bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passive Immunotherapy in Simian Immunodeficiency Virus-Infected Macaques Accelerates the Development of Neutralizing Antibodies
Authors: Haigwood Nancy L. , Montefiori David C. , Sutton William F. , McClure Janela , Watson Andrew J. , Voss Gerald , Hirsch Vanessa M. , Richardson Barbra A. , Letvin Norman L. , Hu Shiu-Lok , Johnson Philip R. 
Published: May 2004

ABSTRACTPassively transferred neutralizing antibodies can block lentivirus infection, but their role in postexposure prophylaxis is poorly understood. In this nonhuman-primate study, the effects of short-term antibody therapy on 5-year disease progression, virus load, and host immunity were explored. We reported previously that postinfection passive treatment with polyclonal immune globulin with high neutralizing titers against SIVsmE660 (SIVIG) significantly improved the 67-week health of SIVsmE660-infectedMacaca mulattamacaques. Four of six treated macaques maintained low or undetectable levels of virus in plasma, compared with one of ten controls, while two rapid progressors controlled viremia only as long as the SIVIG was present. SIVIG treatment delayed the de novo production of envelope (Env)-specific antibodies by 8 weeks (13). We show here that differences in disease progression were also significant at 5 years postinfection, excluding rapid progressors (P= 0.05). Macaques that maintained ≤103virus particles per ml of plasma and ≤30 infectious virus particles per 106mononuclear cells from peripheral blood and lymph nodes had delayed disease onset. All macaques that survived beyond 18 months had measurable Gag-specific CD8+cytotoxic T cells, regardless of treatment. Humoral immunity in survivors beyond 20 weeks was strikingly different in the SIVIG and control groups. Despite a delay in Env-specific binding antibodies, de novo production of neutralizing antibodies was significantly accelerated in SIVIG-treated macaques. Titers of de novo neutralizing antibodies at week 12 were comparable to levels achieved in controls only by week 32 or later. Acceleration of de novo simian immunodeficiency virus immunity in the presence of passively transferred neutralizing antibodies is a novel finding with implications for postexposure prophylaxis and vaccines.
Cell-Cell Fusion Induced by the Avian Reovirus Membrane Fusion Protein Is Regulated by Protein Degradation
Authors: Shmulevitz Maya , Corcoran Jennifer , Salsman Jayme , Duncan Roy 
Published: May 2004

ABSTRACT
The p10 fusion-associated small transmembrane protein of avian reovirus induces extensive syncytium formation in transfected cells. Here we show that p10-induced cell-cell fusion is restricted by rapid degradation of the majority of newly synthesized p10. The small ectodomain of p10 targets the protein for degradation following p10 insertion into an early membrane compartment. Paradoxically, conservative amino acid substitutions in the p10 ectodomain hydrophobic patch that eliminate fusion activity also increase p10 stability. The small amount of p10 that escapes intracellular degradation accumulates at the cell surface in a relatively stable form, where it mediates cell-cell fusion as a late-stage event in the virus replication cycle. The unusual relationship between a nonstructural viral membrane fusion protein and the replication cycle of a nonenveloped virus has apparently contributed to the evolution of a novel mechanism for restricting the extent of virus-induced cell-cell fusion.
Species-Specific Tropism Determinants in the Human Immunodeficiency Virus Type 1 Capsid
Authors: Hatziioannou Theodora , Cowan Simone , von Schwedler Uta K. , Sundquist Wesley I. , Bieniasz Paul D. 
Published: May 2004

