Dual role of the p38 MAPK/cPLA2MAPK/cPLA_2 pathway in the regulation of platelet apoptosis induced by ABT-737 and strong platelet agonists

p38 Mitogen-activated protein (MAP) kinase is involved in the apoptosis of nucleated cells. Although platelets are anucleated cells, apoptotic proteins have been shown to regulate platelet lifespan. However, the involvement of p38 MAP kinase in platelet apoptosis is not yet clearly defined. Therefore, we investigated the role of p38 MAP kinase in apoptosis induced by a mimetic of BH3-only proteins, ABT-737, and in apoptosis-like events induced by such strong platelet agonists as thrombin in combination with convulxin (Thr/Cvx), both of which result in p38 MAP kinase phosphorylation and activation. A p38 inhibitor (SB202190) inhibited the apoptotic events induced by ABT-737 but did not influence those induced by Thr/Cvx. The inhibitor also reduced the phosphorylation of cytosolic phospholipase $A_2$ (cPLA2), an established p38 substrate, induced by ABT-737 or Thr/Cvx. ABT-737, but not Thr/Cvx, induced the caspase 3-dependent cleavage and inactivation of cPLA2. Thus, p38 MAPK promotes ABT-737-induced apoptosis by inhibiting the cPLA2/arachidonate pathway. We also show that arachidonic acid (AA) itself and in combination with Thr/Cvx or ABT-737 at low concentrations prevented apoptotic events, whereas at high concentrations it enhanced such events. Our data support the hypothesis that the p38 MAPK-triggered arachidonate pathway serves as a defense mechanism against apoptosis under physiological conditions

The use of microarrays for the identification of the origin of genes of avian influenza viruses in wild birds

Forty-two strains of avian influenza viruses were isolated from the wild waterfowls’ feces in the city of Moscow. These viruses, as well as reference strains and some experimental reassortants, were analyzed by microarrays. The microarrays contained 176 probes to the different segments of influenza virus genome. The microarray helps to determine 1) the hemagglutinin and neuraminidase proteins subtype; 2) the primary structure of the C-terminal sequence of the viral NS1 protein, which serves as a ligand for the PDZ domain; 3) the presence of stop codons in the reading frame of PB1-F2 as well as the N66S substitution in the PB1-F2 viral protein; 4) the presence of the polybasic site for hemagglutinin cleavage. The viruses of the H3N1, H3N6, H3N8, H4N6, H1N1, H5N3, and H11N9 subtypes were identified from the group of wild birds’ isolates. All isolates contained the ESEV sequence at the C-terminus of the NS1 protein and the full-length reading frame for the PB1-F2 protein. The replacement of N66S in PB1-F2 was found in six strains. However, the presence of the ESEV sequence (ligand of PDZ domain) in the NS1 virus protein and the N66S substitution in PB1-F2 did not lead to the pathogenicity of these viruses for mice. All isolates demonstrated high yield growth in chicken embryos and were infectious and immunogenic for mice, but did not induce any clinical symptoms.Forty-two strains of avian influenza viruses were isolated from the wild waterfowls’ feces in the city of Moscow. These viruses, as well as reference strains and some experimental reassortants, were analyzed by microarrays. The microarrays contained 176 probes to the different segments of influenza virus genome. The microarray helps to determine 1) the hemagglutinin and neuraminidase proteins subtype; 2) the primary structure of the C-terminal sequence of the viral NS1 protein, which serves as a ligand for the PDZ domain; 3) the presence of stop codons in the reading frame of PB1-F2 as well as the N66S substitution in the PB1-F2 viral protein; 4) the presence of the polybasic site for hemagglutinin cleavage. The viruses of the H3N1, H3N6, H3N8, H4N6, H1N1, H5N3, and H11N9 subtypes were identified from the group of wild birds’ isolates. All isolates contained the ESEV sequence at the C-terminus of the NS1 protein and the full-length reading frame for the PB1-F2 protein. The replacement of N66S in PB1-F2 was found in six strains. However, the presence of the ESEV sequence (ligand of PDZ domain) in the NS1 virus protein and the N66S substitution in PB1-F2 did not lead to the pathogenicity of these viruses for mice. All isolates demonstrated high yield growth in chicken embryos and were infectious and immunogenic for mice, but did not induce any clinical symptoms

Interaction and Cooperative Nucleation of InAsSbP Quantum Dots and Pits on InAs(100) Substrate

