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We report a case where two males of dark green snake (Hierophis viridiflavus) disturbed during a ritual combat split away, but shortly after, they were sighted fighting again. Disturbed for a second time, they were rapidly observed fighting for a third time. Mutual biting was not recorded in any round. No female was sighted in the vicinity. This suggests that ritual combats may serve to defend an area to access females, possibly when males follow female’s pheromonal tracks. Furthermore, observations of captive and free-ranging Montpellier snakes (Malpolon monspessulanus) indicate that some males use their nasal secretions to mark an area (observed in both sexes) but also to keep adult females and to deter rivals. Long-lasting ritual combats are exceptional in this species, a single fierce biting clash possibly producing a winner. Overall, ritual combats and chemical signalling may represent two nonexclusive means used by males to increase their opportunities to access, court, fertilize and keep reproductive females.

Andreas David Zimmer, Geoffroy Walbrecq, Ines Kozar, Iris Behrmann, Claude Haan Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg Abstract: The pyruvate dehydrogenase complex (PDC) is an important gatekeeper enzyme connecting glycolysis to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Thereby, it has a strong impact on the glycolytic flux as well as the metabolic phenotype of a cell. PDC activity is regulated via reversible phosphorylation of three serine residues on the pyruvate dehydrogenase (PDH) E1α subunit. Phosphorylation of any of these residues by the PDH kinases (PDKs) leads to a strong decrease in PDC activity. Under hypoxia, the inactivation of the PDC has been described to be dependent on the hypoxia-inducible factor 1 (HIF-1)-induced PDK1 protein upregulation. In this study, we show in two hepatocellular carcinoma cell lines (HepG2 and JHH-4) that, during the adaptation to hypoxia, PDH is already phosphorylated at time points preceding HIF-1-mediated transcriptional events and PDK1 protein upregulation. Using siRNAs and small molecule inhibitor approaches, we show that this inactivation of PDC is independent of HIF-1α expression but that the PDKs need to be expressed and active. Furthermore, we show that reactive oxygen species might be important for the induction of this PDH phosphorylation since it correlates with the appearance of an altered redox state in the mitochondria and is also inducible by H2O2 treatment under normoxic conditions. Overall, these results show that neither HIF-1 expression nor PDK1 upregulation is necessary for the phosphorylation of PDH during the first hours of the adaptation to hypoxia. Keywords: pyruvate dehydrogenase complex, pyruvate dehydrogenase kinase, hypoxia metabolism, glycolytic switch, radical oxygen species

There is increasing evidence to suggest that antibodies directed toward influenza A virus (IAV) neuraminidase (NA) are an important correlate of protection against influenza in humans. Moreover, the potential of NA-specific antibodies to provide broader protection than conventional hemagglutinin (HA) antibodies has been recognized. Here, we describe the isolation of two monoclonal antibodies, N1-7D3 and N1-C4, directed toward the N1 NA. N1-7D3 binds to a conserved linear epitope in the membrane-distal, carboxy-terminal part of the NA and reacted with the NA of seasonal H1N1 isolates ranging from 1977 to 2007 and the 2009 H1N1pdm virus, as well as A/Vietnam/1194/04 (H5N1). However, N1-7D3 lacked NA inhibition (NI) activity and the ability to protect BALB/c mice against a lethal challenge with a range of H1N1 viruses. Conversely, N1-C4 bound to a conformational epitope that is conserved between two influenza virus subtypes, 2009 H1N1pdm and H5N1 IAV, and displayed potent in vitro antiviral activity mediating both NI and plaque size reduction. Moreover, N1-C4 could provide heterosubtypic protection in BALB/c mice against a lethal challenge with 2009 H1N1pdm or H5N1 virus. Glutamic acid residue 311 in the NA was found to be critical for the NA binding and antiviral activity of monoclonal antibody N1-C4. Our data provide further evidence for cross-protective epitopes within the N1 subtype and highlight the potential of NA as an important target for vaccine and therapeutic approaches. IMPORTANCE Influenza remains a worldwide burden on public health. As such, the development of novel vaccines and therapeutics against influenza virus is crucial. Human challenge studies have recently highlighted the importance of antibodies directed toward the viral neuraminidase (NA) as an important correlate of reduced influenza-associated disease severity. Furthermore, there is evidence that anti-NA antibodies can provide broader protection than antibodies toward the viral hemagglutinin. Here, we describe the isolation and detailed characterization of two N1 NA-specific monoclonal antibodies. One of these monoclonal antibodies broadly binds N1-type NAs, and the second displays NA inhibition and in vitro and in vivo antiviral activity against 2009 H1N1pdm and H5N1 influenza viruses. These two new anti-NA antibodies contribute to our understanding of the antigenic properties and protective potential of the influenza virus NA antigen.

