bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monkeypox-Induced Immunity and Failure of Childhood Smallpox Vaccination To Provide Complete Protection
Authors: Karem Kevin L. , Reynolds Mary , Hughes Christine , Braden Zach , Nigam Pragati , Crotty Shane , Glidewell John , Ahmed Rafi , Amara Rama , Damon Inger K. 
Published: August 2007

ABSTRACT
Following the U.S. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. Orthopoxvirus-specific immunoglobulin G (IgG), IgM, CD4, CD8, and B-cell responses were measured at ∼7 to 14 weeks and 1 year postexposure. Associations between immune responses, smallpox vaccination, and epidemiologic and clinical data were assessed. Participants were categorized into four groups: (i) vaccinated cases, (ii) unvaccinated cases, (iii) vaccinated contacts, and (iv) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific IgM, IgG, CD4, CD8, and B-cell responses. Antiorthopoxvirus immune responses consistent with infection were observed in some contacts who did not develop monkeypox. Vaccinated contacts maintained low levels of antiorthopoxvirus IgG, CD4, and B-cell responses, with most lacking IgM or CD8 responses. Preexisting immunity, assessed by high antiorthopoxvirus IgG levels and childhood smallpox vaccination, was associated (in a nonsignificant manner) with mild disease. Vaccination failed to provide complete protection against human monkeypox. Previously vaccinated monkeypox cases manifested antiorthopoxvirus IgM and changes in antiorthopoxvirus IgG, CD4, CD8, or B-cell responses as markers of recent infection. Antiorthopoxvirus IgM and CD8 responses occurred most frequently in monkeypox cases (vaccinated and unvaccinated), with IgG, CD4, and memory B-cell responses indicative of vaccine-derived immunity. Immune markers provided evidence of asymptomatic infections in some vaccinated, as well as unvaccinated, individuals.
Down-Regulation of the Trypanosomatid Signal Recognition Particle Affects the Biogenesis of Polytopic Membrane Proteins but Not of Signal Peptide-Containing Proteins
Authors: Lustig Yaniv , Vagima Yaron , Goldshmidt Hanoch , Erlanger Avigail , Ozeri Vered , Vince James , McConville Malcolm J. , Dwyer Dennis M. , Landfear Scott M. , Michaeli Shulamit 
Published: August 2007

ABSTRACT

Protein translocation across the endoplasmic reticulum is mediated by the signal recognition particle (SRP). In this study, the SRP pathway in trypanosomatids was down-regulated by two approaches: RNA interference (RNAi) silencing of genes encoding SRP proteins in
Trypanosoma brucei
and overexpression of dominant-negative mutants of 7SL RNA in
Leptomonas collosoma
. The biogenesis of both signal peptide-containing proteins and polytopic membrane proteins was examined using endogenous and green fluorescent protein-fused proteins. RNAi silencing of SRP54 or SRP68 in
T. brucei
resulted in reduced levels of polytopic membrane proteins, but no effect on the level of signal peptide-containing proteins was observed. When SRP deficiency was achieved in
L. collosoma
by overexpression of dominant-negative mutated 7SL RNA, a major effect was observed on polytopic membrane proteins but not on signal peptide-containing proteins. This study included two trypanosomatid species, tested various protein substrates, and induced depletion of the SRP pathway by affecting either the levels of SRP binding proteins or that of SRP RNA. Our results demonstrate that, as in bacteria but in contrast to mammalian cells, the trypanosome SRP is mostly essential for the biogenesis of membrane proteins.
Comparison of Single- and Multilocus Sequence Typing and Toxin Gene Profiling for Characterization of Methicillin-Resistant
Staphylococcus aureus
Authors: Cai Yongwei , Kong Fanrong , Wang Qinning , Tong Zhongsheng , Sintchenko Vitali , Zeng Xianyu , Gilbert Gwendolyn L. 
Published: August 2007

