Application of Attribute-Based Encryption in Military Internet of Things Environment.

The Military Internet of Things (MIoT) has emerged as a new research area in military intelligence. The MIoT frequently has to constitute a federation-capable IoT environment when the military needs to interact with other institutions and organizations or carry out joint missions as part of a coalition such as in NATO. One of the main challenges of deploying the MIoT in such an environment is to acquire, analyze, and merge vast amounts of data from many different IoT devices and disseminate them in a secure, reliable, and context-dependent manner.

Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure.

Many fundamental questions on alcohol use disorder (AUD) are frequently difficult to address by examining a single brain structure, but should be viewed from the whole brain perspective. c-Fos is a marker of neuronal activation. Global brain c-Fos profiling in rodents represents a promising platform to study brain functional networks rearrangements in AUD.

Novel Role of Mammalian Cell Senescence-Sustenance of Muscle Larvae of spp.

Muscle larva of the parasitic nematode spp. lives in a portion of muscle fibre transformed to a nurse cell (NC). Based on our previous transcriptomic studies, NC growth arrest was inferred to be accompanied by cellular senescence.

Molecular Mechanism of Thymidylate Synthase Inhibition by N-Hydroxy-dCMP in View of Spectrophotometric and Crystallographic Studies.

Novel evidence is presented allowing further clarification of the mechanism of the slow-binding thymidylate synthase (TS) inhibition by N-hydroxy-dCMP (N-OH-dCMP). Spectrophotometric monitoring documented time- and temperature-, and N-OH-dCMP-dependent TS-catalyzed dihydrofolate production, accompanying the mouse enzyme incubation with N-OH-dCMP and N-methylenetetrahydrofolate, known to inactivate the enzyme by the covalent binding of the inhibitor, suggesting the demonstrated reaction to be uncoupled from the pyrimidine C(5) methylation. The latter was in accord with the hypothesis based on the previously presented structure of mouse TS (cf.

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues.

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively.

UAV Swarms Behavior Modeling Using Tracking Bigraphical Reactive Systems.

Recently, there has been a fairly rapid increase in interest in the use of UAV swarms both in civilian and military operations. This is mainly due to relatively low cost, greater flexibility, and increasing efficiency of swarms themselves. However, in order to efficiently operate a swarm of UAVs, it is necessary to address the various autonomous behaviors of its constituent elements, to achieve cooperation and suitability to complex scenarios.

Alvaxanthone, a Thymidylate Synthase Inhibitor with Nematocidal and Tumoricidal Activities.

With the aim to identify novel inhibitors of parasitic nematode thymidylate synthase (TS), we screened in silico an in-house library of natural compounds, taking advantage of a model of nematode TS three-dimensional (3D) structure and choosing candidate compounds potentially capable of enzyme binding/inhibition. Selected compounds were tested as (i) inhibitors of the reaction catalyzed by TSs of different species, (ii) agents toxic to a nematode parasite model ( grown in vitro), (iii) inhibitors of normal human cell growth, and (iv) antitumor agents affecting human tumor cells grown in vitro. The results pointed to alvaxanthone as a relatively strong TS inhibitor that causes population growth reduction with nematocidal potency similar to the anthelmintic drug mebendazole.

Thymidylate synthase-catalyzed, tetrahydrofolate-dependent self-inactivation by 5-FdUMP.

In view of previous crystallographic studies, N-hydroxy-dCMP, a slow-binding thymidylate synthase inhibitor apparently caused "uncoupling" of the two thymidylate synthase-catalyzed reactions, including the N-methylenetetrahydrofolate one-carbon group transfer and reduction, suggesting the enzyme's capacity to use tetrahydrofolate as a cofactor reducing the pyrimidine ring C(5) in the absence of the 5-methylene group. Testing the latter interpretation, a possibility was examined of a TS-catalyzed covalent self-modification/self-inactivation with certain pyrimidine deoxynucleotides, including 5-fluoro-dUMP and N-hydroxy-dCMP, that would be promoted by tetrahydrofolate and accompanied with its parallel oxidation to dihydrofolate. Electrophoretic analysis showed mouse recombinant TS protein to form, in the presence of tetrahydrofolate, a covalently bound, electrophoretically separable 5-fluoro-dUMP-thymidylate synthase complex, similar to that produced in the presence of N-methylenetetrahydrofolate.

