Structure and Dynamics of Adeno-Associated Virus Serotype 1 VP1-Unique N-Terminal Domain and Its Role in Capsid Trafficking

The importance of the phospholipase A2 domain located within the unique N terminus of the capsid viral protein VP1 (VP1u) in parvovirus infection has been reported. This study used computational methods to characterize the VP1 sequence for adeno-associated virus (AAV) serotypes 1 to 12 and circular dichroism and electron microscopy to monitor conformational changes in the AAV1 capsid induced by temperature and the pHs encountered during trafficking through the endocytic pathway. Circular dichroism was also used to monitor conformational changes in AAV6 capsids assembled from VP2 and VP3 or VP1, VP2, and VP3 at pH 7.5. VP1u was predicted (computationally) and confirmed (in solution) to be structurally ordered. This VP domain was observed to undergo a reversible pH-induced unfolding/refolding process, a loss/gain of α-helical structure, which did not disrupt the capsid integrity and is likely facilitated by its difference in isoelectric point compared to the other VP sequences assembling the capsid. This study is the first to physically document conformational changes in the VP1u region that likely facilitate its externalization from the capsid interior during infection and establishes the order of events in the escape of the AAV capsid from the endosome en route to the nucleus

Light equation on eclipsing binary CV Boo

Короткопериодическая затменная двойная звезда CV Boo изучена методом светового уравнения. Были использованы данные о моментах минимумов из литературы и из наших наблюдений в мае июле 2014 г. Была найдена периодическая вариация орбитального периода системы с периодом ≈ 75 дней. Эта вариация может быть объяснена гравитационным воздействием третьего тела с массой ≈ 0.4 M⊙ на вытянутой орбите с эксцентриситетом e ≈ 0.9. Также обсуждается возможность изменения орбитального периода на больших шкалах времени. Предлагаемое третье тело находится близко к хаотической зоне вокруг центральной двойной, поэтому оно может быть интересно для изучения его динамической эволюции.A short period eclipsing binary star CV Boo is tested for the possible existence of new bodies in the system with a help of the light equation method. We use data about moments of minima from the literature and our observations during May—July 2014. A periodical variation of CV Boo’s orbital period is found, the variation’s period is ≈ 75 days. This variation can be explained by the gravitational influence of a third star with a mass ≈ 0.4M⊙ in an eccentric orbit with e ≈ 0.9. A possibility for orbital period changes in long time scales is discussed. The suggested tertiary companion is near the chaotic zone around the central binary, so it is an interesting example to test its dynamical evolution

Know Your Heart: Rationale, design and conduct of a cross-sectional study of cardiovascular structure, function and risk factors in 4500 men and women aged 35-69 years from two Russian cities, 2015-18

Russia has one of the highest rates of cardiovascular disease in the world. The International Project on Cardiovascular Disease in Russia (IPCDR) was set up to understand the reasons for this. A substantial component of this study was the Know Your Heart Study devoted to characterising the nature and causes of cardiovascular disease in Russia by conducting large cross-sectional surveys in two Russian cities Novosibirsk and Arkhangelsk. The study population was 4542 men and women aged 35-69 years recruited from the general population. Fieldwork took place between 2015-18. There were two study components: 1) a baseline interview to collect information on socio-demographic characteristics and cardiovascular risk factors, usually conducted at home, and 2) a comprehensive health check at a primary care clinic which included detailed examination of the cardiovascular system. In this paper we describe in detail the rationale for, design and conduct of these studies.The International Project on Cardiovascular Disease in Russia (IPCDR) project was supported in part by a Wellcome Trust Strategic Award [100217]. The project was also funded by the Arctic University of Norway, UiT in Tromsø; Norwegian Institute of Public Health; the Norwegian Ministry of Health and Social Affairs

ASASSN-15lh: a superluminous ultraviolet rebrightening observed by Swift and Hubble