Virus replicon particles are capable of infection, genome replication and gene expression, but are unable to produce progeny virions, rendering their use inherently safe. By virtue of this unique combination of features, replicon particles hold great promise for vaccine applications. We previously developed replicon particles of Rift Valley fever virus (RVFV) and demonstrated their high efficacy as a RVFV vaccine in the natural target species. We have now investigated the feasibility of using this nonspreading RVFV (NSR) as a vaccine vector using influenza virus hemagglutinin as a model antigen. NSR particles were designed to express either the full-length hemagglutinin of influenza A virus H1N1 (NSR-HA) or the respective soluble ectodomain (NSR-sHA). The efficacies of the two NSR vector vaccines, applied via either the intramuscular or the intranasal route, were evaluated. A single vaccination with NSR-HA protected all mice from a lethal challenge dose, while vaccination with NSR-sHA was not protective. Interestingly, whereas intramuscular vaccination elicited superior systemic immune responses, intranasal vaccination provided optimal clinical protection.

Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.

Op een zonnig terras in Potsdam bespraken Marijke en ik ooit de tijd rond 1970, waarin het marxisme de Nederlandse universiteiten rood kleurde. Marijke leerde op haar studentenvereniging de Internationale zingen; ik werd als universitair docent geacht mij te verdiepen in "kritiese" of "materialistiese" taalkunde. In die tijd kon je marxistisch-georiënteerde studenten vaak het woord praxis horen gebruiken. Praxis betekende gewoon "praktijk". Desgevraagd beaamden mijn studenten dit, maar, zo zeiden ze, "wij" spreken van "praxis". Het was puur een signaalwoord, waarmee je je als aanhanger van een ideologie kenbaar maakte. Een paar jaar later verdween, met de ideologie, ook het gebruik van praxis uit mijn werksfeer. Ik heb deze boeiende fluctuatie in de Nederlandse woordenschat wat nader onderzocht via de KB-website Historische Kranten. Daarbij bleek het gebruik van praxis wijder verbreid dan ik dacht! Zowel in tijd als in toepassingssfeer. Het oorspronkelijk Duitse praxis werd in het Nederlands overgenomen op diverse gebieden. In de eerste plaats de theologie, voorts de medische en sociale&politieke wetenschappen. Het eerste aangetroffen voorbeeld dateert van 1807, het laatste van 1994. In de hoogtij-jaren’70 bespotten sommige columnisten het gebruik van praxis. Niettemin, "de praxis van het taalgebruik"(Google) leert dat praxis nog onder ons is; ik trof één voorbeeld aan uit 2014.

Sewer systems are costly to construct and even more costly to replace, requiring proper asset management Sewer asset management relies to a large extent on available information. In sewer systems where pipe corrosion is the dominant failure mechanism, visual inspection (CCTV) and core sampling are amongst the methods applied mostly to assess sewer pipe condition. This paper compares visual inspection and drill core analysis in order to enhance further understanding of the limitations and potentials of both methods. Both methods have been applied on a selected sewer reach in the city of the Hague, which was reportedly subject to pipe corrosion. Results show that both methods, visual inspection and core sampling, are associated with large uncertainties and that there is no obvious correlation between results of visual inspection and results of drill core analysis.