An example of InAsSbP quaternary quantum dots (QDs), pits and dots–pits cooperative structures’ growth on InAs(100) substrates by liquid phase epitaxy (LPE) is reported. The interaction and surface morphology of the dots–pits combinations are investigated by the high-resolution scanning electron microscope. Bimodal growth mechanism for the both QDs and pits nucleation is observed. Cooperative structures consist of the QDs banded by pits, as well as the “large” pits banded by the quantum wires are detected. The composition of the islands and the pits edges is found to be quaternary, enriched by antimony and phosphorus, respectively. This repartition is caused by dissociation of the wetting layer, followed by migration (surface diffusion) of the Sb and P atoms in opposite directions. The “small” QDs average density ranges from 0.8 to 2 × 109 cm−2, with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm, respectively. The average density of the “small” pits is equal to (6–10) × 109 cm−2 with dimensions of 5–40 nm in width and depth. Lifshits–Slezov-like distribution for the amount and surface density of both “small” QDs and pits versus their average diameter is experimentally detected. A displacement of the absorption edge toward the long wavelength region and enlargement toward the short wavelength region is detected by the Fourier transform infrared spectrometry

Glycans as receptors for influenza pathogenesis

Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acα2-3Gal linked (α2-3) to Neu5Acα2-6Gal linked (α2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of α2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to α2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.National Institute of General Medical Sciences (U.S.) (Glue Grant U54 GM62116)National Institutes of Health (U.S.) (Grant GM57073)Singapore-MIT Alliance for Research and Technolog

A depth-averaged model for non-isothermal thin-film rimming flow

A model for non-isothermal shear-driven thin-film flow on the inside surface of a stationary circular cylinder is presented. Motivated by an application to film flow in an aero-engine bearing chamber the model extends lubrication theory analysis of thin films to retain the important effects of inertia and heat convection.The accuracy of the depth-averaged temperature model is tested and comparisons illustrate the model is accurate for both conduction- and convection-dominant flows although local inaccuracies are introduced in regions exhibiting sharp changes in boundary temperature when convective effects are strong.Three rimming-flow configurations are considered: uni-directional flow with slowly-varying film height, a solution containing a steep front termed a shock, and a pooling solution where fluid accumulates in a recirculation at the base of the cylinder. The temperature field in the latter two which include recirculation features are greatly influenced by the strength of convection in the film

Possibility of use of information technologies in archaelogical research

The research sets an objective to consider the efficiency of IT application in archeological studies by the example of mobile package design, intended for archeological studies

Adiabatic description of nonspherical quantum dot models

Within the effective mass approximation an adiabatic description of spheroidal and dumbbell quantum dot models in the regime of strong dimensional quantization is presented using the expansion of the wave function in appropriate sets of single-parameter basis functions. The comparison is given and the peculiarities are considered for spectral and optical characteristics of the models with axially symmetric confining potentials depending on their geometric size making use of the total sets of exact and adiabatic quantum numbers in appropriate analytic approximations

Molecular identification of Newcastle disease virus isolated on the poultry farm of the Moscow Oblast in summer of 2022

In August 2022, a sudden death in backyard chickens was reported in the Moscow Oblast (urban district Chernogolovka, settlement Starki). As a result, within just a few days 45 chickens on this farm died or fell ill with the following signs – gray mucus discharge from nostrils and beak, coughing, gasping and rales. On day 1–3 after the onset of symptoms, the chicken died. The Newcastle disease virus, which is a representative of the Paramyxoviruses family, was isolated from the dead poultry. We determined the nucleotide sequences of fragments in F gene (encodes the fusion surface protein) and in NP gene (encodes the nucleocapsid protein). The motif of 109SGGRRQKRFIG119 proteolysis site, typical for the velogenic pathotype, was determined for the F gene, and a phylogenetic analysis was carried out to demonstrate that the isolate belonged to Subgenotype VII, Class II of the subfamily Avulavirinae. The Basic Local Alignment Search Tool revealed that they are most genetically related with isolates from Iran. It was found that the average death time of developing chicken embryos, infected with a minimum infectious dose, was 52 hours, which is typical for the velogenic pathotype. The virus caused 100% death in six-week-old chickens after oral infection and 100% death in all contact chickens, including those kept in cages at a distance, which proves the high level of pathogenicity and contagiousness of the recovered isolate and its ability to transmit both via fecal-oral and aerosols–borne routes. No death cases were reported in mice after intranasal infection with high doses