Identification of a novel mutation in ZAP70 and prenatal diagnosis in a Turkish family with severe combined immunodeficiency disorder

Protein tyrosine kinases (PTKs) play an important role in T cell development and activation. In vitro and in vivo defects, resulting in variable deficiencies in thymic development and in T cell antigen receptor (TCR) signal transduction, in PTKs have been shown. ZAP70, one of those PTKs, is a 70-kDa tyrosine phosphoprotein and associates with the ζ chain and undergoes tyrosine phosphorylation following TCR stimulation. It is expressed in T and natural killer (NK) cells. Several mutations were shown to lead to an autosomal recessive form of severe combined immunodeficiency disease (SCID).     

Selection Shapes the Robustness of Ligand-Binding Amino Acids

The phenotypes of biological systems are to some extent robust to genotypic changes. Such robustness exists on multiple levels of biological organization. We analyzed this robustness for two categories of amino acids in proteins. Specifically, we studied the codons of amino acids that bind or do not bind small molecular ligands. We asked to what extent codon changes caused by mutation or mistranslation may affect physicochemical amino acid properties or protein folding. We found that the codons of ligand-binding amino acids are on average more robust than those of non-binding amino acids. Because mistranslation is usually more frequent than mutation, we speculate that selection for error mitigation at the translational level stands behind this phenomenon. Our observations suggest that natural selection can affect the robustness of very small units of biological organization.     

A New Type of Anatolian Propolis: Evaluation of Its Chemical Composition,Activity Profile and Botanical Origin

This study was undertaken to analyze the phenolic profiles of 19 propolis samples from Turkey by using a high‐performance thin‐layer chromatographic (HPTLC) method in order to identify their plant origins. Furthermore, their antioxidant and antimicrobial activity profiles were comparatively evaluated. For the appraisal of antioxidant potential, total phenolic (TPC) and total flavonoid contents (TFC) of propolis samples were firstly determined and then their effects on free radicals were evaluated by FRAP, ABTS^.+, CUPRAC, DPPH^. and HPTLC‐DPPH^. methods. Antimicrobial activity of propolis samples against Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 11229) and Candida albicans ATCC 10231 were determined by disc diffusion and broth dilution methods. HPTLC fingerprinting analyses revealed that O‐type (botanical origin from Populus nigra L.) was the primarily available propolis type in Turkey. Moreover, 3‐O‐methylquercetin (3MQ) rich propolis was identified as a new propolis type for the first time. Principal component analysis (PCA) indicated that 3MQ‐type propolis differs from the O‐type. Antioxidant activity studies showed that O‐type of propolis possesses higher antioxidant effect than the other tested propolis types. Quercetin, caffeic acid, caffeic acid phenethyl ester (CAPE) and galangin were determined to contribute significantly to the antioxidant potential of O‐type propolis among others. Propolis extracts exerted moderate antimicrobial activity against the tested microorganisms with MIC values between the ranges of 128–512 μg/mL.     

Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells

The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.     

Effect of preservation period on the viscoelastic material properties of soft tissues with implications for liver transplantation

The liver harvested from a donor must be preserved and transported to a suitable recipient immediately for a successful liver transplantation. In this process, the preservation period is the most critical, since it is the longest and most tissue damage occurs during this period due to the reduced blood supply to the harvested liver and the change in its temperature. We investigate the effect of preservation period on the dynamic material properties of bovine liver using a viscoelastic model derived from both impact and ramp and hold experiments. First, we measure the storage and loss moduli of bovine liver as a function of excitation frequency using an impact hammer. Second, its time-dependent relaxation modulus is measured separately through ramp and hold experiments performed by a compression device. Third, a Maxwell solid model that successfully imitates the frequency- and time-dependent dynamic responses of bovine liver is developed to estimate the optimum viscoelastic material coefficients by minimizing the error between the experimental data and the corresponding values generated by the model. Finally, the variation in the viscoelastic material coefficients of bovine liver are investigated as a function of preservation period for the liver samples tested 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, and 48 h after harvesting. The results of our experiments performed with three animals show that the liver tissue becomes stiffer and more viscous as it spends more time in the preservation cycle.     

Evaluation of the natural killer cytotoxicity and the levels of cytokines in rats with type I diabetes mellitus

Type I diabetes mellitus (insulin-dependent DM = IDDM) is a chronic disease characterized by specific destruction of pancreatic beta cells, resulting in an absolute lack of insulin. Immune mechanisms, genetic susceptibility, and environmental factors are all implicated in the pathogenesis of Type 1 diabetes. This study was aimed at determining the efficiency of cytokines, natural killer (NK) cells in the pathophysiology of IDDM. Therefore, we evaluated the plasma levels of cytokines by specific enzyme-linked immunosorbent assay (ELISA) and the cytotoxicity activity of NK cells by anti-candididal index in rats with type I diabetes. We found that the cytotoxicity activity of NK cells in IDDM groups significantly decreased compared to the control groups. The levels of interferon-gamma (IFN-gamma) in IDDM groups were slightly higher than in healthy controls. These results indicate that the changes of T H1 type cytokines such as IFN-gamma and NK cell activity can play a role in the etiology of IDDM. The data may provide new strategies for the treatment of IDDM.     

Certain Non-Standard Coding Tables Appear to be More Robust to Error Than the Standard Genetic Code

Since the identification of the Standard Coding Table as a “universal” method to translate genetic information into amino acids, exceptions to this rule have been reported, and to date there are nearly 20 alternative genetic coding tables deployed by either nuclear genomes or organelles of organisms. Why are these codes still in use and why are new codon reassignments occurring? This present study aims to provide a new method to address these questions and to analyze whether these alternative codes present any advantages or disadvantages to the organisms or organelles in terms of robustness to error. We show that two of the alternative coding tables, The Ciliate, Dasycladacean and Hexamita Nuclear Code (CDH) and The Flatworm Mitochondrial Code (FMC), exhibit an advantage, while others such as The Yeast Mitochondrial Code (YMC) are at a significant disadvantage. We propose that the Standard Code is likely to have emerged as a “local minimum” and that the “coding landscape” is still being searched for a “global” minimum.