bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Factor SPCS1 Regulates the Replication of Japanese Encephalitis Virus through Interactions with Transmembrane Domains of NS2B
Authors: Ma Le , Li Fang , Zhang Jing-Wei , Li Wei , Zhao Dong-Ming , Wang Han , Hua Rong-Hong , Bu Zhi-Gao 
Published: March 2018

ABSTRACT
Signal peptidase complex subunit 1 (SPCS1) is a newly identified host factor that regulates flavivirus replication, but the molecular mechanism is not fully understood. Here, using Japanese encephalitis virus (JEV) as a model, we investigated the mechanism through which the host factor SPCS1 regulates the replication of flaviviruses. We first validated the regulatory function of SPCS1 in JEV propagation by knocking down and knocking out endogenous SPCS1. The loss of SPCS1 function markedly reduced intracellular virion assembly and the production of infectious JEV particles but did not affect cell entry, RNA replication, or translation of the virus. SPCS1 was found to interact with nonstructural protein 2B (NS2B), which is involved in posttranslational protein processing and virus assembly. Serial deletion mutation of the JEV NS2B protein revealed that two transmembrane domains, NS2B(1–49) and NS2B(84–131), interact with SPCS1. Further mutagenesis analysis of conserved flavivirus residues in two SPCS1 interaction domains of NS2B demonstrated that G12A, G37A, and G47A in NS2B(1–49) and P112A in NS2B(84–131) weakened the interaction with SPCS1. Deletion mutation of SPCS1 revealed that SPCS1(91–169), which contains two transmembrane domains, was involved in interactions with both NS2B(1–49) and NS2B(84–131). Taken together, these results demonstrate that SPCS1 affects viral replication by interacting with NS2B, thereby influencing the posttranslational processing of JEV proteins and the assembly of virions.

IMPORTANCE
Understanding virus-host interactions is important for elucidating the molecular mechanisms of virus propagation and identifying potential antiviral targets. Previous reports demonstrated that SPCS1 is involved in the flavivirus life cycle, but the mechanism remains unknown. In this study, we confirmed that SPCS1 participates in the posttranslational protein processing and viral assembly stages of the JEV life cycle but not in the cell entry, genome RNA replication, or translation stages. Furthermore, we found that SPCS1 interacts with two independent transmembrane domains of the flavivirus NS2B protein. NS2B also interacts with NS2A, which is proposed to mediate virus assembly. Therefore, we propose a protein-protein interaction model showing how SPCS1 participates in the assembly of JEV particles. These findings expand our understanding of how host factors participate in the flavivirus replication life cycle and identify potential antiviral targets for combating flavivirus infection.
Caspase-Dependent Apoptosis Induction via Viral Protein ORF4 of Porcine Circovirus 2 Binding to Mitochondrial Adenine Nucleotide Translocase 3
Authors: Lin Cui , Gu Jinyan , Wang Huijuan , Zhou Jianwei , Li Jiarong , Wang Shengnan , Jin Yulan , Liu Changming , Liu Jue , Yang Hanchun , Jiang Ping , Zhou Jiyong 
Published: March 2018

ABSTRACT

Apoptosis is an essential strategy of host defense responses and is used by viruses to maintain their life cycles. However, the apoptotic signals involved in virus replication are poorly known. In the present study, we report the molecular mechanism of apoptotic induction by the viral protein ORF4, a newly identified viral protein of porcine circovirus type 2 (PCV2). Apoptosis detection revealed not only that the activity of caspase-3 and -9 is increased in PCV2-infected and ORF4-transfected cells but also that cytochrome
c
release from the mitochondria to the cytosol is upregulated. Subsequently, ORF4 protein colocalization with adenine nucleotide translocase 3 (ANT3) was observed using structured illumination microscopy. Moreover, coimmunoprecipitation and pulldown analyses confirmed that the ORF4 protein interacts directly with mitochondrial ANT3 (mtANT3). Binding domain analysis further confirmed that N-terminal residues 1 to 30 of the ORF4 protein, comprising a mitochondrial targeting signal, are essential for the interaction with ANT3. Knockdown of
ANT3
markedly inhibited the apoptotic induction of both ORF4 protein and PCV2, indicating that ANT3 plays an important role in ORF4 protein-induced apoptosis during PCV2 infection. Taken together, these data indicate that the ORF4 protein is a mitochondrial targeting protein that induces apoptosis by interacting with ANT3 through the mitochondrial pathway.

