BanLec, a banana lectin, is a potent inhibitor of Middle East respiratory syndrome coronavirus in in vitro assays

Poster Abstract Session - Viral Infections: Treatment and Prevention: no. 1159BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause human infections with multiple clusters two years after the onset of the epidemic. Though mild cases have been recognized, the infection is severe in those with co-morbidities and >30% of patients die from the infection. Our recent structure-based development of a fusion inhibitor is one of the few treatment options for MERS and it led us to hypothesize that other existing antivirals that block cellular entry may also be active against MERS-CoV. BanLec is a jacalin-related banana lectin that has potent anti-HIV activity through binding to glycosylated viral envelope proteins and blocking cellular entry. We assessed the anti-MER-CoV activity of BanLec in cell culture assays. METHODS: The anti-MERS-CoV activity of BanLec was assessed by cytopathic effect (CPE) inhibition, viral yield reduction, and plaque reduction (PRA) assays in Vero, Calu-3, and/or HK2 cells. The cytotoxicity of BanLec was also assessed. RESULTS: The CC50 of BanLec was >10 nM in Vero and Calu-3 cells. CPE was completely absent in Vero and HK2 cells infected with MERS-CoV on 3 dpi with 30.00 nM of BanLec. In Calu-3 cells, CPE was completely absent at 90.00 nM of the drug. The EC50 of BanLec ranged from 3.99-4.82 nM (Table 1). The mean viral loads reduced by 7.13, 3.40, and 3.63 log10 copies/ml in Vero, Calu-3, and HK2 cells respectively (Fig. 1A to C). The highest percentage of plaque reduction at a concentration of >10 nM of BanLec were 100% and 59.5% in Vero cells and HK2 cells respectively (Fig. 2A & B). CONCLUSION: BanLec exhibits potent in vitro anti-MERS-CoV activity. The detailed mechanism and in vivo correlation of its antiviral activity should be further tested in animal models. The potential advantages of using BanLec for MERS include its high stability and the prospect of using it as a topical treatment or prophylaxis for exposed patients. (Table see attachment)BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause human infections with multiple clusters two years after the onset of the epidemic. Though mild cases have been recognized, the infection is severe in those with co-morbidities and >30% of patients die from the infection. Our recent structure-based development of a fusion inhibitor is one of the few treatment options for MERS and it led us to hypothesize that other existing antivirals that block cellular entry may also be active against MERS-CoV. BanLec is a jacalin-related banana lectin that has potent anti-HIV activity through binding to glycosylated viral envelope proteins and blocking cellular entry. We assessed the anti-MER-CoV activity of BanLec in cell culture assays. METHODS: The anti-MERS-CoV activity of BanLec was assessed by cytopathic effect (CPE) inhibition, viral yield reduction, and plaque reduction (PRA) assays in Vero, Calu-3, and/or HK2 cells. The cytotoxicity of BanLec was also assessed. RESULTS: The CC50 of BanLec was >10 nM in Vero and Calu-3 cells. CPE was completely absent in Vero and HK2 cells infected with MERS-CoV on 3 dpi with 30.00 nM of BanLec. In Calu-3 cells, CPE was completely absent at 90.00 nM of the drug. The EC50 of BanLec ranged from 3.99-4.82 nM (Table 1). The mean viral loads reduced by 7.13, 3.40, and 3.63 log10 copies/ml in Vero, Calu-3, and HK2 cells respectively (Fig. 1A to C). The highest percentage of plaque reduction at a concentration of >10 nM of BanLec were 100% and 59.5% in Vero cells and HK2 cells respectively (Fig. 2A & B). CONCLUSION: BanLec exhibits potent in vitro anti-MERS-CoV activity. The detailed mechanism and in vivo correlation of its antiviral activity should be further tested in animal models. The potential advantages of using BanLec for MERS include its high stability and the prospect of using it as a topical treatment or prophylaxis for exposed patients

Selective Metal Cation Capture by Soft Anionic Metal-Organic Frameworks via Drastic Single-Crystal-to-Single-Crystal Transformations

In this paper we describe a novel framework for the discovery of the topical content of a data corpus, and the tracking of its complex structural changes across the temporal dimension. In contrast to previous work our model does not impose a prior on the rate at which documents are added to the corpus nor does it adopt the Markovian assumption which overly restricts the type of changes that the model can capture. Our key technical contribution is a framework based on (i) discretization of time into epochs, (ii) epoch-wise topic discovery using a hierarchical Dirichlet process-based model, and (iii) a temporal similarity graph which allows for the modelling of complex topic changes: emergence and disappearance, evolution, and splitting and merging. The power of the proposed framework is demonstrated on the medical literature corpus concerned with the autism spectrum disorder (ASD) - an increasingly important research subject of significant social and healthcare importance. In addition to the collected ASD literature corpus which we will make freely available, our contributions also include two free online tools we built as aids to ASD researchers. These can be used for semantically meaningful navigation and searching, as well as knowledge discovery from this large and rapidly growing corpus of literature.Comment: In Proc. Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD), 201

Light hadron, Charmonium(-like) and Bottomonium(-like) states

Hadron physics represents the study of strongly interacting matter in all its manifestations and the understanding of its properties and interactions. The interest on this field has been revitalized by the discovery of new light hadrons, charmonium- and bottomonium-like states. I review the most recent experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures; add more references; some correctio

Digit-only sauropod pes trackways from China - evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

The owl spreads its wings: global and international education within the local from critical perspectives

Within an era of a New Knowledge Society, assumptions abound regarding the ‘goodness' and justice of global interconnections and distributions of knowledge through international educational organizations and structures worldwide. Just as George Bush Jr. in attempting to justify the invasion of Iraq made claim to the democratic goodness of the US ‘spreading their freedoms' in the interests of an all-encompassing democratization of the world, so the assumption that sharing educational knowledge, especially an ‘all-knowing North' with a ‘helpless South' is without question for the greater good of all humanity

The professionals speak: Practitioners’ perspectives on professional election campaigning

Faced with some fundamental changes in the socio-cultural, political and media environment, political parties in post-industrialized democracies have started to initiate substantial transformations of both their organizational structures and communicative practices. Those innovations, described as professionalization, become most obvious during election campaigns. In recent times, the number of empirical studies measuring the degree of political parties’ campaign professionalism has grown. They have relied on a broad spectrum of indicators derived from theory which have not been tested for their validity. For the first time, we put these indicators to a ‘reality check’ by asking top-ranked party secretaries and campaign managers in 12 European countries to offer their perceptions of professional election campaigning. Furthermore, we investigate whether any differences in understanding professionalism among party campaign practitioners can be explained by macro (country) and meso (party) factors. By and large, our results confirm the validity of most indicators applied in empirical studies on campaign professionalism so far. There are some party- and country-related differences in assessing campaign professionalism too, but the influence of most factors on practitioners’ evaluations is weak. Therefore, we conclude that largely there is a far-reaching European Union-wide common understanding of professional election campaigning

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function