bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement-Dependent Lysis of Influenza A Virus-Infected Cells by Broadly Cross-Reactive Human Monoclonal Antibodies
Authors: Terajima Masanori , Cruz John , Co Mary Dawn T. , Lee Jane-Hwei , Kaur Kaval , Wilson Patrick C. , Ennis Francis A. 
Published: October 2011

ABSTRACT
We characterized human monoclonal antibodies (MAbs) cloned from influenza virus-infected patients and from influenza vaccine recipients by complement-dependent lysis (CDL) assay. Most MAbs active in CDL were neutralizing, but not all neutralizing MAbs can mediate CDL. Two of the three stalk-specific neutralizing MAbs tested were able to mediate CDL and were more cross-reactive to temporally distant H1N1 strains than the conventional hemagglutination-inhibiting and neutralizing MAbs. One of the stalk-specific MAbs was subtype cross-reactive to H1 and H2 hemagglutinins, suggesting a role for stalk-specific antibodies in protection against influenza illness, especially by a novel viral subtype which can cause pandemics.
Selection with a Peptide Fusion Inhibitor Corresponding to the First Heptad Repeat of HIV-1 gp41 Identifies Two Genetic Pathways Conferring Cross-Resistance to Peptide Fusion Inhibitors Corresponding to the First and Second Heptad Repeats (HR1 and HR2) of gp41
Authors: Wang Wei , De Feo Christopher J. , Zhuang Min , Vassell Russell , Weiss Carol D. 
Published: October 2011

ABSTRACT
We generated four HIV-1 cultures that are resistant to a peptide fusion inhibitor corresponding to the first heptad repeat of gp41 in order to study mechanisms of resistance and gain insights into envelope glycoprotein-mediated membrane fusion. Two genetic pathways emerged that were defined by acquisition of a specific mutation in either the first or second heptad repeat region of gp41 (HR1 or the HR2, respectively). Each pathway was enriched in mutations that clustered in either HR2 and V3 or in HR1 and residues in or near CD4 contact sites. The gp41 mutations in both pathways not only accounted for resistance to the selecting HR1 peptide but also conferred cross-resistance to HR2 peptide fusion inhibitors and enhanced the stability of the six-helix bundle formed by the self-assembly of HR1 and HR2. The gp120 mutations alone enhanced fusion but did not appear to directly contribute to resistance. The implications of these findings for resistance mechanisms and regulation of envelope-mediated fusion are discussed.
Promyelocytic Leukemia Isoform IV Confers Resistance to Encephalomyocarditis Virus via the Sequestration of 3D Polymerase in Nuclear Bodies
Authors: Maroui Mohamed Ali , Pampin Mathieu , Chelbi-Alix Mounira K. 
Published: October 2011

ABSTRACT

Promyelocytic leukemia
(PML) protein is the organizer of nuclear matrix-associated nuclear bodies (NBs), and its conjugation to the small ubiquitin-like modifier (SUMO) is required for the formation of these structures. Several alternatively spliced PML transcripts from a single
PML
gene lead to the production of seven PML isoforms (PML isoform I [PMLI] to VII [PMLVII]), which all share a N-terminal region that includes the RBCC (RING, B boxes, and a α-helical coiled-coil) motif but differ in the C-terminal region. This diversity of PML isoforms determines the specific functions of each isoform. There is increasing evidence implicating PML in host antiviral defense and suggesting various strategies involving PML to counteract viral production. We reported that mouse embryonic fibroblasts derived from PML knockout mice are more sensitive than wild-type cells to infection with encephalomyocarditis virus (EMCV). Here, we show that stable expression of PMLIV or PMLIVa inhibited viral replication and protein synthesis, leading to a substantial reduction of EMCV multiplication. This protective effect required PMLIV SUMOylation and was not observed with other nuclear PML isoforms (I, II, III, V, and VI) or with the cytoplasmic PMLVII. We demonstrated that only PMLIV interacted with EMCV 3D polymerase (3Dpol) and sequestered it within PML NBs. The C-terminal region specific to PMLIV was required for both interaction with 3Dpol and the antiviral properties. Also, depletion of PMLIV by RNA interference significantly boosted EMCV production in interferon-treated cells. These findings indicate the mechanism by which PML confers resistance to EMCV. They also reveal a new pathway mediating the antiviral activity of interferon against EMCV.
Dysfunction of Autophagy Participates in Vacuole Formation and Cell Death in Cells Replicating Hepatitis C Virus
Authors: Taguwa Shuhei , Kambara Hiroto , Fujita Naonobu , Noda Takeshi , Yoshimori Tamotsu , Koike Kazuhiko , Moriishi Kohji , Matsuura Yoshiharu 
Published: October 2011

