bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates
Authors: Bartlett Emmalene J. , Cruz Ann-Marie , Esker Janice , Castaño Adam , Schomacker Henrick , Surman Sonja R. , Hennessey Margaret , Boonyaratanakornkit Jim , Pickles Raymond J. , Collins Peter L. , Murphy Brian R. , Schmidt Alexander C. 
Published: July 2008

ABSTRACT

Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C−), a virus in which expression of the C proteins (C′, C, Y1, and Y2) was silenced without affecting the amino acid sequence of the P protein. Infectious rHPIV1-P(C−) was readily recovered from cDNA, indicating that the four C proteins were not essential for virus replication. Early during infection in vitro, rHPIV1-P(C−) replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident with the onset of an extensive cytopathic effect not observed with wt rHPIV1. rHPIV1-P(C−) infection, but not wt rHPIV1 infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast to wt rHPIV1, rHPIV1-P(C−) and rHPIV1-C
F170S
, a mutant encoding an F170S substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in vitro. However, only rHPIV1-P(C−) induced apoptosis. Thus, the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rHPIV1-P(C−), whereas only the anti-IFN activity is disabled in rHPIV1-C
F170S
. In African green monkeys (AGMs), rHPIV1-P(C−) was considerably more attenuated than rHPIV1-C
F170S
, suggesting that disabling the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1-P(C−) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in primary human airway epithelial cell cultures suggests that it might be overattenuated for use as a vaccine. Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required for virulence in primates.
Frequency and Spectrum of Genomic Integration of Recombinant Adeno-Associated Virus Serotype 8 Vector in Neonatal Mouse Liver
Authors: Inagaki Katsuya , Piao Chuncheng , Kotchey Nicole M. , Wu Xiaolin , Nakai Hiroyuki 
Published: July 2008

ABSTRACT

Neonatal injection of recombinant adeno-associated virus serotype 8 (rAAV8) vectors results in widespread transduction in multiple organs and therefore holds promise in neonatal gene therapy. On the other hand, insertional mutagenesis causing liver cancer has been implicated in rAAV-mediated neonatal gene transfer. Here, to better understand rAAV integration in neonatal livers, we investigated the frequency and spectrum of genomic integration of rAAV8 vectors in the liver following intraperitoneal injection of 2.0 × 10
11
vector genomes at birth. This dose was sufficient to transduce a majority of hepatocytes in the neonatal period. In the first approach, we injected mice with a β-galactosidase-expressing vector at birth and quantified rAAV integration events by taking advantage of liver regeneration in a chronic hepatitis animal model and following partial hepatectomy. In the second approach, we performed a new, quantitative rAAV vector genome rescue assay by which we identified rAAV integration sites and quantified integrations. As a result, we find that at least ∼0.05% of hepatocytes contained rAAV integration, while the average copy number of integrated double-stranded vector genome per cell in the liver was ∼0.2, suggesting concatemer integration. Twenty-three of 34 integrations (68%) occurred in genes, but none of them were near the mir-341 locus, the common rAAV integration site found in mouse hepatocellular carcinoma. Thus, rAAV8 vector integration occurs preferentially in genes at a frequency of 1 in approximately 10
3
hepatocytes when a majority of hepatocytes are once transduced in the neonatal period. Further studies are warranted to elucidate the relationship between vector dose and integration frequency or spectrum.
Influenza A Virus Matrix Protein 1-Specific Human CD8+T-Cell Response Induced in Trivalent Inactivated Vaccine Recipients
Authors: Terajima Masanori , Cruz John , Leporati Anita M. , Orphin Laura , Babon Jenny Aurielle B. , Co Mary Dawn T. , Pazoles Pamela , Jameson Julie , Ennis Francis A. 
Published: July 2008

