Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL‐10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N‐linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection.     

Changes in plasma thiol levels induced by different phases of treatment in breast cancer; the role of commercial extract from black chokeberry

Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox^?) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment.     

Association of common WRAP 53 variant with ovarian cancer risk in the Polish population

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogensis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53–TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53–WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.     

Reproductive success of individuals with different fruit production patterns. What does it mean for the predator satiation hypothesis?

The predator satiation hypothesis states that synchronous periodic production of seeds is an adaptive strategy evolved to reduce the pressure of seed predators. The seed production pattern is crucial to the predator satiation hypothesis, but there are few studies documenting the success of individuals that are in synchrony and out of synchrony with the whole population. This study is based on long-term data on seed production of Sorbus aucuparia and specialised pre-dispersal seed predation by Argyresthia conjugella, in a subalpine spruce forest in the Western Carpathians (Poland). At the population level, we tested whether functional and numerical responses of predators to the variation of fruit production operate. At the individual level, we tested whether individuals with higher interannual variability in their own seed crops and higher synchrony with the population have higher percentages of uninfested fruits. The intensity of pre-dispersal seed predation was high (average 70 %; range 19–100 %). There were both functional and numerical responses of predators to the variation of fruit production at the population level. We found that individuals that were expected to be preferred under seed predator pressure had higher reproductive success. With increasing synchrony of fruit production between individual trees and the population, the percentage of infested fruits decreased. There was also a negative relationship between the interannual variation in individual fruit production and the percentage of infested fruits. These results confirm selection for individuals with a masting strategy. However, the population does not seem well adapted to strong seed predation pressure and we suggest that this may be a result of prolonged diapause of A. conjugella.     

Migratory Masked Shrikes,Lanius nubicus staging at the desert edge: phenology,and sex- and age-related differences in body mass

Migratory Masked Shrikes (Lanius nubicus) were mist-netted during the spring and autumn migrations at Eilat, Israel. Nearly four times more shrikes were trapped during spring than in autumn. This could be explained by either the species assorting to loop migration, or a higher capture rate owing to poor body condition after crossing the Sahara in spring. In spring, no differences in phenology were observed between the sex- and age-groups. In contrast, in autumn juvenile males arrived significantly later than the rest of the population. Significant differences in wing chord length were found between the four sex and age classes (adult male, adult female, juvenile male, juvenile female) both in spring and autumn. However, significant differences in body mass were found only in autumn. In spring, in both sexes, wing length and body mass changed significantly with date of arrival. Masked Shrike in spring were lighter than in autumn. The results suggest that migration over desert is energetically costly and Eilat is a very important staging place for migratory Masked Shrikes.     

A mechanistic model for the light response of photosynthetic electron transport rate based on light harvesting properties of photosynthetic pigment molecules

Models describing the light response of photosynthetic electron transport rate (ETR) are routinely used to determine how light absorption influences energy, reducing power and yields of primary productivity; however, no single model is currently able to provide insight into the fundamental processes that implicitly govern the variability of light absorption. Here we present development and application of a new mechanistic model of ETR for photosystem II based on the light harvesting (absorption and transfer to the core ‘reaction centres’) characteristics of photosynthetic pigment molecules. Within this model a series of equations are used to describe novel biophysical and biochemical characteristics of photosynthetic pigment molecules and in turn light harvesting; specifically, the eigen-absorption cross-section and the minimum average lifetime of photosynthetic pigment molecules in the excited state, which describe the ability of light absorption of photosynthetic pigment molecules and retention time of excitons in the excited state but are difficult to be measured directly. We applied this model to a series of previously collected fluorescence data and demonstrated that our model described well the light response curves of ETR, regardless of whether dynamic down-regulation of PSII occurs, for a range of photosynthetic organisms (Abies alba, Picea abies, Pinus mugo and Emiliania huxleyi). Inherent estimated parameters (e.g. maximum ETR and the saturation irradiance) by our model are in very close agreement with the measured data. Overall, our mechanistic model potentially provides novel insights into the regulation of ETR by light harvesting properties as well as dynamical down-regulation of PSII.     

Sex influences the taxanes content in Taxus baccata

Like other species of the genus Taxus, European yew trees contain taxanes, including paclitaxel (T) and its precursor 10-deacetylbaccatin III (10-DAB). Taxanes are one of the most effective anticancer drugs. This study was undertaken to describe the levels and patterns of taxane variation in the Sudetian region (SW Poland). Paclitaxel (T) and 10-deacetylbaccatin III (10-DAB) concentrations were analysed in five populations. Needles and twigs were analysed from 60 individuals (30 males and 30 females) in each population. In addition, morphometric measurements were taken in the populations to obtain light intensity coefficients (specific leaf area, SLA). High variability in the taxane contents at both intra and interpopulational levels was found. Nevertheless, females had a significantly higher taxane content compared to males. Because taxanes are carbon-based secondary metabolites, females have higher rate of gas exchange of females compared to males. This was probably an adaptation to greater reproductive effort incurred by females. In this regard, female individuals seem to be better for selecting elite cultivars with a higher taxane production. The relationship between light intensity and taxane content was not significant. Shading, important for optimizing crop production, should not reduce the concentration of taxanes.     

Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae

The kinetochore is the macromolecular protein complex that mediates chromosome segregation. The Dsn1 component is crucial for kinetochore assembly and is phosphorylated by the Aurora B kinase. We found that Aurora B phosphorylation of Dsn1 promotes the interaction between outer and inner kinetochore proteins in budding yeast.     

Synthesis of novel isothiazolopyridines and their in vitro evaluation against Mycobacterium and Propionibacterium acnes

In this paper we describe synthesis, structures and some physicochemical properties of 20 isothiazolopyridines 8–13 substituted differently into an isothiazole ring as well as their in vitro antibacterial assays against Mycobacterium tuberculosis H37Rv, Mycobacterium fortuitum PCM 672 and Propionibacterium acnes PCM 2400. Compound 13a was found to be the most active derivative against M. tuberculosis H37Rv, demonstrating 100% growth inhibition of microorganisms in the primary screen (minimum inhibitory concentration [MIC] 6.25 μg/mL). Nineteen of the prepared compounds were evaluated against M. fortuitum PCM 672 and P. acnes PCM 2400 and only compounds 9 and 12d exhibited excellent activity against individual strains of microorganisms with MIC₉₀ <1 μg/mL. The inhibitory action of the remaining isothiazolopyridines towards the tested strains of the microorganism was low, absent, or a non-linear correlation prohibited accurate determination of MIC values. Unexpectedly, seven of the remaining isothiazolopyridines tested against M. fortuitum and P. acnes stimulated growth of the microorganisms in the range 10–50% or even more (10b) under experimental conditions.