bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of sensory gating to mismatch negativity and self‐reported perceptual phenomena in healthy adults
Authors: Kisley Michael A. , Noecker Tara L. , Guinther Paul M. 
Published: June 2004

AbstractTo better understand the possible functional significance of electrophysiological sensory gating measures, response suppression of midlatency auditory event related potential (ERP) components was compared to the mismatch negativity (MMN) and to self‐rated indices of stimulus filtering and passive attention‐switching phenomena in an age‐restricted sample of healthy adults. P1 sensory gating, measured during a paired‐click paradigm, was correlated with MMN amplitude, measured during an acoustic oddball paradigm (intensity deviation). Also, individuals that exhibited less robust P1 suppression endorsed higher rates of “perceptual modulation” difficulties, whereas component N1 suppression was more closely related to “over‐inclusion” of irrelevant sounds into the focus of attention. These findings suggest that the ERP components investigated are not redundant, but correspond to distinct—possibly related—pre‐attentive processing systems.
Latent inhibition mediates N1 attenuation to repeating sounds
Authors: Sable Jeffrey J. , Low Kathy A. , Maclin Edward L. , Fabiani Monica , Gratton Gabriele 
Published: June 2004

AbstractSound repetition typically reduces auditory N1 amplitudes, more so at higher rates. This has been attributed to refractoriness of N1 generators. However, evidence that N1 attenuation is delayed 300–400 ms after the first occurrence of a repeated sound suggests an alternative process, such as inhibition, that requires 300–400 ms to become fully operational. We examined the N1 to trains of fixed‐interval (100, 200, 300, 400 ms) tones for evidence of effects predicted by models of refractoriness and of latent inhibition. Regardless of interval, latency of the eliciting tone from train onset determined N1 amplitudes during the first 400 ms of the train, which decreased in this window. The results show that N1 attenuation cannot be due simply to refractoriness, which would elicit the smallest N1 to the second tone. An inhibitory neural circuit can account for these and previous results, and may be important to auditory perceptual processing.
The effect of the menstrual cycle on electrophysiological and behavioral measures of memory and mood
Authors: O'Reilly Michelle A. , Cunningham Conal J. , Lawlor Brian A. , Walsh Cathal D. , Rowan Michael J. 
Published: June 2004

AbstractEvent‐related potentials (ERPs) were compared between the menses and ovulatory phase of the menstrual cycle in response to visually presented words, some of which were repeated as part of direct and indirect memory tasks. Twelve spontaneously cycling women were tested during the menses and ovulatory phases. For the direct task, participants had to discriminate between new words and those repeated after a mean of six trials. In the indirect task, subjects were required to discriminate between target and nontarget words. Some of the nontarget words were repeated after a mean of six trials. The ERP repetition effect mean amplitude was significantly greater in response to repeated words at both cycle phases but did not differ across the cycle. P300 amplitude was significantly greater during menses than the ovulatory phase. We conclude that context updating mechanisms as indexed by the P300 are sensitive to cyclic hormonal fluctuations.
Heart rate and skin conductance analysis of antecendents and consequences of decision making
Authors: Crone Eveline A. , Somsen Riek J. M. , Beek Bert Van , Van Der Molen Maurits W. 
Published: June 2004

AbstractThe current study examined the pattern of heart rate and skin conductance changes preceding risky choices and following outcome for bad, moderate, and good performers on an analogue of the Iowa gambling task (Bechara, Damasio, Damasio, & Anderson, 1994). The task required a choice between four options; two options were followed by a high reward and, unpredictably, an even higher loss (disadvantageous options) and two other options were followed by a small reward but the unpredictable loss was also small (advantageous options). Anticipatory heart rate slowing and skin conductance level were higher preceding disadvantageous relative to advantageous options, but only for good performers. In contrast, heart rate slowed and skin conductance level increased following loss relative to reward outcomes, and these changes were similar for all performance groups. These findings were interpreted to suggest that decision‐making impairments in bad performers arise from a weak somatic response generated by secondary inducers (i.e., somatic markers), rather than a weak somatic response generated by primary inducers of reward and punishment.
An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection
Authors: Sparks-Thissen Rebecca L. , Braaten Douglas C. , Kreher Scott , Speck Samuel H. , Virgin Herbert W. 
Published: June 2004