ABSTRACT

We compared three novel methicillin-resistant
Staphylococcus aureus
(MRSA) genotyping methods with multilocus sequence typing (MLST) and
spa
typing to assess their utility for routine strain typing. The new methods were
femA
and
nuc
sequence typing and toxin gene profiling (TGP), using a multiplex-PCR-based reverse line blot assay to detect 13 pyrogenic superantigen and exfoliative toxin genes. Forty-two well-characterized MRSA strains, representing 15 MLSTs or 9 clonal clusters (CCs), were genotyped by all methods. Twenty-two
spa
, nine
femA
, and seven
nuc
sequence types were identified. The
femA
sequence types correlated exactly with CCs;
nuc
sequences types were less discriminatory but generally correlated well with
femA
types and CCs. Ten isolates contained none of 13 toxin genes; TGPs of the remainder comprised 1 to 5 toxin genes. The combination of
spa
typing and TGPs identified 26 genotypes among the 42 strains studied. A combination of two or three rapid, inexpensive genotyping methods could potentially provide rapid MRSA strain typing as well as useful information about clonal origin and virulence.
Specific Asparagine-Linked Glycosylation Sites Are Critical for DC-SIGN- and L-SIGN-Mediated Severe Acute Respiratory Syndrome Coronavirus Entry
Authors: Han Dong P. , Lohani Motashim , Cho Michael W. 
Published: August 2007

ABSTRACT
Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV) designated SARS-CoV. The virus utilizes angiotensin-converting enzyme 2 (ACE2) as the primary receptor. Although the idea is less clear and somewhat controversial, SARS-CoV is thought to use C-type lectins DC-SIGN and/or L-SIGN (collectively referred to as DC/L-SIGN) as alternative receptors or as enhancer factors that facilitate ACE2-mediated virus infection. In this study, the function of DC/L-SIGN in SARS-CoV infection was examined in detail. The results of our study clearly demonstrate that both proteins serve as receptors independently of ACE2 and that there is a minimal level of synergy between DC/L-SIGN and ACE2. As expected, glycans on spike (S) glycoprotein are important for DC/L-SIGN-mediated virus infection. Site-directed mutagenesis analyses have identified seven glycosylation sites on the S protein critical for DC/L-SIGN-mediated virus entry. They include asparagine residues at amino acid positions 109, 118, 119, 158, 227, 589, and 699, which are distinct from residues of the ACE2-binding domain (amino acids 318 to 510). Amino acid sequence analyses of S proteins encoded by viruses isolated from animals and humans suggest that glycosylation sites N227 and N699 have facilitated zoonotic transmission.
Cooperation of NF-κB2/p100 Activation and the PDZ Domain Binding Motif Signal in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax1 but Not HTLV-2 Tax2 Is Crucial for Interleukin-2-Independent Growth Transformation of a T-Cell Line
Authors: Higuchi Masaya , Tsubata Chikako , Kondo Rie , Yoshida Sakiko , Takahashi Masahiko , Oie Masayasu , Tanaka Yuetsu , Mahieux Renaud , Matsuoka Masao , Fujii Masahiro 
Published: August 2007

ABSTRACT
Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia, and the distinct pathogenicity of these two closely related viruses is thought to stem from the distinct biological functions of the respective transforming proteins, HTLV-1 Tax1 and HTLV-2 Tax2. In this study, we demonstrate that Tax1 but not Tax2 interacts with NF-κB2/p100 and activates it by inducing the cleavage of p100 into the active transcription factor p52. Using RNA interference methods, we further show that NF-κB2/p100 is required for the transformation induced by Tax1, as determined by the ability to convert a T-cell line (CTLL-2) from interleukin-2 (IL-2)-dependent to -independent growth. While Tax2 shows a reduced transforming activity relative to Tax1, Tax2 fused with a PDZ domain binding motif (PBM) present only in Tax1 shows transforming activity equivalent to that of Tax1 in CTLL-2 cells expressing an inducer of p52 processing. These results reveal that the activation of NF-κB2/p100 plays a crucial role in the Tax1-mediated transformation of T cells and that NF-κB2/p100 activation and PBM function are both responsible for the augmented transforming activity of Tax1 relative to Tax2, thus suggesting that these Tax1-specific functions play crucial roles in HTLV-1 leukemogenesis.
Analysis of Human Cell Heterokaryons Demonstrates that Target Cell Restriction of Cyclosporine-Resistant Human Immunodeficiency Virus Type 1 Mutants Is Genetically Dominant
Authors: Song Chisu , Aiken Christopher 
Published: August 2007