ABSTRACTHepatitis C virus (HCV) is a major cause of chronic liver diseases. A high risk of chronicity is the major concern of HCV infection, since chronic HCV infection often leads to liver cirrhosis and hepatocellular carcinoma. Infection with the HCV genotype 1 in particular is considered a clinical risk factor for the development of hepatocellular carcinoma, although the molecular mechanisms of the pathogenesis are largely unknown. Autophagy is involved in the degradation of cellular organelles and the elimination of invasive microorganisms. In addition, disruption of autophagy often leads to several protein deposition diseases. Although recent reports suggest that HCV exploits the autophagy pathway for viral propagation, the biological significance of the autophagy to the life cycle of HCV is still uncertain. Here, we show that replication of HCV RNA induces autophagy to inhibit cell death. Cells harboring an HCV replicon RNA of genotype 1b strain Con1 but not of genotype 2a strain JFH1 exhibited an incomplete acidification of the autolysosome due to a lysosomal defect, leading to the enhanced secretion of immature cathepsin B. The suppression of autophagy in the Con1 HCV replicon cells induced severe cytoplasmic vacuolation and cell death. These results suggest that HCV harnesses autophagy to circumvent the harmful vacuole formation and to maintain a persistent infection. These findings reveal a unique survival strategy of HCV and provide new insights into the genotype-specific pathogenicity of HCV.
Structural Characterization of the Viral and cRNA Panhandle Motifs from the Infectious Salmon Anemia Virus
Authors: Brinson Robert G. , Szakal Andrea L. , Marino John P. 
Published: October 2011

ABSTRACT
Infectious salmon anemia virus (ISAV) has emerged as a virus of great concern to the aquaculture industry since it can lead to highly contagious and lethal infections in farm-raised salmon populations. While little is known about the transcription/replication cycle of ISAV, initial evidence suggests that it follows molecular mechanisms similar to those found in other orthomyxoviruses, which include the highly pathogenic influenza A (inf A) virus. During the life cycle of orthomyxoviruses, a panhandle structure is formed by the pairing of the conserved 5′ and 3′ ends of each genomic RNA. This structural motif serves both as a promoter of the viral RNA (vRNA)-dependent RNA polymerase and as a regulatory element in the transcription/replication cycle. As a first step toward characterizing the structure of the ISAV panhandle, here we have determined the secondary structures of the vRNA and the cRNA panhandles on the basis of solution nuclear magnetic resonance (NMR) and thermal melting data. The vRNA panhandle is distinguished by three noncanonical U·G pairs and one U·U pair in two stem helices that are linked by a highly stacked internal loop. For the cRNA panhandle, a contiguous stem helix with a protonated C·A pair near the terminus and tandem downstream U·U pairs was found. The observed noncanonical base pairs and base stacking features of the ISAV RNA panhandle motif provide the first insight into structural features that may govern recognition by the viral RNA polymerase.
Site-Specific Proteolytic Cleavage of the Amino Terminus of Herpes Simplex Virus Glycoprotein K on Virion Particles Inhibits Virus Entry
Authors: Jambunathan Nithya , Chowdhury Sona , Subramanian Ramesh , Chouljenko Vladimir N. , Walker Jason D. , Kousoulas Konstantin G. 
Published: October 2011

