Genetic ablation of glutaredoxin-1 causes enhanced resolution of airways hyperresponsiveness and mucus metaplasia in mice with allergic airways disease

Protein-S-glutathionylation (PSSG) is an oxidative modification of reactive cysteines that has emerged as an important player in pathophysiological processes. Under physiological conditions, the thiol transferase, glutaredoxin-1 (Glrx1) catalyses deglutathionylation. Although we previously demonstrated that Glrx1 expression is increased in mice with allergic inflammation, the impact of Glrx1/PSSG in the development of allergic airways disease remains unknown. In the present study we examined the impact of genetic ablation of Glrx1 in the pathogenesis of allergic inflammation and airway hyperresponsiveness (AHR) in mice. Glrx1(-/-) or WT mice were subjected to the antigen, ovalbumin (OVA), and parameters of allergic airways disease were evaluated 48 h after three challenges, and 48 h or 7 days after six challenges with aerosolized antigen. Although no clear increases in PSSG were observed in WT mice in response to OVA, marked increases were detected in lung tissue of mice lacking Glrx1 48 h following six antigen challenges. Inflammation and expression of proinflammatory mediators were decreased in Glrx1(-/-) mice, dependent on the time of analysis. WT and Glrx1(-/-) mice demonstrated comparable increases in AHR 48 h after three or six challenges with OVA. However, 7 days postcessation of six challenges, parameters of AHR in Glrx1(-/-) mice were resolved to control levels, accompanied by marked decreases in mucus metaplasia and expression of Muc5AC and GOB5. These results demonstrate that the Glrx1/S-glutathionylation redox status in mice is a critical regulator of AHR, suggesting that avenues to increase S-glutathionylation of specific target proteins may be beneficial to attenuate AHR.     

Standard Automated Perimetry versus Matrix Frequency Doubling Technology Perimetry in Subjects with Ocular Hypertension and Healthy Control Subjects

Background

To evaluate the relationship and agreement between standard automated perimetry (SAP) and Matrix frequency doubling technology (Matrix-FDT) in subjects with ocular hypertension and healthy control subjects.

Methods

Forty-four eyes of 44 ocular hypertensive subjects and 29 eyes of 29 healthy age-matched control subjects were included in this prospective study. All participants underwent complete ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure measurement, pachymetry, and dilated fundus examination, and showed reliable visual field tests. One randomly selected eye of each participant was examined with SAP (Swedish Interactive Threshold Algorithm [SITA] Standard 24-2 test) and Matrix-FDT (24-2 threshold test), in random order. Correlations between global indices (MD, PSD), regions (2 hemifields, 4 quadrants, 6 sectors) and 52 single field positions were analyzed using Spearman’s rank correlation coefficient.

Results

In both groups, mean deviation values of SAP and Matrix-FDT correlated significantly (OHT subjects: r = 0.47, p<0.005; healthy subjects: r = 0.68; p<0.001, respectively). Pattern standard deviation of SAP and Matrix-FDT showed no significant correlation in healthy subjects but correlated significantly in ocular hypertensive subjects (r = 0.45, p<0.005). In healthy subjects, a significant correlation between SAP and Matrix-FDT was shown in the supero-temporal and infero-temporal sectors of the disc (r = 0.40 and r = 0.38, p<0.05, respectively). In OHT subjects, supero-temporal, supero-nasal and nasal sectors correlated significantly (r = 0.49, 0.62 and 0.38, p≤0.01, respectively). The correlation pattern of individual visual field test locations appeared heterogeneous in both groups.

Conclusions

In both, ocular hypertensive and healthy subjects SAP and Matrix-FDT correlate well. In ocular hypertensive subjects, both techniques showed good correlation in the supero-temporal, supero-nasal, and nasal sectors of the disc. Poor agreement was found in the temporal, infero-temporal and infero-nasal disc sectors. This missing correlation might be related to early retinal nerve fiber layer damage in these regions of the disc, recognized by one of the visual field instruments.     

Reflection of the Mental Reproduction of Emotional Experiences in the EEG Pattern of 10- to 11-Year-Old Children

We studied the effects of mental reproduction of emotions on the EEG characteristics in 10- to 11-year-old children. Independently of the sign of emotions, their reproduction was related to a rise in the modal alpha frequency and to a decrease in the spectral power of the EEG alpha1 subcomponent. Increases in the power of the beta-rhythm and in the ratio between the beta rhythm power and that of the theta rhythm were more manifested upon mental reproduction of positive emotions.     

