Novel phylogenetic algorithm to monitor human tropism in Egyptian H5N1-HPAIV reveals evolution toward efficient human-to-human transmission

Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006–2008 G2 viruses were significantly (p<0.02) more often found in humans than expected from their overall prevalence and this further increased in 2009–2011 (p<0.007). Our approach also identified viruses that acquired additional mutations that we predict to further enhance their human tropism. The extensive evolution of Egyptian H5N1-HPAIV towards a preferential human tropism underlines an urgent need to closely monitor these viruses with respect to molecular determinants of virulence

Can Volcanic Dust Suspended From Surface Soil and Deserts of Iceland Be Transferred to Central Balkan Similarly to African Dust (Sahara)?

In this work we use chemical fingerprints as characteristics ratios of specific crustal elements Ca/Al, Fe/Al, K/Al, Mg/Al, Mn/Al, Ca/Fe, and Mg/Fe to investigate the long-range transport of volcanic aerosols from Iceland. Volcanic dust enters the atmosphere during suspension processes from Icelandic deserts, but mainly from the dust hot spots in remote areas in Iceland, and it is transmitted to the central Balkan area (Belgrade). For this purpose, backward trajectories from Belgrade (φ = 44°48′; λ = 20°28′) in 2012 and 2013, simultaneous with atmospheric aerosols measurements, were calculated by using the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model. We found that about 17% of air masses passed over Icelandic territory and arrived to Balkan area. In almost all of these episodes ratios of some investigated elements in suburban aerosols of Balkan area corresponded to the ratios of elements investigated in surface soil of the Rangárvellir area – South Iceland in the vicinity of volcanoes. We identified several episodes, such as August 6–8, 2012; June 2–6, 2013; June 26–28, 2013; and September 18–20, 2013; with the characteristic ratios of the highest number of investigated elements in atmospheric aerosol of central Balkan corresponding to ratios from Icelandic soil material. This study provides evidence that Icelandic dust can travel long distances showing the importance of High Latitude Dust sources.This study was funded by the Ministry of Education, Science and Technological Development of Serbia (Projects: ON172001, ON176013, and III43007). The preparation of this manuscript was in part funded by the Icelandic Research Fund (Rannis) Grant No. 152248-051 and COST STSM Reference Number: COST-STSM-ES1306-34336 (Grant holder DĐ).Peer Reviewe

Radiation Damage Mechanisms of Chemotherapeutically Active Nitroimidazole Derived Compounds

Photoionization mass spectrometry, photoelectron-photoion coincidence spectroscopic technique, and computational methods have been combined to investigate the fragmentation of two nitroimidazole derived compounds: the metronidazole and misonidazole. These molecules are used in radiotherapy thanks to their capability to sensitize hypoxic tumor cells to radiation by “mimicking” the effects of the presence of oxygen as a damaging agent. Previous investigations of the fragmentation patterns of the nitroimidazole isomers (Bolognesi et al., 2016; Cartoni et al., 2018) have shown their capacity to produce reactive molecular species such as nitric oxide, carbon monoxide or hydrogen cyanide, and their potential impact on the biological system. The results of the present work suggest that different mechanisms are active for the more complex metronidazole and misonidazole molecules. The release of nitric oxide is hampered by the efficient formation of nitrous acid or nitrogen dioxide. Although both metronidazole and misonidazole contain imidazole ring in the backbone, the side branches of these molecules lead to very different bonding mechanisms and properties

Mutations in the PAH gene: A Tool for population genetics study

Fenilketonurija je urođena metabolička bolest prouzrokovana mutacijama u genu za fenilalanin hidroksilazu (PAH). U srpskoj populaciji je identifikovano 19 različitih PAH mutacija. PAH mutacije korišćene su kao molekularni markeri za populaciono-genetičko istraživanje. Niska vrednost homozigotnosti PAH gena (0,10) ukazuje na heterogenost fenilketonurije u Srbiji i odražava brojne migracije u regionu jugoistočne Evrope. U skladu sa tim, osmišljena je strategija molekularne dijagnostike fenilketonurije za Srbiju. U cilju rasvetljavanja porekla najčešće mutacije koja uzrokuje fenilketonuriju u Srbiji, L48S, urađena je haplotipska analiza PCR-RFLP metodom. Naši rezultati sugerišu da je L48S mutacija poreklom iz više populacija sa različitim genetičkim karakteristikama. .Phenylketonuria (PKU), an inborn error of metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. In the Serbian population, 19 different PAH mutations have been identified. We used PAH mutations as molecular markers for population genetics study. The low homozygosity value of the PAH gene (0.10) indicates that PKU in Serbia is heterogeneous, reflecting numerous migrations throughout Southeast Europe. The strategy for molecular diagnostics of PKU was designed accordingly. To elucidate the origin of the most common (L48S) PKU mutation in Serbia, we performed haplotype analysis by PCR-RFLP. Our results suggest that the L48S mutation was imported into Serbia from populations with different genetic backgrounds

Inner shell photofragmentation of 2Cl-pyrimidine studied by mass spectrometry and electron–ion coincidence experiments

Photoelectron spectroscopy, mass spectrometry and electron–ion coincidence experiments combined with tunable synchrotron radiation have been used to study the decay and fragmentation of 2Cl-pyrimidine after Cl(2p), C(1s) and N(1s) excitations. The goal is to investigate how the state- and site-selected excitation and the chemical environment affect the fragmentation paths of the molecule and to make a comparison with fragmentation induced by direct valence ionization. It has been found that the site-selective inner shell excitation affects the branching ratio of the fragments, while the particular fragmentation channels of the cation are determined by the final state populated in the resonant decay of the core excited states. Effects of nuclear motion in the core excited states and the possible ultrafast molecular dissociation following the Cl(2p → σ*) core excitation are discussed

Distribution of A(0.236)/A(0.076) ratios by years for Egyptian H5N1-HPAIV isolated during 2006–2011.

<p>(a) The average values of A(0.236)/A(0.076) for G1 and G2 viruses. (b) Distribution of G1 and G2 viruses by years. (c) The average values of A(0.236)/A(0.076) by years.</p

Comparison of informational spectra of H5N1-HPAIV from poultry and humans isolated 2006–2010.

<p>(a) A/chicken/Egypt/R1/2006, (b) A/Egypt/2763-NAMRU3/2006, (c) A/chicken/Egypt/1029/2010, (d) A/Egypt/N04434/2010.</p

Mutations that increase binding of H5N1-HPAIV HA1 to the human α2,6-linked sialic acid.

<p>Mutations that increase binding of H5N1-HPAIV HA1 to the human α2,6-linked sialic acid.</p

Comparison of sensitivity of MSA-based and ISM-based phylogenetic tree to mutations.

<p>Mutations which are potentially important for human tropism of Egyptian H5N1-HPAIV are included to test the sensitivity of MSA- and ISM-based approach to mutations. (a) The MSA tree and (b) the ISM tree for all 311 unmutated H5N1-HPAIV HA1 sequences belonging to G1 viruses; (c) the MSA tree of panel (a) in which each second sequence was mutated and (d) the ISM tree which corresponds to the mutated and unmutated sequences presented in panel (c). H5N1-HPAIV HA1 sequences selected for mutations D43N, S120D, S129Δ and I151T are in red.</p