How much of a problem is problem gambling?

Problem gambling is conventionally defined by the score in a specific questionnaire exceeding some critical value and data suggests is that 0.7% of adults in the UK could be afflicted. However, the literature has not evaluated the size of the harm associated with such an affliction and this research evaluates the effect of problem gambling on self-reported well-being which, together with a corresponding effect of income on well-being, allows us to construct a money-metric of the (self) harm associated with being a problem gambler. Our estimates suggest that problem gambling imposes a very large reduction in individual well-being

A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus

The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)—a related henipavirus that is ostensibly nonpathogenic—possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.Peer reviewe

A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover

A detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential. The recent isolation of Tacaribe and lymphocytic choriominingitis mammarenaviruses from host-seeking ticks provided evidence for the presence of mammarenaviruses in arthropods, which are established vectors for numerous other viral pathogens. Here, using next generation sequencing to search for other mammarenaviruses in ticks, we identified a novel replication-competent strain of the NW mammarenavirus Tamiami (TAMV-FL), which we found capable of utilizing hTfR1 to enter mammalian cells. During isolation through serial passaging in mammalian immunocompetent cells, the quasispecies of TAMV-FL acquired and enriched mutations leading to the amino acid changes N151K and D156N, within GP. Cell entry studies revealed that both substitutions, N151K and D156N, increased dependence of the virus on hTfR1 and binding to heparan sulfate proteoglycans. Moreover, we show that the substituted residues likely map to the sterically constrained trimeric axis of GP, and facilitate viral fusion at a lower pH, resulting in viral egress from later endosomal compartments. In summary, we identify and characterize a naturally occurring TAMV strain (TAMV-FL) within ticks that is able to utilize hTfR1. The TAMV-FL significantly diverged from previous TAMV isolates, demonstrating that TAMV quasispecies exhibit striking genetic plasticity that may facilitate zoonotic spillover and rapid adaptation to new hosts

QPARSE: searching for long-looped or multimeric G-quadruplexes potentially distinctive and druggable

MOTIVATION: G-quadruplexes (G4s) are non-canonical nucleic acid conformations that are widespread in all kingdoms of life and are emerging as important regulators both in RNA and DNA. Recently, two new higher-order architectures have been reported: adjacent interacting G4s, and G4s with stable long loops forming stem-loop structures. As there are no specialized tools to identify these conformations, we developed QPARSE. RESULTS: QPARSE can exhaustively search for degenerate potential quadruplex-forming sequences (PQSs) containing bulges and/or mismatches at genomic level, as well as either multimeric or long-looped PQS (MPQS and LLPQS respectively). While its assessment vs. known reference datasets is comparable with the state-of-the-art, what is more interesting is its performance in the identification of MPQS and LLPQS that present algorithms are not designed to search for. We report a comprehensive analysis of MPQS in human gene promoters and the analysis of LLPQS on three experimentally validated case studies from HIV-1, BCL2, and hTERT. AVAILABILITY: QPARSE is freely accessible on the web at http://www.medcomp.medicina.unipd.it/qparse/index or downloadable from github as a python 2.7 program https://github.com/B3rse/qparse. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Structural transitions and LAMP1 binding of the LASV GP spikes upon acidification.

<p>(A) GP structures at different pHs are shown from side (top row) and top (bottom row). All volumes were filtered to 17-Å resolution, rendered at molecular threshold corresponding to the expected molecular mass, and colored as in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005418#ppat.1005418.g001" target="_blank">Fig 1</a>. Residual density corresponding to LAMP1 is colored in green. Inserts in the lower left corners show a close-up of the interface between two spike monomers. Insets in the top right corners show Western blot analysis of GP1 and GP2 subunits. The arrowheads indicate the missing density in the central top part and side of the pH 3 structure.</p

Data acquisition and processing statistics.

<p>Data acquisition and processing statistics.</p

Model for Lassa virus entry.

<p>A schematic representation of a hypothetical entry model, derived from the structures determined in this study, is shown. An approximate range of pH in different cellular compartments is depicted as a color gradient from neutral (blue) to very acidic (red). Lassa virus glycoprotein (GP) spike trimer is depicted in three shades of brown and the two different subunits (GP1 and GP2) are labeled. Lysosome-associated membrane protein 1 (LAMP1), an intracellular Lassa virus receptor, is labeled and colored in green. Viral membrane is colored in blue. Different cellular membranes are labeled and colored in gray. Formation of the crevices between GP1 subunits is indicated with white arrows. See text for full description of the entry model.</p

Comparison of arenavirus and filovirus glycoprotein spike structures.

<p>Structures of Lassa virus spike (LASV, this study), spike of the arenenavirus-like virus infecting snakes (University of Helsinki Virus, UHL; EMD-2424), and Ebola virus spike (EBOV) with (EMD-6003) and without (EMD-6004) the mucin-like domain are shown at the same scale for comparison.</p