ABSTRACT
Retroviral tropism is determined in part by cellular restriction factors that block infection by targeting the incoming viral capsid. Indeed, human immunodeficiency virus type 1 (HIV-1) infection of many nonhuman primate cells is inhibited by one such factor, termed Lv1. In contrast, a restriction factor in humans, termed Ref1, does not inhibit HIV-1 infection unless nonnatural mutations are introduced into the HIV-1 capsid protein (CA). Here, we examined the infectivity of a panel of mutant HIV-1 strains carrying substitutions in the N-terminal CA domain in cells that exhibit restriction attributable to Lv1 or Ref1. Manipulation of HIV-1 CA could alter HIV-1 tropism, and several mutations were identified that increased or decreased HIV-1 infectivity in a target-cell-specific manner. Many residues that affected HIV-1 tropism were located in the three variable loops that lie on the outer surface of the modeled HIV-1 conical capsid. Some tropism determinants, including the CypA binding site, coincided with residues whose mutation conferred on HIV-1 CA the ability to saturate Ref1 in human cells. Notably, a mutation that reverses the infectivity defect in human cells induced by CypA binding site mutation inhibits recognition by Ref1. Overall, these findings demonstrate that exposed variable loops in CA and a partial CypA “coat” can modulate restriction and HIV-1 tropism and suggest a model in which the exposed surface of the incoming retroviral capsid is the target for inhibition by host cell-specific restriction factors.
Human Immunodeficiency Virus Type 1 Gag Contains a Dileucine-Like Motif That Regulates Association with Multivesicular Bodies
Authors: Lindwasser O. Wolf , Resh Marilyn D. 
Published: May 2004

ABSTRACT
Multivesicular bodies (MVBs) are cholesterol-enriched organelles formed by the endocytic pathway. The topology of vesicle formation in MVBs is identical to that of retroviral budding from the plasma membrane, and budding of human immunodeficiency virus type 1 (HIV-1) into MVBs in macrophages has recently been visualized. The Gag proteins from HIV-1, as well as many other retroviruses, contain short motifs that mediate interactions with MVBs and other endocytic components, suggesting that Gag proteins directly interface with the endocytic pathway. Here, we show that HIV-1 Gag contains an internalization signal that promotes endocytosis of a chimeric transmembrane fusion protein. Mutation of this motif within Gag strongly inhibits virus-like particle production. Moreover, wild-type Gag, but not the internalization-defective mutation, can be induced to accumulate within CD63-positive MVBs by treatment of cells with U18666A, a drug that redistributes cholesterol from the plasma membrane to MVBs. We propose that HIV-1 Gag contains a signal that promotes interaction with the cellular endocytic machinery and that the site of particle production is regulated by the subcellular distribution of cholesterol.
Respiratory Syncytial Virus (RSV) G Glycoprotein Is Not Necessary for Vaccine-Enhanced Disease Induced by Immunization with Formalin-Inactivated RSV
Authors: Johnson Teresa R. , Teng Michael N. , Collins Peter L. , Graham Barney S. 
Published: May 2004

ABSTRACTFollowing respiratory syncytial virus (RSV) challenge, mice immunized with RSV G or with formalin-inactivated RSV (FI-RSV) exhibit severe disease associated with type 2 cytokine production and pulmonary eosinophilia. This has led to the proposal that the presence of RSV G is the factor in FI-RSV that induces disease-enhancing T-cell responses. Therefore, we evaluated the role of RSV G and its immunodominant region in the induction of aberrant immune responses during FI-RSV immunization. BALB/c mice were immunized with FI preparations of wild-type (wt) RSV or recombinant RSV (rRSV) containing deletions of (i) the entire G gene, (ii) the region of the G gene encoding amino acids 187 to 197 of the immunodominant region, or (iii) the entire SH gene. After challenge, illness, RSV titers, cytokine levels, and pulmonary eosinophilia were measured. Peak RSV titers postchallenge were significantly greater in mice immunized with FI preparations of the deletion viruses than in those immunized with FI-rRSV wt, suggesting that the absence of G or SH in FI-RSV reduced its protective efficacy. Deletion of G or its epitope did not reduce illness, cytokine production, or eosinophilia relative to that in mice immunized with FI-rRSV wt. While cytokine levels and eosinophilia were similar, illness was reduced in mice immunized with SH-deleted FI-RSV. These data suggest that G-specific immune responses may be important for vaccine-induced protection and are not solely the basis for FI-RSV vaccine-enhanced illness. These data suggest that the method of RSV antigen delivery, rather than the protein composition, influences the phenotype of the induced immune responses and that RSV G should not necessarily be excluded from potential vaccine strategies.
Recombinant Sendai Virus Expressing the G Glycoprotein of Respiratory Syncytial Virus (RSV) Elicits Immune Protection against RSV
Authors: Takimoto Toru , Hurwitz Julia L. , Coleclough Chris , Prouser Cecilia , Krishnamurthy Sateesh , Zhan Xiaoyan , Boyd Kelli , Scroggs Ruth A. , Brown Brita , Nagai Yoshiyuki , Portner Allen , Slobod Karen S. 
Published: May 2004

