Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress.

Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H(2)O(2) and protect proteins and DNA from oxidative stress. Here we report that LEDGF is one of the regulatory factors for the AOP2 gene. We found that LEDGF bound to the heat shock element and to stress-related elements in the AOP2 promoter. It trans-activated expression of AOP2-CAT in COS-7 cells and lens epithelial cells overexpressing LEDGF. Mutations in the heat shock element and stress-related elements of the AOP2 promoter reduced LEDGF-dependent trans-activation. Lens epithelial cells showed a higher level of AOP2 mRNA in the presence of LEDGF. Cells overexpressing LEDGF exhibited a higher level of AOP2 protein, the level of which was directly related to the increase in cellular protection. Thus, LEDGF, by activating the AOP2 gene, protected and enhanced the survival of cells under oxidative stress.     

Time of day effect on balance performance,functional capacities and risk of fall in women with rheumatoid arthritis

ABSTRACT

Objective: This study explored the time of day effect of balance performance, functional capacities and risk of fall in three different times in patients with rheumatoid arthritis (RA) and the association between these variations and those of RA symptoms.

Methods: A “discontinual” protocol, composed of three test sessions, carried out at 6 am, 2 pm and 10 pm was set up, in order to investigate the time of day effect of balance performance, functional capacities, risk of fall, stiffness, range of motion, swollen and painful joints in women with RA.

Results: Time Up and Go Test (TUGT), Functional Reach Test (FRT) and tinetti test scores were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. Stiffness, range of motion, swollen and painful joints values were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. A significant difference was observed on the stiffness, range of motion and swollen joints values between 6 am and 10 pm that were higher at 6 am (p < .05).

Using Pearson’s coefficient, correlations were found between RA symptom values; and TUGT, FRT and Tinetti test scores.

Conclusion: Results showed a time of day effect of balance performance, functional capacities and risk of falls in women with RA. This variation indicates an alteration of performance at 6 am and 10 pm. Fluctuations of stiffness, limited range of motion, swollen and painful joints noted are concomitant to those of balance performance, functional capacities, and risk of fall.

Abbreviations: RA: rheumatoid arthritis; H&O questionnaire: Horne and Ostberg questionnaire; PSQI: Pittsburgh sleep quality index; HAQ: health assessment questionnaire; SF-36: the short form-36; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; TUGT: Time Up and Go Test; FRT: Functional Reach Test     

Embryonic poly(A)-binding protein is differently expressed and interacts with the messenger RNAs in the mouse oocytes and early embryos

The embryonic poly(A)-binding protein (EPAB) functions in the translational regulation of the maternal messenger RNAs (mRNAs) required during oocyte maturation, fertilization, and early embryo development. Since there is no antibody specific to mammalian EPAB protein, all studies related to the Epab gene could be performed at the mRNA levels except for the investigations in the Xenopus. In this study, we have produced an EPAB-specific antibody. When we examined its expressional distribution in the mouse gonadal and somatic tissues, the EPAB protein was found to be expressed only in the mouse ovary and testis tissues, but it is undetectable level in the somatic tissues including stomach, liver, heart, small intestine, and kidney. Additionally, the spatial and temporal expression patterns of the EPAB and poly(A)-binding protein cytoplasmic 1 (PABPC1) proteins were analyzed in the mouse germinal vesicle (GV) and metaphase II (MII) oocytes, one-cell, and two-cell embryos. While EPAB expression gradually decreased from GV oocytes to two-cell embryos, the PABPC1 protein level progressively increased from GV oocytes to one-cell embryos and remarkably declined in the two-cell embryos ( P < 0.05). We have also described herein that the EPAB protein interacted with Epab, Pabpc1, Ccnb1, Gdf9, and Bmp15 mRNAs dependent upon the developmental stages of the mouse oocytes and early embryos. As a result, we have first produced an EPAB-specific antibody and characterized its expression patterns and interacting mRNAs in the mouse oocytes and early embryos. The findings suggest that EPAB in cooperation with PABPC1 implicate in the translational control of maternal mRNAs during oogenesis and early embryo development.     

