A combination of repurposed drugs reduces the proliferation and viability of glioblastoma cells

Background: Glioblastoma multiforme (GBM) is a malignant primary brain tumour with high rates of recurrence. The tumour is characterized by high molecular diversity. A strategy to simultaneously target different oncogenic pathways together as well as epigenetic modifications could potentially help to overcome the tumour heterogeneity and prevent the development of therapy resistance. This study analysed the in vitro effect of the approved drugs valproic acid, tranylcypromine and riluzole, known for their interaction with epigenetic modifying enzymes and members of the glutamate pathway, singly and in combination with standard chemo- or radiotherapy treatment, in cultured GBM cells. Materials and methods: We examined the effect of the valproic acid, tranylcypromine and riluzole and their combinations, as well as combined with standard temozolomide chemotherapy and radiotherapy on the viability of the U87MG cell line using the MTT assay. Proliferation and cell invasion were evaluated using anti-Ki-67 antibody staining and xCELLigence system. Moreover, we tested the effect of the drugs and their combination on the expression of the tissue factor pathway inhibitor 2 (TFPI2). Results: Valproic acid, tranylcypromine and riluzole produced a significant effect on cell survival. The most prominent effect on cell viability was achieved by the combination of 50 µM riluzole and 10 mM valproic acid and 10 mM valproic acid and 500 µM tranylcypromine. Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The cell proliferation significantly reduced under the combination treatment of temozolomide with valproic acid and tranylcypromine. We observed no additional effect of the radiation on the cell viability. The reduction of invasion was observed comparing single tranylcypromine to its combination with valproic acid or riluzole. The U87MG cells showed a significant upregulation of TFPI2 under the single treatment with VPA or TCA as well as for all combinations of VPA, TCA and riluzole. Conclusion: The combination of repurposed drugs could increase the treatment efficiency of GBM by reducing the cellular viability and proliferation potential as well as by the upregulation of the tumour-suppressor gene expression.2021-10-1

Evolutionary origin of the nervous system from Ctenophora prospective

Nervous system is one of the key adaptations underlying the evolutionary success of the majority of animal groups. Ctenophores (or comb jellies) are gelatinous marine invertebrates that were probably the first lineage to diverge from the rest of animals. Due to the key phylogenetic position and multiple unique adaptations, the noncentralized nervous system of comb jellies has been in the center of the debate around the origin of the nervous system in the animal kingdom and whether it happened only once or twice. Here, we discuss the latest findings in ctenophore neuroscience and multiple challenges on the way to build a clear evolutionary picture of the origin of the nervous system

Neural Circuits: Avoiding UV light

Living deep within our oceans, lakes, and ponds are small animals known as zooplankton which typically rise to the surface of the water at night and sink towards the bottom during the day. This synchronised movement helps zooplankton avoid harmful ultraviolet (UV) light and escape diurnal predators that hunt during the day (Malloy et al., 1997)

Hydrometallurgical processing technology of titanomagnetite ores

In this paper, we study the possibility of obtaining iron and titanium-vanadium concentrates with highest contents of iron and titanium, respectively, through hydrometallurgical processing of the titanomagnetite ores of the Chineisk deposit. We varied two key parameters to determine the efficiency of the process: (a) concentration of leaching solution (ammonium fluoride); and (b) acidity of solution. Ammonium fluoride concentration was varied from 0.08 mol/L to 4.2 mol/L with the other fixed parameters. It was shown that optimum ammonium fluoride concentration for leaching the ore is 0.42 mol/L; at these concentrations iron and titanium contents are about 62.8 wt % and 3.5 wt % in solid phase, respectively. The acidity of solution was changed by adding of hydrofluoric acid with varied concentration (from 0.86 mol/L to 4.07 mol/L) to ammonium fluoride solution with fixed concentration of 0.42 mol/L. The best results (degree of titanium extraction = 63.7%) were obtained when using a solution of hydrofluoric acid with concentration 4.07 mol/L. In this case, the addition of acid makes it possible to increase the Fe/Ti ratio by 3.4 times in comparison with the original ore. Thus, we conclude that acidity and the concentration of ammonium fluoride solution significantly influences the selectivity of the hydrometallurgical process

The Birth and Death of Toxins with Distinct Functions: A Case Study in the Sea Anemone Nematostella