ABSTRACT
Although RSV causes serious pediatric respiratory disease, an effective vaccine does not exist. To capture the strengths of a live virus vaccine, we have used the murine parainfluenza virus type 1 (Sendai virus [SV]) as a xenogeneic vector to deliver the G glycoprotein of RSV. It was previously shown (J. L. Hurwitz, K. F. Soike, M. Y. Sangster, A. Portner, R. E. Sealy, D. H. Dawson, and C. Coleclough, Vaccine 15:533-540, 1997) that intranasal SV protected African green monkeys from challenge with the related human parainfluenza virus type 1 (hPIV1), and SV has advanced to clinical trials as a vaccine for hPIV1 (K. S. Slobod, J. L. Shenep, J. Lujan-Zilbermann, K. Allison, B. Brown, R. A. Scroggs, A. Portner, C. Coleclough, and J. L. Hurwitz, Vaccine, in press). Recombinant SV expressing RSV G glycoprotein was prepared by using reverse genetics, and intranasal inoculation of cotton rats elicited RSV-specific antibody and elicited protection from RSV challenge. RSV G-recombinant SV is thus a promising live virus vaccine candidate for RSV.
Cleavage Inhibition of the Murine Coronavirus Spike Protein by a Furin-Like Enzyme Affects Cell-Cell but Not Virus-Cell Fusion
Authors: de Haan Cornelis A. M. , Stadler Konrad , Godeke Gert-Jan , Bosch Berend Jan , Rottier Peter J. M. 
Published: May 2004

ABSTRACT
Cleavage of the mouse hepatitis coronavirus strain A59 spike protein was blocked in a concentration-dependent manner by a peptide furin inhibitor, indicating that furin or a furin-like enzyme is responsible for this process. While cell-cell fusion was clearly affected by preventing spike protein cleavage, virus-cell fusion was not, indicating that these events have different requirements.
CD40-Associated TRAF 6 Signaling Is Required for Disease Induction in a Retrovirus-Induced Murine Immunodeficiency
Authors: Green Kathy A. , Ahonen Cory L. , Cook W. James , Green William R. 
Published: May 2004

ABSTRACTLP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy, hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not mediate disease by upregulation of CD80 or CD86. We report here that there is nonetheless a necessity for CD40 signaling competence, specifically an intact tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.
CKII Site in Epstein-Barr Virus Nuclear Protein 2 Controls Binding to hSNF5/Ini1 and Is Important for Growth Transformation
Authors: Kwiatkowski Bogaslaw , Chen Szu Yu Jenny , Schubach William H. 
Published: May 2004

ABSTRACT
Substitution mutagenesis of EBNA2 shows that its interaction with hSNF5/Ini1 involves two sites (286IPP and DQQ313), and a mutation at a CKII phosphorylation site (SS469) is essential for the interaction. An alanine substitution (SS469AA) prevents binding to EBNA2 and diminishes the growth-promotion potential of EBNA2 in the transcomplementation assay.
Human APOBEC3F Is Another Host Factor That Blocks Human Immunodeficiency Virus Type 1 Replication
Authors: Zheng Yong-Hui , Irwin Dan , Kurosu Takeshi , Tokunaga Kenzo , Sata Tetsutaro , Peterlin B. Matija 
Published: May 2004

ABSTRACT
Recently, APOBEC3G has been identified as a host factor that blocks retroviral replication. It introduces G to A hypermutations in newly synthesized minus strand viral cDNA at the step of reverse transcription in target cells. Here, we identified the human APOBEC3F protein as another host factor that blocks human immunodeficiency virus type 1 (HIV-1) replication. Similar to APOBEC3G, APOBEC3F also induced G to A hypermutations in HIV genomic DNA, and the viral Vif protein counteracted its activity. Thus, APOBEC family members might have evolved as a general defense mechanism of the body against retroviruses, retrotransposons, and other mobile genetic elements.
Parietal Lobe Lesions Disrupt Saccadic Remapping of Inhibitory Location Tagging
Authors: Sapir Ayelet , Hayes Amy , Henik Avishai , Danziger Shai , Rafal Robert 
Published: May 2004

