Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM.     

Single-step preparation of rutile-type CrNbO4 and CrTaO4 oxides from oxalate precursors–characterization and properties

Chromium niobate and tantalate (CrNbO₄ and CrTaO₄) were synthesized by pyrolysis of the oxalate-based heterometallic complexes [Cr₂(bpy)₄(μ-O)₄Nb₂(C₂O₄)₄]·3H₂O (Cr-Nb) and [Cr(bpy)₂(H₂O)(μ-O)Ta(C₂O₄)₃]₂·3.5H₂O (Cr-Ta) (bpy = 2,2'-bipyridine). Compared to conventional solid-state synthesis, herein studied oxides are prepared at lower temperatures, in one step without repeating grinding procedures. The structure, morphology, and optical properties of the as-synthesized oxides were characterized using powder X-ray diffraction (PXRD), field emission scanning electron microscopy (SEM), the thermogravimetric and differential thermal analysis (TG/DTA) and UV-vis diffuse reflectance spectroscopy (UV-vis DRS). The determined band gap energies of CrNbO₄ and CrTaO₄ are 2.39 and 2.82 eV, respectively, which prompted us to investigate photocatalytic activity of these oxides in degradation of dyes. Microscopy studies show that the particles of both oxides began to aggregate into bigger particles, leading to an increase in grain size. Additionally, magnetization measurements on both oxides revealed spin-glass behavior at low temperatures.     

Bi2Ti2O7‐based pyrochlore nanoparticles and their superior photocatalytic activity under visible light

Nanoparticles of Bi₂Ti₂O₇ pyrochlore were synthesized by a coprecipitation method. They exhibit a high visible‐light photoactivity for decolorization of a methyl‐orange dye solution in the presence of a sacrificial agent, H₂O₂. The same pyrochlore system with an Ag co‐catalyst showed even faster kinetics under only visible light and an unprecedentedly high photoactivity in the UV range.     

Evaluation of peach and nectarine fruit quality and correlations between sensory and chemical attributes

Sensory attributes and chemical composition in peach and nectarine fruits of nine different cultivars were evaluated and compared. The cultivars investigated in the research were: ‘Maria Marta’, ‘Romestar’, ‘325 × A/8’, ‘224 × A/13’, ‘V × S/4’, ‘Bea’, ‘Maria Aurelia’, ‘Venus’ and ‘Spring Red’. In sensory evaluation the ‘Maria Aurelia’ was the highest rated, and the ‘224 × A/13’ was the lowest. The cultivars ‘325 × A/8’, ‘224 × A/13’, ‘V × S/4’ and ‘Spring Red’ were poor in sugars; however, the ‘Spring Red’ was rich in organic acids. Similarly, the ‘Maria Aurelia’ and ‘Venus’ fruits had higher contents of organic acids and were also rich in sugars. Furthermore, the relationships among sensory and chemical attributes of fruit quality were studied. The sensory evaluations of sweetness, taste, and aroma were well correlated with some chemically measured attributes of peach and nectarine quality: sweetness was influenced by citric acid, shikimic acid and sugars/organic acids ratio; aroma was correlated with total organic acids, sucrose, sorbitol and malic acid; taste was related to malic/citric acid ratio, total sugars, sucrose, sorbitol and malic acid. The results of the research indicate that sensory evaluation provides a good tool in the quick assessment of peach and nectarine fruit quality. Copyright © 2005 Society of Chemical Industry     

Commonly applied smoothing of IR spectra showed unappropriate for the identification of plant leaf samples

The use of infrared spectroscopy has spread from single compound research to the investigation of complex biological samples. In infrared spectroscopy, spectral pre-treatment techniques have been assumed to be equally applicable and effective in the analysis of biological samples with complex chemical composition and structure. In this research, the most commonly used pre-treatment techniques were investigated based on the identification of species from whole leaf samples of pharmaceutically important Epilobium and Hypericum genera. Two spectral collection modes were used; whole leaf transmission and KBr-tablet transmission mode. The results of this study do not support the current standard in pre-treatment methods. After the frequency decomposition of a spectral signal by Fourier transform and wavelet decomposition, it was revealed that the important information of whole plant leaf as an example of biological samples was contained in the spectral details. Therefore, smoothing techniques were not appropriate because high frequency information is lost. A vast majority of published work used a Savitzky-Golay smoothing method on infrared spectra of complex biological samples. This method was shown to be less effective. In contrast, taking the derivative of the spectra showed significantly better results; with this pre-treatment method, the overlapping bands become more evident.     

Computerized segmentation of whole-body bone scintigrams and its use in automated diagnostics

Bone scintigraphy or whole-body bone scan is one of the most common diagnostic procedures in nuclear medicine used in the last 25 years. Pathological conditions, technically poor image resolution and artefacts necessitate that algorithms use sufficient background knowledge of anatomy and spatial relations of bones in order to work satisfactorily. A robust knowledge based methodology for detecting reference points of the main skeletal regions that is simultaneously applied on anterior and posterior whole-body bone scintigrams is presented. Expert knowledge is represented as a set of parameterized rules which are used to support standard image-processing algorithms. Our study includes 467 consecutive, non-selected scintigrams, which is, to our knowledge the largest number of images ever used in such studies. Automatic analysis of whole-body bone scans using our segmentation algorithm gives more accurate and reliable results than previous studies. Obtained reference points are used for automatic segmentation of the skeleton, which is applied to automatic (machine learning) or manual (expert physicians) diagnostics. Preliminary experiments show that an expert system based on machine learning closely mimics the results of expert physicians.     

Pressure drop and heat transfer in gas-cooled rod bundles

Extensive experimental and analytical investigations of fluid flow and heat transfer in gas-cooled rod bundles have been carried out. Different bundle geometries with partially or fully roughened rod surfaces were tested in a carbon dioxide loop. An advanced and comprehensive measuring control and instrumentation are important design features of this experiment. Comprehensive thermal hydraulic subchannel analysis computer codes have been developed in order to assist fuel element design calculation for gas-cooled reactors. The experiments, codes and their verification procedure are described and the results of comparisons between measured and calculated pressure and temperature distributions are given.     

5‐Benzylidenethiazolidin‐4‐ones as Multitarget Inhibitors of Bacterial Mur Ligases

Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series of hydroxy‐substituted 5‐benzylidenethiazolidin‐4‐ones were synthesized and tested as inhibitors of Mur ligases. The most potent compound 5 a was active against MurD–F with IC₅₀ values between 2 and 6 μm, making it a promising multitarget inhibitor of Mur ligases. Antibacterial activity against different strains, inhibitory activity against protein kinases, mutagenicity and genotoxicity of 5 a were also investigated, and kinetic and NMR studies were conducted.