394 research outputs found
Designed oligomers of cyanovirin-N show enhanced HIV neutralization
Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN_2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN_2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants
An analog to digital converter controls bistable transfer competence development of a widespread bacterial integrative and conjugative element.
Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase, which arises only in 3-5% of individual cells. The mechanisms controlling this bistable switch between non-active and transfer competent cells have long remained enigmatic. Using a variety of genetic tools and epistasis experiments in P. putida, we uncovered an 'upstream' cascade of three consecutive transcription factor-nodes, which controls transfer competence initiation. One of the uncovered transcription factors (named BisR) is representative for a new regulator family. Initiation activates a feedback loop, controlled by a second hitherto unrecognized heteromeric transcription factor named BisDC. Stochastic modelling and experimental data demonstrated the feedback loop to act as a scalable converter of unimodal (population-wide or 'analog') input to bistable (subpopulation-specific or 'digital') output. The feedback loop further enables prolonged production of BisDC, which ensures expression of the 'downstream' functions mediating ICE transfer competence in activated cells. Phylogenetic analyses showed that the ICEclc regulatory constellation with BisR and BisDC is widespread among Gamma- and Beta-proteobacteria, including various pathogenic strains, highlighting its evolutionary conservation and prime importance to control the behaviour of this wide family of conjugative elements
Human Rights and the War on Terror: Complete 2005 - 2007 Topical Research Digest
“9/11 changed everything.” Not really. In fact, there has been far more continuity than change over the past six years in both international and domestic politics. Nonetheless, human rights often have been harmed—although not by terrorism but by “the war on terror.
Bureaucracy as a Lens for Analyzing and Designing Algorithmic Systems
Scholarship on algorithms has drawn on the analogy between algorithmic systems and bureaucracies to diagnose shortcomings in algorithmic decision-making. We extend the analogy further by drawing on Michel Crozier’s theory of bureaucratic organizations to analyze the relationship between algorithmic and human decision-making power. We present algorithms as analogous to impartial bureaucratic rules for controlling action, and argue that discretionary decision-making power in algorithmic systems accumulates at locations where uncertainty about the operation of algorithms persists. This key point of our essay connects with Alkhatib and Bernstein’s theory of ’street-level algorithms’, and highlights that the role of human discretion in algorithmic systems is to accommodate uncertain situations which inflexible algorithms cannot handle. We conclude by discussing how the analysis and design of algorithmic systems could seek to identify and cultivate important sources of uncertainty, to enable the human discretionary work that enhances systemic resilience in the face of algorithmic errors.Peer reviewe
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Mock juror perceptions of child witnesses on the autism spectrum: the impact of providing diagnostic labels and information about autism
Research suggests that autistic children can provide accurate and forensically useful eyewitness evidence. However, members of a jury also rely on non-verbal behaviours when judging the credibility of a witness, and this could determine the verdict of a case. We presented mock jurors with videos (from an experimental study) of one of two child witnesses on the autism spectrum being interviewed about a mock minor crime. Results demonstrated that providing jurors with generic information about autism and/or informing them of the child’s diagnostic label differentially affected credibility ratings, but not for both children. Implications for how to present information about child witnesses with autism to a jury – highlighting the need for approaches tailored to individual children – are discussed
Viral protein targeting to the cortical endoplasmic reticulum is required for cell–cell spreading in plants
Sorting signal-mediated oligomerization and localization of the viral protein TGBp3 to curved ER tubules is essential for viral movement between cells in plants
Pervasive Hitchhiking at Coding and Regulatory Sites in Humans
Much effort and interest have focused on assessing the importance of natural
selection, particularly positive natural selection, in shaping the human genome.
Although scans for positive selection have identified candidate loci that may be
associated with positive selection in humans, such scans do not indicate whether
adaptation is frequent in general in humans. Studies based on the reasoning of
the MacDonald–Kreitman test, which, in principle, can be used to
evaluate the extent of positive selection, suggested that adaptation is
detectable in the human genome but that it is less common than in Drosophila or
Escherichia coli. Both positive and purifying natural
selection at functional sites should affect levels and patterns of polymorphism
at linked nonfunctional sites. Here, we search for these effects by analyzing
patterns of neutral polymorphism in humans in relation to the rates of
recombination, functional density, and functional divergence with chimpanzees.
We find that the levels of neutral polymorphism are lower in the regions of
lower recombination and in the regions of higher functional density or
divergence. These correlations persist after controlling for the variation in GC
content, density of simple repeats, selective constraint, mutation rate, and
depth of sequencing coverage. We argue that these results are most plausibly
explained by the effects of natural selection at functional
sites—either recurrent selective sweeps or background
selection—on the levels of linked neutral polymorphism. Natural
selection at both coding and regulatory sites appears to affect linked neutral
polymorphism, reducing neutral polymorphism by 6% genome-wide and by
11% in the gene-rich half of the human genome. These findings suggest
that the effects of natural selection at linked sites cannot be ignored in the
study of neutral human polymorphism
A cross-national examination of motivation to volunteer: religious context, national value patterns, and nonprofit regimes
Although motivation to volunteer (MTV) is one of the most frequently researched topics in the field of volunteering research, few studies have compared and explained MTV cross-nationally. Using data from the 1990 World Values Surveys, this study examines if and how specific societal characteristics are asso-ciated with self-reported motivations to volunteer, focusing on national religious context, dominant value patterns, and institutional variations in terms of welfare state regimes and characteristics of the nonprofit sector. Across all countries stud-ied, people who volunteered expressed both altruistic and self-oriented motiva-tions, but we observed important cross-national variations in the emphasis put on both motivational dimensions. Besides the influence of individual-level character-istics, we found partial evidence for a contextual understanding of motivation to volunteer. With respect to religion, we expected a beneficial relationship with al-truistic motivations. While such a positive relationship was found at the individual level, the evidence for a religious national context was ambiguous: on the one hand, no relationship was found between extensive religious networks and support for altruistic motivations; on the other, strong religious beliefs among the general population were negatively associated with both altruistic and self-interested MTV. The prevalence of a post-material value pattern did not represent a threat to feelings of altruism, and produced mixed findings concerning self-interested MTV. Finally, welfare states with lower social spending, a large nonprofit sector with little revenue from government, and an active citizenry, in terms of a high rate of volunteering, stimulated the expression of altruistic motivations
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