ABSTRACTThe host cell protein cyclophilin A (CypA) binds to CA of human immunodeficiency virus type 1 (HIV-1) and promotes HIV-1 infection of target cells. Disruption of the CypA-CA interaction, either by mutation of the CA residue at G89 or P90 or with the immunosuppressive drug cyclosporine (CsA), reduces HIV-1 infection. Two CA mutants, A92E and G94D, previously were identified by selection for growth of wild-type HIV-1 in cultures of CD4+HeLa cell cultures containing CsA. Interestingly, infection of some cell lines by these mutants is enhanced in the presence of CsA, while in other cell lines these mutants are minimally affected by the drug. Little is known about this cell-dependent phenotype of the A92E and G94D mutants, except that it is not dependent on expression of the host factor TRIM5α. Here, we show that infection by the A92E and G94D mutants is restricted at an early postentry stage of the HIV-1 life cycle. Analysis of heterokaryons between CsA-dependent HeLa-P4 cells and CsA-independent 293T cells indicated that the CsA-dependent infection by A92E and G94D mutants is due to a dominant cellular restriction. We also show that addition of CsA to target cells inhibits infection by wild-type HIV-1 prior to reverse transcription. Collectively, these results support the existence of a cell-specific human cellular factor capable of restricting HIV-1 at an early postentry step by a CypA-dependent mechanism.
Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain
Authors: Wathelet Marc G. , Orr Melissa , Frieman Matthew B. , Baric Ralph S. 
Published: August 2007

ABSTRACTThe severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV nonstructural protein 1 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1 while having little effect on those of STAT2, JAK1, and TYK2. We engineered an attenuated mutant of nsp1 in SARS-CoV through reverse genetics, and the resulting mutant virus was viable and replicated as efficiently as wild-type virus in cells with a defective IFN response. However, mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nsp1 is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.
Differential Effects of Mutations in NS4B on West Nile Virus Replication and Inhibition of Interferon Signaling
Authors: Evans Jared D. , Seeger Christoph 
Published: August 2007

ABSTRACT
West Nile virus (WNV) is a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis. Previously, we demonstrated that replication of WNV inhibits the interferon (IFN) signal transduction pathway by preventing the accumulation of phosphorylated Janus kinase 1 (JAK1) and tyrosine kinase 2 (Tyk2) (J. T. Guo et al., J. Virol. 79:1343-1350, 2005). Through a genetic analysis, we have now identified a determinant on the nonstructural protein 4B (NS4B) that controls IFN resistance in HeLa cells expressing subgenomic WNV replicons lacking the structural genes. However, in the context of infectious genomes, the same determinant did not influence IFN signaling. Thus, our results indicate that NS4B may be sufficient to inhibit the IFN response in replicon cells and suggest a role for structural genes, or as yet unknown interactions, in the inhibition of the IFN signaling pathway during WNV infections.
Differential Virus Replication, Cytokine Production, and Antigen-Presenting Function by Microglia from Susceptible and Resistant Mice Infected with Theiler's Virus
Authors: Jin Young-Hee , Mohindru Mani , Kang Min H. , Fuller Alyson C. , Kang Bongsu , Gallo Daniel , Kim Byung S. 
Published: August 2007

ABSTRACTInfection with Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) causes an immune system-mediated demyelinating disease similar to human multiple sclerosis in susceptible but not resistant strains of mice. To understand the underlying mechanisms of differential susceptibility, we analyzed viral replication, cytokine production, and costimulatory molecule expression levels in microglia and macrophages in the CNS of virus-infected resistant C57BL/6 (B6) and susceptible SJL/J (SJL) mice. Our results indicated that message levels of TMEV, tumor necrosis factor alpha, beta interferon, and interleukin-6 were consistently higher in microglia from virus-infected SJL mice than in those from B6 mice. However, the levels of costimulatory molecule expression, as well as the ability to stimulate allogeneic T cells, were significantly lower in TMEV-infected SJL mice than in B6 mice. In addition, microglia from uninfected naïve mice displayed differential viral replication, T-cell stimulation, and cytokine production, similar to those of microglia from infected mice. These results strongly suggest that different levels of intrinsic susceptibility to TMEV infection, cytokine production, and T-cell activation ability by microglia contribute to the levels of viral persistence and antiviral T-cell responses in the CNS, which are critical for the differential susceptibility to TMEV-induced demyelinating disease between SJL and B6 mice.
Adeno-Associated Viruses Can Induce Phosphorylation of eIF2α via PKR Activation, Which Can Be Overcome by Helper Adenovirus Type 5 Virus-Associated RNA
Authors: Nayak Ramnath , Pintel David J. 
Published: August 2007