ABSTRACTAmong 17 HLA-A2-positive healthy adults, CD8+T-cell responses against an HLA-A2-restricted matrix protein 1 (M1) epitope increased after immunization with trivalent inactivated influenza vaccine (TIV) in two individuals. The presence of M1 in TIV was confirmed by Western blotting. T-cell cytotoxicity assays showed that TIV is processed and the epitope is presented by antigen-presenting cells to an M1 epitope-specific CD8+T-cell line for specific lysis. These data show that TIV, which is formulated to contain surface glycoproteins to induce serotype-specific antibody responses, also contains M1, capable of inducing subtype cross-reactive CD8+T-cell responses in some vaccinees.
A Hepatitis C Virus
cis
-Acting Replication Element Forms a Long-Range RNA-RNA Interaction with Upstream RNA Sequences in NS5B
Authors: Diviney Sinéad , Tuplin Andrew , Struthers Madeleine , Armstrong Victoria , Elliott Richard M. , Simmonds Peter , Evans David J. 
Published: July 2008

ABSTRACT

The genome of hepatitis C virus (HCV) contains
cis
-acting replication elements (CREs) comprised of RNA stem-loop structures located in both the 5′ and 3′ noncoding regions (5′ and 3′ NCRs) and in the NS5B coding sequence. Through the application of several algorithmically independent bioinformatic methods to detect phylogenetically conserved, thermodynamically favored RNA secondary structures, we demonstrate a long-range interaction between sequences in the previously described CRE (5BSL3.2, now SL9266) with a previously predicted unpaired sequence located 3′ to SL9033, approximately 200 nucleotides upstream. Extensive reverse genetic analysis both supports this prediction and demonstrates a functional requirement in genome replication. By mutagenesis of the Con-1 replicon, we show that disruption of this alternative pairing inhibited replication, a phenotype that could be restored to wild-type levels through the introduction of compensating mutations in the upstream region. Substitution of the CRE with the analogous region of different genotypes of HCV produced replicons with phenotypes consistent with the hypothesis that both local and long-range interactions are critical for a fundamental aspect of genome replication. This report further extends the known interactions of the SL9266 CRE, which has also been shown to form a “kissing loop” interaction with the 3′ NCR (P. Friebe, J. Boudet, J. P. Simorre, and R. Bartenschlager, J. Virol. 79:380-392, 2005), and suggests that cooperative long-range binding with both 5′ and 3′ sequences stabilizes the CRE at the core of a complex pseudoknot. Alternatively, if the long-range interactions were mutually exclusive, the SL9266 CRE may function as a molecular switch controlling a critical aspect of HCV genome replication.
A crustal-scale cross-section through the Tauern Window (eastern Alps) from geophysical and geological data
Authors: Lammerer B. , Gebrande H. , Lüschen E. , Veselá P. 
Published: July 2008

Abstract

A restorable geological cross-section through the entire crust of the Tauern Window is presented. It is drawn from surface geology and seismic data of the TRANSALP vibroseis section using balancing software. The architecture of the window is characterized by three horses in a large duplex structure and folded granitic sills. The duplex was later uplifted along two large faults at its northern rim. The first is a blind fault along the deep-reaching sub-Tauern ramp with a displacement of 17 km. The tip of the hanging wall block wedged underneath the Austroalpine and Penninic nappes and caused a triangle structure. This led to backthrusting and backfolding within the marginal rocks of the window. At the second one, the Tauern North Boundary Fault occurred in our retrodeformation, a throw of
c
. 3 km. A total shortening of the crust or parts of the crust of
c
. 60 km in north–south direction led to uplift of the Tauern Window.
Neotectonic faulting, uplift and seismicity in the central and western Swiss Alps
Authors: Ustaszewski Michaela , Pfiffner O. Adrian 
Published: July 2008