IMPORTANCE
The porcine circovirus type 2 (PCV2) protein ORF4 is a newly identified viral protein; however, little is known about its functions. Apoptosis is an essential strategy of the host defense response and is used by viruses to maintain their life cycles. In the present study, we report the molecular mechanism of the apoptosis induced by the ORF4 protein. The ORF4 protein contains a mitochondrial targeting signal and is an unstable protein that is degraded by the proteasome-dependent pathway. Viral protein ORF4 triggers caspase-3- and -9-dependent cellular apoptosis in mitochondria by directly binding to ANT3. We conclude that the ORF4 protein is a mitochondrial targeting protein and reveal a mechanism whereby circovirus recruits ANT3 to induce apoptosis.
A Vaccine Platform against Arenaviruses Based on a Recombinant Hyperattenuated Mopeia Virus Expressing Heterologous Glycoproteins
Authors: Carnec Xavier , Mateo Mathieu , Page Audrey , Reynard Stéphanie , Hortion Jimmy , Picard Caroline , Yekwa Elsie , Barrot Laura , Barron Stéphane , Vallve Audrey , Raoul Hervé , Carbonnelle Caroline , Ferron François , Baize Sylvain 
Published: March 2018

ABSTRACT

Several Old World and New World arenaviruses are responsible for severe endemic and epidemic hemorrhagic fevers, whereas other members of the
Arenaviridae
family are nonpathogenic. To date, no approved vaccines, antivirals, or specific treatments are available, except for Junín virus. However, protection of nonhuman primates against Lassa fever virus (LASV) is possible through the inoculation of the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with LASV. We reasoned that this virus, modified by using reverse genetics, would represent the basis for the generation of a vaccine platform against LASV and other pathogenic arenaviruses. After showing evidence of exoribonuclease (ExoN) activity in NP of MOPV, we found that this activity was essential for multiplication in antigen-presenting cells. The introduction of multiple mutations in the ExoN site of MOPV NP generated a hyperattenuated strain (MOPV
ExoN6b
) that is (i) genetically stable over passages, (ii) has increased immunogenic properties compared to those of MOPV, and (iii) still promotes a strong type I interferon (IFN) response. MOPV
ExoN6b
was further modified to harbor the envelope glycoproteins of heterologous pathogenic arenaviruses, such as LASV or Lujo, Machupo, Guanarito, Chapare, or Sabia virus in order to broaden specific antigenicity while preserving the hyperattenuated characteristics of the parental strain. Our MOPV-based vaccine candidate for LASV, MOPEVAC
LASV
, was used in a one-shot immunization assay in nonhuman primates and fully protected them from a lethal challenge with LASV. Thus, our hyperattenuated strain of MOPV constitutes a promising new live-attenuated vaccine platform to immunize against several, if not all, pathogenic arenaviruses.

IMPORTANCE
Arenaviruses are emerging pathogens transmitted to humans by rodents and responsible for endemic and epidemic hemorrhagic fevers of global concern. Nonspecific symptoms associated with the onset of infection make these viruses difficult to distinguish from other endemic pathogens. Moreover, the unavailability of rapid diagnosis in the field delays the identification of the virus and early care for treatment and favors spreading. The vaccination of exposed populations would be of great help to decrease morbidity and human-to-human transmission. Using reverse genetics, we generated a vaccine platform for pathogenic arenaviruses based on a modified and hyperattenuated strain of the nonpathogenic Mopeia virus and showed that the Lassa virus candidate fully protected nonhuman primates from a lethal challenge. These results showed that a rationally designed recombinant MOPV-based vaccine is safe, immunogenic, and efficacious in nonhuman primates.
Countdown for UK Child Survival 2017: mortality progress and targets
Authors: Viner Russell M , Ward Joseph L , Wolfe Ingrid 
Published: March 2018