ABSTRACT

Mutants of adenovirus type 5 (Ad5) virus-associated RNA I deficient in inhibiting the activation and subsequent phosphorylation of protein kinase R (PKR) could neither function as helpers for adeno-associated virus type 5 (AAV5) replication nor enhance AAV5 protein accumulation in either the presence or absence of Ad5 E4Orf6 and E2a. Furthermore, a short region of the AAV5 capsid gene RNA leader sequence surrounding the AUG of VP1 could induce the phosphorylation of eIF2α. Both short interfering RNA directed against PKR and the addition of the herpes simplex virus ICP34.5 protein enhanced the accumulation of AAV5 capsid protein in the presence of the AAV5 capsid gene PKR-inducing element, suggesting that VA RNA acted to overcome direct AAV5-induced activation of PKR that led to the phosphorylation of eIF2α. The expression of both the closely related goat-derived AAV and the prototype AAV2 capsid gene transcription units also induced the phosphorylation of eIF2α, suggesting that the induction of the PKR/eIF2α cellular response may be a previously unrecognized general feature of at least the
Dependovirus
genus of the
Parvovirinae
.
Experimental Transmission ofPospiviroidPopulations to Weed Species Characteristic of Potato and Hop Fields
Authors: Matoušek J. , Orctová L. , Ptáček J. , Patzak J. , Dědič P. , Steger G. , Riesner D. 
Published: August 2007

ABSTRACTWeed plants characteristic for potato and hop fields have not been considered in the past as potential hosts that could transmit and lead to spreading of potato spindle tuber (PSTVd) and hop stunt (HSVd) viroids, respectively. To gain insight into this problem, we biolistically inoculated these weed plants with viroid populations either as RNA or as cDNA. New potential viroid host species, collected in central Europe, were discovered. From 12 weed species characteristic for potato fields, high viroid levels, detectable by molecular hybridization, were maintained after both RNA and DNA transfers inChamomilla reculitaandAnthemis arvensis. Low viroid levels, detectable by reverse transcription-PCR (RT-PCR) only, were maintained after plant inoculations with cDNA inVeronica argensisandAmaranthus retroflexus. In these two species PSTVd concentrations were 105and 103times, respectively, lower than in tomato as estimated by real-time PCR. From 14 weeds characteristic for hop fields, high HSVd levels were detected inGalinsoga ciliataafter both RNA and DNA transfers. HSVd was found, however, not to be transmissible by seeds of this weed species. Traces of HSVd were detectable by RT-PCR in HSVd-cDNA-inoculatedAmaranthus retroflexus. Characteristic monomeric (+)-circular and linear viroid RNAs were present in extracts from weed species propagating viroids to high levels, indicating regular replication, processing, and circularization of viroid RNA in these weed species. Sequence analyses of PSTVd progenies propagated inC. reculitaandA. arvensisshowed a wide spectrum of variants related to various strains, from mild to lethal variants; the sequence variants isolated fromA. retroflexusandV. argensisexhibited similarity or identity to the superlethal AS1 viroid variant. All HSVd clones fromG. ciliatacorresponded to a HSVdg variant, which is strongly pathogenic for European hops.
The p122 Subunit of
Tobacco Mosaic Virus
Replicase Is a Potent Silencing Suppressor and Compromises both Small Interfering RNA- and MicroRNA-Mediated Pathways
Authors: Csorba Tibor , Bovi Aurelie , Dalmay Tamás , Burgyán József 
Published: August 2007