Abstract
Maintaining a coherent percept of the visual scene while eye position continuously changes requires that saccades be accompanied by remapping of the visual environment. We studied saccadic remapping in patients with unilateral lesions in the intraparietal sulcus and healthy controls, using inhibition of return (IOR)—an inhibitory tag that enables efficient visual search. In healthy controls, IOR was found at both retinal and environmental locations of the cue, indicating that the inhibitory tag had been remapped into environmental coordinates. In contrast, right parietal patients demonstrated IOR only at the retinal location of the cue, indicating that the intraparietal sulcus is involved in remapping of the environment after eye movements to afford a stable, environmentally based reference frame. Note that patients did not show environmental IOR in either visual field. These results also suggest that this region may be the neural substrate for encoding inhibitory spatial tags in an environmentally based reference frame.
Two Visual Motion Processing Deficits in Developmental Dyslexia Associated with Different Reading Skills Deficits
Authors: Wilmer Jeremy B. , Richardson Alexandra J. , Chen Yue , Stein John F. 
Published: May 2004

Abstract
Developmental dyslexia is associated with deficits in the processing of visual motion stimuli, and some evidence suggests that these motion processing deficits are related to various reading subskills deficits. However, little is known about the mechanisms underlying such associations. This study lays a richer groundwork for exploration of such mechanisms by more comprehensively and rigorously characterizing the relationship between motion processing deficits and reading subskills deficits. Thirty-six adult participants, 19 of whom had a history of developmental dyslexia, completed a battery of visual, cognitive, and reading tests. This battery combined motion processing and reading subskills measures used across previous studies and added carefully matched visual processing control tasks. Results suggest that there are in fact two distinct motion processing deficits in developmental dyslexia, rather than one as assumed by previous research, and that each of these deficits is associated with a different type of reading subskills deficit. A deficit in detecting coherent motion is selectively associated with low accuracy on reading subskills tests, and a deficit in discriminating velocities is selectively associated with slow performance on these same tests. In addition, evidence from visual processing control tasks as well as self-reports of ADHD symptoms suggests that these motion processing deficits are specific to the domain of visual motion, and result neither from a broader visual deficit, nor from the sort of generalized attention deficit commonly comorbid with developmental dyslexia. Finally, dissociation between these two motion processing deficits suggests that they may have distinct neural and functional underpinnings. The two distinct patterns of motion processing and reading deficits demonstrated by this study may reflect separable underlying neurocognitive mechanisms of developmental dyslexia.
ERP Effects of Subject—Verb Agreement Violations in Patients with Broca's Aphasia
Authors: Wassenaar Marlies , Brown Colin M. , Hagoort Peter 
Published: May 2004

Abstract
This article presents electrophysiological data on on-line syntactic processing during auditory sentence comprehension in patients with Broca's aphasia. Event-related brain potentials (ERPs) were recorded from the scalp while subjects listened to sentences that were either syntactically correct or contained violations of subject-verb agreement. Three groups of subjects were tested: Broca patients (n = 10), nonaphasic patients with a right-hemisphere (RH) lesion (n = 5), and healthy agedmatched controls (n = 12). The healthy, control subjects showed a P600/SPS effect as response to the agreement violations. The nonaphasic patients with an RH lesion showed essentially the same pattern. The overall group of Broca patients did not show this sensitivity. However, the sensitivity was modulated by the severity of the syntactic comprehension impairment. The largest deviation from the standard P600/SPS effect was found in the patients with the relatively more severe syntactic comprehension impairment. In addition, ERPs to tones in a classical tone oddball paradigm were also recorded. Similar to the normal control subjects and RH patients, the group of Broca patients showed a P300 effect in the tone oddball condition. This indicates that aphasia in itself does not lead to a general reduction in all cognitive ERP effects. It was concluded that deviations from the standard P600/SPS effect in the Broca patients reflected difficulties with on-line maintaining of number information across clausal boundaries for establishing subject-verb agreement.
Motor Sequence Complexity and Performing Hand Produce Differential Patterns of Hemispheric Lateralization
Authors: Haaland Kathleen Y. , Elsinger Catherine L. , Mayer Andrew R. , Durgerian Sally , Rao Stephen M. 
Published: May 2004

