bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of ETIF Deletion on Safety and Immunogenicity of Equine Herpesvirus Type 1-Vectored Vaccines
Authors: Hofmann-Sieber Helga , Wild Jens , Fiedler Nicole , Tischer Karsten , von Einem Jens , Osterrieder Nikolaus , Hofmann Heike , Köstler Josef , Wagner Ralf 
Published: September 2010

ABSTRACTHeterologous gene transfer by viral vector systems is often limited by factors such as preexisting immunity, toxicity, low packaging capacity, or weak immunogenic potential. A novel viral vector system derived from equine herpesvirus type 1 (EHV-1) not only overcomes some of these obstacles but also promotes the robust expression of a delivered transgene and the induction of antigen-specific immune responses. Regarding an enhanced safety profile, we assessed the impact of the gene encoding the sole essential tegument protein, ETIF, on the replication and immunogenicity of recombinant EHVs. The deletion of ETIF severely attenuates replication in permissive RK13 cells and a human lung epithelial cell line but without influencing transgene expression. Whereas the intranasal administration of a recombinant luciferase EHV in BALB/c mice resulted in transgene expression in nasal cavities and lungs for 5 to 6 days, the ETIF deletion limited expression to 2 days and resulted in 30-fold-less luminescence. Attenuated replication was accompanied by a decreased capacity to induce CD8+T cells against a delivered HIV Gag transgene in BALB/c mice following repeated intranasal application. However, a single subcutaneous immunization with agagDNA vaccine primed specific T cells for substantial expansion by two subsequent intranasal booster immunizations with either thegagrecombinant ETIF mutant or the parental virus. In addition to inducing Gag-specific serum antibodies, this prime-boost strategy clearly outperformed three sequential immunizations with the parental or EHV-ΔETIF virus or repeated DNA vaccination by inducing substantial specific secretory IgA (sIgA) titers.
SUMOylation Promotes PML Degradation during Encephalomyocarditis Virus Infection
Authors: El Mchichi Bouchra , Regad Tarik , Maroui Mohamed-Ali , Rodriguez Manuel S. , Aminev Aleksey , Gerbaud Sylvie , Escriou Nicolas , Dianoux Laurent , Chelbi-Alix Mounira K. 
Published: September 2010

ABSTRACT
The promyelocytic leukemia (PML) protein is expressed in the diffuse nuclear fraction of the nucleoplasm and in matrix-associated structures, known as nuclear bodies (NBs). PML NB formation requires the covalent modification of PML to SUMO. The noncovalent interactions of SUMO with PML based on the identification of a SUMO-interacting motif within PML seem to be required for further recruitment within PML NBs of SUMOylated proteins. RNA viruses whose replication takes place in the cytoplasm and is inhibited by PML have developed various strategies to counteract the antiviral defense mediated by PML NBs. We show here that primary fibroblasts derived from PML knockout mice are more sensitive to infection with encephalomyocarditis virus (EMCV), suggesting that the absence of PML results in an increase in EMCV replication. Also, we found that EMCV induces a decrease in PML protein levels both in interferon-treated cells and in PMLIII-expressing cells. Reduction of PML was carried out by the EMCV 3C protease. Indeed, at early times postinfection, EMCV induced PML transfer from the nucleoplasm to the nuclear matrix and PML conjugation to SUMO-1, SUMO-2, and SUMO-3, leading to an increase in PML body size where the viral protease 3C and the proteasome component were found colocalizing with PML within the NBs. This process was followed by PML degradation occurring in a proteasome- and SUMO-dependent manner and did not involve the SUMO-interacting motif of PML. Together, these findings reveal a new mechanism evolved by EMCV to antagonize the PML pathway in the interferon-induced antiviral defense.
A 27-Amino-Acid Deletion in the Neuraminidase Stalk Supports Replication of an Avian H2N2 Influenza A Virus in the Respiratory Tract of Chickens
Authors: Sorrell Erin M. , Song Haichen , Pena Lindomar , Perez Daniel R. 
Published: September 2010