ABSTRACTCD4 T cells are important for control of infection with murine gammaherpesvirus 68 (γHV68), but it is not known whether CD4 T cells function via provision of help to other lymphocyte subsets, such as B cells and CD8 T cells, or have an independent antiviral function. Moreover, under conditions of natural infection, the CD4 T-cell response is not sufficient to eliminate infection. To determine the functional capacities of CD4 T cells under optimal or near-optimal conditions and to determine whether CD4 T cells can control γHV68 infection in the absence of CD8 T cells or B cells, we studied the effect of ovalbumin (OVA)-specific CD4 T cells on infection with a recombinant γHV68 that expresses OVA. OVA-specific CD4 T cells limited acute γHV68 replication and prolonged the life of infected T-cell receptor-transgenic RAG (DO.11.10/RAG) mice, demonstrating CD4 T-cell antiviral activity, independent of CD8 T cells and B cells. Despite CD4 T-cell-mediated control of acute infection, latent infection was established in DO.11.10/RAG mice. However, OVA-specific CD4 T cells reduced the frequency of latently infected cells both early (16 days postinfection) and late (42 days postinfection) after infection of mice containing CD8 T cells and B cells (DO.11.10 mice). These results show that OVA-specific CD4 T cells have B-cell and CD8 T-cell-independent antiviral functions in the control of acute infection and can, in the absence of preexisting CD8 T-cell or B-cell immunity, inhibit the establishment of gammaherpesvirus latency.
Regulation of Hepatitis B Virus Core Promoter by Transcription Factors HNF1 and HNF4 and the Viral X Protein
Authors: Zheng Yanyan , Li Jie , Ou Jing-hsiung 
Published: June 2004

ABSTRACT
Hepatitis B virus (HBV) core promoter contains a binding site for nuclear receptors. A natural double mutation in this binding site, which changes nucleotide (nt) 1765 from A to T and nt 1767 from G to A, selectively abolishes the binding of several nuclear receptors without affecting that of HNF4. This double mutation also creates a binding site for the transcription factor HNF1 and changes two amino acids in the overlapping X protein sequence. In this study, we have examined the roles of HNF1, HNF4, and the X protein in the regulation of the core promoter activities in Huh7 hepatoma cells. Our results indicate that HNF4 could stimulate the expression of the precore RNA and the core RNA from the core promoter of both the wild-type (WT) HBV and the double mutant, although its effect on the former was more prominent. In contrast, HNF1, which did not affect the WT core promoter, suppressed the precore RNA expression of the double mutant. Further analysis using HBV genomic constructs, with and without the ability to express the X protein, indicates that the X protein did not affect the HNF4 activity on the core promoter and affected the HNF1 activity on the core promoter of only the double mutant. Thus, our results indicate that the phenotypic differences of HBV WT and double-mutant core promoters are at least partially due to the differential activities of HNF1, HNF4, and the X protein on these two promoters.
Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages
Authors: Peters Paul J. , Bhattacharya Jayanta , Hibbitts Samantha , Dittmar Matthias T. , Simmons Graham , Bell Jeanne , Simmonds Peter , Clapham Paul R. 
Published: June 2004

ABSTRACTComplete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4+CCR5+cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.
Identification of an Antigenic Determinant on the S2 Domain of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Capable of Inducing Neutralizing Antibodies
Authors: Zhang Hong , Wang Guangwen , Li Jian , Nie Yuchun , Shi Xuanling , Lian Gewei , Wang Wei , Yin Xiaolei , Zhao Yang , Qu Xiuxia , Ding Mingxiao , Deng Hongkui 
Published: June 2004

ABSTRACT
Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.
Selection, Transmission, and Reversion of an Antigen-Processing Cytotoxic T-Lymphocyte Escape Mutation in Human Immunodeficiency Virus Type 1 Infection
Authors: Allen Todd M. , Altfeld Marcus , Yu Xu G. , O'Sullivan Kristin M. , Lichterfeld Mathias , Le Gall Sylvie , John Mina , Mothe Bianca R. , Lee Paul K. , Kalife Elizabeth T. , Cohen Daniel E. , Freedberg Kenneth A. , Strick Daryld A. , Johnston Mary N. , Sette Alessandro , Rosenberg Eric S. , Mallal Simon A. , Goulder Philip J. R. , Brander Christian , Walker Bruce D. 
Published: June 2004

ABSTRACT

Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8
+
T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.
Selection Pressure-Driven Evolution of the Epstein-Barr Virus-Encoded Oncogene LMP1 in Virus Isolates from Southeast Asia
Authors: Burrows Jacqueline M. , Bromham Lindell , Woolfit Megan , Piganeau Gwenaël , Tellam Judy , Connolly Geoff , Webb Natasha , Poulsen Leith , Cooper Leanne , Burrows Scott R. , Moss Denis J. , Haryana Sofia M. , Ng Mun , Nicholls John M. , Khanna Rajiv 
Published: June 2004

ABSTRACT

The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene,
LMP1
, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that
LMP1
sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.
Nuclear Sequestration of Cellular Chaperone and Proteasomal Machinery during Herpes Simplex Virus Type 1 Infection
Authors: Burch April D. , Weller Sandra K. 
Published: June 2004