A Framework for Constructing a Secure Domain of Sensor Nodes.

Application of the Internet of Things (IoT) in some critical areas (e.g., military) is limited mainly due to the lack of robust, secure, and trusted measures needed to ensure the availability, confidentiality, and integrity of information throughout its lifecycle.

Oxidative stress and inhibition of nitric oxide generation underlie methotrexate-induced senescence in human colon cancer cells.

The response of human colon cancer C85 cells to methotrexate takes the form of reversible growth arrest of the type of stress-induced senescence. In the present study it is shown that during C85 cell progression into methotrexate-induced senescence, dihydrofolate reductase, the primary intracellular target for the drug, is stabilized at the protein level and its enzymatic activity, assayed in crude cellular extracts, decreases by 2-fold. Dihydrofolate reductase inhibition results in an increase in dihydrobiopterin level and an ultimate decrease in the tetrahydrobiopterin: dihydrobiopterin ratio in senescent cells.

Wnt signaling in regulation of biological functions of the nurse cell harboring Trichinella spp.

Background: The nurse cell (NC) constitutes in mammalian skeletal muscles a confined intracellular niche to support the metabolic needs of muscle larvae of Trichinella spp. encapsulating species. The main biological functions of NC were identified as hypermitogenic growth arrest and pro-inflammatory phenotype, both inferred to depend on AP-1 (activator protein 1) transcription factor.

Properties of phosphorylated thymidylate synthase.

Thymidylate synthase (TS) may undergo phosphorylation endogenously in mammalian cells, and as a recombinant protein expressed in bacterial cells, as indicated by the reaction of purified enzyme protein with Pro-Q® Diamond Phosphoprotein Gel Stain (PGS). With recombinant human, mouse, rat, Trichinella spiralis and Caenorhabditis elegans TSs, expressed in Escherichia coli, the phosphorylated, compared to non-phosphorylated recombinant enzyme forms, showed a decrease in Vmax(app), bound their cognate mRNA (only rat enzyme studied), and repressed translation of their own and several heterologous mRNAs (human, rat and mouse enzymes studied). However, attempts to determine the modification site(s), whether endogenously expressed in mammalian cells, or recombinant proteins, did not lead to unequivocal results.

Synthesis, reactivity and biological activity of N(4)-boronated derivatives of 2'-deoxycytidine.

By seeking new stable boron-containing nucleoside derivatives, potential BNCT boron delivery agents, a novel synthetic approach was tested, aimed at a boron attachment via a single bond to an aliphatic carbon of sp(3) hybridization. The latter allowed successful modification of deoxycytidine in the reaction with 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of the deoxynucleoside amino group. For new compounds, detailed NMR, LDI HRMS (Laser Desorption/Ionization High-Resolution Mass Spectrometry) analyses along with in vivo phosphorylation studies, toxicity assays and DFT modelling are presented.

Immunofluorescent localization of thymidylate synthase in the development of Trichinella spiralis and Caenorhabditis elegans.

Localization of thymidylate synthase protein in Trichinella spiralis and Caenorhabditis elegans development was followed with the use of confocal microscopy, revealing similar expression patterns in both nematode species. In T. spiralis premature muscle larvae and C.

Tyrosine nitration affects thymidylate synthase properties.

Highly purified preparations of thymidylate synthase, isolated from calf thymus, and L1210 parental and FdUrd-resistant cells, were found to be nitrated, as indicated by a specific reaction with anti-nitro-tyrosine antibodies, suggesting this modification to appear endogenously in normal and tumor tissues. Each human, mouse and Ceanorhabditis elegans recombinant TS preparation, incubated in vitro in the presence of NaHCO(3), NaNO(2) and H(2)O(2) at pH 7.5, underwent tyrosine nitration, leading to a V(max)(app) 2-fold lower following nitration of 1 (with human or C.

Nurse cell of Trichinella spp. as a model of long-term cell cycle arrest.

Nurse cell (NC), formed from skeletal muscle cells upon infection with parasitic nematode trichina, presents a rare system of long-term suspension in the cell cycle. Signaling pathways and general biological functions of Trichinella spiralis NC, inferred from network analysis of competitive expression microarray data (NC vs. C2C12 myoblasts and myotubes), performed in Ingenuity Pathways Analysis (IPA) software and confirmed by Real-Time PCR, are presented.