ABSTRACT

One of the functions of RNA silencing in plants is to defend against molecular parasites, such as viruses, retrotransposons, and transgenes. Plant viruses are inducers, as well as targets, of RNA silencing-based antiviral defense. Replication intermediates or folded viral RNAs activate RNA silencing, generating small interfering RNAs (siRNAs), which are the key players in the antiviral response. Viruses are able to counteract RNA silencing by expressing silencing-suppressor proteins. It has been shown that many of the identified silencing-suppressor proteins bind long double-stranded RNA or siRNAs and thereby prevent assembly of the silencing effector complexes. In this study, we show that the 122-kDa replicase subunit (p122) of crucifer-infecting
Tobacco mosaic virus
(cr-TMV) is a potent silencing-suppressor protein. We found that the p122 protein preferentially binds to double-stranded 21-nucleotide (nt) siRNA and microRNA (miRNA) intermediates with 2-nt 3′ overhangs inhibiting the incorporation of siRNA and miRNA into silencing-related complexes (e.g., RNA-induced silencing complex [RISC]) both in vitro and in planta but cannot interfere with previously programmed RISCs. In addition, our results also suggest that the virus infection and/or sequestration of the siRNA and miRNA molecules by p122 enhances miRNA accumulation despite preventing its methylation. However, the p122 silencing suppressor does not prevent the methylation of certain miRNAs in
hst-15
mutants, in which the nuclear export of miRNAs is compromised.
Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection
Authors: Noueiry Amine O. , Olivo Paul D. , Slomczynska Urszula , Zhou Yi , Buscher Ben , Geiss Brian , Engle Michael , Roth Robert M. , Chung Kyung Min , Samuel Melanie , Diamond Michael S. 
Published: August 2007

ABSTRACT
West Nile virus (WNV) has spread throughout the United States and Canada and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to acute flaccid paralysis and lethal encephalitis. No therapy or vaccine is currently approved for use in humans. Using high-throughput screening assays that included a luciferase expressing WNV subgenomic replicon and an NS1 capture enzyme-linked immunosorbent assay, we evaluated a chemical library of over 80,000 compounds for their capacity to inhibit WNV replication. We identified 10 compounds with strong inhibitory activity against genetically diverse WNV and Kunjin virus isolates. Many of the inhibitory compounds belonged to a chemical family of secondary sulfonamides and have not been described previously to inhibit WNV or other related or unrelated viruses. Several of these compounds inhibited WNV infection in the submicromolar range, had selectivity indices of greater than 10, and inhibited replication of other flaviviruses, including dengue and yellow fever viruses. One of the most promising compounds, AP30451, specifically blocked translation of a yellow fever virus replicon but not a Sindbis virus replicon or an internal ribosome entry site containing mRNA. Overall, these compounds comprise a novel class of promising inhibitors for therapy against WNV and other flavivirus infections in humans.
Insanity Proceedings and Black-White State Hospital Admission Rate Differences
Authors: See Joel 
Published: August 2007

THIS study attempted to determine if the higher state hospital admission rates of blacks are due to greater proportions of blacks being adjudicated incompetent at county insanity hearings. The records of 2,264 cases from 12 Florida counties in 1969 and observations and interviews in the county courts were used to answer this question. With the exception of a slight difference in middle-sized counties, the higher rates of state hospital admission were found to be due to initial differences in petitioning to the court rather than to adjudication differences. The lack of difference is due to the fact that the proportion competent, when refined, proves to be very small for both blacks and whites, thus allowing for little variation by ethnicity. The operation of a racial stereotype was, however, demonstrated in a detailed analysis of one large county. The literature on state mental hospital admissions is replete with examples of higher rates for blacks when comparisons are made with whites (see, for example, 6, 8, 1). In fact, a recent review of such work concluded that blacks are often overrepresented at admission by ratios as high as 2: 1 (3). There has been little research, however, on the structural factors responsible for this pattern. This study asks if these differences occur because blacks are more likey than whites to be declared incompetent at county insanity hearings.
Wilhelm Dilthey Forerunner of Humanist Social Thought
Authors: Brown Richard H. 
Published: August 2007

HUMANIST sociology is as a meadow in the forest of positivist science. Much of this space was cleared by Wilhelm Dilthey, not only through his attack on the fundamental assumptions of positivism, but also through his formulation of a critical method by which the works of free human consciousness could be understood. The first tenet of positivsm is that the world is made up of "out there" objectively knowable "facts." Dilthey undercut this notion by asserting that the subject matter of the human studies was not mere "facts" of nature, but rather objectified expressions and the human mind. The second central assumption of positivism is that these "facts" are explainable or determined by general casual laws. In contrast, Dilthey asserted that, while we can explain the natural world, human action must be understood through an interpretive rather than a casual logic. In demonstrating and specifically describing such an interpretive procedure, Dilthey provided an epistemological and methodological grounding for a humanistic science of man.