Skin barrier function in patients under radiation therapy due to the head and neck cancers - Preliminary study

AimTo present the possibility of non-invasive monitoring of the skin after radiotherapy in regards of epidermal barrier function.BackgroundRadiodermatitis constitutes 95% of all side effects in patients after radiotherapy. The proper assessment of the severity of radiodermatitis can be determined using semi-quantitative clinical scores [Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)].The most accepted way to analyze the epidermal barrier function is to determine Transepidermal Water Loss (TEWL).Material and methodsIn prospective study, we included 16 patients diagnosed with head and neck cancer treated with radiotherapy or concomitant chemoradiation in whom we performed non-invasive assessments of the skin barrier function, including TEWL measurement. The final analysis included 6 patients (4 treated with adjuvant radiotherapy, 2 with radical chemoradiation). Clinical assessment of irradiated skin was based on target lesion score (TLS) and CTCAE v 4.0ResultsThe mean TLS score in the middle of irradiation was 1.6 points, after last irradiation it was 2.3 points; 3 months later the mean TLS score was: 0. CTCAE v 4.0 criteria: 2 patients had grade 0, 3 patients - grade 1; 1 patient - grade 2. There were statistically significant differences in TEWL related to irradiated skin in the following time intervals: before vs. in the middle; before vs. day after; in the middle vs. day after; in the middle vs. 3 months after; day after vs. 3 months after.ConclusionsThe study showed that radiotherapy causes skin barrier dysfunction in all patients independently of clinical radiodermatitis. The biophysical features of this dysfunction can precede clinical symptoms and they can be assessed by non-invasive and objective methods.     

Only mothers feed mature offspring in European Ceratina bees

Parental care directed to adult offspring is uncommon in animals. Such parental care has been documented in Xylocopinae bees (Hymenoptera: Apidae). Moreover, some Ceratina bees (Xylocopinae) are known to feed mature siblings, and feeding of mature siblings is achieved by dwarf eldest daughters when mothers died. These daughters are intentionally malnourished by mothers and usually originate from the first brood cell. Here, we examined the pattern of care provided to young adults in three small European carpenter bees: Ceratina (Ceratina) cucurbitina, C. (Euceratina) chalybea, and C. (E.) nigrolabiata. Observations of nest departures and arrivals were performed to study foraging behavior. We detected intensive foraging behavior of mothers in all three studied species. However, we did not observe regular foraging behavior of daughters in any species. The experimental removal of mothers in C. cucurbitina led to the emigration of young adults and did not initiate foraging activity in daughters. We conclude that the feeding of siblings does not occur in these species unlike in the American species C. calcarata. We detected female-biased sex ratios in the first brood cell in C. cucurbitina and C. chalybea. Female offspring in the first brood cell was smaller than other female offspring only in C. cucurbitina. Our results show that a female-biased sex ratio and the small size of daughters in the first brood cell do not provide sufficient evidence for demonstrating the existence of an altruistic daughter and also that the pattern of maternal investment is not exclusively shaped by social interactions.     

PPAR-gamma-independent inhibitory effect of rosiglitazone on glucose synthesis in primary cultured rabbit kidney-cortex tubules

Therapeutic effect of rosiglitazone has been reported to result from an improvement of insulin sensitivity and inhibition of glucose synthesis. As the latter process occurs in both liver and kidney cortex the aim of this study was to elucidate the rosiglitazone action on glucose formation in both tissues. Primary cultured cells of both liver and kidney cortex grown in defined medium were use throughout. To identify the mechanism responsible for drug-induced changes, intracellular gluconeogenic intermediates and enzyme activities were determined. In contrast to hepatocytes, the administration of a 10 micromol/L concentration of rosiglitazone to renal tubules resulted in about a 70% decrease in the rate of gluconeogenesis, accompanied by an approximately 75% decrease in alanine utilization and a 35% increase in lactate synthesis. The effect of rosiglitazone was not abolished by GW9662, the PPAR-gamma irreversible antagonist, indicating that this action is not dependent on PPAR-gamma activation. In view of rosiglitazone-induced changes in gluconeogenic intermediates and a diminished incorporation of 14CO2 into pyruvate, it is likely that the drug causes a decline in flux through pyruvate carboxylase and (or) phosphoenolpyruvate carboxykinase. It is likely that the hypoglycemic action of rosiglitazone is PPAR-gamma independent and results mainly from its inhibitory effects on renal gluconeogenesis.     