Abstract
Studies in brain damaged patients conclude that the left hemisphere is dominant for controlling heterogeneous sequences performed by either hand, presumably due to the cognitive resources involved in planning complex sequential movements. To determine if this lateralized effect is due to asymmetries in primary sensorimotor or association cortex, whole-brain functional magnetic resonance imaging was used to measure differences in volume of activation while healthy right-handed subjects performed repetitive (simple) or heterogeneous (complex) finger sequences using the right or left hand. Advanced planning, as evidenced by reaction time to the first key press, was greater for the complex than simple sequences and for the left than right hand. In addition to the expected greater contralateral activation in the sensorimotor cortex (SMC), greater left hemisphere activation was observed for left, relative to right, hand movements in the ipsilateral left superior parietal area and for complex, relative to simple, sequences in the left premotor and parietal cortex, left thalamus, and bilateral cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the overall MR signal intensity was greater in the left than right SMC, the extent of this asymmetry did not vary with hand or complexity level. In contrast, signal intensity in the parietal and premotor cortex was greater in the left than right hemisphere and for the complex than simple sequences. Signal intensity in the caudal anterior cerebellum was greater bilaterally for the complex than simple sequences. These findings suggest that activity in the SMC is associated with execution requirements shared by the simple and complex sequences independent of their differential cognitive requirements. In contrast, consistent with data in brain damaged patients, the left dorsal premotor and parietal areas are engaged when advanced planning is required to perform complex motor sequences that require selection of different effectors and abstract organization of the sequence, regardless of the performing hand.
Old Efforts at New Uses: A Brief History of Chemurgy and the American Search for Biobased Materials
Authors: Finlay Mark R. 
Published: May 2004

SummaryThe American search for biobased and renewable raw materials has a long history of intermittent success and frustration. This article traces the history of the chemurgy movement‐a precursor to what are now sometimes called agricultural “new uses” initiatives‐from its context of the 1920s through its emergence as a political force in the mid‐1930s, when chemurgy offered a strategy for industries and governments interested in reviving the agricultural economy and reducing dependence upon foreign sources of industrial raw materials. Chemurgists put pressure upon the U.S. Department of Agriculture to devote greater attention to crop utilization research, efforts that were operational in time to make important contributions to the U.S. economy during World War II. This article devotes considerable attention to the postwar era, a period not discussed in most histories of chemurgy. The article concludes with a tentative assessment of issues that caused chemurgy to falter in the past as well as precautionary lessons for the contemporary study of biobased materials.
Comparing the Land Requirements, Energy Savings, and Greenhouse Gas Emissions Reduction of Biobased Polymers and Bioenergy
Authors: Dornburg Veronika , Lewandowski Iris , Patel Martin 
Published: May 2004

SummaryThis study compares energy savings and greenhouse gas (GHG) emission reductions of biobased polymers with those of bioenergy on a per unit of agricultural land‐use basis by extending existing life‐cycle assessment (LCA) studies. In view of policy goals to increase the energy supply from biomass and current efforts to produce biobased polymers in bulk, the amount of available land for the production of nonfood crops could become a limitation. Hence, given the prominence of energy and greenhouse issues in current environmental policy, it is desirable to include land demand in the comparison of different biomass options. Over the past few years, numerous LCA studies have been prepared for different types of bio‐based polymers, but only a few of these studies address the aspect of land use. This comparison shows that referring energy savings and GHG emission reduction of biobased polymers to a unit of agricultural land, instead of to a unit of polymer produced, leads to a different ranking of options. If land use is chosen as the basis of comparison, natural fiber composites and thermoplastic starch score better than bioenergy production from energy crops, whereas polylactides score comparably well and polyhydroxyalkaonates score worse. Additionally, including the use of agricultural residues for energy purposes improves the environmental performance of bio‐based polymers significantly. Moreover, it is very likely that higher production efficiencies will be achieved for biobased polymers in the medium term. Biobased polymers thus offer interesting opportunities to reduce the utilization of nonrenewable energy and to contribute to GHG mitigation in view of potentially scarce land resources.