BackgroundThe Countdown for UK Child Survival tracks recent UK child mortality trends and makes recommendations for improvement.MethodsWe used data from the WHO World Mortality Database to calculate mortality from 1970 to 2014 for 0–19 year olds in the UK and a comparable group of wealthy countries (the EU15+). We used Poisson regression models to assess the significance of apparent differences. We extrapolated model coefficients to estimate future disparites between the UK and the EU15+ to 2030. We proposed goals and intermediate indicators to track UK mortality in keeping with the UN Sustainable Development Goals.ResultsUK infant mortality continues to track in the worst decile of EU15+ mortality with 1–4 year mortality in the worst quartile. Annual reductions in total UK mortality have been significantly lower than the EU15+ since 1990 for infant, postneonatal and 1–4 year mortality. If current trends persist, by 2030 UK infant mortality and 1–4 year mortality could be respectively 180% and 145% of EU15+ median mortality. UK non-communicable disease (NCD) mortality among 1–4 years and 15–19 years persists in the worst quartile. UK injury mortality continues in the best quartile. A framework of goals and indicators for UK child survival and health is presented.DiscussionUK mortality among under 10 years of age continues to diverge from the EU15+ median, and UK NCD mortality remains persistently poor. We propose a set of goals to improve UK childhood survival by 2030 and an annual Countdown mechanism to monitor progress towards these targets.
Aortic elongation part II: the risk of acute type A aortic dissection
Authors: Heuts Samuel , Adriaans Bouke P , Gerretsen Suzanne , Natour Ehsan , Vos Rein , Cheriex Emile C , Crijns Harry J G M , Wildberger Joachim E , Maessen Jos G , Schalla Simon , Sardari Nia Peyman 
Published: March 2018

ObjectivesProphylactic surgery for prevention of acute type A aortic dissection (ATAAD) is reserved for patients with an ascending aortic aneurysm ≥55 mm. Identification of additional risk predictors is warranted since over 70% of patients presenting with ATAAD have a non-dilated aorta or an aneurysm that would not have met the diameter criterion for preventative surgery. Aim of the study was to evaluate ascending aortic elongation as a risk factor for ATAAD and to compare aortic lengths between ATAAD patients and healthy controls.MethodsAortic lengths and diameters of ATAAD patients were measured on three-dimensional modelled computed tomography and adjusted to predissection dimensions in this cross-sectional single-centre study. Logistic regression was used to evaluate the relation between ATAAD and aortic dimensions. Lengths of different aortic segments were compared with a healthy control group using propensity score matching.ResultsTwo-hundred and fifty patients were included in the study (ATAAD, n=40; controls, n=210). Ascending aortic length and diameter proved to be independent predictors for ATAAD (OR=5.3, CI 2.5 to 11.4, p<0.001 and OR=8.6, CI 2.4 to 31.0, p=0.001). Eighty patients were matched based on propensity scores (ATAAD n=40, controls n=40). The ascending aorta was longer and more dilated in ATAAD patients compared with healthy controls (78.6±8.8 mm vs 68.9±7.2 mm, p<0.001, 34.4 mm ±3.2. vs 39.4 mm ±5.7, p<0.001, respectively). No differences were found in lengths of the aortic arch and descending aorta.ConclusionsAscending aortic length could serve as an independent predictor for ATAAD. Future studies addressing indications for prophylactic surgery should also investigate aortic length.
Repeated large-scale mass-transport deposits and consequent rapid sedimentation in the western part of the Bay of Bengal, India
Authors: Yamamoto Yuzuru , Chiyonobu Shun , Kanamatsu Toshiya , Ahagon Naokazu , Aoike Kan , Kamiya Nana , Ojima Takanori , Hirose Takehiro , Sugihara Takamitsu , Saito Saneatsu , Kinoshita Masataka , Kubo Yusuke , Yamada Yasuhiro ,   NGHP-02 Scientists
Published: March 2018