ABSTRACT
Herpes simplex virus type 1 (HSV-1) encodes a portal protein that forms a large oligomeric structure believed to provide the conduit for DNA entry and exit from the capsid. Chaperone proteins often facilitate the folding and multimerization of such complex structures. In this report, we show that cellular chaperone proteins, components of the 26S proteasome, and ubiquitin-conjugated proteins are sequestered in discrete foci in the nucleus of the infected cell. The immediate-early viral protein ICP0 was shown to be necessary to establish these foci at early times during infection and sufficient to redistribute chaperone molecules in transfected cells. Furthermore, we found that not only is the portal protein, UL6, localized to these sites during infection, but it is also a substrate for ubiquitin modification. Our results suggest that HSV-1 has evolved an elegant mechanism for facilitating protein quality control at specialized foci within the nucleus.
Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection
Authors: Radhakrishnan Sujatha , Gordon Jennifer , Del Valle Luis , Cui Jianqi , Khalili Kamel 
Published: June 2004

ABSTRACT
The human polyomavirus, JC virus (JCV), encodes two regulatory proteins at the early (T antigen) and the late (agnoprotein) phases of viral infection whose activities are important for the production of the viral capsid proteins and the dysregulation of several host factors and their functions. For this study, we designed and utilized an RNA interference strategy via small interfering RNAs (siRNAs) that targeted the expression of T antigen and agnoprotein in human astrocytic cells. The treatment of cells with specific siRNA oligonucleotides targeting a conserved region of T antigen, nucleotides (nt) 4256 to 4276 (Mad-1 strain), caused a >50% decline in the level of T antigen and in its transcriptional activity upon the viral capsid genes as well as a significant reduction in viral DNA replication in infected cells. Similarly, a single siRNA that aimed at nt 324 to 342 of agnoprotein noticeably reduced early and late viral protein production. A combined treatment of the infected cells with both T-antigen and agnoprotein siRNAs completely abolished viral capsid protein production, indicative of the ability of the siRNAs to effectively halt multiplication of the virus in infected cells. These observations provide a new avenue for possible treatments of patients with the JCV-induced demyelinating disease progressive multifocal leukoencephalopathy.
“Sleeping Beauty”: Quiescence inSaccharomyces cerevisiae
Authors: Gray Joseph V. , Petsko Gregory A. , Johnston Gerald C. , Ringe Dagmar , Singer Richard A. , Werner-Washburne Margaret 
Published: June 2004

SUMMARYThe cells of organisms as diverse as bacteria and humans can enter stable, nonproliferating quiescent states. Quiescent cells of eukaryotic and prokaryotic microorganisms can survive for long periods without nutrients. This alternative state of cells is still poorly understood, yet much benefit is to be gained by understanding it both scientifically and with reference to human health. Here, we review our knowledge of one “model” quiescent cell population, in cultures of yeast grown to stationary phase in rich media. We outline the importance of understanding quiescence, summarize the properties of quiescent yeast cells, and clarify some definitions of the state. We propose that the processes by which a cell enters into, maintains viability in, and exits from quiescence are best viewed as an environmentally triggered cycle: the cell quiescence cycle. We synthesize what is known about the mechanisms by which yeast cells enter into quiescence, including the possible roles of the protein kinase A, TOR, protein kinase C, and Snf1p pathways. We also discuss selected mechanisms by which quiescent cells maintain viability, including metabolism, protein modification, and redox homeostasis. Finally, we outline what is known about the process by which cells exit from quiescence when nutrients again become available.
Subphysiologic Apolipoprotein E (ApoE) Plasma Levels Inhibit Neointimal Formation After Arterial Injury in ApoE-Deficient Mice
Authors: Wientgen Hilke , Thorngate Fayanne E. , Omerhodzic Sabina , Rolnitzky Linda , Fallon John T. , Williams David L. , Fisher Edward A. 
Published: June 2004

Objective—Apolipoprotein E (apoE) reduces mouse atherosclerosis progression independent of plasma cholesterol level effects. A mouse artery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation.Methods and Results—ApoE-deficient (apoE−/−), wild-type (WT), and transgenic apoE−/− mice (secreting apoE at different levels from adrenal glands) underwent femoral artery injury. Mice with low expression of plasma apoE (0.1% of WT) had cholesterol levels approximately half those of apoE−/− littermates (but still ≈6× >WT). Mice with higher expression (HE; 2% to 3% of WT) of plasma apoE had cholesterol levels approximately twice those of WT. Injured WT mouse (versus apoE−/−) arteries had a smaller mean intima-to-media (I/M) ratio (0.87 versus 1.96;P<0.05). HE mice tended to have lower mean I/M ratios (1.3;P>0.05 versus apoE−/− mice). Multiple regression analysis indicated that apoE levels were significantly associated with reduced I/M ratios, but plasma cholesterol levels were not, before or after adjusting for apoE. In addition, foam cell content of the neointima and media of injured arteries, a negative prognostic indicator in postangioplasty human lesions, was inversely related to plasma apoE levels.Conclusions—Similar to its effects on atherosclerosis progression, in a mouse model of restenosis, a subphysiological level of apoE was associated with beneficial effects on lesion size/composition.