Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

TECHNOLOGY OF BREAD, ENHANCED THE BODY RESISTANCE TO THE ACTION OF STRESSORS

Introduction: Nowadays, the frequent and prolonged stress has a negative influence on metabolism, resulting in free radicals accumulation. Oxidative stress launches a metabolic cascade, irreversibly damaging the cell.Aim: The aim of this paper is to study the possible involvement of soluble carbohydrates in antioxidant mechanisms as molecular interceptors of active forms of oxygen and the possible influence of fucoidan on the hormonal status.Materials and Methods: We uesd bread wheat flour (gluten 28.5%, ash content 0.55), enriched with the herbal supplement fucoidan. The preparation of raw material was carried out according to the technological instructions for the production of bread. Hormones were determined by ELISA (total T3-vector Best RU; T4 total-vector Best, RU; cortisol-Best vector, RU).The experiment: We selected two groups of subjects. One group received regular bread and the other - bread with fucoidan for 28 days. Blood was collected twice before and after the consumption of bread to study the levels of cortisol, T3, T4.We used the recommended dose of fucoidan for humans - 100 mg per day and daily intake of bread of 325-345 g.The effect of herbal supplements on the sensory and chemical indicators of bread quality was determined. Optical microscope Altami-136T (Altami, Russia) was used to study the activity of the yeast cells with fucoidan. Microscopic studies were performed on Jeol JEM-2100 (Jeol Ltd., Japan).The obtained results confirmed the possibility of using fucoidan to improve the quality of fresh bread. The residual content of fucoidan in the finished product was 0.196±0.0015 mg/g. This demonstrates the thermal stability of fucoidan in the composition of bread.This study showed that after eating bread with fucoidan there was a tendency to normalise the levels of T3 and T4, and the levels of cortisol remained unchanged

Tilt observations in the normal mode frequency band at the Geodynamic Observatory Cueva de los Verdes, Lanzarote

We have conducted observations with the aid of a seismo-tiltmeter station, which is based on the Ostrovsky pendulum and installed at the Geodynamic Observatory Cueva de los Verdes at Lanzarote Island since 1995. In this station the signal is separated into two frequency bands – tidal tilts (from 0 to 5 mHz) and ground oscillations in the frequency range of free Earth’s normal modes (from 0.2 to 5 mHz). The later band, called accelerometer channel, has additional amplification. We analyzed the background records in the frequency range of Earth’s free oscillations from August 2000 to September 2001, as well as, Earth’s normal modes after strong earthquakes. We found several distinctive persistent peaks in the spectra of background oscillations. Both amplitudes of distinguished peaks and noises have seasonal variations. We found that spectra of background oscillations are different in the frequency interval between 1.4 and 2.5 mHz for North- South and East-West components