ABSTRACT
Herpes simplex virus 1 (HSV-1) glycoprotein K (gK) is expressed on virions and functions in entry, inasmuch as HSV-1(KOS) virions devoid of gK enter cells substantially slower than is the case for the parental KOS virus (T. P. Foster, G. V. Rybachuk, and K. G. Kousoulas, J. Virol. 75:12431–12438, 2001). Deletion of the amino-terminal 68-amino-acid (aa) portion of gK caused a reduction in efficiency and kinetics of virus entry similar to that of the gK-null virus in comparison to the HSV-1(F) parental virus. The UL20 membrane protein and gK were readily detected on double-gradient-purified virion preparations. Immuno-electron microscopy confirmed the presence of gK and UL20 on purified virions. Coimmunoprecipitation experiments using purified virions revealed that gK interacted with UL20, as has been shown in virus-infected cells (T. P. Foster, V. N. Chouljenko, and K. G. Kousoulas, J. Virol. 82:6310–6323, 2008). Scanning of the HSV-1(F) viral genome revealed the presence of a single putative tobacco etch virus (TEV) protease site within gD, while additional TEV predicted sites were found within the UL5 (helicase-primase helicase subunit), UL23 (thymidine kinase), UL25 (DNA packaging tegument protein), and UL52 (helicase-primase primase subunit) proteins. The recombinant virus gDΔTEV was engineered to eliminate the single predicted gD TEV protease site without appreciably affecting its replication characteristics. The mutant virus gK-V5-TEV was subsequently constructed by insertion of a gene sequence encoding a V5 epitope tag in frame with the TEV protease site immediately after gK amino acid 68. The gK-V5-TEV, R-gK-V5-TEV (revertant virus), and gDΔTEV viruses exhibited similar plaque morphologies and replication characteristics. Treatment of the gK-V5-TEV virions with TEV protease caused approximately 32 to 34% reduction of virus entry, while treatment of gDΔTEV virions caused slightly increased virus entry. These results provide direct evidence that the gK and UL20 proteins, which are genetically and functionally linked to gB-mediated virus-induced cell fusion, are structural components of virions and function in virus entry. Site-specific cleavage of viral glycoproteins on mature and fully infectious virions utilizing unique protease sites may serve as a generalizable method of uncoupling the roles of viral glycoproteins in virus entry and virion assembly.
Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion
Authors: Bose Sayantan , Welch Brett D. , Kors Christopher A. , Yuan Ping , Jardetzky Theodore S. , Lamb Robert A. 
Published: October 2011

ABSTRACTParamyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 Å, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.
Prevalence and characterisation of, and producers' attitudes towards, hock lesions in UK dairy cattle
Authors: Potterton S. L. , Green M. J. , Millar K. M. , Brignell C. J. , Harris J. , Whay H. R. , Huxley J. N. 
Published: October 2011

The objectives of this paper were to characterise lesions found at the hock and to establish their prevalence across a large sample of dairy cows in the UK. In addition, the study aimed to examine farmers' perceptions of these lesions. Seventy‐seven farms were visited; both hocks on a random sample of approximately 50 cows were scored on a categorical scale for hair loss, ulceration and swelling. In addition, the size and location of lesions were marked on a hock map. A questionnaire designed to explore attitudes towards lesions was conducted with the owner. Hair loss and ulceration were seen at five locations. Hair loss was identified on 5,619 of 6,896 hocks (mild: 43.7 per cent; moderate: 25.1 per cent; severe: 12.6 per cent) and 1,137 of 6,896 hocks had areas of ulceration (mild: 8.6 per cent; moderate: 5.8 per cent; severe: 2.1 per cent). The majority of lesions were small; however, a small proportion had extensive areas of hair loss (maximum size 113.3 cm2) and ulceration (maximum size 95.5 cm2). Moderate swelling was recorded on 20 per cent of hocks, and 2.0 per cent had severe swelling. Interview results suggested that more than 90 per cent of participants were aware of hock lesions and a third had sought treatment for them; most felt that lesions had at least some impact on productivity and welfare.
Palaeomagnetic results from Upper Triassic red-beds and CAMP lavas of the Argana Basin, Morocco
Authors: Deenen Martijn , Langereis Cor , Krijgsman Wout , Hachimi Hind El , Chellai El Hassane 
Published: October 2011