Abstract
Our study aims to characterize the post-glacial neotectonic activity by finding surface expressions of recently active tectonic faults. The central and western Swiss Alps were chosen as the study area because surface uplift rates are very high, indicating ongoing uplift of the external basement massifs. Moreover, the Valais area coincides with enhanced seismic activity. Active faults were searched by mapping lineaments on aerial photographs and subsequent field studies. Three main types of faults could be distinguished: gravitational faults (i.e. faults related to mass movements); tectonic faults; and composite faults (i.e. tectonic faults with a component of gravitational and post-glacial rebound-related reactivation). A large number of tectonic faults were found (over 1700), but only two unequivocally post-glacially active tectonic faults could be distinguished. Indications for their post-glacial (re-)activation are displaced Quaternary landforms or sediments. Large gravitational faults, as well as composite faults often correlate with deep-seated gravitational slope deformations (DSGSD). The latter occur mainly along valley slopes, particularly where a pervasive foliation strikes parallel to the valley. Fault orientations show correlations either with the regional main foliation (e.g. Aar and Gotthard massif), the orientation of valleys (e.g. Bedretto and Urseren valley), or pre-existing tectonic structures (e.g. faults parallel to joints that are perpendicular to the strike of major structures in the Helvetic nappes). Comparisons of fault orientations with orientations of nodal planes of earthquake focal mechanisms of the last 20 years show a poor indicative correlation. The central and western Swiss Alps host a large number of faults prone for reactivation in today's stress field. However, for most of these faults, no indications of their last phase of activity exist. The low number of unambiguously active tectonic faults suggests that the current strain is either predominantly aseismic or, alternatively, cumulated seismic moment is too low for producing surface rupture.
Tectonics and sedimentation during convergence of the ALCAPA and Tisza–Dacia continental blocks: the Pienide nappe emplacement and its foredeep (N. Romania)
Authors: Tischler M. , Matenco L. , Filipescu S. , Gröger H. R. , Wetzel A. , Fügenschuh B. 
Published: July 2008

Abstract
The juxtaposition of the ALCAPA and Tisza–Dacia continental blocks, although one of the key issues in the evolution of the Carpathians, is not well known in terms of associated effects on the sedimentary systems during frontal foreland development. Most of the contact between ALCAPA and Tisza–Dacia being covered by post-tectonic deposits, these effects can best be observed in northern Romania. Sedimentological data on facies, palaeocurrents and modal composition of sandstones combined with micropalaeontological data and 2D well-calibrated seismic lines constrain the tectonic history of the contact zone between ALCAPA and Tisza–Dacia. Pervasive deposition of sand-dominated siliciclastics beginning in late Early Oligocene (Late Rupelian) times is interpreted to reflect the onset of convergence between ALCAPA and Tisza–Dacia in the study area. The depocentre of coarse siliciclastic material migrates southward, finally forming a southeastward-thinning clastic wedge in the Transylvanian Basin. This Burdigalian-age clastic wedge is interpreted as fill of a flexural foreland basin that formed in response to the coeval thrusting of parts of ALCAPA (Pienides) over Tisza–Dacia. A shift from an E–W to SE–NW striking basin axis during Oligocene times towards a WSW–ENE oriented basin axis during Burdigalian times is interpreted as a result of clockwise rotation of Tisza–Dacia during basin formation.
Metamorphism of metasediments at the scale of an orogen: a key to the Tertiary geodynamic evolution of the Alps
Authors: Bousquet Romain , Oberhänsli Roland , Goffé Bruno , Wiederkehr Michael , Koller Friedrich , Schmid Stefan M. , Schuster Ralf , Engi Martin , Berger Alfons , Martinotti Giorgio 
Published: July 2008

Abstract
Major discoveries in metamorphic petrology, as well as other geological disciplines, have been made in the Alps. The regional distribution of Late Cretaceous–Tertiary metamorphic conditions, documented in post-Hercynian metasediments across the entire Alpine belt from Corsica–Tuscany in the west to Vienna in the east, is presented in this paper. In view of the uneven distribution of information, we concentrate on type and grade of metamorphism; and we elected to distinguish between metamorphic paths where either pressure and temperature peaked simultaneously, or where the maximum temperature was reached at lower pressures, after a significant temperature increase on the decompression path.
The results show which types of process caused the main metamorphic imprint: a subduction process in the western Alps, a collision process in the central Alps, and complex metamorphic structures in the eastern Alps, owing to a complex geodynamic and metamorphic history involving the succession of the two types of process. The western Alps clearly show a relatively simple picture, with an internal (high-pressure dominated) part thrust over an external greenschist to low-grade domain, although both metamorphic domains are structurally very complex. Such a metamorphic pattern is generally produced by subduction followed by exhumation along a cool decompression path. In contrast, the central Alps document conditions typical of subduction (and partial accretion), followed by an intensely evolved collision process, often resulting in a heating event during the decompression path of the early-subducted units. Subduction-related relics and (collisional/decompressional) heating phenomena in different tectonic edifices characterize the Tertiary evolution of the Eastern Alps. The Tuscan and Corsica terrains show two different kinds of evolution, with Corsica resembling the western Alps, whereas the metamorphic history in the Tuscan domain is complex owing to the late evolution of the Apennines. This study confirms that careful analysis of the metamorphic evolution of metasediments at the scale of an entire orogen may change the geodynamic interpretation of mountain belts.
Northern Apennine–Corsica orogenic system: an updated overview
Authors: Molli Giancarlo 
Published: July 2008