The cnidarian Nematostella vectensis has become an established lab model, providing unique opportunities for venom evolution research. The Nematostella venom system is multimodal: involving both nematocytes and ectodermal gland cells, which produce a toxin mixture whose composition changes throughout the life cycle. Additionally, their modes of interaction with predators and prey vary between eggs, larvae, and adults, which is likely shaped by the dynamics of the venom system. Nv1 is a major component of adult venom, with activity against arthropods (through specific inhibition of sodium channel inactivation) and fish. Nv1 is encoded by a cluster of at least 12 nearly identical genes that were proposed to be undergoing concerted evolution. Surprisingly, we found that Nematostella venom includes several Nv1 paralogs escaping a pattern of general concerted evolution, despite belonging to the Nv1-like family. Here, we show two of these new toxins, Nv4 and Nv5, are lethal for zebrafish larvae but harmless to arthropods, unlike Nv1. Furthermore, unlike Nv1, the newly identified toxins are expressed in early life stages. Using transgenesis and immunostaining, we demonstrate that Nv4 and Nv5 are localized to ectodermal gland cells in larvae. The evolution of Nv4 and Nv5 can be described either as neofunctionalization or as subfunctionalization. Additionally, the Nv1-like family includes several pseudogenes being an example of nonfunctionalization and venom evolution through birth-and-death mechanism. Our findings reveal the evolutionary history for a toxin radiation and point toward the ecological function of the novel toxins constituting a complex cnidarian venom.publishedVersio

The preparation of the Ti-Al alloys based on intermetallic phases

This article deals with a method of obtaining materials in the Ti-Al system. Research was carried out in accordance with the phase diagram of the system state. It was established, that both single-phase and multiphase systems, containing finely dispersed intermetallic compositions of phases Ti3Al, TiAl and TiAl3, are formed. Additionally, it was found that the pure finely dispersed (coherent-scattering region (CSR) up to 100 nm) intermetallic compound TiAl3 is formed at molar ratio of Ti:Al = 1:3. Experimentally proved the possibility of produce the complex composition of alloys and intermetallic compounds and products based on them

Comparison of bitumen–rubber use in extreme conditions in Russia and South Africa

The development of the use of crumb rubber from used tyres in asphalt started in the USSR during the 1960s independently and in parallel with the research in the USA and Western World during the 1970s. The result is that different processes were developed for making bitumen-rubber asphalt. The objective of the paper is to present and compare the bitumen-rubber specifications and asphalt experience in Russia and in South Africa (which was derived from the USA approach). The focus is on the wet process even though more recently the dry method has been used. Firstly, the properties of the constituent components are presented and discussed, where after the properties and manufacture of bitumen-rubber are compared. Finally, the properties of bitumen-rubber asphalt are compared and the experience and performance is presented. It was found that although the initial approach from the two schools differed, there are currently major similarities, even though the temperature ranges of use are vastly different. Bitumen-rubber has been shown to cater effectively for a wide range of environmental conditions and is superior to unmodified bitumen.http://www.tandfonline.com/loi/trmp202018-01-31hb2016Civil Engineerin

Some like it hot: population-specific adaptations in venom production to abiotic stressors in a widely distributed cnidarian

Background: In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, whose synthesis may be metabolically expensive. The potentially high cost of venom production has been hypothesized to drive population-specific variation in venom expression due to differences in abiotic conditions. However, the effects of environmental factors on venom production have been rarely demonstrated in animals. Here, we explore the impact of specific abiotic stresses on venom production of distinct populations of the sea anemone Nematostella vectensis (Actiniaria, Cnidaria) inhabiting estuaries over a broad geographic range where environmental conditions such as temperatures and salinity vary widely. Results: We challenged Nematostella polyps with heat, salinity, UV light stressors, and a combination of all three factors to determine how abiotic stressors impact toxin expression for individuals collected across this species’ range. Transcriptomics and proteomics revealed that the highly abundant toxin Nv1 was the most downregulated gene under heat stress conditions in multiple populations. Physiological measurements demonstrated that venom is metabolically costly to produce. Strikingly, under a range of abiotic stressors, individuals from different geographic locations along this latitudinal cline modulate differently their venom production levels. Conclusions: We demonstrate that abiotic stress results in venom regulation in Nematostella. Together with anecdotal observations from other cnidarian species, our results suggest this might be a universal phenomenon in Cnidaria. The decrease in venom production under stress conditions across species coupled with the evidence for its high metabolic cost in Nematostella suggests downregulation of venom production under certain conditions may be highly advantageous and adaptive. Furthermore, our results point towards local adaptation of this mechanism in Nematostella populations along a latitudinal cline, possibly resulting from distinct genetics and significant environmental differences between their habitats.publishedVersio

Corrosion resistance of neodymium and dysprosium hydrides

This paper describes the methods of obtaining hydrides of rare earth elements such as dysprosium and neodymium. The properties and corrosion resistance of these elements are investigated. A synthesis method of monophasic dysprosium and neodymium dihydrides is presented. Synthesized dihydrides are agglomerates with an average size of 3-50 µm and are formed by crystalline grains of a nanometer size. BET specific surface area, morphology, elemental analyses and composition of samples have been studied. Corrosion stability in aqueous solutions of hydrochloric acid and sodium hydroxide were studied. It was determined that both hydrides undergo hydrolysis in acid and alkaline mediums. Neodymium hydride is more stable to corrosion than dysprosium hydride, which is proved by its longer exposure to aggressive medium to hydrides. The formation of insoluble /poorly soluble products of corrosion can make a significant contribution to the process of powder dissolution