ABSTRACT
The events and mechanisms that lead to interspecies transmission of, and host adaptation to, influenza A virus are unknown; however, both surface and internal proteins have been implicated. Our previous report highlighted the role that Japanese quail play as an intermediate host, expanding the host range of a mallard H2N2 virus, A/mallard/Potsdam/178-4/83 (H2N2), through viral adaptation. This quail-adapted virus supported transmission in quail and increased its host range to replicate and be transmitted efficiently in chickens. Here we report that of the six amino acid changes in the quail-adapted virus, a single change in the hemagglutinin (HA) was crucial for transmission in quail, while the changes in the polymerase genes favored replication at lower temperatures than those for the wild-type mallard virus. Reverse genetic analysis indicated that all adaptive mutations were necessary for transmission in chickens, further implicating quail in extending this virus to terrestrial poultry. Adaptation of the quail-adapted virus in chickens resulted in the alteration of viral tropism from intestinal shedding to shedding and transmission via the respiratory tract. Sequence analysis indicated that this chicken-adapted virus maintained all quail-adaptive mutations, as well as an additional change in the HA and, most notably, a 27-amino-acid deletion in the stalk region of neuraminidase (NA), a genotypic marker of influenza virus adaptation to chickens. This stalk deletion was shown to be responsible for the change in virus tropism from the intestine to the respiratory tract.
Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression
Authors: Mlotshwa Mandla , Riou Catherine , Chopera Denis , de Assis Rosa Debra , Ntale Roman , Treunicht Florette , Woodman Zenda , Werner Lise , van Loggerenberg Francois , Mlisana Koleka , Abdool Karim Salim , Williamson Carolyn , Gray Clive M. 
Published: September 2010

ABSTRACT

Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (
P
= 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (
P
= 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (
r
= 0.61;
P
= 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection.
Altered Receptor Specificity and Cell Tropism of D222G Hemagglutinin Mutants Isolated from Fatal Cases of Pandemic A(H1N1) 2009 Influenza Virus
Authors: Liu Yan , Childs Robert A. , Matrosovich Tatyana , Wharton Stephen , Palma Angelina S. , Chai Wengang , Daniels Rodney , Gregory Victoria , Uhlendorff Jennifer , Kiso Makoto , Klenk Hans-Dieter , Hay Alan , Feizi Ten , Matrosovich Mikhail 
Published: September 2010

ABSTRACT
Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of α2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease.
Terrestrialization in the Late Devonian: a palaeoecological overview of the Red Hill site, Pennsylvania, USA
Authors: Cressler Walter L. , Daeschler Edward B. , Slingerland Rudy , Peterson Daniel A. 
Published: September 2010

AbstractAlluvial floodplains were a critical setting during the Late Devonian for the evolution of terrestriality among plants, invertebrate and vertebrates. The Red Hill site in Pennsylvania, US, provides a range of information about the physical and biotic setting of a floodplain ecosystem along the southern margin of the Euramerican landmass during the late Famennian age. An avulsion model for floodplain sedimentation is favoured in which a variety of inter-channel depositional settings formed a wide range of aquatic and terrestrial habitats. The Red Hill flora demonstrates ecological partitioning of the floodplain landscape at a high taxonomic level. In addition to progymnosperm forests, lycopsid wetlands and zygopterid fern glades, the flora includes patches of early spermatophytes occupying sites disturbed by fires. The Red Hill fauna illustrates the development of a diverse penecontemporaneous community including terrestrial invertebrates and a wide range of vertebrates that were living within aquatic habitats. Among the vertebrates are several limbed tetrapodomorphs that inhabited the burgeoning shallow water habitats on the floodplain.
Terrestrialization: the early emergence of the concept
Authors: Janvier Philippe 
Published: September 2010

Abstract
The transition from water to land is perhaps the most dramatic event in the history of life after the rise of photosynthesis, sexuality and predation. During the late Neoproterozoic and the early Palaeozoic, some green plants, fungi and animals happened to overcome the constraints that linked them to the primeval aquatic environment of life, became progressively adapted to the terrestrial, aerobic environment and finally contributed to its change through time. We do not know how many taxa initially survived this trial, but we have some indication of the result in extant life: a threefold world of pluricellular terrestrial organisms, all depending on each other to various degrees and surrounded by a cryptic world of bacteria and unicellular eukaryotes. Fossils provide us with acceptable information about the evolutionary history of only two of these worlds: embryophytes and bilateralian animals. The molecules of their living representatives can only begin to tell us how they gained the complexity that allowed them to achieve this remarkable adaptation to life on land and in air.
An organic geochemical perspective on terrestrialization
Authors: Versteegh Gerard J. M. , Riboulleau Armelle 
Published: September 2010

Abstract

The colonization of land required new strategies for safe gamete/diaspore dispersal, and to cope with desiccation, harmful radiation, fire and gravity. Accordingly, the morphology, behaviour and physiology of the organisms changed. Here, we explore to what extent physiological adaptations, reflected in the molecular content of the sediments, add to our understanding of the terrestrialization. Many compounds considered characteristic of land organisms do not provide valuable information from the fossil record since (1) they were not preserved; (2) they occur or correspond to substances that evolved prior to the terrestrialization (e.g. cutan vs. algaenan, cellulose); or (3) they have been changed diagenetically and/or catagenetically. The latter leads to geo(macro)molecules without a chemical fingerprint relating them to their original bio(macro)molecules despite, sometimes, excellent morphological preservation of the organic remains. Nevertheless, some molecular markers and their stable isotopes provide independent information on the terrestrialization process. The odd predominance of
n
-alkane surface waxes is a feature already apparent in early land plants and could, with caution, be used as such. Furthermore, fossil terpenoids and their derivatives are valuable for reconstructing the evolution of major plant groups. The radiation of the phenylpropanoid pathway with for example, sporopollenin and lignin seems to be closely related to the evolution of land plants.
Early seed plant radiation: an ecological hypothesis
Authors: Prestianni C. , Gerrienne P. 
Published: September 2010

Abstract

The earliest steps of seed plant evolution have been extensively studied during the past 25 years. There is a growing body of evidence indicating that the first major spermatophyte radiation occurred during the Late Devonian. At least fourteen Late Devonian species are now recognized, and our knowledge of the diversity of those early seed plants has dramatically increased. Five morphotypes of seeds have been defined, mostly based on cupule morphology and on the number and degree of fusion of the integumentary lobes. In this paper, we critically discuss the abundant environmental information in order to characterize the environment in which this radiation occurred. Sedimentological information indicates that seed plants evolved in disturbed environments. It is suggested that early seed plants thrived in the shade of the dominating
Archaeopteris
, and that their evolution was canalized by this strong biotic pressure. We also confirm the previous suggestion that the variability of seed morphotypes can be explained by the weak abiotic selective pressure that existed in the
Archaeopteris
understory.
The sedimentary environment of the Late Devonian East Greenland tetrapods
Authors: Astin T. R. , Marshall J. E. A. , Blom H. , Berry C. M. 
Published: September 2010

Abstract

The Late Devonian early tetrapods in East Greenland occur in the Celsius Bjerg Group. Key occurrences are located in a detailed stratigraphic section used here to interpret the sedimentary palaeoenvironments. The palaeoenvironment for the Britta Dal Formation (which contains both
Ichthyostega
and
Acanthostega
) is reinterpreted. The Britta Dal Formation channels have flat bases, are poorly channelized, are of low sinuosity and are part of a very major distributory system that periodically experienced extreme flooding. The tetrapod fossils were recovered from an ephemeral system that was not permanently habitable in the immediate area. Plant megafossils are poorly preserved casts and impressions dominated by lycopsids and fern-like plants. The overbank siltstones are dominated by arid soil forming processes and comprise a spectacular sequence of vertisols. The 1174 m
in situ Ichthyostega
locality in Paralleldal was relocated and occurs just below the midpoint of the second megacycle in the Britta Dal Formation.
Target of Rapamycin Signaling in Leukemia and Lymphoma
Authors: Vu Collin , Fruman David A. 
Published: September 2010

AbstractGrowth factors and many oncogenes activate the lipid kinase phosphoinositide 3-kinase (PI3K), initiating a signaling cascade that includes the protein kinases AKT and target of rapamycin (TOR). The PI3K/AKT/TOR signaling pathway is a significant contributor to disease in various human cancers, including hematologic malignancies. Here we discuss different strategies to inhibit TOR for the treatment of leukemia, lymphoma, and myeloma. The TOR enzyme exists in two complexes in cells, TORC1 and TORC2. The majority of preclinical and clinical efforts to target TOR have involved using rapamycin and its analogs (rapalogs), which suppress TORC1 only partially and do not acutely inhibit TORC2. A new class of small molecules targeting the ATP-binding site of the TOR kinase, termed active-site TOR inhibitors (asTORi), achieves greater inhibition of both TOR complexes, resulting in broader suppression of the PI3K/AKT/TOR signaling network. Preclinical evidence suggests that asTORi have greater efficacy than rapalogs in Philadelphia chromosome–positive acute lymphoblastic leukemia and in T-cell lymphoma. These agents also show greater tolerability in animal models relative to rapalogs or inhibitors of PI3K. These findings encourage broader evaluation of asTORi efficacy in acute myeloid leukemia, B-cell lymphoma, myeloma, and other blood cancers. Clin Cancer Res; 16(22); 5374–80. ©2010 AACR.
Preload Dependency of Left Ventricular Torsion
Authors: Weiner Rory B. , Weyman Arthur E. , Khan Abigail May , Reingold Jason S. , Chen-Tournoux Annabel A. , Scherrer-Crosbie Marielle , Picard Michael H. , Wang Thomas J. , Baggish Aaron L. 
Published: September 2010

Background—
Left ventricular (LV) rotation results from contraction of obliquely oriented myocardial fibers. The net difference between systolic apical counterclockwise rotation and basal clockwise rotation is left ventricular torsion (LVT). Although LVT is altered in various cardiac diseases, determinants of LVT are incompletely understood.

Methods and Results—

LV end-diastolic volume, LV apical and basal rotation, peak systolic LVT, and peak early diastolic untwisting rate were measured by speckle-tracking echocardiography in healthy subjects (n=8) before and after infusion of a weight-based normal saline bolus (2.1±0.3 L). Saline infusion led to a significant increase in end-diastolic LV internal diameter (45.9±3.7 versus 47.6±4.2 mm;
P
=0.002) and LV end-diastolic volume (90.0±21.6 versus 98.3±19.6 mL;
P
=0.01). Stroke volume (51.3±10.9 versus 63.0±15.5 mL;
P
=0.003) and cardiac output (3.4±0.8 versus 4.4±1.5 L/min;
P
=0.007) increased, whereas there was no change in heart rate and blood pressure. There was a significant increase in the magnitude of peak systolic apical rotation (7.5±2.4° versus 10.5±2.8°;
P
<0.001) but no change in basal rotation (−4.1±2.3° versus −4.8±3.1°;
P
=0.44). Accordingly, peak systolic LVT increased by 33% after saline infusion (11.2±1.3° versus 14.9±1.7°;
P
<0.001). This saline-induced increase in LVT was associated with a marked increase in peak early diastolic untwisting rate (72.3±21.4 versus 136.8±30.0 degrees/s;
P
<0.001).

Conclusions—
Peak systolic LVT and peak early diastolic untwisting rate are preload-dependent. Changes in LV preload should be considered when interpreting results of future LVT studies.
Load Modulation of BOLD Response and Connectivity Predicts Working Memory Performance in Younger and Older Adults
Authors: Nagel Irene E. , Preuschhof Claudia , Li Shu-Chen , Nyberg Lars , Bäckman Lars , Lindenberger Ulman , Heekeren Hauke R. 
Published: September 2010

Abstract
Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n-back task in 30 younger adults (21–31 years) and 30 older adults (60–71 years). Individual differences in the WM network's responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.
Erroneous Model Field Representations in Multiple Pseudoproxy Studies: Corrections and Implications*
Authors: Smerdon Jason E. , Kaplan Alexey , Amrhein Daniel E. 
Published: September 2010

Abstract
Pseudoproxy experiments evaluate statistical methods used to reconstruct climate fields from paleoclimatic proxies during the Common Era. These experiments typically employ output from millennial simulations by general circulation models (GCMs). It is demonstrated that multiple published pseudoproxy studies have used erroneously processed GCM surface temperature fields: the NCAR Community Climate System Model (CCSM), version 1.4, field was incorrectly oriented geographically and the GKSS ECHO-g FOR1 field was corrupted by a hemispheric-scale smoothing in the Western Hemisphere. These problems are not associated with the original model simulations; they instead arose because of incorrect processing of the model data for the pseudoproxy experiments. The consequences of these problems are evaluated for the studies in which the incorrect fields were used. Some quantitative results are invalidated by the findings: these include all experiments that used the corrupted ECHO-g field and those aspects of previous CCSM experiments that focused on Niño-3 reconstructions. Other results derived from the CCSM field can be reinterpreted based on the information provided herein and their qualitative characteristics remain similar.
Towards an integrated approach to sexual health services: The contribution of NICE guidance on one-to-one interventions to prevent STIs and under 18 conceptions
Authors: Killoran Amanda , McCormick Geraldine 
Published: September 2010

Objective: To describe the development of the National Institute for Health and Clinical Excellence (NICE) evidence-based guidance on one-to-one interventions for prevention of STIs and under 18 conceptions, as a focus for an integrated approach to sexual health services. Method: Documentation of the process for developing NICE guidance that is ‘evidence based’ and ‘independent’. Stages were: scoping the focus of the guidance; critical appraisal and synthesis of different types of evidence; economic modelling; preparation of draft recommendations; field testing their relevance and feasibility for implementation in the English context. Results: The best available evidence demonstrates that one-to-one structured discussions with practitioners offer an effective means to support vulnerable young people and those at risk of STI infection to change their sexual behaviour and reduce their level of risk. Economic modelling demonstrated that many forms of one-to-one interventions can be cost-effective, including those involving sessions of structures discussion or counselling. Recommendations integrate the identification of high-risk groups and the need to offer information and advice on prevention of STIs including HIV and under 18 conceptions into the mainstream of heath and other services. Conclusion: Although one-to-one interventions are a comparatively narrow component of a strategic programme for the prevention of STIs and under 18 conceptions, this focus is central to addressing these challenges. This supports a much more integrated approach to service provision, within the context of modernization of sexual health services.