bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus DNA Integration Occurs Early in the Viral Life Cycle in an
In Vitro
Infection Model via Sodium Taurocholate Cotransporting Polypeptide-Dependent Uptake of Enveloped Virus Particles
Authors: Tu Thomas , Budzinska Magdalena A. , Vondran Florian W. R. , Shackel Nicholas A. , Urban Stephan 
Published: February 2018

ABSTRACT

Chronic infection by hepatitis B virus (HBV) is the major contributor to liver disease worldwide. Though HBV replicates via a nuclear episomal DNA (covalently closed circular DNA [cccDNA]), integration of HBV DNA into the host cell genome is regularly observed in the liver in infected patients. While reported as a prooncogenic alteration, the mechanism(s) and timing of HBV DNA integration are not well understood, chiefly due to the lack of
in vitro
infection models that have detectable integration events. In this study, we have established an
in vitro
system in which integration can be reliably detected following HBV infection. We measured HBV DNA integration using inverse nested PCR in primary human hepatocytes, HepaRG-NTCP, HepG2-NTCP, and Huh7-NTCP cells after HBV infection. Integration was detected in all cell types at a rate of >1 per 10,000 cells, with the most consistent detection in Huh7-NTCP cells. The integration rate remained stable between 3 and 9 days postinfection. HBV DNA integration was efficiently blocked by treatment with a 200 nM concentration of the HBV entry inhibitor Myrcludex B, but not with 10 μM tenofovir, 100 U of interferon alpha, or a 1 μM concentration of the capsid assembly inhibitor GLS4. This suggests that integration of HBV DNA occurs immediately after infection of hepatocytes and is likely independent of
de novo
HBV genome replication in this model. Site analysis revealed that HBV DNA integrations were distributed over the entire human genome. Further, integrated HBV DNA sequences were consistent with double-stranded linear HBV DNA being the major precursor. Thus, we have established an
in vitro
system to interrogate the mechanisms of HBV DNA integration.

IMPORTANCE
Hepatitis B virus (HBV) is a common blood-borne pathogen and, following a chronic infection, can cause liver cancer and liver cirrhosis. Integration of HBV DNA into the host genome occurs in all known members of the
Hepadnaviridae
family, despite this form not being necessary for viral replication. HBV DNA integration has been reported to drive liver cancer formation and persistence of virus infection. However, when and the mechanism(s) by which HBV DNA integration occurs are not clear. In this study, we have developed and characterized an
in vitro
system to reliably detect HBV DNA integrations that result from a true HBV infection event and that closely resemble those found in patient tissues. Using this model, we showed that integration occurs when the infection is first established. Importantly, we provide here a system to analyze molecular factors involved in HBV integration, which can be used to develop strategies to halt its formation.
Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates
Authors: Saunders Kevin O. , Santra Sampa , Parks Robert , Yates Nicole L. , Sutherland Laura L. , Scearce Richard M. , Balachandran Harikrishnan , Bradley Todd , Goodman Derrick , Eaton Amanda , Stanfield-Oakley Sherry A. , Tartaglia James , Phogat Sanjay , Pantaleo Giuseppe , Esteban Mariano , Gomez Carmen E. , Perdiguero Beatriz , Jacobs Bertram , Kibler Karen , Korber Bette , Montefiori David C. , Ferrari Guido , Vandergrift Nathan , Liao Hua-Xin , Tomaras Georgia D. , Haynes Barton F. 
Published: February 2018

ABSTRACT
A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge.

IMPORTANCE
The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model.
Herpes Simplex Virus 1 Dramatically Alters Loading and Positioning of RNA Polymerase II on Host Genes Early in Infection
Authors: Birkenheuer Claire H. , Danko Charles G. , Baines Joel D. 
Published: February 2018

ABSTRACT
Herpes simplex virus 1 (HSV-1) transcription is mediated by cellular RNA polymerase II (Pol II). Recent studies investigating how Pol II transcription of host genes is altered after HSV-1 are conflicting. Chromatin immunoprecipitation sequencing (ChIP-seq) studies suggest that Pol II is almost completely removed from host genes at 4 h postinfection (hpi), while 4-thiouridine (4SU) labeling experiments show that host transcription termination is extended at 7 hpi, implying that a significant amount of Pol II remains associated with host genes in infected cells. To address this discrepancy, we used precision nuclear run-on analysis (PRO-seq) to determine the location of Pol II to single-base-pair resolution in combination with quantitative reverse transcription-PCR (qRT-PCR) analysis at 3 hpi. HSV-1 decreased Pol II on approximately two-thirds of cellular genes but increased Pol II on others. For more than 85% of genes for which transcriptional termination could be statistically assessed, Pol II was displaced to positions downstream of the normal termination zone, suggesting extensive termination defects. Pol II amounts at the promoter, promoter-proximal pause site, and gene body were also modulated in a gene-specific manner. qRT-PCR of selected RNAs showed that HSV-1-induced extension of the termination zone strongly correlated with decreased RNA and mRNA accumulation. However, HSV-1-induced increases of Pol II occupancy on genes without termination zone extension correlated with increased cytoplasmic mRNA. Functional grouping of genes with increased Pol II occupancy suggested an upregulation of exosome secretion and downregulation of apoptosis, both of which are potentially beneficial to virus production.

