Natural Killer Cells—An Epigenetic Perspective of Development and Regulation

Based on their ability to recognize and eliminate various endo- and exogenous pathogens as well as pathological alterations, Natural Killer (NK) cells represent an important part of the cellular innate immune system. Although the knowledge about their function is growing, little is known about their development and regulation on the molecular level. Research of the past decade suggests that modifications of the chromatin, which do not affect the base sequence of the DNA, also known as epigenetic alterations, are strongly involved in these processes. Here, the impact of epigenetic modifications on the development as well as the expression of important activating and inhibiting NK-cell receptors and their effector function is reviewed. Furthermore, external stimuli such as physical activity and their influence on the epigenetic level are discussed.     

Textural,Rheological and Sensory Properties and Oxidative Stability of Nut Spreads—A Review

Tree nuts are rich in macro and micronutrients, phytochemicals, tocopherols and phenolic compounds. The development of nut spreads would potentially increase the food uses of nuts and introduce consumers with a healthier, non-animal breakfast snack food. Nut spreads are spreadable products made from nuts that are ground into paste. Roasting and milling (particle size reduction) are two important stages for the production of nut spreads that affected the textural, rheological characteristic and overall quality of the nut spread. Textural, color, and flavor properties of nut spreads play a major role in consumer appeal, buying decisions and eventual consumption. Stability of nut spreads is influenced by its particle size. Proper combination of ingredients (nut paste, sweetener, vegetable oil and protein sources) is also required to ensure a stable nut spread product is produced. Most of the nut spreads behaved like a non-Newtonian pseudo-plastic fluid under yield stress which help the producers how to start pumping and stirring of the nut spreads. Similar to other high oil content products, nut spreads are susceptible to autoxidation. Their oxidation can be controlled by application of antioxidants, using processing techniques that minimize tocopherol and other natural antioxidant losses.     

Effect of type of polymerization catalyst system on the degradation and stabilization of polyethylenes in the melt state—Part 4: Comparative antioxidant effectiveness on organoleptic extractables

Several polyethylene resins using Ziegler, metallocene, and Phillips catalyst technologies were examined to obtain more detailed information about the effect of different polymerization catalyst systems on the production of extractable thermo-oxidative degradation products formed during melt processing cycles. This produces volatile organoleptic components (VOCs and extractable) such as hydrocarbons, alcohols, aldehydes, ketones, and carboxylic acids. Although some of the oxidation products are in-chain bound, many are produced as free, easily extractable entities or volatile components. The purpose of this study is to identify the nature of the products by gas chromatography–mass spectrometry (GC–MS) and FTIR analysis. The identity of the VOCs formed is necessary to modify the product's quality or establish which are toxic and/or leachable with food products. The results show that the evolution of carbonyl products, nature, and quantity is influenced significantly by the polymer type and catalyst used. Over 300 organoleptics low molar mass degradation products, such as alkane, alkene, carbonyl, and alcohol functionalities were detected by GC–MS analysis coupled with FTIR analysis on hexane extractables. Certain stabilizers can control the generation of certain functionalities and inhibit others. Of importance was the discovery of the relationship between additive activity and structure and inhibition of the formation of specific types of oxidation functionalities to a particular catalyst system.     

Mechanisms of Lin28-Mediated miRNA and mRNA Regulation—A Structural and Functional Perspective

Lin28 is an essential RNA-binding protein that is ubiquitously expressed in embryonic stem cells. Its physiological function has been linked to the regulation of differentiation, development, and oncogenesis as well as glucose metabolism. Lin28 mediates these pleiotropic functions by inhibiting let-7 miRNA biogenesis and by modulating the translation of target mRNAs. Both activities strongly depend on Lin28’s RNA-binding domains (RBDs), an N-terminal cold-shock domain (CSD) and a C-terminal Zn-knuckle domain (ZKD). Recent biochemical and structural studies revealed the mechanisms of how Lin28 controls let-7 biogenesis. Lin28 binds to the terminal loop of pri- and pre-let-7 miRNA and represses their processing by Drosha and Dicer. Several biochemical and structural studies showed that the specificity of this interaction is mainly mediated by the ZKD with a conserved GGAGA or GGAGA-like motif. Further RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq) studies confirmed this binding motif and uncovered a large number of new mRNA binding sites. Here we review exciting recent progress in our understanding of how Lin28 binds structurally diverse RNAs and fulfills its pleiotropic functions.     

