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

Characterization of conserved properties of hemagglutinin of H5N1 and human influenza viruses: possible consequences for therapy and infection control

<p>Abstract</p> <p>Background</p> <p>Epidemics caused by highly pathogenic avian influenza virus (HPAIV) are a continuing threat to human health and to the world's economy. The development of approaches, which help to understand the significance of structural changes resulting from the alarming mutational propensity for human-to-human transmission of HPAIV, is of particularly interest. Here we compare informational and structural properties of the hemagglutinin (HA) of H5N1 virus and human influenza virus subtypes, which are important for the receptor/virus interaction.</p> <p>Results</p> <p>Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an HA domain which may modulate interaction with receptor. We also found that about one third of H5N1 viruses which are isolated during the 2006/07 influenza outbreak in Egypt possibly evolve towards receptor usage similar to that of seasonal H1N1.</p> <p>Conclusion</p> <p>The presented results may help to better understand the interaction of influenza virus with its receptor(s) and to identify new therapeutic targets for drug development.</p

ISPITIVANJE SORTI ŠLJIVE RANOG VREMENA SAZREVANJA PLODA NA PODRUČJU ČAČKA

Although there are more than 6000 plum varieties originated from different wild species from Europe, Asia and North America, there is a constant need to develop new varieties with better characteristics, tolerant/resistant to adverse environmental factors and the most important diseases, in the first place Sharka virus. In addition, one of the most important aims of plum breeding in the world is to create varieties of early and late ripening time in order to prolong the season of fresh fruits on the market as much as possible. The aim of this study was to examine the most significant pomological and productive characteristics of two domestic (ʻBorankaʼ and ʻČačanska ranaʼ) and three introduced (ʻOpalʼ, ʻKatinkaʼ and ʻTegeraʼ) early ripening plum varieties. The most important phenological (phenophase of flowering and fruit ripening) and morphometric characteristics (fruit and stone mass, flesh percentage ratio, fruit dimensions and sphericity), as well as tree vigour (trunk cross-sectional area) and yield (yield per tree and yield efficiency) were examined.Publishe

Physical Activity and Natural Anti-VIP Antibodies: Potential Role in Breast and Prostate Cancer Therapy

BACKGROUND: There is convincing evidence from numerous clinical and epidemiological studies that physical activity can reduce the risk for breast and prostate cancer. The biological mechanisms underlying this phenomenon remain elusive. Herein we suggest a role for naturally produced antibodies reactive with the vasoactive intestinal peptide (VIP) in the suppression of breast and prostate cancer, which we believe could offer a possible molecular mechanism underlying control of these cancers by physical exercise. METHODOLOGY AND RESULTS: We found that sera from individuals having breast and prostate cancers have decreased titers of VIP natural antibodies as demonstrated by a lower reactivity against peptide NTM1, having similar informational and structural properties as VIP. In contrast, sera collected from elite athletes, exhibited titers of natural NTM1-reactive antibodies that are significantly increased, suggesting that physical activity boosts production of these antibodies. SIGNIFICANCE: Presented results suggest that physical exercise stimulates production of natural anti-VIP antibodies and likely results in suppression of VIP. This, in turn, may play a protective role against breast and prostate cancers. Physical exercise should be further investigated as a potential tool in the treatment of these diseases

Predicted enhanced human propensity of current avian-like H1N1 swine influenza virus from China

Influenza A virus (IAV) subtypes against which little or no pre-existing immunity exists in humans represent a serious threat to global public health. Monitoring of IAV in animal hosts is essential for early and rapid detection of potential pandemic IAV strains to prevent their spread. Recently, the increased pandemic potential of the avian-like swine H1N1 IAV A/swine/Guangdong/104/2013 has been suggested. The virus is infectious in humans and the general population seems to lack neutralizing antibodies against this virus. Here we present an in silico analysis that shows a strong human propensity of this swine virus further confirming its pandemic potential. We suggest mutations which would further enhance its human propensity. We also propose conserved antigenic determinants which could serve as a component of a prepandemic vaccine. The bioinformatics tool, which can be used to further monitor the evolution of swine influenza viruses towards a pandemic virus, are described here and are made publically available (http://www.vin.bg.ac.rs/180/tools/iav-mon.php; http://www.biomedprotection.com/iav-mon.php)