Abstract
The aim of this paper is to describe some aspects of the Northern Apennine/Corsica orogenic system, a classical and still-debated subject in the geology of the central Mediterranean. After a necessarily short historical outline, a general updated overview of the Northern Apennine and Corsica is presented. The results of recent research on metamorphic units representative of the former continental margins have been used to constrain some key events of the geological history of the Northern Apennine/Corsica orogenic system and its relationship with the western Alps. Many still-controversial topics are tackled in this paper, which calls for further data and studies. In particular, the early stages of the oceanic convergence recorded by the Ligurian units of the Apennine and by Corsican ophiolites need refinement of structural and chronological data sets. Similarly, the deep structure of the inner Northern Apennine is far from being well explored; nevertheless, three crustal-scale cross-sections across the Northern Apennine are presented to show differences in the crustal and near-surface architecture at the orogen scale and to discuss some points of the Apennine history, namely the relationships between shortening in the external and exhumation/extension in the internal domains, from the Oligocene onward.
Evolution of an Early Permian extensional detachment fault from synintrusive, mylonitic flow to brittle faulting (Grassi Detachment Fault, Orobic Anticline, southern Alps, Italy)
Authors: Froitzheim N. , Derks J. F. , Walter J. M. , Sciunnach D. 
Published: July 2008

Abstract

Lower Permian volcanic and sedimentary rocks of the Collio Formation in the Orobic Anticline do not rest with a depositional contact on the Variscan basement but are separated from it by the subhorizontal Grassi Detachment Fault, consisting of a cataclasite layer underlain by mylonite. Field relations indicate that both the cataclasite and the mylonite are Early Permian in age. The mylonite formed in a continuous process before, during, and after the intrusion of the Val Biandino Quartz Diorite in the footwall of the detachment fault. Microstructure and quartz texture of the mylonite indicate top-to-the-southeast displacement. Quartz textures of mylonite close to the intrusive bodies are characterized by c-axis single maxima near the Y-direction of the finite strain, indicating prism <a>glide as the dominant gliding system and hence high temperatures (above
c.
500 °C) during mylonitization. This is explained by heat advection through the rising quartz diorite melt. During detachment faulting, the footwall of the Grassi Detachment Fault was bowed up to form a metamorphic core complex. The Ponteranica Conglomerate was deposited as a proximal, syntectonic fan-delta on the southeast side of the metamorphic core complex late in its evolution. The unconformity of the Verrucano Lombardo over the Collio Formation and the basement results from erosion of the topography created by detachment faulting, core complex updoming, and block tilting. These results indicate dramatic SE–NW stretching (in present-day coordinates) of the South-Alpine crust during the Early Permian. The return from the thickened, orogenic crust at the end of the Hercynian orogeny to the normal crustal thickness (
c.
30 km) of Late Permian and Early Triassic times was accommodated to a large extent by crustal extension, at least in this part of the southern Alps.
Tertiary cooling and exhumation history in the Maramures area (internal eastern Carpathians, northern Romania): thermochronology and structural data
Authors: Gröger H. R. , Fügenschuh B. , Tischler M. , Schmid S. M. , Foeken J. P. T. 
Published: July 2008