Cell-type specificity of the Anabaena fdxN-element rearrangement requires xisH and xisl

The fdxN element, along with two other DNA elements, is excised from the chromosome during heterocyst differentiation in Anabaena sp. strain PCC 7120. Previous work showed that rearrangement of the fdxN element requires the xisF gene, which encodes a site-specific recombinase, and suggested that at least one other heterocyst-specific factor is involved. Here we report that the xisH and xisl genes are necessary for the heterocyst-specific excision of the fdxN element. Deletion of a 3.2 kb region downstream of the xisF gene blocked the fdxN-element rearrangement in hetero-cysts. The 3.2 kb deletion was complemented by the two overlapping genes xisH and xisl. Interestingly, extra copies of xlsHI on a replicating plasmid resulted in the xisF-dependent excision of the fdxN element in vegetative cells. Therefore, xisHI are involved in the control of cell-type specificity of the fdxN rearrangement. The xisHI genes had no effect on the two other DNA rearrangements. The xisHl-induced excision of the fdxN element produced strains lacking the element and demonstrates that the 55 kb element contains no essential genes. xisH and xisl do not show similarity to any known genes.     

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.     

Anaerobic C–H Oxyfunctionalization: Coupling of Nitrate Reduction and Quinoline Hydroxylation in Recombinant Pseudomonas putida

Whole‐cell biocatalysis for C–H oxyfunctionalization depends on and is often limited by O₂ mass transfer. In contrast to oxygenases, molybdenum hydroxylases use water instead of O₂ as an oxygen donor and thus have the potential to relieve O₂ mass transfer limitations. Molybdenum hydroxylases may even allow anaerobic oxyfunctionalization when coupled to anaerobic respiration. To evaluate this option, the coupling of quinoline hydroxylation to denitrification is tested under anaerobic conditions employing Pseudomonas putida (P. putida) 86, capable of aerobic growth on quinoline. P. putida 86 reduces both nitrate and nitrite, but at low rates, which does not enable significant growth and quinoline hydroxylation. Introduction of the nitrate reductase from Pseudomonas aeruginosa enables considerable specific quinoline hydroxylation activity (6.9 U g_CDW^?1) under anaerobic conditions with nitrate as an electron acceptor and 2‐hydroxyquinoline as the sole product (further metabolization depends on O₂). Hydroxylation‐derived electrons are efficiently directed to nitrate, accounting for 38% of the respiratory activity. This study shows that molybdenum hydroxylase‐based whole‐cell biocatalysts enable completely anaerobic carbon oxyfunctionalization when coupled to alternative respiration schemes such as nitrate respiration.     

Retraction Note: Acaricidal and pathogenic effects of the entomopathogenic fungus Beauveria bassiana on engorged females of the fowl tick,Argas persicus (Argasidae)

Experimental and Applied Acarology -     

New biochemical insights into the dynamics of water molecules at the GMP or IMP binding site of human GMPR enzyme: A molecular dynamics study

Human GMP reductase (hGMPR) enzyme is involved in a cellular metabolic pathway, converting GMP into IMP, and also it is an important target for anti-leukemic agents. Present computational investigations explain dynamical behavior of water molecules during the conformational transition process from GMP to IMP using molecular dynamics simulations. Residues at substrate-binding site of cancerous protein (PDB Id. 2C6Q) are mostly more dynamic in nature than the normal protein (PDB Id. 2BLE). Nineteen conserved water molecules are identified at the GMP/IMP binding site and are classified as (i) conserved stable dynamic and (ii) infrequent dynamic. Water molecules W11, W14, and W16 are classified as conserved stable dynamic due to their immobile character, whereas remaining water molecules (W1, W2, W3, W4, W5, W7, W8, W9, W10, W12, W13, W15, W17, W18, and W19) are infrequent with dynamic nature. Entrance or displacement of these infrequent water molecules at GMP/IMP sites may occur due to forward and backward movement of reference residues involving ligands. Four water molecules of hGMPR-I and nine water molecules of hGMPR-II are observed in repetitive transitions from GMP to IMP pathway, which indicates discrimination between two isoforms of hGMPRs. Water molecules in cancerous protein are more dynamic and unstable compared to normal protein. These water molecules execute rare dynamical events at GMP binding site and could assist in detailed understanding of conformational transitions that influence the hGMPR's biological functionality. The present study should be of interest to the experimental community engaged in leukemia research and drug discovery for CML cancer.     

Derivation and validation of clinical phenotypes for COPD: a systematic review

Background

The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease. Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes. Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics. We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.

Methods

Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD. Data were extracted independently.

Results

9156 citations were retrieved, of which, 8 studies were included. The number of subjects ranged from 213 to 1543. Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings. Statistical methods used to derive phenotypes varied by study. The number of phenotypes identified ranged from 2 to 5. Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.

Conclusions

The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease. This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users.