TOR and S6K1 promote translation reinitiation of uORF‐containing mRNAs via phosphorylation of eIF3h

Mammalian target‐of‐rapamycin (mTOR) triggers S6 kinase (S6K) activation to phosphorylate targets linked to translation in response to energy, nutrients, and hormones. Pathways of TOR activation in plants remain unknown. Here, we uncover the role of the phytohormone auxin in TOR signalling activation and reinitiation after upstream open reading frame (uORF) translation, which in plants is dependent on translation initiation factor eIF3h. We show that auxin triggers TOR activation followed by S6K1 phosphorylation at T449 and efficient loading of uORF‐mRNAs onto polysomes in a manner sensitive to the TOR inhibitor Torin‐1. Torin‐1 mediates recruitment of inactive S6K1 to polysomes, while auxin triggers S6K1 dissociation and recruitment of activated TOR instead. A putative target of TOR/S6K1—eIF3h—is phosphorylated and detected in polysomes in response to auxin. In TOR‐deficient plants, polysomes were prebound by inactive S6K1, and loading of uORF‐mRNAs and eIF3h was impaired. Transient expression of eIF3h‐S178D in plant protoplasts specifically upregulates uORF‐mRNA translation. We propose that TOR functions in polysomes to maintain the active S6K1 (and thus eIF3h) phosphorylation status that is critical for translation reinitiation.     

Effect of recording electrode position along a muscle fibre on surface potential power spectrum

Extracellular action potentials produced by a muscle fibre of finite length were calculated for recordings at the skin surface. The sensitivity of power spectra to variations in propagation velocity (ν) and intracellular action potential (IAP) duration (T_in) was studied theoretically. The magnitude and distribution of the spectral power of muscle fibre potentials depend on the electrode longitudinal position. The relative shifts of the spectra in dB induced by variation in ν or T_in hardly depend on the longitudinal position of the electrode. A variation in ν affects only the power spectrum positive slope and the initial part of the high-frequency roll-off and a variation in T_in affects only the remaining part of the high-frequency roll-off. The total spectral amplitude is practically non-sensitive to variations in the wavelength, b = ν.T_in. The total power is sensitive to variations in ν, T_in as well as in b, and its relative changes depend on the electrode longitudinal position. The whole power spectrum is shifted along the frequency axis and mode (F_max), median (F_med) and mean (F_mean) frequencies have practically equal percentage changes only when ν and T_in vary jointly in such a way that the product ν.T_in keeps unchanged.     

Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies

Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.     

Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia–reperfusion injury

The unfolded protein response (UPR) – the endoplasmic reticulum stress response – is found in various pathologies including ischemia–reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods – a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems) – we identified the IRE1α–XBP1 and the ATF6 pathways as the main UPR effectors involved in cell’s adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI.     

Molar Microwear of Narrow-Headed Vole (<Emphasis Type="Italic">Microtus gregalis</Emphasis> Pall., 1779) Depending on the Feed Abrasiveness

In the narrow-headed vole, enamel microwear of the first mandibular molar (of the protoconid and entoconid anterior enamel wall) was studied under the laboratory conditions and at the fixed feed composition. The classic parameters and the area of the enamel prism lesion were taken into account. The enamel lesion patterns caused by the tooth–tooth and tooth–food interactions have been determined. Differences were found between the voles kept on feed with different abrasive properties, as well as between the lingual and buccal conids of the first mandibular molar. In the Microtus species, the ratio of micro-lesions (pits and scratches) did not depend on the abrasive properties of the feed consumed. The extent of preservation of the enamel contour anterior edge depended on the feed composition and could be used as an indicator for indirect evaluation of the Microtus species diet.     

Data Identification for Improving Gene Network Inference using Computational Algebra

Identification of models of gene regulatory networks is sensitive to the amount of data used as input. Considering the substantial costs in conducting experiments, it is of value to have an estimate of the amount of data required to infer the network structure. To minimize wasted resources, it is also beneficial to know which data are necessary to identify the network. Knowledge of the data and knowledge of the terms in polynomial models are often required a priori in model identification. In applications, it is unlikely that the structure of a polynomial model will be known, which may force data sets to be unnecessarily large in order to identify a model. Furthermore, none of the known results provides any strategy for constructing data sets to uniquely identify a model. We provide a specialization of an existing criterion for deciding when a set of data points identifies a minimal polynomial model when its monomial terms have been specified. Then, we relax the requirement of the knowledge of the monomials and present results for model identification given only the data. Finally, we present a method for constructing data sets that identify minimal polynomial models.     

Revealing the reviving secret of the white dead nettle (Lamium album L.)

Lamium album, commonly known as white dead nettle or non-stinging nettle is a flowering herbaceous plant, native throughout Europe, Western Asia and North Africa. From ancient times this plant has been endowed with revival, curative and culinary virtues. In the past, in the traditional and folk medicine white dead nettle has been used mainly for its anti-inflammatory, astringent and anti-septic activity. Nowadays significant amount of knowledge on the efficacy of extracts and raw material of L. album is accumulated and a number of health-related beneficial activities have been scientifically proven. In vitro analyses conducted in various model systems have demonstrated antiviral, antimicrobial, antioxidant, anticancer, cytoprotective, wound healing and other important pharmacological effects. The present review summarizes the recent information on the phytochemical features of this pharmacologically important species. The findings on the chemical composition, biological activities and the pharmacological properties underlying the revival secret of white dead nettle are described and discussed in the view of potential applications for treatment of human diseases. Trends for further research are outlined.