Abstract

The National Gas Hydrate Program Expedition 02 was conducted in early 2015 using the Drilling Vessel
Chikyu
in the western part of the Bay of Bengal, India. During drilling off Vishakhapatnam, NE India, some bottom-simulating reflectors were penetrated, and numerous mass-transport deposits (MTDs) were identified. The recovered cores were composed of post-late Miocene muddy slope deposits containing the late Miocene–Pliocene hiatus that is widespread in that region. Based on detailed visual core descriptions and calcareous nannofossil biostratigraphy, two major MTD-rich intervals were identified: the Pleistocene interval above the hiatus, and the middle–late Miocene interval below it. Although the MTDs in both intervals are composed of variously coloured clay–silt blocks in an olive-black or olive-grey silty clay matrix (muddy MTDs), the Pleistocene MTDs consist of larger-sized blocks (mostly less than a few metres but with some >10 m) without clear shear fabrics, whereas the Miocene MTDs contain smaller blocks (<0.1 m) with asymmetrical shear fabrics. The muddy blocks are composed of older components (Pliocene–Cretaceous) compared with the depositional ages of the MTDs. The high abundance of MTDs above the hiatus and the depositional ages of the interbedded coherent layers indicate that large-scale MTDs occurred repeatedly during the Pleistocene. Such repeated MTDs contributed to maintaining the high sedimentation rate in this area and potentially provided stable pressure and temperature conditions for the formation of gas hydrates.
New evidence for a major late Quaternary submarine landslide on the external western levee of Laurentian Fan
Authors: Normandeau Alexandre , Campbell D. Calvin , Piper David J. W. , Jenner Kimberley A. 
Published: March 2018

Abstract

The Laurentian Fan is one of the largest submarine fans on the western margin of the North Atlantic. Recently acquired high-resolution multibeam bathymetric data (60 m horizontal resolution) reveal a major mass-transport deposit (MTD) on the Western Levee of Western Valley (WLWV), covering >14 000 km
2
in water depths from 3900 to >5000 m. Typical submarine landslide features are observed such as headscarps that in places reach the crest of the levee, crown cracks, extensional ridges, blocky debris and flow lineations. Multiple headwalls are observed on 3.5 kHz sub-bottom profiles, indicating that the landslide retrogressed upslope. While the upper parts of the MTD consist of intact blocks that were displaced downslope as ridges and troughs, the lower parts exhibit a
c.
30 m thick incoherent to transparent acoustic facies, typical of debris flows. Landslide geomorphology therefore suggests that it was generated as a retrogressive spread and that slide blocks disintegrated downslope to become a blocky landslide with a surficial debris flow. The blocky landslide/debris flow extends downslope
c.
90 km and partially fills a submarine channel. The superposition of the MTD filling the channel and its location at the top of the stratigraphic succession in the levee suggests that it is late Quaternary in age, possibly Holocene. Deeper seismic reflection data also show that this is a rare event during the Quaternary; it is the largest MTD observed in the upper
c.
375 m of the levee succession and among the largest and deepest in the western North Atlantic.
A consistent global approach for the morphometric characterization of subaqueous landslides
Authors: Clare Michael , Chaytor Jason , Dabson Oliver , Gamboa Davide , Georgiopoulou Aggeliki , Eady Harry , Hunt James , Jackson Christopher , Katz Oded , Krastel Sebastian , León Ricardo , Micallef Aaron , Moernaut Jasper , Moriconi Roberto , Moscardelli Lorena , Mueller Christof , Normandeau Alexandre , Patacci Marco , Steventon Michael , Urlaub Morelia , Völker David , Wood Lesli , Jobe Zane 
Published: March 2018

Abstract
Landslides are common in aquatic settings worldwide, from lakes and coastal environments to the deep sea. Fast-moving, large-volume landslides can potentially trigger destructive tsunamis. Landslides damage and disrupt global communication links and other critical marine infrastructure. Landslide deposits act as foci for localized, but important, deep-seafloor biological communities. Under burial, landslide deposits play an important role in a successful petroleum system. While the broad importance of understanding subaqueous landslide processes is evident, a number of important scientific questions have yet to receive the needed attention. Collecting quantitative data is a critical step to addressing questions surrounding subaqueous landslides.
Quantitative metrics of subaqueous landslides are routinely recorded, but which ones, and how they are defined, depends on the end-user focus. Differences in focus can inhibit communication of knowledge between communities, and complicate comparative analysis. This study outlines an approach specifically for consistent measurement of subaqueous landslide morphometrics to be used in the design of a broader, global open-source, peer-curated database. Examples from different settings illustrate how the approach can be applied, as well as the difficulties encountered when analysing different landslides and data types. Standardizing data collection for subaqueous landslides should result in more accurate geohazard predictions and resource estimation.
Subsurface controls on the development of the Cape Fear Slide Complex, central US Atlantic Margin
Authors: Hill Jenna C. , Brothers Daniel S. , Hornbach Matthew J. , Sawyer Derek E. , Shillington Donna J. , Bécel Anne 
Published: March 2018

