On the applied stress dependence of the subgrain size

The present work studies the collection of experimental data from which Raj and Pharr (Mater. Sci. Eng., 81 (1986) 217) deduced a universal empirical dependence of the subgrain size on the applied stress. In accord with their result and some theoretical predictions the normalized subgrain size d_s/b was ssumed to be proportional to G/σ (G is the shear modulus, b the Burgers vector length, σ the applied stress). The evaluated factor of proportionality K₁, having the value within the interval from 0.76 to 180 in the inspected data sets, was discussed from the point of view of various factors which can influence the experimental data.     

Contrast-Free FLIM Reveals Metabolic Changes in Pathological Islets of Langerhans

FLIM (Fluorescence Lifetime Imaging Microscopy) is a powerful tool that could be used in the future to diagnose islet cell recovery after therapy. The identification of appropriate FLIM parameters is required to determine islet quality and islet cell metabolism throughout the organ under various conditions of insulin deficiency. The aim of the work was to identify key FLIM parameters, changes of which are characteristic of pancreatic pathologies. The τm, τ1, τ2, α1, α2 and α1/α2 of free and bound forms of NAD(P)H of the islet cells of animals (rats and pigs) and of humans with and without pathologies were measured and analyzed. The data were confirmed by IHC and histological studies. We identified three FLIM parameters in islet cells from animals with streptozotocin (STZ)-induced diabetes mellitus (DM) and from humans with chronic pancreatitis + type 2 diabetes (T2D), which differ in the same way: τm and α2 take lower values compared to the nonpathological islet cells, while α1/α2 takes higher values. In islet cells from patients with adenocarcinoma (PDAC) and chronic pancreatitis, these parameters had reverse tendency relative to the norm or did not differ. Thus, minimally invasive and non-contrast FLIM methods may, in the future, be used to diagnose pathological islet cells.     

Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids

Muscarinic acetylcholine receptors expressed in the central nervous system mediate various functions, including cognition, memory, or reward. Therefore, muscarinic receptors represent potential pharmacological targets for various diseases and conditions, such as Alzheimer’s disease, schizophrenia, addiction, epilepsy, or depression. Muscarinic receptors are allosterically modulated by neurosteroids and steroid hormones at physiologically relevant concentrations. In this review, we focus on the modulation of muscarinic receptors by neurosteroids and steroid hormones in the context of diseases and disorders of the central nervous system. Further, we propose the potential use of neuroactive steroids in the development of pharmacotherapeutics for these diseases and conditions.     

Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.     

Carbosilane Metallodendrimers with Cyclopentadienyldichlorotitanium(IV) End Groups

Dendritic polyols of the second and third generation 2G-OH₈ (1), 2G-OH₁₆ (2), and 3G-OH₁₆ (3) were prepared by hydroboration/oxidation of allyl-terminated carbosilane dendrimers and used as supports for the immobilization of cyclopentadienyltrichlorotitanium(IV) complexes via alcoholysis. The reaction of 1–3 with CpTiCl₃ gave metallodendrimers 2G-(OTiCpCl₂)₈ (4a), 2G-(OTiCpCl₂)₁₆ (5a), and 3G-(OTiCpCl₂)₁₆ (6a), respectively, whereas the reaction of 1 and 3 with CpSi^FTiCl₃ (CpSi^F = C₅H₄SiMe₂CH₂CH₂C₈F₁₇) yielded peripherally fluorinated metallodendrimers 2G-(OTiCpSi^FCl₂)₈ (4b) and 3G-(OTiCpSi^FCl₂)₁₆ (6b). All metallodendrimers were characterized by multinuclear NMR spectroscopy. The suggested structures were supported by comparison with model 1-propoxycomplexes 10a,b. To identify side products of the alcoholysis reaction, hydrolytic behavior of the starting trichloro complexes was studied both in solid state and in solution. The main products of hydrolysis in solution were identified as μ-oxocomplexes 8a,b whereas hydrolysis in solid state yielded mainly hydroxycomplexes 7a,b.     

Cultivar differences of total anthocyanins and anthocyanidins in red and purple-fleshed potatoes and their relation to antioxidant activity

Total anthocyanins (TAC) and individual anthocyanidins (AN) after hydrolysis were measured in 15 red and purple-fleshed potato cultivars produced in five different locations in the Czech Republic and a new cultivar Blaue St. Galler from Switzerland. It was found that TAC, expressed as cyanidin content, varied between 0.7 mg 100 g⁻¹ FW (cv. Blue Congo) and 74.3 mg 100 g⁻¹ FW (cv. Blaue Ludiano). Major differences in cultivars were found for AN relative abundance. For cv. Highland Burgundy Red a high proportion of pelargonidin (98.7%) was characteristic, whereas cv. British Columbia Blue contained almost exclusively cyanidin. Cultivars Violette and Vitelotte showed a relatively high content of malvidin. Cultivar Shetland Black differed from others with its higher content of peonidin (on average 36.7%). High petunidin abundance in the cultivars Valfi, Blue Congo, Salad Blue, Blaue St. Galler, Blaue Hindel Bank, Blaue Ludiano, Blaue Schweden, Farbe Kartoffel and Salad Red was found. TAC and AN contents highly corresponded with antioxidant activity (AA) determined with the ABTS, FRAP and DPPH assays in vitro. High AA was shown by the cultivars Vitelotte, Violette, Blaue Ludiano, Hafija, and Highland Burgundy Red. Increased height above sea level, higher annual sum of precipitation, and lower annual average temperatures caused higher AA and TAC. A high degree of hydroxylation and/or methoxylation of individual anthocyanidins could contribute in conjunction with other phenolics to high AA (peonidin, delphinidin and malvidin in the cultivars Blue Congo, Highland Burgundy Red and Shetland Black). Consequently, new red and purple-fleshed cultivars with high TAC and highly methoxylated and/or hydroxylated AN could be a promising source of favourable antioxidants in human nutrition.     

MALDI-TOF MS and Morphology Studies of Thiacalixarene-Silsesquioxane Products of Oligo- and Polycondensation

For the first time condensed silsesquioxane derivatives of tetratrialkoxysilyl compounds have been characterized by MALDI-TOF mass spectrometry. Tetrasubstituted p-tert-butyl thiacalix[4]arene derivatives containing organosilicon fragments with variable stereochemistry were chosen as organosilicon compounds for polycondensation. Information obtained from mass spectra was used to deduce both the structures of oligomeric derivatives, as well as the structure of silsesquioxane framework. The morphology of formed polysilsesquioxanes was investigated by scanning and transmission electron microscopy.