Molecular operation of metals into the function and state of photosystem II

Action sites of different metals in the electron transport reactions of Photosystem II (PS II) evaluated by delayed fluorescence in the ms range (ms DF) and pigment-pigment, pigment-protein and protein-protein interaction states by electrophoretic measurements are presented. The main targets for the metals action were shown to be:(i) Cd(2+), Ni(2+), Co(2+)-Y(z) or CaMn(4)-cluster on the donor site with dependence on pH;(ii) Ni(2+), Co(2+), Zn(2+), Al(3+), Mn(2+) between Q(A) and Q(B) on the acceptor site; effect of Al(3+) and Mn(2+) is observed only in acidic pH. Investigated metals bring about monomerization of oligomeric and dimeric chlorophyll-protein complexes (CPC) and destabilization of protein-protein interactions. Molecular mechanisms of metals interference with the structure of PS II are discussed.     

Virus-induced changes in photosynthetic parameters and peroxidase isoenzyme contents in tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis> L.) plants

Tomato samples were collected from the field of Absheron peninsula in Azerbaijan in order to evaluate the incidence of main Tobamoviruses. According to results of serological and molecular tests, Tomato mosaic virus (ToMV), Tobacco mosaic virus (TMV), and Pepper mild mottle virus (PMMoV) were detected as single and mixed infections (TMV + PMMoV; ToMV + PMMoV) in various tomato samples. It was found that Tobamovirus infection caused an increase in the content of malondialdehyde, alterations in the activities of peroxidase enzymes and quantitative and qualitative changes in their molecular isoforms. A comparison of thylakoid membrane polypeptides from virus-infected leaves indicated a decrease in the content of the thylakoid membrane polypeptides with molecular masses of 123, 55, 47, 33, 28–24, 17, and 15 kD. PSII efficiency and the content of chlorophylls (a and b) were significantly lower in the virus-infected leaves.     

Diurnal temperature-related variations in photosynthetic enzyme activities of two C<Subscript>4</Subscript> species of Chenopodiaceae grown in natural environment

The effects of the diurnal variations in ambient temperature on some C₃ and C₄ enzymes in the Salsola dendroides and Suaeda altissima species of Chenopodiaceae family were studied during the intensive vegetation period. Activities of phosphoenolpyruvate carboxylase (PEPC) and cytosolic aspartate aminotransferase (AsAT) were shown to decrease in both species in the afternoon and evening. The activity of the mitochondrial AsAT decreased in S. altissima, remained relatively constant in S. dendroides during the day. The activity of alanine aminotransferase was high in the S. dendroides species in the morning and evening and decreased in the S. altissima species by the evening. Glucose-6-phosphate activated PEPC in both species throughout the day. The study of the redox status-regulated C₃ enzymes showed temperature-related increases in NADP-glyceraldehyde 3-phosphate dehydrogenase activity in both plants, in fructose-2,6-bisphosphatase activity in the S. altissima species, and in NADP-MDH activity in the S. dendroides species in the afternoon.     

Cytogenetic mapping with centromeric bacterial artificial chromosomes contigs shows that this recombination‐poor region comprises more than half of barley chromosome 3H

Genetic maps are based on the frequency of recombination and often show different positions of molecular markers in comparison to physical maps, particularly in the centromere that is generally poor in meiotic recombinations. To decipher the position and order of DNA sequences genetically mapped to the centromere of barley (Hordeum vulgare) chromosome 3H, fluorescence in situ hybridization with mitotic metaphase and meiotic pachytene chromosomes was performed with 70 genomic single‐copy probes derived from 65 fingerprinted bacterial artificial chromosomes (BAC) contigs genetically assigned to this recombination cold spot. The total physical distribution of the centromeric 5.5 cM bin of 3H comprises 58% of the mitotic metaphase chromosome length. Mitotic and meiotic chromatin of this recombination‐poor region is preferentially marked by a heterochromatin‐typical histone mark (H3K9me2), while recombination enriched subterminal chromosome regions are enriched in euchromatin‐typical histone marks (H3K4me2, H3K4me3, H3K27me3) suggesting that the meiotic recombination rate could be influenced by the chromatin landscape.     

Airway responsiveness depends on the diffusion rate of methacholine across the airway wall

During methacholine challenge tests of airway responsiveness, it is invariably assumed that the administered dose of agonist is accurately reflected in the dose that eventually reaches the airway smooth muscle (ASM). However, agonist must traverse a variety of tissue obstacles to reach the ASM, during which the agonist is subjected to both enzymatic breakdown and removal by the bronchial and pulmonary circulations. This raises the possibility that a significant fraction of the deposited agonist may never actually make it to the ASM. To understand the nature of this effect, we measured the time course of changes in airway resistance elicited by various durations of methacholine aerosol in mice. We fit to these data a computational model of a dynamically contracting airway responding to agonist that diffuses through an airway compartment, thereby obtaining rate constants that reflect the diffusive barrier to methacholine. We found that these barriers can contribute significantly to the time course of airway narrowing, raising the important possibility that alterations in the diffusive barrier presented by the airway wall may play a role in pathologically altered airway responsiveness.