467 research outputs found

    Décoll/age. bulletin aktueller ideen: a manual for navigating the interstitial spaces between surviving and living

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    This article focuses on the first issue of décoll/age, a Fluxus-affiliated magazine edited by West German artist Wolf Vostell. Paying particular attention to the title – and conceptual guiding principle – of the magazine, I examine how the first issue traces the correspondence between décollage, as an emancipatory act of participation in the public sphere, and the intermediary, ‘do-it-yourself’ aesthetics of Fluxus. I argue that décoll/age 1 is emphatically geared to the ‘unskilled’ reader, and consolidates the idea of the deliberately deskilled artist devoted to the democratization or even ‘collectivisation’ of cultural production. Drawing upon the content of the magazine, I examine the ways in which Fluxus artists in décoll/age developed methods of performative identification with their readers through strategies of deskilling and argue that the issue acts as though a ‘manual’ for the absurd choreography of Cold War life

    All-or-none switching of transcriptional activity on single DNA molecules caused by a discrete conformational transition

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    Recently, it has been confirmed that long duplex DNA molecules with sizes larger than several tens of kilo-base pairs (kbp), exhibit a discrete conformational transition from an elongated coil state to a compact globule state upon the addition of various kinds of chemical species that usually induce DNA condensation. In this study, we performed a single-molecule observation on a large DNA, Lambda ZAP II DNA (ca. 41 kbp), in a solution containing RNA polymerase and substrates along with spermine, a tetravalent cation, at different concentrations, by use of fluorescence staining of both DNA and RNA. We found that transcription, or RNA production, is completely inhibited in the compact state, but is actively performed in the unfolded coil state. Such an all-or-none effect on transcriptional activity induced by the discrete conformational transition of single DNA molecules is discussed in relation to the mechanism of the regulation of large-scale genetic activity.Comment: 14 pages, 2 figure

    Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

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    Environmental enteric dysfunction (EED) refers to a subclinical disorder of intestinal function common in tropical countries and in settings of poverty and economic disadvantage. The enteropathy that underlies this syndrome is characterized by mucosal inflammation and villus blunting mediated by T cell activation. Epithelial cell disruption and microbial translocation drive systemic inflammation. EED in young children is associated geographically with growth failure, malnutrition, and greatly impaired responses to oral vaccines, notably rotavirus and poliovirus vaccines. In this review, we describe the pathophysiology of EED and examine the evidence linking EED and oral vaccine failure. This evidence is far from conclusive. Although our understanding of EED is still sketchy, there is limited evidence of disturbed innate immunity, B cell disturbances including aggregation into lymphoid follicles, and autoantibody generation. Pathways of T cell activation and the possibility of dendritic cell anergy, which could help explain oral vaccine failure, require further work

    Epithelial abnormalities in the small intestine of Zambian children with stunting

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    BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy. RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE. CONCLUSION: Epithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation

    Genetic Characterization of H3N2 Influenza Viruses Isolated from Pigs in North America, 1977–1999: Evidence for Wholly Human and Reassortant Virus Genotypes

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    Since 1998, H3N2 viruses have caused epizootics of respiratory disease in pigs throughout the major swine production regions of the U.S. These outbreaks are remarkable because swine influenza in North America had previously been caused almost exclusively by H1N1 viruses. We sequenced the full-length protein coding regions of all eight RNA segments from four H3N2 viruses that we isolated from pigs in the Midwestern U.S. between March 1998 and March 1999, as well as from H3N2 viruses recovered from a piglet in Canada in January 1997 and from a pig in Colorado in 1977. Phylogenetic analyses demonstrated that the 1977 Colorado and 1997 Ontario isolates are wholly human influenza viruses. However, the viruses isolated since 1998 from pigs in the Midwestern U.S. are reassortant viruses containing hemagglutinin, neuraminidase and PB1 polymerase genes from human influenza viruses, matrix, non-structural and nucleoprotein genes from classical swine viruses, and PA and PB2 polymerase genes from avian viruses. The HA proteins of the Midwestern reassortant swine viruses can be differentiated from those of the 1995 lineage of human H3 viruses by 12 amino acid mutations in HA1. In contrast, the Sw:ONT:97 virus, which did not spread from pig-to-pig, lacks 11 of these changes

    Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection

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    AbstractGiven the lethality of H5N1 avian influenza viruses (AIV) and the recurring spread from poultry to humans, an effective vaccine against H5N1 viruses may be needed to prevent a pandemic. We generated experimental vaccine vectors based on recombinant vesicular stomatitis virus (VSV) expressing the H5 hemagglutinin (HA) from an H5N1 virus isolated in 1997. The HA gene was expressed either from an attenuated wild-type VSV vector or from a single-cycle vector containing a deletion of the VSV G gene. We found that all of the vectors induced potent neutralizing antibody titers against the homologous and antigenically heterologous H5N1 viruses isolated in 2004 and 2005. Vaccination of mice with any combination of prime or prime/boost vectors provided long-lasting protection (>7 months) against challenge with AIV, even in animals receiving a single dose of single-cycle vaccine. Our data indicate that these recombinants are promising vaccine candidates for pandemic influenza

    DNA Vaccine Expressing Conserved Influenza Virus Proteins Protective Against H5N1 Challenge Infection in Mice

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    Influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. If an unexpected strain, as in the 1997 H5N1 Hong Kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. Therefore, strategies based on conserved influenza antigens should be explored. We studied DNA vaccination in mice with plasmids expressing conserved nucleoprotein (NP) and matrix (M) from an H1N1 virus. After vaccination, mice were challenged with A/H5N1 viruses of low, intermediate, and high lethality. A/NP+A/M DNA vaccination reduced replication of A/Hong Kong/486/97 (HK/486), a nonlethal H5N1 strain, and protected against lethal challenge with more virulent A/Hong Kong/156/97 (HK/156). After HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone protected poorly against this highly virulent strain. In the absence of antigenically matched hemagglutinin-based vaccines, DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus

    Mirrorless lasing: a theoretical perspective

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    Mirrorless lasing has been a topic of particular interest for about a decade due to promising new horizons for quantum science and applications. In this work, we review first-principles theory that describes this phenomenon, and discuss degenerate mirrorless lasing in a vapor of Rb atoms, the mechanisms of amplification of light generated in the medium with population inversion between magnetic sublevels within the D2D_2 line, and challenges associated with experimental realization

    Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration

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    Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening

    Traditional circumcision during manhood initiation rituals in the Eastern Cape, South Africa: a pre-post intervention evaluation

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    <p>Abstract</p> <p>Background</p> <p>Circumcisions undertaken in non-clinical settings can have significant risks of serious adverse events, including death. The aim of this study was to test an intervention for safe traditional circumcision in the context of initiation into manhood among the Xhosa, Eastern Cape, South Africa.</p> <p>Methods</p> <p>Traditional surgeons and nurses registered with the health department were trained over five days on ten modules including safe circumcision, infection control, anatomy, post-operative care, detection and early management of complications and sexual health education. Initiates from initiation schools of the trained surgeons and nurses were examined and interviewed on 2<sup>nd</sup>, 4<sup>th</sup>, 7<sup>th </sup>and 14<sup>th </sup>day after circumcision.</p> <p>Results</p> <p>From 192 initiates physically examined at the 14th day after circumcision by a trained clinical nurse high rates of complications were found: 40 (20.8%) had mild delayed wound healing, 31 (16.2%) had a mild wound infection, 22 (10.5%) mild pain and 20 (10.4%) had insufficient skin removed. Most traditional surgeons and nurses wore gloves during operation and care but did not use the recommended circumcision instrument. Only 12% of the initiates were circumcised before their sexual debut and they reported a great deal of sexual risk behaviour.</p> <p>Conclusion</p> <p>Findings show weak support for scaling up traditional male circumcision.</p
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