Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya

The young massive SMC cluster NGC 330 seen by MUSE III. Stellar parameters and rotational velocities

The origin of initial rotation rates of stars, and how a star's surface rotational velocity changes during the evolution, either by internal angular momentum transport or due to interactions with a binary companion, remain open questions in stellar astrophysics. Here, we aim to derive the physical parameters and study the distribution of (projected) rotational velocities of B-type stars in the 35 Myr-old, massive cluster NGC 330 in the Small Magellanic Cloud. NGC 330 is in an age range where the number of post-interaction binaries is predicted to be high near the cluster turnoff (TO). We develop a simultaneous photometric and spectroscopic grid-fitting method adjusting atmosphere models on multi-band Hubble Space Telescope photometry and Multi Unit Spectroscopic Explorer spectroscopy. This allows us to homogeneously constrain the physical parameters of over 250 B and Be stars, brighter than mF814W = 18.8 mag. The rotational velocities of Be stars in NGC 330 are significantly higher than the ones of B stars. The rotational velocities vary as a function of the star's position in the color-magnitude diagram, qualitatively following predictions of binary population synthesis. A comparison to younger clusters shows that stars in NGC 330 rotate more rapidly on average. The rotational velocities of the 35 Myr old population in NGC 330 quantitatively agree with predictions for a stellar population that underwent significant binary interactions: the bulk of the B stars could be single stars or primaries in pre-interaction binaries. The rapidly spinning Be stars could be mass and angular momentum gainers in previous interactions, while those Be stars close to the TO may be spun-up single stars. The slowly rotating, apparently single stars above the TO could be merger products. The different vsini-characteristics of NGC 330 compared to younger populations can be understood in this framework.Comment: 18 pages (incl. appendix), 15 figures, 3 tables, accepted for publication in A&

Optical and near-infrared observations of the Fried Egg Nebula

Context. The fate of a massive star during the latest stages of its evolution is highly dependent on its mass-loss rate and geometry and therefore knowing the geometry of the circumstellar material close to the star and its surroundings is crucial. Aims. We aim to provide insight into the nature (i.e. geometry, rates) of mass-loss episodes, and in particular, the connection between the observed asymmetries due to the mass lost in a fast wind or during a previous, prodigious mass-losing phase. In this context, yellow hypergiants offer a good opportunity to study mass-loss events. Methods. We analysed a large set of optical and near-infrared data in spectroscopic and photometric, spectropolarimetric, and interferometric (GRAVITY/VLTI) modes, towards the yellow hypergiant IRAS 17163−3907. We used X-shooter optical observations to determine the spectral type of this yellow hypergiant and we present the first model-independent, reconstructed images of IRAS 17163−3907 at these wavelengths tracing milli-arcsecond scales. Lastly, we applied a 2D radiative transfer model to fit the dereddened photometry and the radial profiles of published diffraction-limited VISIR images at 8.59 μm, 11.85 μm, and 12.81 μm simultaneously, adopting a revised distance determination using Gaia Data Release 2 measurements. Results. We constrain the spectral type of IRAS 17163−3907 to be slightly earlier than A6Ia (Teff ∼ 8500 K). The interferometric observables around the 2 μm window towards IRAS 17163−3907 show that the Brγ emission appears to be more extended and asymmetric than the Na I and the continuum emission. Interestingly, the spectrum of IRAS 17163−3907 around 2 μm shows Mg II emission that is not previously seen in other objects of its class. In addition, Brγ shows variability in a time interval of four months that is not seen towards Na I. Lastly, in addition to the two known shells surrounding IRAS 17163−3907, we report on the existence of a third hot inner shell with a maximum dynamical age of only 30 yr. Conclusions. The 2 μm continuum originates directly from the star and not from hot dust surrounding the stellar object. The observed spectroscopic variability of Brγ could be a result of variability in the mass-loss rate. The interpretation of the presence of Na I emission at closer distances to the star compared to Brγ has been a challenge in various studies. To address this, we examine several scenarios. We argue that the presence of a pseudo-photosphere, which was traditionally considered to be the prominent explanation, is not needed and that it is rather an optical depth effect. The three observed distinct mass-loss episodes are characterised by different mass-loss rates and can inform theories of mass-loss mechanisms, which is a topic still under debate both in theory and observations. We discuss these in the context of photospheric pulsations and wind bi-stability mechanisms

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Investigating the effect of child maltreatment on early adolescent peer-on-peer sexual aggression: testing a multiple mediator model in a non-incarcerated sample of Danish adolescents

Objective: The aim of the present study was to investigate the relationship between child maltreatment and severe early adolescent peer-on-peer sexual aggression, using a multiple mediator model. Methods: The study comprised 330 male Grade 9 students with a mean age of 14.9 years (SD=0.5). Results: Estimates from the mediation model indicated significant indirect effects of child physical abuse on sexual aggression via peer influence and insecure-hostile masculinity. No significant total effect of child sexual abuse and child neglect on sexual aggression was found. Conclusions: Findings of the present study identify risk factors that are potentially changeable and therefore of value in informing the design of prevention programs aiming at early adolescent peer-on-peer sexual aggression in at-risk youth

Discussing atypical sexual harassment as a controversial issue in bystander programmes: One UK campus study

This research emanates from an anti-sexual violence bystander programme delivered at an English university. Fifteen students were identified through purposive and convenience sampling to take part in focus groups. Discussions emerged regarding atypical sexual harassment. There is a gap in the literature exploring sexual harassment outside of the male perpetrator and female victim narrative which this paper contributes to. This paper considers four conversational themes: ‘unwanted touching: women to men’, ‘sexual banter: women to men’, ‘sexual stereotypes: women and men’, and ‘developing stronger ethical subjectivity’. This paper recognises most sexual harassment occurs from men to women, and acknowledges criticism of focussing otherwise when resources are limited, noting this risks obscuring the enduring power differentials between the sexes. It contends that exploring a controversial issue, such as male experience of sexual harassment, might help bystander programmes by developing ethical subjectivity in undergraduate students. Exploring sexual behaviour as a spectrum may lead to counter hegemonic discourses to emerge

Pathogenesis of bat rabies in a natural reservoir: Comparative susceptibility of the straw-colored fruit bat (Eidolon helvum) to three strains of Lagos bat virus.

Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation. To allow comparison between strains, we ensured the same titer of virus was inoculated in the same location of the brain of each bat. All bats (n = 3 per strain) were infected, and developed neurological signs, and fatal meningoencephalitis with lyssavirus antigen expression in neurons. There were three main differences among the groups. First, time to death was substantially shorter in the Senegal and Ghana groups (4 to 6 days) than in the Nigeria group (8 days). Second, each virus strain produced a distinct clinical syndrome. Third, the spread of virus to peripheral tissues, tested by hemi-nested reverse transcriptase PCR, was frequent (3 of 3 bats) and widespread (8 to 10 tissues positive of 11 tissues examined) in the Ghana group, was frequent and less widespread in the Senegal group (3/3 bats, 3 to 6 tissues positive), and was rare and restricted in the Nigeria group (1/3 bats, 2 tissues positive). Centrifugal spread of virus from brain to tissue of excretion in the oral cavity is required to enable lyssavirus transmission. Therefore, the Senegal and Ghana strains seem most suitable for further pathogenesis, and for transmission, studies in the straw-colored fruit bat

Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses

Background With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses. Method To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection. Results All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection. Conclusion Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses

Bystander responses to a violent incident in an immersive virtual environment

Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the ingroup condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation