A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions

Herpes viruses are prevalent and well characterized human pathogens. Despite extensive study, much remains to be learned about the structure of the genome packaging and release machinery in the capsids of these large and complex double-stranded DNA viruses. However, such machinery is well characterized in tailed bacteriophage, which share a common evolutionary origin with herpesvirus. In tailed bacteriophage, the genome exits from the virus particle through a portal and is transferred into the host cell by a complex apparatus (i.e. the tail) located at the portal vertex. Here we use electron cryo-tomography of human herpes simplex type-1 (HSV-1) virions to reveal a previously unsuspected feature at the portal vertex, which extends across the HSV-1 tegument layer to form a connection between the capsid and the viral membrane. The location of this assembly suggests that it plays a role in genome release into the nucleus and is also important for virion architecture

Inner tegument protein pUL37 of herpes simplex virus type 1 is involved in directing capsids to the trans-Golgi network for envelopment

Secondary envelopment of herpes simplex virus type 1 has been demonstrated as taking place at the trans-Golgi network (TGN). The inner tegument proteins pUL36 and pUL37 and the envelope glycoproteins gD and gE are known to be important for secondary envelopment. We compared the cellular localizations of capsids from a virus mutant lacking the UL37 gene with those of a virus mutant lacking the genes encoding gD and gE. Although wild-type capsids accumulated at the TGN, capsids of the pUL37− mutant were distributed throughout the cytoplasm and showed no association with TGN-derived vesicles. This was in contrast to capsids from a gD−gE− mutant, which accumulated in the vicinity of TGN vesicles, but did not colocalize with them, suggesting that they were transported to the TGN but were unable to undergo envelopment. We conclude that the inner tegument protein pUL37 is required for directing capsids to the TGN, where secondary envelopment occurs

Cognitive Dysfunction in Adult Chd With Different Structural Complexity

OBJECTIVE: We carried out a cross-sectional study to assess cognitive function in a sample of adult CHD patients, within the Functioning in Adult Congenital Heart Disease study London. The association between cognitive functioning and disease complexity was examined. METHODS: A total of 310 patients participated in this study. Patients were classified into four structural complexity groups – tetralogy of Fallot, transposition of the great arteries, single ventricle, and simple conditions. Each patient underwent neuropsychological assessment to evaluate cognitive function, including memory and executive function, and completed questionnaires to assess depression and anxiety. RESULTS: Among all, 41% of the sample showed impaired performance (>1.5 SD below the normative mean) on at least three tests of cognitive function compared with established normative data. This was higher than the 8% that was expected in a normal population. The sample exhibited significant deficits in divided attention, motor function, and executive functioning. There was a significant group difference in divided attention (F=5.01, p=0.002) and the mean total composite score (F=5.19, p=0.002) between different structural complexity groups, with the simple group displaying better cognitive function. CONCLUSION: The results indicate that many adult CHD patients display impaired cognitive function relative to a healthy population, which differs in relation to disease complexity. These findings may have implications for clinical decision making in this group of patients during childhood. Possible mechanisms underlying these deficits and how they may be reduced or prevented are discussed; however, further work is needed to draw conclusive judgements

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Gaia Data Release 3: Processing and validation of BP/RP low-resolution spectral data

(Abridged) Blue (BP) and Red (RP) Photometer low-resolution spectral data is one of the exciting new products in Gaia Data Release 3 (Gaia DR3). We calibrate about 65 billion individual transit spectra onto the same mean BP/RP instrument through a series of calibration steps, including background subtraction, calibration of the CCD geometry and an iterative procedure for the calibration of CCD efficiency as well as variations of the line-spread function and dispersion across the focal plane and in time. The calibrated transit spectra are then combined for each source in terms of an expansion into continuous basis functions. Time-averaged mean spectra covering the optical to near-infrared wavelength range [330, 1050] nm are published for approximately 220 million objects. Most of these are brighter than G = 17.65 but some BP/RP spectra are published for sources down to G = 21.43. Their signal- to-noise ratio varies significantly over the wavelength range covered and with magnitude and colour of the observed objects, with sources around G = 15 having S/N above 100 in some wavelength ranges. The top-quality BP/RP spectra are achieved for sources with magnitudes 9 < G < 12, having S/N reaching 1000 in the central part of the RP wavelength range. Scientific validation suggests that the internal calibration was generally successful. However, there is some evidence for imperfect calibrations at the bright end G < 11, where calibrated BP/RP spectra can exhibit systematic flux variations that exceed their estimated flux uncertainties. We also report that due to long-range noise correlations, BP/RP spectra can exhibit wiggles when sampled in pseudo-wavelength.Comment: Submitted to A&

Single-lens mass measurement in the high-magnification microlensing event Gaia 19bld located in the Galactic disc

CONTEXT: Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius θ_{E} and microlensing parallax π_{E} can be measured, it is possible to determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of θ_{E} and, if the microlensing parallax is also measured, the mass of the lens. AIMS: We present the photometric analysis of Gaia19bld, a high-magnification (A ≈ 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the Gaia satellite and the very high brightness of I = 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event. METHODS: Gaia19bld was discovered by the Gaia satellite and was subsequently intensively followed up with a network of ground-based observatories and the Spitzer Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from Gaia, Spitzer, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance. RESULTS: We compute the mass of the lens to be 1.13 ± 0.03 M_{⊙} and derive its distance to be 5.52_{−0.64}^{+0.35} kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes

A decade with vamdc: Results and ambitions

This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&amp;M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&amp;M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&amp;M data from more than one database. Finally, we present our vision for the future of VAMDC.</jats:p

Single-lens mass measurement in the high-magnification microlensing event Gaia19bld located in the Galactic disc

This work was supported from the Polish NCN grants: Preludium No. 2017/25/N/ST9/01253, Harmonia No. 2018/30/M/ST9/00311, MNiSW grant DIR/WK/2018/12, Daina No. 2017/27/L/ST9/03221, and by the Research Council of Lithuania, grant No. S-LL-19-2. The OGLE project has received funding from the NCN grant MAESTRO 2014/14/A/ST9/00121 to AU. We acknowledge the European Commission’s H2020 OPTICON grant No. 730890. YT acknowledges the support of DFG priority program SPP 1992 “Exploring the Diversity of Extrasolar Planets” (WA 1047/11-1). EB and RS gratefully acknowledge support from NASA grant 80NSSC19K0291. Work by AG was supported by JPL grant 1500811. Work by JCY was supported by JPL grant 1571564. SJF thanks Telescope Live for access to their telescope network. NN acknowledges the support of Data Science Research Center, Chiang Mai University. FOE acknowledges the support from the FONDECYT grant nr. 1201223. MK acknowledges the support from the NCN grant No. 2017/27/B/ST9/02727.Context. Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius θE and microlensing parallax πE can be measured, it is possible to determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of θE and, if the microlensing parallax is also measured, the mass of the lens.  Aims. We present the photometric analysis of Gaia19bld, a high-magnification (A approximate to 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the Gaia satellite and the very high brightness of I = 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event.  Methods. Gaia19bld was discovered by the Gaia satellite and was subsequently intensively followed up with a network of ground-based observatories and the Spitzer Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from Gaia, Spitzer, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance.  Results. We compute the mass of the lens to be 1.13 ± 0.03 M⊙ and derive its distance to be 5.52-0.64+0.35 kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes.Publisher PDFPeer reviewe