Calcium in Red Blood Cells—A Perilous Balance

Ca²⁺ is a universal signalling molecule involved in regulating cell cycle and fate, metabolism and structural integrity, motility and volume. Like other cells, red blood cells (RBCs) rely on Ca²⁺ dependent signalling during differentiation from precursor cells. Intracellular Ca²⁺ levels in the circulating human RBCs take part not only in controlling biophysical properties such as membrane composition, volume and rheological properties, but also physiological parameters such as metabolic activity, redox state and cell clearance. Extremely low basal permeability of the human RBC membrane to Ca²⁺ and a powerful Ca²⁺ pump maintains intracellular free Ca²⁺ levels between 30 and 60 nM, whereas blood plasma Ca²⁺ is approximately 1.8 mM. Thus, activation of Ca²⁺ uptake has an impressive impact on multiple processes in the cells rendering Ca²⁺ a master regulator in RBCs. Malfunction of Ca²⁺ transporters in human RBCs leads to excessive accumulation of Ca²⁺ within the cells. This is associated with a number of pathological states including sickle cell disease, thalassemia, phosphofructokinase deficiency and other forms of hereditary anaemia. Continuous progress in unravelling the molecular nature of Ca²⁺ transport pathways allows harnessing Ca²⁺ uptake, avoiding premature RBC clearance and thrombotic complications. This review summarizes our current knowledge of Ca²⁺ signalling in RBCs emphasizing the importance of this inorganic cation in RBC function and survival.     

A Comparative Study of the Biosorption of Iron(III)—Cyanide Complex Anions to Rhizopus arrhizus and Chlorella vulgaris

ABSTRACT

In this study a comparative biosorption of iron(III)—cyanide complex anions from aqueous solutions to Rhizopus arrhizus and Chlorella vulgaris was investigated. The iron(III)—cyanide complex ion-binding capacities of the biosorbents were shown as a function of initial pH, initial iron(III)—cyanide complex ion, and biosorbent concentrations. The results indicated that a significant reduction of iron(III)—cyanide complex ions was achieved at pH 13, a highly alkaline condition for both the biosorbents. The maximum loading capacities of the biosorbents were found to be 612.2 mg/g for R. arrhizus at 1996.2 mg/L initial iron(III)—cyanide complex ion concentration and 387.0 mg/g for C. vulgaris at 845.4 mg/L initial iron(III)—cyanide complex ion concentration at this pH. The Freundlich, Langmuir, and Redlich-Peterson adsorption models were fitted to the equilibrium data at pH 3, 7, and 13. The equilibrium data of the biosorbents could be best fitted by all the adsorption models over the entire concentration range at pH 13.     

Applicability of Vacuum Impregnation to Modify Physico-Chemical,Sensory and Nutritive Characteristics of Plant Origin Products—A Review

Vacuum impregnation is a non-destructive method of introducing a solution with a specific composition to the porous matrices of fruit and vegetables. Mass transfer in this process is a result of mechanically induced differences in pressure. Vacuum impregnation makes it possible to fill large volumes of intercellular spaces in tissues of fruit and vegetables, thus modifying physico-chemical properties and sensory attributes of products. This method may be used, e.g., to reduce pH and water activity of the product, change its thermal properties, improve texture, color, taste and aroma. Additionally, bioactive compounds may be introduced together with impregnating solutions, thus improving health-promoting properties of the product or facilitating production of functional food.     

