Diminished Akt phosphorylation in neurons lacking glutathione peroxidase-1 (Gpx1) leads to increased susceptibility to oxidative stress-induced cell death

We have previously identified an increased susceptibility of glutathione peroxidase-1 (Gpx1)-/- mice to neuronal apoptosis following mid-cerebral artery (MCA) occlusion. This study was designed to elucidate the mechanisms involved in elevated neuronal cell death arising from an altered endogenous oxidant state. This was addressed in both an in vitro and in vivo model of oxidative stress in the form of exogenous H2O2 and cerebral ischaemia, respectively. Increased levels of cell death were detected in primary neurons lacking Gpx1 following the addition of exogenous H2O2. This increased apoptosis correlated with a down-regulation in the activation of the phospho-inositide 3-kinase [PI3K]-Akt survival pathway. The importance of this pathway in protecting against H2O2-induced cell death was highlighted by the increased susceptibility of wildtype neurons to apoptosis when treated with the PI3K inhibitor, LY294002. The Gpx1-/- mice also demonstrated elevated neuronal cell death following MCA occlusion. Although Akt phosphorylation was detected in the Gpx1-/- brains, activation was not seen in later reperfusion events, as demonstrated in wildtype brains. Previous studies have highlighted the importance of Akt phosphorylation in protecting against neuronal cell death following cerebral ischaemia-reperfusion. Our results suggest that the increased susceptibility of Gpx1-/- neurons to H2O2-induced apoptosis and neuronal cell death in vivo following cerebral ischaemia-reperfusion injury can be attributed in part to diminished activation of Akt. Perturbations in key anti-apoptotic mechanisms as a result of an altered redox state may have implications in the study of oxidative stress-mediated neuropathologies.     

Clustering of protein families into functional subtypes using Relative Complexity Measure with reduced amino acid alphabets

Background  

Phylogenetic analysis can be used to divide a protein family into subfamilies in the absence of experimental information. Most phylogenetic analysis methods utilize multiple alignment of sequences and are based on an evolutionary model. However, multiple alignment is not an automated procedure and requires human intervention to maintain alignment integrity and to produce phylogenies consistent with the functional splits in underlying sequences. To address this problem, we propose to use the alignment-free Relative Complexity Measure (RCM) combined with reduced amino acid alphabets to cluster protein families into functional subtypes purely on sequence criteria. Comparison with an alignment-based approach was also carried out to test the quality of the clustering.     

Evaluation of four colourimetric susceptibility tests for the rapid detection of multidrug-resistant Mycobacterium tuberculosis isolates

The purpose of this study is to evaluate four rapid colourimetric methods, including the resazurin microtitre assay (REMA), malachite green decolourisation assay (MGDA), microplate nitrate reductase assay (MNRA) and crystal violet decolourisation assay (CVDA), for the rapid detection of multidrug-resistant (MDR) tuberculosis. Fifty Mycobacterium tuberculosis isolates were used in this study. Eighteen isolates were MDR, two isolates were only resistant to isoniazid (INH) and the remaining isolates were susceptible to both INH and rifampicin (RIF). INH and RIF were tested in 0.25 µg/mL and 0.5 µg/mL, respectively. The agar proportion method was used as a reference method. MNRA and REMA were performed with some modifications. MGDA and CVDA were performed as defined in the literature. The agreements of the MNRA for INH and RIF were 96% and 94%, respectively, while the agreement of the other assays for INH and RIF were 98%. In this study, while the specificities of the REMA, MGDA and CVDA were 100%, the specificity of the MNRA was lower than the others (93.3% for INH and 90.9% for RIF). In addition, while the sensitivity of the MNRA was 100%, the sensitivities of the others were lower than that of the MNRA (from 94.1-95%). The results were reported on the seventh-10th day of the incubation. All methods are reliable, easy to perform, inexpensive and easy to evaluate and do not require special equipment.     

Changes in brain size during the menstrual cycle

Background

There is increasing evidence for hormone-dependent modification of function and behavior during the menstrual cycle, but little is known about associated short-term structural alterations of the brain. Preliminary studies suggest that a hormone-dependent decline in brain volume occurs in postmenopausal, or women receiving antiestrogens, long term. Advances in serial MR-volumetry have allowed for the accurate detection of small volume changes of the brain. Recently, activity-induced short-term structural plasticity of the brain was demonstrated, challenging the view that the brain is as rigid as formerly believed.

Methodology/Principal Findings

We used MR-volumetry to investigate short-term brain volume changes across the menstrual cycle in women or a parallel 4 week period in men, respectively. We found a significant grey matter volume peak and CSF loss at the time of ovulation in females. This volume peak did not correlate with estradiol or progesterone hormone levels. Men did not show any significant brain volume alterations.

Conclusions/Significance

These data give evidence of short-term hormone-dependent structural brain changes during the menstrual cycle, which need to be correlated with functional states and have to be considered in structure-associated functional brain research.     