IMPORTANCE
This study provides a map of RNA polymerase II location on host genes after infection with HSV-1 with greater detail than previous ChIP-seq studies and rectifies discrepancies between ChIP-seq data and 4SU labeling experiments with HSV-1. The data show the effects that a given change in RNA Pol II location on host genes has on the abundance of different RNA types, including nuclear, polyadenylated mRNA and cytoplasmic, polyadenylated mRNA. It gives a clearer understanding of how HSV-1 augments host transcription of some genes to provide an environment favorable to HSV-1 replication.
Adjustments to Photosystem Stoichiometry and Electron Transfer Proteins Are Key to the Remarkably Fast Growth of the Cyanobacterium
Synechococcus elongatus
UTEX 2973
Authors: Ungerer Justin , Lin Po-Cheng , Chen Hui-Yuan , Pakrasi Himadri B. 
Published: February 2018

ABSTRACT

At the genome level,
Synechococcus elongatus
UTEX 2973 (
Synechococcus
2973) is nearly identical to the model cyanobacterium
Synechococcus elongatus
PCC 7942 (
Synechococcus
7942) with only 55 single nucleotide differences separating the two strains. Despite the high similarity between the two strains,
Synechococcus
2973 grows three times faster, accumulates significantly more glycogen, is tolerant to extremely high light intensities, and displays higher photosynthetic rates. The high homology between the two strains provides a unique opportunity to examine the factors that lead to increased photosynthetic rates. We compared the photophysiology of the two strains and determined the differences in
Synechococcus
2973 that lead to increased photosynthetic rates and the concomitant increase in biomass production. In this study, we identified inefficiencies in the electron transport chain of
Synechococcus
7942 that have been alleviated in
Synechococcus
2973. Photosystem II (PSII) capacity is the same in both strains. However,
Synechococcus
2973 exhibits a 1.6-fold increase in PSI content, a 1.5-fold increase in cytochrome
b
6
f
content, and a 2.4-fold increase in plastocyanin content on a per cell basis. The increased content of electron carriers allows a higher flux of electrons through the photosynthetic electron transport chain, while the increased PSI content provides more oxidizing power to maintain upstream carriers ready to accept electrons. These changes serve to increase the photosynthetic efficiency of
Synechococcus
2973, the fastest growing cyanobacterium known.

IMPORTANCE
As the global population increases, the amount of arable land continues to decrease. To prevent a looming food crisis, crop productivity per acre must increase. A promising target for improving crop productivity is increasing the photosynthetic rates in crop plants. Cyanobacteria serve as models for higher plant photosynthetic systems and are an important test bed for improvements in photosynthetic productivity. In this study, we identified key factors that lead to improved photosynthetic efficiency and increased production of biomass of a cyanobacterium. We suggest that the findings presented herein will give direction to improvements that may be made in other photosynthetic organisms to improve photosynthetic efficiency.
Population exposure to smoking and tobacco branding in the UK reality show ‘Love Island’
Authors: Barker Alexander B , Opazo Breton Magdalena , Cranwell Jo , Britton John , Murray Rachael L 
Published: February 2018

BackgroundReality television shows are popular with children and young adults; inclusion of tobacco imagery in these programmes is likely to cause smoking in these groups. Series 3 of the UK reality show Love Island, broadcast in 2017, attracted widespread media criticism for high levels of smoking depicted. We have quantified this tobacco content and estimated the UK population exposure to generic and branded tobacco imagery generated by the show.MethodsWe used 1-min interval coding to quantify actual or implied tobacco use, tobacco paraphernalia or branding, in alternate episodes of series 3 of Love Island, and Census data and viewing figures from Kantar Media to estimate gross and per capita tobacco impressions.ResultsWe coded 21 episodes comprising 1001 min of content. Tobacco imagery occurred in 204 (20%) intervals; the frequency of appearances fell significantly after media criticism. An identifiable cigarette brand, Lucky Strike Double Click, appeared in 16 intervals. The 21 episodes delivered an estimated 559 million gross tobacco impressions to the UK population, predominantly to women, including 47 million to children aged <16 and 44 million gross impressions of Lucky Strike branding, including 4 million to children <16.ConclusionDespite advertising legislation and broadcasting regulations intended to protect children from smoking imagery in UK television, series 3 of Love Island delivered millions of general and branded tobacco impressions both to children and adults in the UK. More stringent controls on tobacco content in television programmes are urgently needed.
Evidence for Pressure‐Independent Sympathetic Modulation of Central Pulse Wave Velocity
Authors: Nardone Massimo , Incognito Anthony V. , Millar Philip J. 
Published: February 2018

Background
Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial, mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure.