We present and discuss ultraviolet and optical photometry from the Ultraviolet/Optical Telescope and X-ray limits from the X-Ray Telescope on Swift and imaging polarimetry and ultraviolet/optical spectroscopy with the Hubble Space Telescope of ASASSN-15lh. It has been classified as a hydrogenpoor superluminous supernova (SLSN I) more luminous than any other supernova observed. ASASSN- 15lh is not detected in the X-rays in individual or coadded observations. From the polarimetry we determine that the explosion was only mildly asymmetric. We find the flux of ASASSN-15lh to increase strongly into the ultraviolet, with a ultraviolet luminosity a hundred times greater than the hydrogen-rich, ultraviolet-bright SLSN II SN 2008es. We find objects as bright as ASASSN-15lh are easily detectable beyond redshifts of ∼4 with the single-visit depths planned for the Large Synoptic Survey Telescope. Deep near-infrared surveys could detect such objects past a redshift of ∼20 enabling a probe of the earliest star formation. A late rebrightening – most prominent at shorter wavelengths – is seen about two months after the peak brightness, which is itself as bright as a superluminous supernova. The ultraviolet spectra during the rebrightening are dominated by the continuum without the broad absorption or emission lines seen in SLSNe or tidal disruption events and the early optical spectra of ASASSN-15lh. Our spectra show no strong hydrogen emission, showing only Lyα absorption near the redshift previously found by optical absorption lines of the presumed host. The properties of ASASSN-15lh are extreme when compared to either SLSNe or tidal disruption events

SN 2021gno: a Calcium-rich transient with double-peaked light curves

We present extensive ultraviolet (UV) and optical photometric and optical spectroscopic follow-up of supernova (SN)~2021gno by the "Precision Observations of Infant Supernova Explosions" (POISE) project, starting less than two days after the explosion. Given its intermediate luminosity, fast photometric evolution, and quick transition to the nebular phase with spectra dominated by [Ca~II] lines, SN~2021gno belongs to the small family of Calcium-rich transients. Moreover, it shows double-peaked light curves, a phenomenon shared with only four other Calcium-rich events. The projected distance from the center of the host galaxy is not as large as other objects in this family. The initial optical light-curve peaks coincide with a very quick decline of the UV flux, indicating a fast initial cooling phase. Through hydrodynamical modelling of the bolometric light curve and line velocity evolution, we found that the observations are compatible with the explosion of a highly-stripped massive star with an ejecta mass of $0.8\,M_\odot$ and a $^{56}$Ni mass of $0.024~M_{\odot}$. The initial cooling phase (first light curve peak) is explained by the presence of an extended circumstellar material comprising $\sim$$10^{-2}\,M_{\odot}$ with an extension of $1100\,R_{\odot}$. We discuss if hydrogen features are present in both maximum-light and nebular spectra, and its implications in terms of the proposed progenitor scenarios for Calcium-rich transients.Comment: 21 pages, 13 figures, accepted for publication in MNRA

Capsid Antibodies to Different Adeno-Associated Virus Serotypes Bind Common Regions

Interactions between viruses and the host antibody immune response are critical in the development and control of disease, and antibodies are also known to interfere with the efficacy of viral vector-based gene delivery. The adeno-associated viruses (AAVs) being developed as vectors for corrective human gene delivery have shown promise in clinical trials, but preexisting antibodies are detrimental to successful outcomes. However, the antigenic epitopes on AAV capsids remain poorly characterized. Cryo-electron microscopy and three-dimensional image reconstruction were used to define the locations of epitopes to which monoclonal fragment antibodies (Fabs) against AAV1, AAV2, AAV5, and AAV6 bind. Pseudoatomic modeling showed that, in each serotype, Fabs bound to a limited number of sites near the protrusions surrounding the 3-fold axes of the T=1 icosahedral capsids. For the closely related AAV1 and AAV6, a common Fab exhibited substoichiometric binding, with one Fab bound, on average, between two of the three protrusions as a consequence of steric crowding. The other AAV Fabs saturated the capsid and bound to the walls of all 60 protrusions, with the footprint for the AAV5 antibody extending toward the 5-fold axis. The angle of incidence for each bound Fab on the AAVs varied and resulted in significant differences in how much of each viral capsid surface was occluded beyond the Fab footprints. The AAV-antibody interactions showed a common set of footprints that overlapped some known receptor-binding sites and transduction determinants, thus suggesting potential mechanisms for virus neutralization by the antibodies