Interactions of 2'-fluoro-substituted dUMP analogues with thymidylate synthase.

A series of 2'-fluoro-substituted dUMP/FdUMP analogues were synthesized, their interaction with human recombinant thymidylate synthase investigated, and structural (1)H and (19)F NMR study of the corresponding nucleosides performed. While 2'-F-dUMP (fluorine in the "down" configuration), in striking contrast to 2'-F-ara-UMP (fluorine in the "up" configuration) and 2',2''-diF-dUMP, showed substrate activity, 2'-F-ara-UMP and 2',2''-diF-dUMP were classic inhibitors, and 2',5-diF-ara-UMP behaved as a strong slow-binding inhibitor, suggesting the 2'-F substituent in the "up" position to interfere with the active center cysteine thiol addition to the pyrimidine C(6) and the pyrimidine C(5)-F to prevent this interference. In support, the direct through space heteronuclear coupling J(HF) was observed for the fluorine "up" derivatives, 2'-F-ara-U and 2',5-diF-ara-U, causing the splitting of the H(6) resonance lines.

Two Aspergillus nidulans genes encoding methylenetetrahydrofolate reductases are up-regulated by homocysteine.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate in the synthesis of methionine from homocysteine. We have cloned and characterized two Aspergillus nidulans genes encoding MTHFRs: metA and metF. Mutations in either gene result in methionine requirement; the metA-encoded enzyme is responsible for only 10-15% of total MTHFR activity.

Cerebral circulation insufficiency - correlation of CTA-visualized atherosclerotic lesions in extra- and intracranial arteries.

Background: To analyze the co-occurrence of atherosclerotic lesions in CT angiograms of extra and intracranial arteries in patients with cerebral circulation insufficiency.

Material/methods: Extra-and intracranial CTA was performed in 70 patients with symptoms of cerebral circulation insufficiency. Co-occurrence of atherosclerotic lesions at both levels and correlation between the degree of atherosclerosis and sex, age, and clinical symptoms were evaluated.

Altered mouse leukemia L1210 thymidylate synthase, associated with cell resistance to 5-fluoro-dUrd, is not mutated but rather reflects posttranslational modification.

Thymidylate synthase purified from 5-fluoro-dUrd-resistant mouse leukemia L1210 cells (TSr) was less sensitive to slow-binding inhibition by 5-fluoro-dUMP than the enzyme from the parental cells (TSp), both enzyme forms differing also in sensitivity to several other dump analogues, apparent molecular weights of monomer and dimer, and temperature dependence of the catalyzed reaction. Direct sequencing of products obtained from RT-PCR, performed on total RNA isolated from the parental and 5-fluoro-dUrd-resistant cells, proved both nucleotide sequences to be identical to the mouse thymidylate synthase coding sequence published earlier (NCBI protein database access no. NP_067263).

Trichinella spiralis infection affects p47(phox) protein expression in guinea-pig alveolar macrophages.

To establish whether NADPH oxidase activation, responsible for previously demonstrated Trichinella spiralis-induced respiratory burst, results from assembling of membrane and cytosolic NADPH oxidase components and/or increased expression of the oxidase complex proteins, the superoxide anion production and expression of the regulatory p47(phox) subunit were measured in cultured alveolar macrophages obtained during T. spiralis infection of guinea pigs. The results demonstrate for the first time helminth parasite-infection-induced stimulation of NADPH oxidase p47(phox) subunit protein expression, with the effect being decreased by in vivo treatment with cyclosporin A, previously shown to inhibit T.

Increased thymidine kinase activity in human thyroid toxic adenomas: effects of exposure to epidermal growth factor in vitro.

Unlabelled: The activity of thymidine kinase (TK-EC 2.7.1.

Effect of cyclosporin A on immunological response in lungs of guinea pigs infected with Trichinella spiralis.

The effects of cyclosporin A (CsA), a potent immunosuppressive drug with antiparasitic activity, on the innate immunological response in guinea pig lungs during an early period (6th and 14th days) after T. spiralis infection were studied. CsA treatment of T.