Methods and Results

To address this limitation, we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation. Blood pressure and carotid‐femoral aortic pulse wave velocity (cf‐
PWV
) were measured in 32 healthy participants (24±2 years; women: n=15) before and during 12‐minute applications of low‐level lower body negative pressure; −7 mm Hg) and lower body positive pressure; +7 mm Hg), applied in a random order. Fibular nerve microneurography was used to collect muscle sympathetic nerve activity (
MSNA
) in a subset (n=8) to confirm peripheral sympathetic responses. During lower body negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all
P
>0.05);
MSNA
burst frequency (+15%;
P
=0.007), total
MSNA
(+44%;
P
=0.006), and cf‐
PWV
(∆+0.3±0.2 m/s;
P
<0.001) increased. In total, 28 (88%) of participants observed an increase in cf‐
PWV
greater than the baseline typical error of measurement. During lower body positive pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all
P
>0.05), though blood pressure increased (
P
<0.05) and pulse pressure decreased (
P
=0.01);
MSNA
burst frequency (−4%;
P
=0.37), total
MSNA
(−7%;
P
=0.89), and cf‐
PWV
(∆0.0±0.2 m/s;
P
=0.68) were not statistically different.

Conclusions

These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic
PWV
in young participants independent of a change in distending or pulsatile blood pressure or heart rate.
SURF: Understanding and Predicting Urban Convection and Haze
Authors: Liang X. , Miao S. , Li J. , Bornstein R. , Zhang X. , Gao Y. , Chen F. , Cao X. , Cheng Z. , Clements C. , Dabberdt W. , Ding A. , Ding D. , Dou J. J. , Dou J. X. , Dou Y. , Grimmond C. S. B. , González-Cruz J. E. , He J. , Huang M. , Huang X. , Ju S. , Li Q. , Niyogi D. , Quan J. , Sun J. , Sun J. Z. , Yu M. , Zhang J. , Zhang Y. , Zhao X. , Zheng Z. , Zhou M. 
Published: February 2018

AbstractUrbanization modifies atmospheric energy and moisture balances, forming distinct features [e.g., urban heat islands (UHIs) and enhanced or decreased precipitation]. These produce significant challenges to science and society, including rapid and intense flooding, heat waves strengthened by UHIs, and air pollutant haze. The Study of Urban Impacts on Rainfall and Fog/Haze (SURF) has brought together international expertise on observations and modeling, meteorology and atmospheric chemistry, and research and operational forecasting. The SURF overall science objective is a better understanding of urban, terrain, convection, and aerosol interactions for improved forecast accuracy. Specific objectives include a) promoting cooperative international research to improve understanding of urban summer convective precipitation and winter particulate episodes via extensive field studies, b) improving high-resolution urban weather and air quality forecast models, and c) enhancing urban weather forecasts for societal applications (e.g., health, energy, hydrologic, climate change, air quality, planning, and emergency response management). Preliminary SURF observational and modeling results are shown (i.e., turbulent PBL structure, bifurcating thunderstorms, haze events, urban canopy model development, and model forecast evaluation).
A Long-Term Overshooting Convective Cloud-Top Detection Database over Australia Derived from MTSAT Japanese Advanced Meteorological Imager Observations
Authors: Bedka Kristopher M. , Allen John T. , Punge Heinz Jurgen , Kunz Michael , Simanovic Denis 
Published: February 2018

