Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.     

Effect of Cover Brine Type on the Quality of Meat from Herring Marinades

Effects of vinegar, oil, and sour cream brines on meat quality of 4 popular cold marinades from herring were investigated in the study. Cover brine type affected the composition and nutritive value of meat as well as the sensory and microbiological quality of marinated herring. Qualitative differences resulted from cover brine penetration into meat, and from diffusion of components from meat to vinegar brine. Compared to oil and sour cream, vinegar brine contributed to increased concentrations of salt and acetic acid, hardness, color brightness of marinades meat and to increased microbial contamination of meat. Furthermore, vinegar caused nitrogen losses to 15%, including valuable products of protein hydrolysis, enzymes, and total volatile bases. The rolling up of fillets reduced diffusion even by 50%. In turn, oil and sour cream were causing mainly a higher fat content and overall sensory evaluation of the marinades.     

New lake district in Europe: origin and hydrochemical characteristics

This article presents a new lake district in Southern Poland created as a result of human activity in the Upper Silesian region. The area has been named the Upper Silesian Anthropogenic Lake District. The lake density of the Lake District as delineated by the authors (with an area of 6766 km²) is 2.74%. It includes 4773 water bodies of various origins – reservoirs retained by dams, flooded mineral workings, water bodies formed in subsidence basins and hollows, levee ponds, residual water bodies following river regulation and other water bodies. These are located in urban‐industrial, rural‐agricultural or quasi‐natural areas. The hydrochemical diversity of water bodies is conditioned by their origin, location in the catchment and function. Studies have shown the widespread occurrence of eutrophication processes in limnic waters within the Lake District. The diverse origin and hydrochemical properties of water bodies within the Upper Silesian Anthropogenic Lake District make it special among other anthropogenic lake districts.     

Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.     

Ventilation system with spiral recuperator

A new kind of longitudinal flow spiral recuperator for the heat recovery in ventilation systems of buildings was studied experimentally and analytically.The aim of this work is to analyze the possibility of using air handling units with new type of spiral recuperator in order to recover heat in ventilation systems of buildings. For the reason that the air flows are parallel to the symmetry axis of the longitudinal flow spiral recuperator, in this unit pressure drops are smaller than in commonly known spiral exchangers. Because of the counter flow, a greater value of thermal effectiveness ? is reached for the same value of the number of transfer units in comparison to cross-flow recuperators.The exploitation of the new type of spiral recuperator in winter periods brings significant savings. The results obtained from computations are very encouraging for a widespread use of these devices.     

Correlating the effects of ash elements and their association in the fuel matrix with the ash release during pulverized fuel combustion

During pulverized fuel combustion, inorganic elements such as alkalis, sulfur, chlorine, calcium and magnesium, as well as a range of minor elements are partly released into the gas phase. These gas-borne species can nucleate, coagulate and condense to form either aerosol particles or sticky layers on ash particles, leading to ash deposition and corrosion problems in power utilities. Furthermore, the fine aerosols can lead to harmful gaseous and particulate emissions. It is well documented that the mode of occurrence and the chemical speciation of ash forming elements in the coal/biomass structure are important for the release behavior of mineral components. In the presented work, this is investigated by performing quantitative elemental investigations of ash releases for two different coals (a Polish and a UK coal) and six diverse biomass fuels (Wood bark, Wood chips, Waste wood, Olive residue, Saw dust and Straw). The tests are performed within the Lab-scale Combustion Simulator (LCS) of the Energy Research Centre of the Netherlands (ECN). The operating conditions applied were that of a typical pulverized fuel (PF) fired boiler i.e. atmospheric pressure, high temperatures of 1400-1650 °C, and high heating rate of 10⁵ K/s. Gas phase elemental release of alkalis, sulfur, chlorine, calcium and magnesium has been quantified at relevant high carbon conversion levels. With the performed set of experiments several of the past observations from the literature are reconfirmed. In addition to this, based on the extensive data pool at hand, a simple but reliable (R² > 0.95) set of linear correlations have been proposed to predict the elemental release of potassium, sodium, chlorine and sulfur. It is also concluded that such linear expressions can be particularly effective for the prediction of elemental release from the fuels of similar characteristics, such as woody biomass.     

Novel adhesive system based on 1,3-dimethylol-4,5-dihydroxyethyleneurea (DMDHEU) and hyperbranched polyglycerols

Two hyperbranched polyglycerols bearing 1,1,1-tris(hydroxymethyl)propane or Bisphenol A core and terminal hydroxyl functionality were examined as components of novel wood adhesive systems. Two 1,3-dimethylol-4,5-dihydroxyethyleneurea resins (DMDHEU) were used as crosslinkers. Shear strength tests revealed that the adhesives containing up to 75 wt% of renewable glycerol-derived polyglycerols retained performance comparable to that of neat DMDHEU. The results give way to extending the area of application of hyperbranched polyglycerols in the field of wood adhesives.     

Modification of physicochemical properties of actin filaments suppresses cell fragmentation in the execution phase of staurosporine-induced apoptotic processes

Effects of jasplakinolide (JSP), a stabilizer of F-actin, and latrunculin A (LTA), a destabilizer of F-actin, on a series of events occurring in the execution phase of staurosporine (STS)-induced apoptotic processes were studied using human osteosarcoma 143B cells. Time-dependent apparent increases of the population of cells with collapsed membrane potential of mitochondria (Delta Psi(m)) caused by STS treatment were not due to actual decreases in the Delta Psi(m) per cell, but due to the fragmentation of cells resulting in decreases in the number of active mitochondria per cell. Decreases in the Delta Psi(m) in fragmented cells occurred late in the execution phase. Both JSP and LAT failed to prevent STS-induced release of cytochrome c from mitochondria followed by the activation of caspases 3 and 9, the cleavage of poly (ADP-ribose) polymerase (PARP) and apoptotic nuclear fragmentation. However, both drugs prevented STS-induced apoptotic cell fragmentation and decreases in the Delta Psi(m). These results indicate that physicochemical states of actin filaments play a certain role in the execution phase of STS-induced apoptotic processes.