Testing the magnetar scenario for superluminous supernovae with circular polarimetry

Superluminous supernovae (SLSNe) are at least ∼5 times more luminous than common supernovae (SNe). Especially hydrogen-poor SLSN-I are difficult to explain with conventional powering mechanisms. One possible scenario that might explain such luminosities is that SLSNe-I are powered by an internal engine, such as a magnetar or an accreting black hole. Strong magnetic fields or collimated jets can circularly polarize light. In this work, we measured circular polarization of two SLSNe-I with the FOcal Reducer and low dispersion Spectrograph (FORS2) mounted at the ESO’s Very Large Telescope (VLT). PS17bek, a fast evolving SLSN-I, was observed around peak, while OGLE16dmu, a slowly evolving SLSN-I, was observed 100 days after maximum. Neither SLSN shows evidence of circularly polarized light, however, these non-detections do not rule out the magnetar scenario as the powering engine for SLSNe-I. We calculate the strength of the magnetic field and the expected circular polarization as a function of distance from the magnetar, which decreases very fast. Additionally, we observed no significant linear polarization for PS17bek at four epochs, suggesting that the photosphere near peak is close to spherical symmetry

The morphology of the asteroidal dust around White Dwarf Stars : optical and near-infrared pulsations in G29-38

More than 36 yr have passed since the discovery of the infrared excess from circumstellar dust orbiting the white dwarf G29-38, which at 17.5 pc it is the nearest and brightest of its class. The precise morphology of the orbiting dust remains only marginally constrained by existing data, subject to model-dependent inferences, and thus fundamental questions of its dynamical origin and evolution persist. This study presents a means to constrain the geometric distribution of the emitting dust using stellar pulsations measured at optical wavelengths as a variable illumination source of the dust, which reradiates primarily in the infrared. By combining optical photometry from the Whole Earth Telescope with 0.7–2.5 μm spectroscopy obtained with SpeX at NASA’s Infrared Telescope Facility, we detect luminosity variations at all observed wavelengths, with variations at most wavelengths corresponding to the behavior of the pulsating stellar photosphere, but toward the longest wavelengths the light curves probe the corresponding time variability of the circumstellar dust. In addition to developing methodology, we find the pulsation amplitudes decrease with increasing wavelength for principal pulsation modes, yet increase beyond ≈2 μm for nonlinear combination frequencies. We interpret these results as combination modes derived from the principal modes of identical ℓ values and discuss the implications for the morphology of the warm dust. We also draw attention to some discrepancies between our findings and theoretical expectations for the results of the nonlinearity imposed by the surface convection zone on mode–mode interactions and on the behavior of the first harmonic of the highest-amplitude pulsation mode

Close, bright and boxy: the superluminous SN 2018hti

SN~2018hti was a very nearby (z=0.0614) superluminous supernova with an exceedingly bright absolute magnitude of -22.2 mag in r-band at maximum. The densely sampled pre-maximum light curves of SN~2018hti show a slow luminosity evolution and constrain the rise time to ~50 rest-frame days. We fitted synthetic light curves to the photometry to infer the physical parameters of the explosion of SN 2018hti for both the magnetar and the CSM-interaction scenarios. We conclude that one of two mechanisms could be powering the luminosity of SN 2018hti; interaction with ~10 Msun of circumstellar material or a magnetar with a magnetic field of B_p~1.3e13 G and initial period of P_spin~1.8 ms. From the nebular spectrum modelling we infer that SN 2018hti likely results from the explosion of a ~40 Msun progenitor star.</p