Lidocaine Sensitizes the Cytotoxicity of Cisplatin in Breast Cancer Cells via Up-Regulation of RARβ2 and RASSF1A Demethylation

It has been reported that lidocaine is toxic to various types of cells. And a recent study has confirmed that lidocaine exerts a demethylation effect and regulates the proliferation of human breast cancer cell lines. To recognize a potential anti-tumor effect of lidocaine, we evaluated the DNA demethylation by lidocaine in human breast cancer lines, MCF-7 and MDA-MB-231 cells, and determined the influence of demethylation on the toxicity to these cells of cisplatin, which is a commonly utilized anti-tumor agent for breast cancer. Results demonstrated that lidocaine promoted a significant global genomic demethylation, and particularly in the promoters of tumor suppressive genes (TSGs), RARβ2 and RASSF1A. Further, the lidocaine treatment increased cisplatin-induced apoptosis and enhanced cisplatin-induced cytotoxicity. The combined treatment with both lidocaine and cisplatin promoted a significantly higher level of MCF-7 cell apoptosis than singular lidocaine or cisplatin treatment. Moreover, the abrogation of RARβ2 or RASSF1A expression inhibited such apoptosis. In conclusion, the present study confirms the demethylation effect of lidocaine in breast cancer cells, and found that the demethylation of RARβ2 and RASSF1A sensitized the cytotoxicity of cisplatin in breast cancer cells.     

Comparative in vitro Studies of the Topoisomerase I Inhibition and Anticancer Activities of Metallated N-Confused Porphyrins and Metallated Porphyrins

Using the original approach, a series of metallated N-confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL-60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and effects on the cell cycle as well as the kinetics of proliferative activity of porphyrins and their respective metallated complexes in real time have been developed. The inhibitory activity of metallated porphyrins against human topoisomerase I and the possible mechanism of inhibition have been carried out by modelling using molecular docking.     

The anodic behaviour of iron in ethanol—water solutions in the presence and absence of NaClO4 as the supporting electrolyte

The anodic behaviour of iron in ethanol—water solutions and the effect of NaClO₄ have been investigated on the basis of potentiostatic polarization curves and electrochemical impedance plots. The influence of the water content in ethanol (6–80 vol.%) on the anodic polarization curves without a supporting electrolyte is to increase the anodic current density monotonically with potential. Furthermore, for a given potential, the current density is higher when the water content is increased. In the presence of NaClO₄ the polarization curves shift towards more high current in the low anodic potential range. Thus, addition of NaClO₄ not only increases the conductivity of ethanol solutions in its role as a supporting electrolyte, but it also modifies the electrochemical process significantly.     

Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach

Background: Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA. Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively. Controls (n = 16) received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size. Results: Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation), compared to 29.3 ± 9.8 in mice with eight months (p = 0.49), 24.9 ± 21.3 with 12 months (p = 0.26), and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27). In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16) compared to controls and also after adjustment for cMB size (p = 0.13). Conclusion: Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed.     

Structure and Function of the Catalyst and the Promoter in Co—Mo Hydrodesulfurization Catalysts

Simply stated, a membrane is a barrier which is capable of redistributing components in a fluid stream through a driving force such as the difference in pressure, concentration, or electrical potential. When a concentration or electrical potential gradient provides the necessary driving force, this barrier separation process is called dialysis or electrodialysis. Most of the membrane processes are based on an applied pressure difference across the membranes.     

Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.     

Studying the mechanism of the interaction between silicon nitride, oxygen, and nitrogen in heating and the processes of defect formation in Si3N4 — gas systems

The method of precision thermal massometry is used to study the interaction between silicon nitride, oxygen, and nitrogen in nonisothermal heating at 300 -1300 K and a partial gas pressure of 19,998.3 Pa (150 Torr). The behavior of Si₃N₄ heated in forevacuum is studied. A special computer analysis of the experimentally obtained dependencies has provided kinetic equations for analyzing and determining the mechanisms of these processes and computing their activation energy. The experimental data are used for creating a hypothesis that the nitrogen sublattice of Si₃N₄ is dispersed before the beginning of its interaction with oxygen and nitrogen.     

Production of succinic acid in basket and mobile bed bioreactors—Comparative analysis of substrate mass transfer aspects

The glucose mass transfer in the biosynthesis of succinic acid with immobilized Actinobacil us succinogenes cel s has been comparatively analyzed for a bioreactor with mobile bed vs. a stationary basket bioreactor. The process has been considered to occur under substrate and product inhibitory effects. The results indicated that the biore-actor with mobile bed is more efficient for biocatalyst particles with a diameter over 3 mm, while the basket bio-reactor is more efficient for smal er biocatalyst particles and basket bed thickness below 5 mm. The performances of both configurations of immobilized A. succinogenes cell beds were found to be superior to the column packed bed bioreactor.     