Pyridinium-2-carbaldoximes with quinolinium carboxamide moiety are simultaneous reactivators of acetylcholinesterase and butyrylcholinesterase inhibited by nerve agent surrogates

The pyridinium-2-carbaldoximes with quinolinium carboxamide moiety were designed and synthesised as cholinesterase reactivators. The prepared compounds showed intermediate-to-high inhibition of both cholinesterases when compared to standard oximes. Their reactivation ability was evaluated in vitro on human recombinant acetylcholinesterase (hrAChE) and human recombinant butyrylcholinesterase (hrBChE) inhibited by nerve agent surrogates (NIMP, NEMP, and NEDPA) or paraoxon. In the reactivation screening, one compound was able to reactivate hrAChE inhibited by all used organophosphates and two novel compounds were able to reactivate NIMP/NEMP-hrBChE. The reactivation kinetics revealed compound 11 that proved to be excellent reactivator of paraoxon-hrAChE better to obidoxime and showed increased reactivation of NIMP/NEMP-hrBChE, although worse to obidoxime. The molecular interactions of studied reactivators were further identified by in silico calculations. Molecular modelling results revealed the importance of creation of the pre-reactivation complex that could lead to better reactivation of both cholinesterases together with reducing particular interactions for lower intrinsic inhibition by the oxime.     

Seasonal beta-diversity of dry grassland vegetation: Divergent peaks of above-ground biomass and species richness

Question

Temperate grasslands are known for their high plant diversity and distinct seasonality. However, their intra-annual community dynamics are still largely overlooked by ecologists. Therefore, we explored the seasonal alpha- and beta-diversity patterns of vascular plants and their relationships to above-ground biomass in a rocky steppe (Festucion valesiacae).

Location

Pavlov Hills, SE Czech Republic.

Methods

For one year, we monitored the plant community of the rocky steppe at monthly intervals in 42 permanent plots of 0.25 m². We examined seasonal changes in above-ground biomass (estimated from the cover and height of living plant parts) and seasonal beta-diversity, which we partitioned into turnover and nestedness components and their quantitative counterparts: balanced changes and abundance gradients.

Results

We identified a pronounced seasonal pattern of above-ground biomass, species richness and composition. Total above-ground biomass was highest in June (summer), with a peak representing only 60% of total annual production (sum of individual species' maxima). However, the observed peak in species richness occurred in March (early spring), with 80% of the total species number recorded throughout the year. Accordingly, nestedness and abundance gradient patterns differed in the spring months, while seasonal turnover and balanced changes in abundance were generally congruent. Annual, short-lived, and perennial species exhibited different seasonal patterns of species richness and biomass production, although a sharp increase in biomass and a peak in species richness in spring were universal across the community.

Conclusions

Seasonal climatic constraints on plant growth are key determinants of primary production dynamics. Plants adapt to these constraints by adjusting their life cycles in different ways. In dry grasslands, the complexity of plant responses to climatic seasonality can result in seasonal beta-diversity patterns with divergent peaks in biomass and species richness.     

Three-year study on trace mineral concentration in the blood plasma of Shetland pony mares

Changes in some trace minerals concentrations (calcium, inorganic phosphorus, magnesium, zinc, iron, copper, sodium and potassium) in blood plasma were investigated during a three-year period in Shetland pony mares. Blood plasma mineral concentrations were determined by the atomic absorption method and colorimetric method. The three-year averages were in micrograms/ml; Na 4630 +/- 168; K 277 +/- 3.8; Ca 171 +/- 3.8; P 31.5 +/- 0.74; Fe 1.92 +/- 0.14; Zn 1.07 +/- 0.04 and Cu 1.06 +/- 0.02. Two trace minerals (magnesium in inorganic phosphorus) showed only long-term tendency changes--upward or downward trends were not connected with the season. Most of the investigated minerals showed both a long-term change tendency and more or less marked seasonally related concentration changes, being higher during autumn or winter (zinc, sodium), or during spring and summer (calcium, copper, iron and potassium). Some interrelationships between particular trace mineral concentrations in blood plasma were also observed.     