ABSTRACTA 10-yr geostationary (GEO) overshooting cloud-top (OT) detection database using Multifunction Transport Satellite (MTSAT) Japanese Advanced Meteorological Imager (JAMI) observations has been developed over the Australian region. GEO satellite imagers collect spatially and temporally detailed observations of deep convection, providing insight into the development and evolution of hazardous storms, particularly where surface observations of hazardous storms and deep convection are sparse and ground-based radar or lightning sensor networks are limited. Hazardous storms often produce one or more OTs that indicate the location of strong updrafts where weather hazards are typically concentrated, which can cause substantial impacts on the ground such as hail, damaging winds, tornadoes, and lightning and to aviation such as turbulence and in-flight icing. The 10-yr OT database produced using an automated OT detection algorithm is demonstrated for analysis of storm frequency, diurnally, spatially, and seasonally relative to known features such as the Australian monsoon, expected regions of hazardous storms along the southeastern coastal regions of southern Queensland and New South Wales, and the preferential extratropical cyclone track along the Indian Ocean and southern Australian coast. A filter based on atmospheric instability, deep-layer wind shear, and freezing level was used to identify OTs that could have produced hail. The filtered OT database is used to generate a hail frequency estimate that identifies a region extending from north of Brisbane to Sydney and the Goldfields–Esperance region of eastern Western Australia as the most hail-prone regions.
Polarimetric Observations of Chaff Using the WSR-88D Network
Authors: Kurdzo James M. , Williams Earle R. , Smalley David J. , Bennett Betty J. , Patterson David C. , Veillette Mark S. , Donovan Michael F. 
Published: February 2018

AbstractChaff is a radar countermeasure typically used by military branches in training exercises around the United States. Chaff within view of the S-band WSR-88D beam can appear prominently on radar users’ displays. Knowledge of chaff characteristics is useful for radar users to discriminate between chaff and weather echoes and for automated algorithms to do the same. The WSR-88D network provides dual-polarimetric capabilities across the United States, leading to the collection of a large database of chaff cases. This database is analyzed to determine the characteristics of chaff in terms of the reflectivity factor and polarimetric variables on large scales. Particular focus is given to the dynamics of differential reflectivity ZDR in chaff and its dependence on height. In contrast to radar observations of chaff for a single event, this study is able to reveal a repeatable and new pattern of radar chaff observations. A discussion about the observed characteristics is presented, and hypotheses for the observed ZDR dynamics are put forth.
Influence of the Madden–Julian Oscillation and Caribbean Low-Level Jet on East Pacific Easterly Wave Dynamics
Authors: Whitaker Justin W. , Maloney Eric D. 
Published: February 2018

Abstract
The east Pacific warm pool exhibits basic-state variability associated with the Madden–Julian oscillation (MJO) and Caribbean low-level jet (CLLJ), which affects the development of easterly waves (EWs). This study compares and contrasts composite changes in the background environment, eddy kinetic energy (EKE) budgets, and EW tracks during MJO and CLLJ events. While previous studies have shown that the MJO influences jet activity in the east Pacific, the influence of the MJO and CLLJ on the east Pacific and EWs is not synonymous. The CLLJ is a stronger modulator of the ITCZ than the MJO, while the MJO has a more expansive influence on the northeastern portion of the basin. Anomalous low-level westerly MJO and CLLJ periods are associated with favorable conditions for EW development paralleling the Central American coast, contrary to previous findings about the relationship of the CLLJ to EWs. Easterly MJO and CLLJ periods support enhanced ITCZ EW development, although the CLLJ is a greater modulator of EW tracks in this region, which is likely associated with stronger moisture and convection variations and their subsequent influence on the EKE budget. ITCZ EW growth during easterly MJO periods is more reliant on barotropic conversion than during strong CLLJ periods, when eddy available potential energy (EAPE)-to-EKE conversion associated with ITCZ convection is more important. Thus, the influence of these phenomena on east Pacific EWs should be considered distinct.
The Thermally Driven Ocean Circulation with Realistic Bathymetry
Authors: Gjermundsen Ada , LaCasce Joseph H. , Denstad Liv 
Published: February 2018

AbstractThe global circulation driven solely by relaxation to an idealized surface temperature profile and to interior mixing is examined. Forcing by winds and evaporation/precipitation is excluded. The resulting circulation resembles the observed in many ways, and the overturning is of similar magnitude. The overturning is driven by large-scale upwelling in the interior (which is relatively large, because of the use of a constant mixing coefficient). The compensating downwelling occurs in the northern North Atlantic and in the Ross and Weddell Seas, with an additional, smaller contribution from the northern North Pacific. The latter is weaker because the Bering Strait limits the northward extent of the flow. The downwelling occurs in frictional layers near the boundaries and depends on the lateral shear in the horizontal flow. The shear, in turn, is linked to the imposed surface temperature gradient via thermal wind, and as such, the downwelling can be reduced or eliminated in selected regions by removing the surface gradient. Doing so in the northern North Atlantic causes the (thermally driven) Antarctic Circumpolar Current to intensify, increasing the sinking along Antarctica. Eliminating the surface gradient in the Southern Ocean increases the sinking in the North Atlantic and Pacific. As there is upwelling also in the western boundary currents, the flow must increase even more to accomplish the necessary downwelling. The implications of the results are then considered, particularly with respect to Arctic intensification of global warming, which will reduce the surface temperature gradient.