Abstract

The Cape Fear Slide is one of the largest (>25 000 km
3
) submarine slope failure complexes on the US Atlantic margin. Here we use a combination of new high-resolution multichannel seismic data (MCS) from the National Science Foundation Geodynamic Processes at Rifting and Subducting Margins (NSF GeoPRISMS) Community Seismic Experiment and legacy industry MCS to derive detailed stratigraphy of this slide and constrain the conditions that lead to slope instability. Limited outer-shelf and upper-slope accommodation space during the Neogene, combined with lowstand fluvial inputs and northwards Gulf Stream sediment transport, appears to have contributed to thick Miocene and Pliocene deposits that onlapped the lower slope. This resulted in burial of an upper-slope bypass zone developed from earlier erosional truncation of Paleogene strata. These deposits created a broad ramp that allowed accumulation of thick Quaternary strata across a low-gradient (<3.5°) upper slope. Upslope of one of the larger headwalls, undulating Quaternary strata appear to downlap onto a buried failure plane. Many of the nested headwalls of the upper-slope portion of slide complex are underlain by deformed strata, which may be the result of fluid migration associated with localized subsidence from salt migration. These new data and observations suggest that antecedent margin physiography, sediment loading and substrate fluid flow were key factors in preconditioning the Cape Fear slope for failure.
Shear margin moraine, mass transport deposits and soft beds revealed by high-resolution P-Cable three-dimensional seismic data in the Hoop area, Barents Sea
Authors: Bellwald Benjamin , Planke Sverre 
Published: March 2018

Abstract

High-resolution seismic data are powerful tools that can help the offshore industries to better understand the nature of the shallow subsurface and plan the development of vulnerable infrastructure. Submarine mass movements and shallow gas are among the most significant geohazards in petroleum prospecting areas. A variety of high-resolution geophysical datasets collected in the Barents Sea have significantly improved our knowledge of the shallow subsurface in recent decades. Here we use a
c.
200 km
2
high-resolution P-Cable 3D seismic cube from the Hoop area, SW Barents Sea, to study a 20–65 m thick glacial package between the seabed and the Upper Regional Unconformity (URU) horizons. Intra-glacial reflections, not visible in conventional seismic reflection data, are well imaged. These reflections have been mapped in detail to better understand the glacial deposits and to assess their impact on seabed installations. A shear margin moraine, mass transport deposits and thin soft beds are examples of distinct units only resolvable in the P-Cable 3D seismic data. The top of the shear margin moraine is characterized by a positive amplitude reflection incised by glacial ploughmarks. Sedimentary slide wedges and shear bands are characteristic sedimentary features of the moraine. A soft reflection locally draping the URU is interpreted as a coarser grained turbidite bed related to slope failure along the moraine. The bed is possibly filled with gas. Alternatively, this negative amplitude reflection represents a thin, soft bed above the URU. This study shows that P-Cable 3D data can be used successfully to identify and map the external and internal structures of ice stream shear margin moraines and that this knowledge is useful for site-survey investigations.
Hard-rock aquifer response to pumping and sustainable yield of wells in some areas of Mediterranean Region
Authors: Baiocchi Antonella , Lotti Francesca , Piscopo Vincenzo , Sammassimo Valentina 
Published: March 2018

Abstract

Pumping tests carried out in three highly tectonized Mediterranean areas, which share similar climate conditions, were used to characterize hard-rock aquifers and examine the issue of the sustainable yield of wells. On the basis of the identified drawdown trends and hydraulic parameters, pumping scenarios were simulated through different methods. The results show that the long-term trend in the drawdown and the initial thickness of the aquifer constrain the sustainable yield of a well. In the worst cases examined, namely those related to an aquifer with a barrier boundary and a delayed response of the aquifer, the sustainable well yield is 1–2 L s
−1
. These well discharge values are significant when compared with those found in other regions of the world, and may be related to the dense network of the discontinuities which characterizes the sites.