Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice

Tat-interactive protein 60 kDa (TIP60, also known as lysine acetyltransferase 5 [KAT5]) is a member of the MYST protein family with histone acetyltransferase activity. Recent studies have reported that TIP60 has multiple functions in many signal transduction mechanisms, especially p53-mediated apoptosis. Although the activation of apoptosis signaling pathways requires the presence of cellular reactive oxygen species (ROS) at a certain level, an imbalance between the production and consumption of ROS in cells results in oxidative stress (OS). In this study, we investigated for the first time how the absence of the Tip60 gene in the liver affects gene expression, enzyme activity, and protein expression of the hepatic antioxidant members localized in the cytoplasm, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST). First, we successfully generated liver-specific Tip60 knockout mice (mutants) using Cre/LoxP recombination. The reduced glutathione level and nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) expression, a marker of OS, increased significantly in the Tip60 mutant liver. Gene expression, activity, and protein expression of the enzymatic antioxidant system, including SOD, CAT, GR, GPx, and GST were investigated in mutants and control groups. Despite a significant correlation between the gene, enzyme activity, and protein content for CAT and GR, this was not true for SOD and GPx. The overall results suggest that TIP60 acts on the hepatic antioxidant system both at the gene and protein levels, but the actual effect of the deletion of Tip60 is observed at the protein level, especially for SOD and GPx.     

Novel Cytotoxic Sesquiterpene Ester Derivatives from the Roots of Ferula mervynii

This study is the first chemical investigation of Ferula mervynii M. Sağıroğlu & H. Duman, an endemic species to Eastern Anatolia. The isolations of nine compounds including six previously undescribed sesquiterpene esters, 8-trans-cinnamoyltovarol ( 1 ), 8-trans-cinnamoylantakyatriol ( 3 ), 6-acetyl-8-trans-cinnamoyl-3-epi-antakyatriol ( 5 ), 6-acetyl-8-trans-cinnamoylshiromodiol ( 6 ), 6-acetyl-8-trans-cinnamoylfermedurone ( 7 ), and 6-acetyl-8-trans-cinnamoyl-(1S),2-epoxyfermedurone ( 8 ), were described along with three known sesquiterpene esters, 6-acetyl-8-benzoyltovarol ( 2 ), 6-acetyl-8-trans-cinnamoylantakyatriol ( 4 ), and ferutinin ( 9 ). The structures of novel compounds were elucidated through extensive spectroscopic analyses and quantum chemistry calculations. The putative biosynthetic pathways for compounds 7 and 8 were discussed. The extracts and isolated compounds were tested for cytotoxic activity against the COLO 205, K-562, MCF-7 cancer cell lines, and Human Umbilical Vein Endothelial Cell (HUVEC) lines using MTT assay. Compound 4 showed the highest activity against the MCF-7 cell lines with an IC₅₀ value of 16.74±0.21 μM.     

Wear Behavior of Plasma Oxidized CoCrMo Alloy under Dry and Simulated Body Fluid Conditions

In this study, CoCrMo alloy was oxidized in plasma environment at the temperatures of 600 ℃ to 800 ℃ for 1 h to 5 h with 100% 02 gas and its tribological behavior was investigated. After the plasma oxidizing process, the compound and diffusion layers were formed on the surface. XRD results show that Cr203, a-Co and ε-Co phases diffracted from the modified layers after plasma oxidizing. The untreated and treated CoCrMo samples were subjected to wear tests both in dry and simulated body fluid conditions, and normal loads of 2 N and 10 N were used. For the sliding wear test, alumina balls were used as counter materials. It was observed that the wear resistance of CoCrMo alloy was increased after the plasma oxidizing process. The lowest wear rate was obtained from the samples that were oxidized at 800 ℃ for 5 h. It was detected that both wear environment and load have significant effects on the wear behavior of this alloy, and the wear resistance of oxidized CoCrMo alloy is higher when oxide-based counterface is used. The wear rates of both untreated and plasma oxidized samples increase under high loads.     

Phylostat: a web-based tool to analyze paralogous clade divergence in phylogenetic trees

Phylogenetic trees are useful tools to infer evolutionary relationships between genetic entities. Phylogenetics enables not only evolution-based gene clustering but also the assignment of gene duplication and deletion events to the nodes when coupled with statistical approaches such as bootstrapping. However, extensive gene duplication and deletion events bring along a challenge in interpreting phylogenetic trees and require manual inference. In particular, there has been no robust method of determining whether one of the paralog clades systematically shows higher divergence following the gene duplication event as a sign of functional divergence. Here, we provide Phylostat, a graphical user interface that enables clade divergence analysis, visually and statistically. Phylostat is a web-based tool built on phylo.io to allow comparative clade divergence analysis, which is available at https://phylostat.adebalilab.org under an MIT open-source licence.     

Construction of Predictive Models to Describe Apparent and Complex Viscosity Values of O/W Model System Meat Emulsions Using Adaptive Neuro – Fuzzy Inference System (ANFIS) and Artificial Neural Networks (ANN)

This paper introduces an adaptive neuro ?C fuzzy inference system (ANFIS) and artificial neural networks (ANN) models to predict the apparent and complex viscosity values of model system meat emulsions. Constructed models were compared with multiple linear regression (MLR) modeling based on their estimation performance. The root mean square error (RMSE), mean absolute error (MAE) and determination coefficient (R ²) statistics were performed to evaluate the accuracy of the models tested. Comparison of the models showed that the ANFIS model performed better than the ANN and MLR models to estimate the apparent and complex viscosity values of the model system meat emulsions. Coefficients of determination (R ²) calculated for estimation performance of ANFIS modeling to predict apparent and complex viscosity of the emulsions were 0.996 and 0.992, respectively. Similar R ² values (0.991 and 0.985) were obtained when estimating the performance of the ANN model. In the present study, use of the constructed ANFIS models can be suggested to effectively predict the apparent and complex viscosity values of model system meat emulsions.     

Electromagnetic effects – From cell biology to medicine

In this review we compile and discuss the published plethora of cell biological effects which are ascribed to electric fields (EF), magnetic fields (MF) and electromagnetic fields (EMF). In recent years, a change in paradigm took place concerning the endogenously produced static EF of cells and tissues. Here, modern molecular biology could link the action of ion transporters and ion channels to the “electric” action of cells and tissues. Also, sensing of these mainly EF could be demonstrated in studies of cell migration and wound healing. The triggers exerted by ion concentrations and concomitant electric field gradients have been traced along signaling cascades till gene expression changes in the nucleus.Far more enigmatic is the way of action of static MF which come in most cases from outside (e.g. earth magnetic field).All systems in an organism from the molecular to the organ level are more or less in motion. Thus, in living tissue we mostly find alternating fields as well as combination of EF and MF normally in the range of extremely low-frequency EMF. Because a bewildering array of model systems and clinical devices exits in the EMF field we concentrate on cell biological findings and look for basic principles in the EF, MF and EMF action.As an outlook for future research topics, this review tries to link areas of EF, MF and EMF research to thermodynamics and quantum physics, approaches that will produce novel insights into cell biology.     

In vitro and in vivo effects of iron on the expression and activity of glucose 6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase,and glutathione reductase in rat spleen

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long‐term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6‐phosphate dehydrogenase (G6PD), 6‐phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level.