Effect of population size and selection on Toll-like receptor diversity in populations of Galápagos mockingbirds

The interactions of evolutionary forces are difficult to analyse in free-living populations. However, when properly understood, they provide valuable insights into evolutionary biology and conservation genetics. This is particularly important for the interplay of genetic drift and natural selection in immune genes that confer resistance to disease. The Galápagos Islands are inhabited by four closely related species of mockingbirds (Mimus spp.). We used 12 different-sized populations of Galápagos mockingbirds and one population of their continental relative northern mockingbird (Mimus polyglottos) to study the effects of genetic drift on the molecular evolution of immune genes, the Toll-like receptors (TLRs: TLR1B, TLR4 and TLR15). We found that neutral genetic diversity was positively correlated with island size, indicating an important effect of genetic drift. However, for TLR1B and TLR4, there was little correlation between functional (e.g., protein) diversity and island size, and protein structural properties were largely conserved, indicating only a limited effect of genetic drift on molecular phenotype. By contrast, TLR15 was less conserved and even its putative functional polymorphism correlated with island size. The patterns observed for the three genes suggest that genetic drift does not necessarily dominate selection even in relatively small populations, but that the final outcome depends on the degree of selection constraint that is specific for each TLR locus.     

Growth, survival and generative reproduction in a population of a widespread annual hemiparasite Melampyrum pratense

Melampyrum pratense is one of the most successful root-hemiparasitic species of temperate Europe occurring in various habitats including both forest and open communities. The species shares its life history traits (large seeds, annuality, lack of clonality) with most of other hemiparasitic Orobanchaceae. Due to lack of vegetative propagation, the reproductive success of a M. pratense individual largely depends on the seed production. We used an individual-based observation of ontogenetic development of plants and analysed the development of spatial distribution of individuals to reveal links between fecundity of individuals and their vegetative growth in the context of population dynamics within one growing season. We demonstrated a tight dependency of seed production on vegetative growth and survival till the end of the growing season. Plants that were still alive and big (due to a high number of lateral branches) in the end of August produced the highest numbers of seeds. These were several times higher than the population average due to positively skewed distribution of seed production across individuals. The rate of premature mortality was rather low (below 50%) once seedlings successfully emerged and was most likely caused by intraspecific competition. By contrast, moderate level of herbivory (stem clipping by grazers) had a limited effect on the survival and the inflicted biomass losses seemed compensated. Therefore, despite being an annual, M. pratense appears well-adapted to its life in perennial-dominated forest communities, which is also underpinned by its hemiparasitic strategy providing essential resources and allowing to avoid below-ground competition.     

Biochemical properties of nematode O-acetylserine(thiol)lyase paralogs imply their distinct roles in hydrogen sulfide homeostasis

O-Acetylserine(thiol)lyases (OAS-TLs) play a pivotal role in a sulfur assimilation pathway incorporating sulfide into amino acids in microorganisms and plants, however, these enzymes have not been found in the animal kingdom. Interestingly, the genome of the roundworm Caenorhabditis elegans contains three expressed genes predicted to encode OAS-TL orthologs (cysl-1–cysl-3), and a related pseudogene (cysl-4); these genes play different roles in resistance to hypoxia, hydrogen sulfide and cyanide. To get an insight into the underlying molecular mechanisms we purified the three recombinant worm OAS-TL proteins, and we determined their enzymatic activities, substrate binding affinities, quaternary structures and the conformations of their active site shapes. We show that the nematode OAS-TL orthologs can bind O-acetylserine and catalyze the canonical reaction although this ligand may more likely serve as a competitive inhibitor to natural substrates instead of being a substrate for sulfur assimilation. In addition, we propose that S-sulfocysteine may be a novel endogenous substrate for these proteins. However, we observed that the three OAS-TL proteins are conformationally different and exhibit distinct substrate specificity. Based on the available evidences we propose the following model: CYSL-1 interacts with EGL-9 and activates HIF-1 that upregulates expression of genes detoxifying sulfide and cyanide, the CYSL-2 acts as a cyanoalanine synthase in the cyanide detoxification pathway and simultaneously produces hydrogen sulfide, while the role of CYSL-3 remains unclear although it exhibits sulfhydrylase activity in vitro. All these data indicate that C. elegans OAS-TL paralogs have distinct cellular functions and may play different roles in maintaining hydrogen sulfide homeostasis.