Binding of herpes simplex virus-1 US11 to specific RNA sequences

Herpes simplex virus-1 US11 is a RNA-binding protein with a novel RNA-binding domain. US11 has been reported to exhibit sequence- and conformation-specific RNA-binding, but the sequences and conformations important for binding are not known. US11 has also been described as a double-stranded RNA (dsRNA)-binding protein. To investigate the US11–RNA interaction, we performed in vitro selection of RNA aptamers that bind US11 from a RNA library consisting of >10(14) 80 base sequences which differ in a 30 base randomized region. US11 bound specifically to selected aptamers with an affinity of 70 nM. Analysis of 23 selected sequences revealed a strong consensus sequence. The US11 RNA-binding domain and ≤46 bases of selected RNA containing the consensus sequence were each sufficient for binding. US11 binding protected the consensus motif from hydroxyl radical cleavage. RNase digestions of a selected aptamer revealed regions of both single-stranded RNA and dsRNA. We observed that US11 bound two different dsRNAs in a sequence non-specific manner, but with lower affinity than it bound selected aptamers. The results define a relatively short specific sequence that binds US11 with high affinity and indicate that dsRNA alone does not confer high-affinity binding

Feline Cryptococcosis

Cryptococcosis is a disease common to most animals and is produced by a yeast-like fungus, Cryptococcus neoformans. The organism is round to ovid in shape, reproduces by budding and has a characteristic mucinous capsule

Misty, Spellbound and the lost Gothic of British girls’ comics.

This article is a case study of the 1970s British girls’ comics Spellbound (DC Thomson, 1976–1977) and Misty (IPC, 1978–1980). These mystery anthology comics followed the more famous American horror comics from publishers like EC Comics - but were aimed at pre-teen girls. The article situates these comics with respect to Gothic critical theory and within the wider landscape of British girls’ comics. Firstly, it closely considers and compares the structure and content of their stories with respect to theories of the terror and horror Gothic. It discovers that both comics offer similar fare, with a subversive streak that undercuts established horror archetypes. The article then looks closely at both titles’ aesthetics and their use of the page to draw comparisons. It uses comics theory and Gothic cinematic theory to demonstrate that the appearance of Misty is more strongly Gothic than the aesthetic of Spellbound. Finally, it considers a selection of stories from both comics and analyses their common themes using Gothic critical theory. It argues that both comics rework Gothic themes into new forms that are relevant to their pre-teen and teenage readers. It concludes by summarising the study’s findings and suggesting that these comics offer a “Gothic for Girls” that is part cautionary tale and part bildungsroman. This article is published as part of a collection on Gothic and horror

Patterning the geographies of organ transplantation: corporeality, generosity and justice

publication-status: PublishedThis is the author's post-print version of an article published in Transactions of the Institute of British Geographers, 2006, Vol. 31, Issue 3 pp. 257 – 271 Copyright © 2006 Institute of British Geographers / Royal Geographical Society. The definitive version is available at www3.interscience.wiley.comOrgan transplantation is now an established treatment for patients with end-stage organ failure, yet there are spatial inequalities in access to this procedure. This paper explores the uneven geographies of kidney transplantation in London, arguing that inequalities in access to organ transplantation are created through interlocking spatialities of corporeal difference, enacted through global movements of populations, national organ transplantation protocols and the internal immunological spaces of the body. The combination of these processes, operating at different scales, has produced a distinctive configuration in the embodiment of risk in relation to kidney transplants, particularly born by London's Black and Asian communities. Two ethical dimensions to this geography of organ transplantation are explored here: the ethical responsiveness to others shaping the generous practices of organ donation, and the medical practices categorizing difference through techniques of blood typing, tissue matching and the spatial organization of organ transplantation. In concluding, I argue both are critical to understanding the links between ethics and justice in the geographies of organ exchange in London. Further, I suggest geography is central to political debate about the exchange of biological material elsewhere, for it is only through tracing the intersection of ethical, corporeal and technological practices in situ that we can fully reflect on questions of justice within the developing bioeconomy

Uganda’s HIV Prevention Success: The Role of Sexual Behavior Change and the National Response. Commentary on Green et al. (2006)

The paper by Green et al. (vol. 10, this issue

Direct Visualization of Laser-Driven Electron Multiple Scattering and Tunneling Distance in Strong-Field Ionization

Using a simple model of strong-field ionization of atoms that generalizes the well-known 3-step model from 1D to 3D, we show that the experimental photoelectron angular distributions resulting from laser ionization of xenon and argon display prominent structures that correspond to electrons that pass by their parent ion more than once before strongly scattering. The shape of these structures can be associated with the specific number of times the electron is driven past its parent ion in the laser field before scattering. Furthermore, a careful analysis of the cutoff energy of the structures allows us to experimentally measure the distance between the electron and ion at the moment of tunnel ionization. This work provides new physical insight into how atoms ionize in strong laser fields and has implications for further efforts to extract atomic and molecular dynamics from strong-field physics

Organ donation, ethnicity and the negotiation of death: ethnographic insights from the UK

The introduction of end-of-life care criteria in the UK aims at standardising the processes of care at the end of life, including how medical decisions on death are communicated to the families of dying and (brain) dead patients. In the setting of the intensive care unit, these activities are routinely complicated by the imperative to secure donor organs for transplantation: where recent changes to donation services have seen the accommodation of organ donation procedures into end-of-life care routines. This has ramifications for understanding how medical decisions around death and dying are brokered with the families of potential organ donors. Drawing on an ethnographic study in England, this paper will document how communications around death get turned into a particular matter of concern for the practice of requesting organ donation from minority ethnic families. It shows how attempts to resolve differences of opinion between health professionals and families about a diagnosis of brain stem death or dying are mediated by sets of brokering practices: specifically, those termed technological, authoritative and religious brokering. These practices, we argue, not only facilitate a family’s acceptance of their relative’s death, but also serve to make possible a decision on organ donation

Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate.

Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation.We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in Pichia pastoris.The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus in vitro. Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses in vivo remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies