bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas
Authors: Franklin S. P. , Troyer J. L. , Terwee J. A. , Lyren L. M. , Boyce W. M. , Riley S. P. D. , Roelke M. E. , Crooks K. R. , VandeWoude S. 
Published: August 2007

ABSTRACT

With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family
Lentiviridae
represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the
Felidae
, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (
Lynx rufus
) and 31 pumas (
Puma concolor
) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species.
The Coronavirus Spike Protein Induces Endoplasmic Reticulum Stress and Upregulation of Intracellular Chemokine mRNA Concentrations
Authors: Versteeg Gijs A. , van de Nes Paula S. , Bredenbeek Peter J. , Spaan Willy J. M. 
Published: August 2007

ABSTRACT

Murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS) coronavirus (CoV) are two of the best-studied representatives of the family
Coronaviridae
. During CoV infection, numerous cytokines and chemokines are induced in vitro and in vivo. Human interleukin 8 and its mouse functional counterpart, CXCL2, are early-expressed chemokines. Here we show that SARS-CoV and MHV induce endoplasmic reticulum (ER) stress and Cxcl2 mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation, while expression of the other structural genes did not. Additional experiments with UV-inactivated virus, cell-cell fusion-blocking antibodies, and an MHV mutant with a defect in spike protein maturation demonstrated that spike-host interactions in the ER are responsible for the induction of ER stress and subsequent Cxcl2 mRNA transcription. Despite significant increases in levels of Cxcl2 mRNA and functional nucleus-to-cytoplasm RNA transport, no CXCL2 protein was released into the medium from MHV-infected cells. Yet Sendai virus-infected cells showed substantial Cxcl2 mRNA induction and a simultaneous increase in levels of secreted CXCL2 protein. Our results demonstrate that expression of CoV spike proteins induces ER stress, which could subsequently trigger innate immune responses. However, at that point in infection, translation of host mRNA is already severely reduced in infected cells, preventing the synthesis of CXCL2 and ER stress proteins despite their increased mRNA concentrations.
Probing the Flavivirus Membrane Fusion Mechanism by Using Monoclonal Antibodies
Authors: Stiasny Karin , Brandler Samantha , Kössl Christian , Heinz Franz X. 
Published: August 2007

ABSTRACT
In this study, we investigated in a flavivirus model (tick-borne encephalitis virus) the mechanisms of fusion inhibition by monoclonal antibodies directed to the different domains of the fusion protein (E) and to different sites within each of the domains by using in vitro fusion assays. Our data indicate that, depending on the location of their binding sites, the monoclonal antibodies impaired early or late stages of the fusion process, by blocking the initial interaction with the target membrane or by interfering with the proper formation of the postfusion structure of E, respectively. These data provide new insights into the mechanisms of flavivirus fusion inhibition by antibodies and their possible contribution to virus neutralization.
Suppression of Viral Replication by Stress-Inducible GADD34 Protein via the Mammalian Serine/Threonine Protein Kinase mTOR Pathway
Authors: Minami Kahori , Tambe Yukihiro , Watanabe Ryosuke , Isono Takahiro , Haneda Masataka , Isobe Ken-ichi , Kobayashi Toshiyuki , Hino Okio , Okabe Hidetoshi , Chano Tokuhiro , Inoue Hirokazu 
Published: August 2007

ABSTRACT
GADD34 is a protein that is induced by a variety of stressors, including DNA damage, heat shock, nutrient deprivation, energy depletion, and endoplasmic reticulum stress. Here, we demonstrated that GADD34 induced by vesicular stomatitis virus (VSV) infection suppressed viral replication in wild-type (WT) mouse embryo fibroblasts (MEFs), whereas replication was enhanced in GADD34-deficient (GADD34-KO) MEFs. Enhanced viral replication in GADD34-KO MEFs was reduced by retroviral gene rescue of GADD34. The level of VSV protein expression in GADD34-KO MEFs was significantly higher than that in WT MEFs. Neither phosphorylation of eIF2α nor cellular protein synthesis was correlated with viral replication in GADD34-KO MEFs. On the other hand, phosphorylation of S6 and 4EBP1, proteins downstream of mTOR, was suppressed by VSV infection in WT MEFs but not in GADD34-KO MEFs. GADD34 was able to associate with TSC1/2 and dephosphorylate TSC2 at Thr1462. VSV replication was higher in TSC2-null cells than in TSC2-expressing cells, and constitutively active Akt enhanced VSV replication. On the other hand, rapamycin, an mTOR inhibitor, significantly suppressed VSV replication in GADD34-KO MEFs. These findings demonstrate that GADD34 induced by VSV infection suppresses viral replication via mTOR pathway inhibition, indicating that cross talk between stress-inducible GADD34 and the mTOR signaling pathway plays a critical role in antiviral defense.
Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells
Authors: Owen Rachel E. , Yamada Eriko , Thompson Catherine I. , Phillipson Louisa J. , Thompson Clare , Taylor Elizabeth , Zambon Maria , Osborn Helen M. I. , Barclay Wendy S. , Borrow Persephone 
Published: August 2007

ABSTRACTNatural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-α-2,3-lactose (3′SL-PAA) and SA-α-2,6-N-acetyl lactosamine (6′SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in HA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in HA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.
Replication-Competent Herpes Simplex Virus 1 Isolates Selected from Cells Transfected with a Bacterial Artificial Chromosome DNA Lacking Only the U
L
49 Gene Vary with Respect to the Defect in the U
L
41 Gene Encoding Host Shutoff RNase
Authors: Sciortino Maria Teresa , Taddeo Brunella , Giuffrè-Cuculletto Maria , Medici Maria Antonietta , Mastino Antonio , Roizman Bernard 
Published: August 2007

ABSTRACT

To generate a null U
L
49 gene mutant of herpes simplex virus 1 (HSV-1), we deleted from the viral DNA, encoded as a bacterial artificial chromosome (BAC), the U
L
49 open reading frame and, in a second step, restored it. Upon transfection into Vero cells, the BAC-ΔU
L
49 DNA yielded foci of degenerated cells that could not be expanded and a few replication-competent clones. The replication-competent viral clones derived from independent transfections yielded viruses that expressed genes with some delay, produced smaller plaques, and gave lower yields than wild-type virus. A key finding is that the independently derived replication-competent viruses lacked the virion host shutoff (
vhs
) activity expressed by the RNase encoded by the U
L
41 gene. One mutant virus expressed no
vhs
protein, whereas two others, derived from independent transfections, produced truncated
vhs
proteins consistent with the spontaneous in-frame deletion. In contrast, cells infected with the virus recovered upon transfection of the BAC-U
L
49R DNA (R-U
L
49) accumulated a full-length
vhs
protein, indicating that in the parental BAC-ΔU
L
49 DNA, the U
L
41 gene was intact. We conclude that expression of the
vhs
protein in the absence of U
L
49 protein is lethal, a conclusion bolstered by the evidence reported elsewhere that in transfected cells
vhs
requires both VP16 and VP22, the product of U
L
49, to be neutralized.
Construction of a Doxycycline-Dependent Simian Immunodeficiency Virus Reveals a Nontranscriptional Function of Tat in Viral Replication
Authors: Das Atze T. , Klaver Bep , Harwig Alex , Vink Monique , Ooms Marcel , Centlivre Mireille , Berkhout Ben 
Published: August 2007

ABSTRACT

In the quest for an effective vaccine against human immunodeficiency virus (HIV), live attenuated virus vaccines have proven to be very effective in the experimental model system of simian immunodeficiency virus (SIV) in macaques. However, live attenuated HIV vaccines are considered unsafe for use in humans because the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. As an alternative approach, we earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (DOX). Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient DOX administration. Since the effectiveness and safety of such a conditionally live AIDS vaccine should be tested in macaques, we constructed a similar DOX-dependent SIVmac239 variant in which the Tat-TAR (
trans
-
a
cting
r
esponsive) transcription control mechanism was functionally replaced by the DOX-inducible Tet-On regulatory mechanism. Moreover, this virus can be used as a tool in SIV biology studies and vaccine research because both the level and duration of replication can be controlled by DOX administration. Unexpectedly, the new SIV variant required a wild-type Tat protein for replication, although gene expression was fully controlled by the incorporated Tet-On system. This result suggests that Tat has a second function in SIV replication in addition to its role in the activation of transcription.
The higher plant PII signal transduction protein: structure, function and properties
Authors: Moorhead Greg B.G. , Ferrar Tony S. , Chen Yan M. , Mizuno Yutaka , Smith Catherine S. , Ng Kenneth K.S. , Muench Douglas G. , Lohmeier-Vogel Elke 
Published: August 2007

The PII carbon/nitrogen sensing protein was discovered in Escherichia coli (Migula 1895) Castellani and Chalmers 1919, over 40 years ago. Orthologues have been discovered in three kingdoms of life making it one of the most ancient and conserved signaling proteins known. Recent advances in the field have established its primary binding partner in plants as N-acetyl glutamate kinase and the crystal structure has revealed features unique to plants that likely contribute to its function in vivo. Here, we review the properties, function, and novel structural features of this chloroplast-localized metabolic sensor of higher plants.
Population differentiation of the lodgepole pine (Pinus contorta) and jack pine (Pinus banksiana) complex in Alberta: growth, survival, and responses to climate
Authors: Rweyongeza Deogratias M. , Dhir Narinder K. , Barnhardt Leonard K. , Hansen Christine , Yang Rong-Cai 
Published: August 2007

Growth and survival of 33 populations from a species complex involving interior lodgepole pine ( Pinus contorta Dougl. ex Loud. var. latifolia Engelm.) and jack pine ( Pinus banksiana Lamb.) and their natural hybrids in Alberta were evaluated at ages 5, 10, and 15 years in eight test sites across Alberta. We determined population differentiations by estimating Mahalanobis distances between populations from the canonical discriminant analysis of the total variability and by calculating dissimilarity indexes between populations from the quadratic regression of overall growth and survival on the overall climate. The grouping of the populations based on the Mahalanobis distances showed that most jack pine populations could be separated from lodgepole and hybrid populations, but no further subdivision was possible to distinguish lodgepole from hybrid populations. This clustering pattern was remarkably similar to the grouping based on molecular markers as shown in our earlier study. This pattern of grouping is best explained by a clear elevational demarcation between jack pine at low elevations and lodgepole pine and hybrids at midrange and high elevations. The grouping of the populations based on the dissimilarity indexes revealed a somewhat contrasting pattern; most lodgepole pine populations were in one group, whereas jack pine and hybrid populations were mixed up in the other group. The two contrasting patterns of grouping suggest that nonclimatic factors such as edaphic preference and habitat disturbances are also important in determining population distributions and niche spaces in the lodgepole – jack pine complex.
Interaction of Antiprotozooal Drugs with Biomolecules. An ESR and UV-Vis Spectroelectrochemical Study.
Authors: Sanchez Urban Guadalupe Diana , Diaz de Leon-Luna Pedro , Bautista Martinez Jose Antonio A. , Frontana Carlos E. , Gonzalez I. , Aguilar-Martinez Martha 
Published: August 2007

Cyclic voltammetric study in aprotic medium of antiprotozooal nitro compounds, Nifurtimox, Benznidazol and Niclosamide in the presence of glutathione and triolein, compounds that mimic the cellular constituents of the living being, were carried out in order to investigate the interactions of these compounds with the electrogenerated intermediaries in the reduction of the nitro compounds. Glutathione caused an important shift potential of the dianion radical (peak IIc) of nifurtimox and benznidazol and a minimum interaction with the radical anions (peak Ic). However, a significant change in the voltammetric behavior of nifurtimox was observed for both peaks Ic and IIc with triolein.	Niclosamide presented more complicated responses. ESR experiments with nifurtimox showed that the nitro radical anion is interacting with triolein, even at very small concentrations.
Pharmacodynamic and pharmacokinetic study of chronic low-dose metronomic cyclophosphamide therapy in mice
Authors: Emmenegger Urban , Shaked Yuval , Man Shan , Bocci Guido , Spasojevic Ivan , Francia Giulio , Kouri Andrew , Coke Robert , Cruz-Munoz William , Ludeman Susan M. , Colvin O. Michael , Kerbel Robert S. 
Published: August 2007

AbstractProlonged, frequently administered low-dose metronomic chemotherapy (LDM) is being explored (pre)clinically as a promising antiangiogenic antitumor strategy. Although appealing because of a favorable side effect profile and mostly oral dosing, LDM involves new challenges different from conventional maximum tolerated dose chemotherapy. These include possible altered pharmacokinetic characteristics due to long-term drug exposure potentially resulting in acquired resistance and increased risk of unfavorable drug interactions. We therefore compared the antitumor and antivascular effects of LDM cyclophosphamide (CPA) given to mice that had been pretreated with either LDM CPA or normal saline, obtained blood 4-hydroxy-CPA (activated CPA) concentrations using either gas chromatography/mass spectrometry or liquid chromatography/tandem mass spectrometry in mice treated with LDM CPA, and measured hepatic and intratumoral activity of enzymes involved in the biotransformation of CPA and many other drugs [i.e., cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase]. Exposure of mice to LDM CPA for ≥8 weeks did not compromise subsequent activity of LDM CPA therapy, and biologically active 4-hydroxy-CPA levels were maintained during long-term LDM CPA administration. Whereas the effects on CYP3A4 were complex, aldehyde dehydrogenase activity was not affected. In summary, our findings suggest that acquired resistance to LDM CPA is unlikely accounted for by altered CPA biotransformation. In the absence of reliable pharmacodynamic surrogate markers, pharmacokinetic parameters might become helpful to individualize/optimize LDM CPA therapy. LDM CPA-associated changes of CYP3A4 activity point to a potential risk of unfavorable drug interactions when compounds that are metabolized by CYP3A4 are coadministered with LDM CPA. [Mol Cancer Ther 2007;6(8):2280–9]
Activation of a Nuclear Factor κB/Interleukin-1 Positive Feedback Loop by Amphiregulin in Human Breast Cancer Cells
Authors: Streicher Katie L. , Willmarth Nicole E. , Garcia Jose , Boerner Julie L. , Dewey T. Gregory , Ethier Stephen P. 
Published: August 2007

Abstract
We have recently shown that an amphiregulin-mediated autocrine loop is responsible for growth factor–independent proliferation, motility, and invasive capacity of some aggressive breast cancer cells, such as the SUM149 breast cancer cell line. In the present study, we investigated the mechanisms by which amphiregulin activation of the epidermal growth factor receptor (EGFR) regulates these altered phenotypes. Bioinformatic analysis of gene expression networks regulated by amphiregulin implicated interleukin-1α (IL-1α) and IL-1β as key mediators of amphiregulin's biological effects. The bioinformatic data were validated in experiments which showed that amphiregulin, but not epidermal growth factor, results in transcriptional up-regulation of IL-1α and IL-1β. Both IL-1α and IL-1β are synthesized and secreted by SUM149 breast cancer cells, as well as MCF10A cells engineered to express amphiregulin or MCF10A cells cultured in the presence of amphiregulin. Furthermore, EGFR, activated by amphiregulin but not epidermal growth factor, results in the prompt activation of the transcription factor nuclear factor–κB (NF-κB), which is required for transcriptional activation of IL-1. Once synthesized and secreted from the cells, IL-1 further activates NF-κB, and inhibition of IL-1 with the IL-1 receptor antagonist results in loss of NF-κB DNA binding activity and inhibition of cell proliferation. However, SUM149 cells can proliferate in the presence of IL-1 when EGFR activity is inhibited. Thus, in aggressive breast cancer cells, such as the SUM149 cells, or in normal human mammary epithelial cells growing in the presence of amphiregulin, EGFR signaling is integrated with NF-κB activation and IL-1 synthesis, which cooperate to regulate the growth and invasive capacity of the cells. (Mol Cancer Res 2007;5(8):847–62)
A Model of the Air–Sea Momentum Flux and Breaking-Wave Distribution for Strongly Forced Wind Waves
Authors: Kukulka Tobias , Hara Tetsu , Belcher Stephen E. 
Published: August 2007

Abstract
Under high-wind conditions, breaking surface waves likely play an important role in the air–sea momentum flux. A coupled wind–wave model is developed based on the assumption that in the equilibrium range of surface wave spectra the wind stress is dominated by the form drag of breaking waves. By conserving both momentum and energy in the air and also imposing the wave energy balance, coupled equations are derived governing the turbulent stress, wind speed, and the breaking-wave distribution (total breaking crest length per unit surface area as a function of wavenumber). It is assumed that smaller-scale breaking waves are sheltered from wind forcing if they are in airflow separation regions of longer breaking waves (spatial sheltering effect). Without this spatial sheltering, exact analytic solutions are obtained; with spatial sheltering asymptotic solutions for small- and large-scale breakers are derived. In both cases, the breaking-wave distribution approaches a constant value for large wavenumbers (small-scale breakers). For low wavenumbers, the breaking-wave distribution strongly depends on wind forcing. If the equilibrium range model is extended to the spectral peak, the model yields the normalized roughness length (Charnock coefficient) of growing seas, which increases with wave age and is roughly consistent with earlier laboratory observations. However, the model does not yield physical solutions beyond a critical wave age, implying that the wind input to the wave field cannot be dominated by breaking waves at all wavenumbers for developed seas (including field conditions).
Analysis of Supercritical Stratified Tidal Flow in a Scottish Fjord
Authors: Stashchuk Nataliya , Inall Mark , Vlasenko Vasiliy 
Published: August 2007

Abstract
The baroclinic tidal regime of the fjord Loch Etive (Scotland) is studied. Analysis is performed on the basis of both in situ data and numerical simulations, with the use of a fully nonlinear nonhydrostatic fine-resolution model. It was found that the crest of the sill that separates Loch Etive into inner and outer parts is subjected to a supercritical flow regime with maximum Froude numbers in excess of 5. Strong supercritical conditions lead to the formation of flow separation just above the sill’s crest. As is inherent to jet-type fjordic systems, this, in turn, leads to a weak nonlinear baroclinic wave response. On the other hand, observations and numerical results also revealed the presence of propagating internal tidal waves with amplitudes up to 10 m, several kilometers from the constriction. It is shown that these baroclinic tidal waves are excited during the ebb phase over a section of the inner flank of the sill, at a depth below 30 m, where the local Froude number is substantially less than unity. Thus Loch Etive simultaneously exhibits both weak nonlinear response due to strong supercritical conditions with flow separation over the sill and a significant linear baroclinic tidal response due to the deeper flank of the sill. In this respect, exhibiting both jet- and wave-type behavior, Loch Etive can be referred to as a “hybrid type” fjord: the authors suggest that many jet-type fjords will also generate a significant baroclinic response and should correctly fit into this new category.