the factor group approach (□ denotes the cationic vacancies). The tetragonal I41/a (C4h(6)) space group with Z=2 has been applied in the discussion. The influence of the structural changes induced by the defects in the CdMoO4 host lattice on the vibrational symmetry rules has been analyzed. The assignment of the observed bands to the internal and external modes has been proposed.

A targeted therapy for protein and lipid kinases in chronic lymphocytic leukemia.

Protein kinases (PKs) and lipid kinases (LKs) are good choices for targets of signal transduction therapy as these enzymes are involved in signaling pathways, and are often related to the pathogenesis of lymphoid malignancies. The attractiveness of PKs and LKs as drug able targets is enhanced by the fact that they are enzymes whose biological activity can be turned off by drugs that block their catalytic site. In the last few years small molecular kinase inhibitors (KIs) have been synthesized and become available for preclinical studies and clinical trials. The first KI, introduced into clinical practice in 1998, was imatinib mesylate, which became the first choice drug in chronic myeloid leukemia. More recently, several KIs have been developed to target the proximal B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, AVL-263). These agents are currently evaluated in early clinical trials in chronic lymphocytic leukemia (CLL) and other diseases. Cyclin-dependent kinase (Cdk) inhibitors, flavopiridol (alvocidib), BMS-387032 (SNS-032), sunitinib and sorafenib are currently under evaluation in clinical trials for relapsed/refractory CLL. Multi-tyrosine kinase inhibitors including vandetanib (ZD6474) bosutinib (SKI-606), TKI258 (CHIR-258), pazopanib (GW786034) and axitinib (AG013736) have been also developed for the treatment of lymphoid malignancies. Phosphatidylinositol 3-kinases (PI3K ) are a family of lipid kinases that mediate signals from cell surface receptors. CAL-101 (GS-1101) is an oral PI3Kδ-specific inhibitor which has shown preclinical and clinical activity against CLL. This article summarizes recent achievements in the mechanism of action, pharmacological properties and clinical activity and toxicity of PK and LK inhibitors in CLL.