Synthesis of 4��,7-Diacetoxyapigenin and Its Apoptotic Induction in Human Hep G2 Cells

In this study, 4′,7-diacetoxyapigenin [4-(7-acetoxy-5-hydroxy-4-oxo-4H-chromen-2-yl) phenyl acetate] was synthesized for the first time. Its chemical structure was identified by UV, ESI-MS, ¹H and ¹³C-NMR. It could inhibit the proliferation of Hep G2 cells in a dose-dependent manner and induce the significant increase of the G0/G1 cell population. After treatment by 4′,7-diacetoxyapigenin, phosphatidylserine of Hep G2 cells could significantly translocate to the surface of the membrane. The increase of an early apoptotic population was observed by both annexin-FITC and PI staining. It was concluded that 4′,7-diacetoxyapigenin not only induced cells to enter into apoptosis, but also affected the progress of the cell cycle.     

Terminal Alkynes as Raman Probes of α-Synuclein in Solution and in Cells

Conformational changes in α-synuclein (α-syn) are central to its biological function and Parkinson's disease pathology. Here, terminal alkynes (homopropargylglycine) were employed as environmentally sensitive Raman probes at residues 1, 5, 116, and 127 to characterize soluble (disordered), micelle-bound (α-helical), and fibrillar (β-sheet) α-syn. Along with the full-length protein, a disease-related C-terminal truncation (1–115) was also studied. For the first time, β-sheet α-syn amyloid structure was detected by the amide-I band in N27 dopaminergic rat cells, where a reciprocal relationship between levels of fibrils and lipids was seen. Site-specific spectral features of the terminal alkynes also revealed the heterogeneity of the cellular environment. This work shows the versatility of Raman microspectroscopy and the power of unnatural amino acids in providing structural and residue-level insights in solution and in cells.     

Comparative Studies on the Mechanochemistry of Guaiacylglycerol- and Veratrylglycerol- β -Guaiacyl Ether

Treatments of guaiacylglycerol- and veratrylglycerol-β-guaiacyl ether [I] and [II] with CBM, VBM and laboratory refiner furnished α-(2-methoxyphenoxy)-β-hydroxypropioguaiacone 1 as the major product in addition to a few small compounds 2-7 in relatively low yields. In addition, 5,5′-condensation reaction of compound [I] gave compounds 8 9, and 10. Alternatively, Cα-Cβ splitting reaction of veratrylglycerol-β-guaiacyl ether [II] occurrsby the mechanical treatment to give a number of products (6,11-14, and 15). Compounds [II] also formed p-carbonyl phenol 1 and products 2 4, and 7 by an alternate route. For comparison, mechanical treatments of vanillyT alcohol [III],α-methyl vanillyl alcohol [IV], and veratryl alcohol [V] were made with a ceramic ball mill (CBM), vibration ball mill (VBM), respectively. Former two gave vanillin 15 and acetovanillone 16, but no product was found from veratryl alcohol [V].     

Metabolic Compartmentation �C A System Level Property of Muscle Cells: Real Problems of Diffusion in Living Cells

Problems of quantitative investigation of intracellular diffusion and compartmentation of metabolites are analyzed. Principal controversies in recently published analyses of these problems for the living cells are discussed. It is shown that the formal theoretical analysis of diffusion of metabolites based on Fick''s equation and using fixed diffusion coefficients for diluted homogenous aqueous solutions, but applied for biological systems in vivo without any comparison with experimental results, may lead to misleading conclusions, which are contradictory to most biological observations. However, if the same theoretical methods are used for analysis of actual experimental data, the apparent diffusion constants obtained are orders of magnitude lower than those in diluted aqueous solutions. Thus, it can be concluded that local restrictions of diffusion of metabolites in a cell are a system-level properties caused by complex structural organization of the cells, macromolecular crowding, cytoskeletal networks and organization of metabolic pathways into multienzyme complexes and metabolons. This results in microcompartmentation of metabolites, their channeling between enzymes and in modular organization of cellular metabolic networks. The perspectives of further studies of these complex intracellular interactions in the framework of Systems Biology are discussed.