Abstract

The continental Argana Basin of Morocco is the trans-Atlantic counterpart of the extensively studied Fundy, Hartford and Newark basins in north-eastern America, that have provided the astrochronologically tuned geomagnetic polarity timescale (GPTS) for the late Triassic and earliest Jurassic. The Argana red-bed successions also show astronomically driven time control, which allowed trans-Atlantic correlations and revealed that the interval towards volcanism of the Central Atlantic Magmatic Province (CAMP) is without any significant hiatuses. Here, we present palaeomagnetic results from the cyclically bedded upper Triassic red-beds and the intercalated volcanics associated with CAMP. Our composite Argana section comprises an interval of 3.5–4.0 Ma, but its magnetostratigraphic pattern does not allow a straightforward correlation to the Newark GPTS. The continental red-bed deposits of the Bigoudine Formation demonstrate a dominant magnetic overprint that could only be removed at temperatures above 600 °C. We suggest that this overprint could have been caused by a period of (Jurassic,
c
. 170 Ma) magmatism that caused pervasive overprinting of the Triassic palaeomagnetic signal. Correlations between the sections in the Tazantoute region are not straightforward, hampered by the presence of a magmatic sill. The CAMP lava sequences of Tazantoute are all of normal polarity and record secular variation in a manner that agrees with short-lived pulses of CAMP activity in Morocco. Our results indicate that the sedimentary successions of the Argana Basin have the potential to evaluate the Newark GPTS, but that detailed palaeomagnetic analyses of more suitable sections with long(er) cyclostratigraphic records are required.
Towards a better understanding of African topography: a review of passive-source seismic studies of the African crust and upper mantle
Authors: Fishwick Stewart , Bastow Ian D. 
Published: October 2011

Abstract

Explaining the cause and support of Africa's varied topography remains a fundamental question for our understanding of the long-term evolution of the continent. As geodynamical modelling becomes more frequently used to investigate this problem, it is important to understand the seismological results that can be incorporated into these models. Crustal thickness estimates are crucial for calculating components of topography that are isostatically compensated. Variations in seismic velocity help constrain variations in subsurface temperature and density and thus buoyancy; measurements of anisotropy can also be used to determine the contribution of the mantle flow field to dynamic topography. In this light, we review the results of passive seismic studies across Africa. At the continental scale there are significant differences in crustal models, meaning large uncertainties in corrections for isostatic topography. In east Africa, multiple seismic experiments have provided firm constraints on crustal and mantle structure. Tomographic images illuminate a broad (
c.
500 km wide) low-velocity region in the upper mantle, with possible connection to the African Superplume in the lower mantle. These observations, alongside the variations in radial anisotropy, strongly suggest that the mantle flow field contributes significantly to the uplift of the region. Beneath southern Africa, low velocities are observed near the base of the continental lithosphere; the depth to transition zone discontinuities however suggests that they are not linked to the superplume beneath. It is thus less clear what role the sublithospheric mantle plays in supporting the region's high topography. Many of Africa's secondary topographic features (e.g. Atlas, Hoggar, Bie Dome) are underlain by slow velocities at depths of 100–150 km and are adjacent to rapid changes in lithospheric thickness. Whether these variations in lithospheric structure promote small-scale convection or simply guide the larger-scale mantle flow field remains ambiguous.
Tectonic evolution of the Central Steep Zone, Axum area, northern Ethiopia: inferences from magnetic and geochemical data
Authors: De Wall Helga , Dietl Carlo , Jungmann Olga , Tegene Ashenafi T. , Pandit Manoj K. 
Published: October 2011

Abstract

Northern Ethiopia is marked by a fanning system of thrust planes with NW-dipping structures in the east and southeast-dipping in the west. The central zone of this large-scale (200 km long) structure is formed by a
c.
10 km wide zone of localized strain and amphibolites facies metamorphic conditions (680 °C and 3.4 kbar) referred to as the Central Steep Zone (CSZ). The CSZ comprises a mafic rock assemblage of amphibolite, serpentinite showing ocean-floor characteristics and calc-silicate schist. A monzonite intrusion in the central part of the CSZ post-dates the deformation and is related to partial melting of the mafic rocks. Magnetic fabric measurements reveal NE-trending (043°) steep foliations in the CSZ with vertical orientation of lineation, parallel to the axes of micro-folds. This high-strain zone is interpreted as central zone of a positive flower structure on the basis of simultaneous flattening and shear movement, typical for transpressive kinematics. The CSZ has a northern continuation into the Nafka terrane of Eritrea where it can be traced over a distance of 200 km. This high-strain belt forms a major structure in the context of Arabian–Nubian Shield (ANS) collision tectonics during the closure of the Mozambique Ocean and assembly of Gondwana.
Constraining the timing of deformation in the southwestern Central Zone of the Damara Belt, Namibia
Authors: Longridge L. , Gibson R. L. , Kinnaird J. A. , Armstrong R. A. 
Published: October 2011