Diversity of killer cell immunoglobulin-like receptor genes in Southern Turkey

Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed by natural killer (NK) cells and regulate NK cells’ activity. KIR genes are highly polymorphic markers, characterized by a wide diversity, and can therefore be considered as good population genetic markers. The aim of this study was to determine KIR gene frequencies, ratios of haplotypes and genotypes in Southern Turkey and also to compare the data with other worldwide populations studied previously. The study group consisted of 200 non-related individuals from Southern Turkey. The percentage of each KIR gene in the population group was determined by direct counting. Differences between populations in the distribution of each KIR gene and genotype profile were estimated by two-tailed Fisher Exact test. The most frequent non-framework KIR genes detected in Southern Turkey population were: KIR 2DL1 (97%), KIR 3DL1 (91%), KIR 2DS4 (92%) and the pseudogene 2DP1 (96%). Fourty different genotypes were found in 200 subjects and AA1 genotype was the most frequent (27%). Among 40 different genotypes, ten of these were described for the first time in this study and were added to the database () numerized as genotype ID from 400 to 409. Gene frequencies and found genotypes demonstrated similarity of Southern Turkey’s KIR repertoire with the KIR repertoires of Middle East and European population. High variability seen in KIR genome in this region is thought to be formed as a result of migration and settlement of different civilizations in this region and heterogenity formed in time.     

Death-associated protein 5 (DAP5/p97/NAT1) contributes to retinoic acid-induced granulocytic differentiation and arsenic trioxide-induced apoptosis in acute promyelocytic leukemia

All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) induce differentiation and apoptosis in acute promyelocytic leukemia (APL) cells. Here we investigated the role and regulation of death-associated protein-5 (DAP5/p97/NAT1), a novel inhibitor of translational initiation, in APL cell differentiation and apoptosis. We found that ATRA markedly induced DAP5/p97 protein and gene expression and nuclear translocation during terminal differentiation of APL (NB4) and HL60 cells but not differentiation-resistant cells (NB4.R1 and HL60R), which express very low levels of DAP5/p97. At the differentiation inducing concentrations, ATO (<0.5 μM), dimethyl sulfoxide, 1,25-dihydroxy-vitamin-D3, and phorbol-12-myristate 13-acetate also significantly induced DAP5/p97 expression in NB4 cells. However, ATO administered at apoptotic doses (1–2 μM) induced expression of DAP5/p86, a proapoptotic derivative of DAP5/p97. ATRA and ATO-induced expression of DAP5/p97 was associated with inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Furthermore, DAP5/p97 expression was upregulated by inhibition of the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway via LY294002 and via rapamycin. Finally, knockdown of DAP5/p97 expression by small interfering RNA inhibited ATRA-induced granulocytic differentiation and ATO-induced apoptosis. Together, our data reveal new roles for DAP5/p97 in ATRA-induced differentiation and ATO-induced apoptosis in APL and suggest a novel regulatory mechanism by which PI3K/Akt/mTOR pathway inhibition mediates ATRA- and ATO-induced expression of DAP5/p97. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. B. Ozpolat and U. Akar contributed equally.     

Ultrahigh Contrast One-Way Optical Transmission Through a Subwavelength Slit

We computationally demonstrate one-way optical transmission characteristics of a subwavelength slit. We comparatively study the effect in single layer and double layer metallic corrugations. We also investigate the effect of a dielectric spacer layer between double corrugations to control the volumetric coupling of plasmon and optical modes. We computationally show unidirectional transmission behavior with an ultrahigh contrast ratio of 53.4 dB at λ?=?1.56 μm. Volumetric coupling efficiency through the nanoslit strongly depends on the efficient excitation of both the surface plasmon resonance and metal–insulator–metal waveguide modes. We show that the behavior is tunable in a wide spectral range.     

Taxonomic study of the tetrahedral, pentagonal and hexagonal spongy spumellarian Radiolaria from the middle Carnian (Late Triassic) of the Köseyahya nappe (Elbistan, SE Turkey) and other Triassic localities

This article is a taxonomic study of all spongy radiolarian taxa with five to six coplanar and four tetrahedrally disposed spines or spongy arms occurring in the middle Carnian from the Köseyahya section, near the town of Elbistan, SE Turkey. This fauna is characteristic of the Tetraporobrachia haeckeli radiolarian Zone, and comes from an 8 m thick succession of clayey–cherty limestones occurring at the lower part of the section. In addition, a few species from the Middle and Upper Triassic from other areas have been also included in this study to improve some generic diagnoses and to better understand the diversity and evolutionary trends of some genera, subfamilies and families. The taxonomy at the generic and suprageneric levels is based primarily on the types of microsphere. This new approach allowed new taxonomic arrangements of genera and suprageneric units, and suggested new and unexpected phylogenetic relationships among these radiolarians and between them and younger radiolarians. The authors discuss and describe 42 species, of which 36 are new, and 12 genera of which three are new (Charlottalum, Pentaspongodisculus, and Trimiducaella). The genera Pseudohagiastrum Pessagno, Natraglia Pessagno, Cantalum Pessagno and others are reinterpreted. All the genera studied, except Charlottalum, are assigned to three subfamilies, of which two (Pseudohagiastrinae and Trimiducinae) are new, and to two families (Angulobracchiidae and Relindellidae). The genus Charlottalum is described to replace the genus Cantalum, which has been erroneously used until present for Late Triassic pantanelliids with four tetrahedrally disposed three-bladed spines.     

Biotechnological potential of Actinobacteria from Canadian and Azorean volcanic caves

Applied Microbiology and Biotechnology - Caves are regarded as extreme habitats with appropriate conditions for the development of Actinobacteria. In comparison with other habitats, caves have not...