Noviji rezultati oplemenjivanja voćaka u Institutu za voćarstvo, Čačak

The Fruit Research Institute Čačak has seventy years long tradition in breeding of continental fruit species. The continual multi-disciplinary scientific and research work conducted so far has resulted in the releasing of 41 different cultivars. In addition to the named and released cultivars, for promising candidate cultivars have been selected (three plums and one peach) and entered for releasing, while there is also a large number of promising genotypes that are currently under intense evaluation. The paper presents an overview of the most significant biological and productive characteristic of the 12 new cultivars of pome and stone fruits, including seven plum cultivars (Boranka, Timočanka, Zlatka, Nada, Mildora, Krina and Pozna plava), two pear cultivars (Julijana and Anđelija) and three sour cherry cultivars (Sofija, Nevena and Iskra).Institut za voćarstvo, Čačak ima sedamdeset godina dugu tradiciju oplemenjivačkog rada na stvaranju novih sorti kontinentalnih vrsta voćaka. Do sada je kao rezultat kontinuiranog, multidisciplinarnog naučnoistraživačkog rada priznata 41 sorta različitih vrsta voćaka. Pored priznatih sorti, izdvojene su četiri kandidat sorte (tri šljive i jedna breskve) koje su u postupku priznavanja, kao i veliki broj perspektivnih genotipova koji se intenzivno proučavaju. U radu je prikazan pregled najznačajnijih bioloških i proizvodnih osobina 12 novije priznatih sorti jabučastih i koštičavih vrsta voćaka, i to: sedam sorti šljive (Boranka, Timočanka, Zlatka, Nada, Mildora, Krina i Pozna plava), dve sorte kruške (Julijana i Anđelija) i tri sorte višnje (Sofija, Nevena i Iskra)

In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profil

Could Inelastic Interactions Induce Quantum Probabilistic Transitions?

What are quantum entities? Is the quantum domain deterministic or probabilistic? Orthodox quantum theory (OQT) fails to answer these two fundamental questions. As a result of failing to answer the first question, OQT is very seriously defective: it is imprecise, ambiguous, ad hoc, non-explanatory, inapplicable to the early universe, inapplicable to the cosmos as a whole, and such that it is inherently incapable of being unified with general relativity. It is argued that probabilism provides a very natural solution to the quantum wave/particle dilemma and promises to lead to a fully micro-realistic, testable version of quantum theory that is free of the defects of OQT. It is suggested that inelastic interactions may induce quantum probabilistic transitions

At-Risk and Recent-Onset Type 1 Diabetic Subjects Have Increased Apoptosis in the CD4+CD25+(high) T-Cell Fraction

BACKGROUND: In experimental models, Type 1 diabetes T1D can be prevented by adoptive transfer of CD4+CD25+ FoxP3+ suppressor or regulatory T cells. Recent studies have found a suppression defect of CD4+CD25+(high) T cells in human disease. In this study we measure apoptosis of CD4+CD25+(high) T cells to see if it could contribute to reduced suppressive activity of these cells. METHODS AND FINDINGS: T-cell apoptosis was evaluated in children and adolescent 35 females/40 males subjects comprising recent-onset and long-standing T1D subjects and their first-degree relatives, who are at variable risk to develop T1D. YOPRO1/7AAD and intracellular staining of the active form of caspase 3 were used to evaluate apoptosis. Isolated CD4+CD25+(high) and CD4+CD25− T cells were co-cultured in a suppression assay to assess the function of the former cells. We found that recent-onset T1D subjects show increased apoptosis of CD4+CD25+(high) T cells when compared to both control and long-standing T1D subjects p<0.0001 for both groups. Subjects at high risk for developing T1D 2–3Ab+ve show a similar trend p<0.02 and p<0.01, respectively. On the contrary, in long-standing T1D and T2D subjects, CD4+CD25+(high) T cell apoptosis is at the same level as in control subjects p = NS. Simultaneous intracellular staining of the active form of caspase 3 and FoxP3 confirmed recent-onset FoxP3+ve CD4+CD25+(high) T cells committed to apoptosis at a higher percentage 15.3±2.2 compared to FoxP3+ve CD4+CD25+(high) T cells in control subjects 6.1±1.7 p<0.002. Compared to control subjects, both recent-onset T1D and high at-risk subjects had significantly decreased function of CD4+CD25+(high) T cells p = 0.0007 and p = 0.007, respectively. CONCLUSIONS: There is a higher level of ongoing apoptosis in CD4+CD25+(high) T cells in recent-onset T1D subjects and in subjects at high risk for the disease. This high level of CD4+CD25+(high) T-cell apoptosis could be a contributing factor to markedly decreased suppressive potential of these cells in recent-onset T1D subjects