Abstract

Structural investigations and U–Pb sensitive high-resolution ion microprobe (SHRIMP) dating of rocks from the southwestern Central Zone of the Damara Belt, Namibia, reveal that a major SE-verging deformation event (D2) occurred at between 520 and 508 Ma. During D2, SE-verging simple shear and NE–SW pure shear extension in a constrictional stress field produced recumbent, south- to SE-verging, kilometre-scale folds and ductile shear zones, a NE–SW extensional lineation and conjugate shear bands, and was coeval with granitoid emplacement and high-grade metamorphism. The timing of this event is constrained by anatectic leucosomes in D2 shear zones (511±18 Ma) and extensional shear bands (508.4±8.7 Ma) as well as by syntectonic grey granites (520.4±4.2 Ma), and is similar to ages for high-grade metamorphism in the Central Zone. An upright folding event (D3) occurred at
c
. 508 Ma, resulting in the formation of basement-cored fold interference domes. The timing of deformation and metamorphism at 520–508 Ma in the mid-crustal SW Central Zone contrasts with ages of 560–540 Ma for shallow crustal NW-verging folding and thrusting elsewhere in the Central Zone that was concomitant with voluminous magmatism. This magmatism led to metamorphism and anatexis of the basement and the emplacement of anatectic red granites at 539±17 to 535.6±7.2 Ma, which contain 1013±21 Ma inherited zircons. The Central Zone therefore contains a record of crustal thickening, heating of the mid-crust, exhumation and orogen-parallel extension over the life of an orogen.
The Palaeozoic palaeogeography of central Gondwana
Authors: Torsvik Trond H. , Cocks L. Robin M. 
Published: October 2011

Abstract
Nine new palaeogeographical maps of central Gondwana are presented at intervals within the Palaeozoic from the Middle Cambrian at 510 Ma to the end of the Permian at 250 Ma. The area covered includes all of Africa, Madagascar, India and Arabia as well as adjacent regions, including parts of southern Europe, much of South America (including the Falkland Isles) and Antarctica. After final assembly in the Late Neoproterozoic the southern margin was largely passive throughout the Palaeozoic, apart from some local orogeny in the Cambrian in the final stages of the largely Neoproterozoic Pan-African Orogeny and during the Late Palaeozoic Gondwanide Orogeny. The northern peri-Gondwana margin was active during the Early Palaeozoic but the NW part became passive by the earliest Ordovician when the Rheic Ocean opened between Gondwana and Avalonia. This was eventually followed by the latest Silurian or Early Devonian opening of the Palaeotethys Ocean between Gondwana and Iberia, Armorica and associated terranes and, much later, the rifting and opening of the Neotethys Ocean near the close of the Permian. In the Late Carboniferous, Gondwana merged with Laurussia to form Pangea. That accretion took place outside the area to the NW, although the consequent orogenic activity extended to Morocco and Algeria. Most of the centre of Gondwana was land throughout the Palaeozoic but with extensive shelf seas over the craton margins, particularly the northern margin from the Cambrian to the Devonian on which the important north African and Arabian hydrocarbon source rocks were deposited in the Lower Silurian (with the chief reservoirs in the adjacent Upper Ordovician) and Upper Devonian. There were also substantial Upper Carboniferous and later non-marine lake basins in central and southern Africa in which the Karroo Supergroup was deposited. The South Pole was located within the area from the Early Palaeozoic to the Mid-Permian and central Gondwana was therefore greatly affected by two ice ages: the short but sharp Hirnantian glaciation at the end of the Ordovician and another lasting sporadically for more than 25 Ma during the later Carboniferous and Early Permian.