Abstract
The Tertiary kinematic history of the Maramures area is constrained by integrating thermochronological (fission track and (U–Th)/He analysis) data with field-based structural investigations. This study focuses on the tectonic evolution of the northern rim of the Tisza–Dacia block during collision with the European margin. Cretaceous nappe stacking, related metamorphism as well as Late Cretaceous exhumation are evidenced by zircon fission track data. Subsequent Palaeogene to Early Miocene sedimentation led to burial heating and annealing of fission tracks in apatite. Final tectonic uplift was initiated during the convergence of Tisza–Dacia with the European margin, associated with transpressional deformation (16 to 12 Ma). This led to Mid-Miocene exhumation, recorded by apatite fission track cooling ages in the western part of the study area. Transtension between 12 and 10 Ma caused brittle deformation along E–W trending strike-slip faults and SW–NE trending normal faults, delimiting blocks that were tilted towards the SW. This fragmentation of the crust led to enhanced exhumation at rates of 1 mm/a in the central part of the study area, as is documented by Middle to Late Miocene cooling ages (13 to 7 Ma). The outside estimate for the total amount of exhumation since Middle Miocene times is 7 km.
Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro
Authors: Gatt Alex , van Veen Joost J. , Woolley Anita M. , Kitchen Steve , Cooper Peter , Makris Michael 
Published: July 2008

SummaryEven though new anticoagulants are being devised with the notion that they do not require regular monitoring, when bleeding occurs, it is important to have an antidote and a reliable test to confirm whether the anticoagulant effects are persisting. We examined the effects of five heparinoids, unfractionated heparin (UFH), tinzaparin, enoxaparin, danaparoid and fondaparinux on the traditional APTT and anti-Xa assays as well as on the calibrated automated thrombogram (CAT). We also studied the ability of protamine sulphate (PS), NovoSeven®, FEIBA® and FFP to reverse maximum anticoagulation induced by the different heparinoids. The CAT was the only test to detect the coagulopathy of all the anticoagulants. PS produced complete reversal of UFH, and this could be monitored with all three tests. Tinzaparin can also be completely neutralised in vitro with high doses of PS, but the maximum enoxaparin reversal achieved with PS is only approximately 60%. Fondaparinux does not significantly affect the APTT and PS has no significant effect on its reversal. Only NovoSeven was able to correct the fondaparinux induced CAT abnormalities whilst having no effect on the anti-Xa level. None of the reversal agents was very effective in danaparoid spiked plasma but NovoSeven, at high dose, increased the ETP by 40% and reduced the anti-Xa level from 0.93 to 0.78 IU/ml. We conclude that the CAT is superior to the traditional coagulation tests in that it not only detects the coagulopathy of all the he-parinoids but can be also be used to monitor their reversal.
Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo
Authors: Wang Bing , Wang Li , Zhou Xiao-Bo , Liu Ya-Min , Wang Mei , Qin Hao , Wang Chong-Bao , Liu Ju , Yu Xiao-Jiang , Zang Wei-Jin 
Published: July 2008

SummaryClot-targeted microbubbles (TMB) were developed based on oligopeptide specific to the glycoprotein IIb/IIIa receptor on active platelets. In this study, we aimed to elucidate the thrombolysis effect of this TMB in both intraarterial and intravenous application and compare the clot lysis efficiency of the TMB and untargeted microbubbles(UTMB) in presence of external low frequency ultrasound (LFUS) (800kHz, 2.4w/cm2, pulse-wave). An acute arterial occlusion model was induced in rabbits by blocking the common carotid artery with an autogenous clot. Animals were randomized to five groups to receive the following treatment: 1) intra-arterial TMB and LFUS (IA TMB/LFUS); 2) intravenous TMB and LFUS (IV TMB/LFUS); 3) intravenous untargeted-microbubbles and LFUS (IV UTMB/LFUS);4) LFUS only; 5) intra-arterial normal saline (NS) control. Declotting score and a variation of thrombolysis-in-myocardial-infarction (TIMI) flow scale were applied to assess clot clearance and flow restore according to the angiogram. IA TMB/LFUS treatment produced highest declotting score (3.5 ± 0.53) and success rate (100%).IV TMB/LFUS treatment produced a higher declotting score (1.95 ± 1.12) than LFUS treatment (0.53 ± 0.38) (P=0.026).and higher TIMI (1.94 ± 0.62 vs.0.47 ± 0.44, P=0.020).When administrated intravenously, TMB/LFUS created a higher declotting score (1.95 ± 1.12) than that of UTMB/LFUS (0.61 ± 0.43) (P=0.033).The superiority was observed in TIMI also (1.94 ± 0.62 vs.0.72 ± 0.25, P=0.041).The results demonstrate that either intra-arterial or intravenous TMB is effective in clearing clot in-vivo model. The TMB showed advantage over UTMB in systemic administration.