The DNA-binding domain of human papillomavirus type 18 E1. Crystal structure, dimerization, and DNA binding

High risk types of human papillomavirus, such as type 18 (HPV-18), cause cervical carcinoma, one of the most frequent causes of cancer death in women worldwide. DNA replication is one of the central processes in viral maintenance, and the machinery involved is an excellent target for the design of antiviral therapy. The papillomaviral DNA replication initiation protein E1 has origin recognition and ATP-dependent DNA melting and helicase activities, and it consists of a DNA-binding domain and an ATPase/helicase domain. While monomeric in solution, E1 binds DNA as a dimer. Dimerization occurs via an interaction of hydrophobic residues on a single alpha-helix of each monomer. Here we present the crystal structure of the monomeric HPV-18 E1 DNA-binding domain refined to 1.8-A resolution. The structure reveals that the dimerization helix is significantly different from that of bovine papillomavirus type 1 (BPV-1). However, we demonstrate that the analogous residues required for E1 dimerization in BPV-1 and the low risk HPV-11 are also required for HPV-18 E1. We also present evidence that the HPV-18 E1 DNA-binding domain does not share the same nucleotide and amino acid requirements for specific DNA recognition as BPV-1 and HPV-11 E1

Category fluency in psychometric schizotypy: How altering emotional valence and cognitive load affects performance

Introduction. In clinical high-risk populations, category fluency deficits are associated with conversion to psychosis. However, their utility as clinical risk markers is unclear in psychometric schizotypy, a group experiencing schizophrenia-like traits that is at putative high risk for psychosis. Methods. We examined whether introducing affective or cognitive load, two important stress vulnerability markers, altered category fluency performance in schizotypy (n = 42) and non-schizotypy (n = 38) groups. To investigate this question, we developed an experimental paradigm where all participants were administered category fluency tests across baseline, pleasant valence, unpleasant valence, and cognitive load conditions. Results. Compared to the non-schizotypy group, those with schizotypy performed significantly worse in pleasant and unpleasant valence conditions, but not cognitive load or baseline fluency tests. Conclusions. This study demonstrated the role of affect – but not cognitive load – on category fluency in psychometric schizotypy, as group differences only emerged once affective load was introduced. One explanation for this finding is that semantic memory may be unimpaired under normal conditions in psychometric schizotypy, but may be compromised once affective load is presented. Future studies should examine whether fluency deficits – particularly when affect is induced – predict future conversion to psychosis in psychometric schizotypy cohorts

An Impacting Descent Probe for Europa and the other Galilean Moons of Jupiter

We present a study of an impacting descent probe that increases the science return of spacecraft orbiting or passing an atmosphere-less planetary body of the solar system, such as the Galilean moons of Jupiter. The descent probe is a carry-on small spacecraft (< 100 kg), to be deployed by the mother spacecraft, that brings itself onto a collisional trajectory with the targeted planetary body in a simple manner. A possible science payload includes instruments for surface imaging, characterisation of the neutral exosphere, and magnetic field and plasma measurement near the target body down to very low-altitudes (~1 km), during the probe's fast (~km/s) descent to the surface until impact. The science goals and the concept of operation are discussed with particular reference to Europa, including options for flying through water plumes and after-impact retrieval of very-low altitude science data. All in all, it is demonstrated how the descent probe has the potential to provide a high science return to a mission at a low extra level of complexity, engineering effort, and risk. This study builds upon earlier studies for a Callisto Descent Probe (CDP) for the former Europa-Jupiter System Mission (EJSM) of ESA and NASA, and extends them with a detailed assessment of a descent probe designed to be an additional science payload for the NASA Europa Mission.Comment: 34 pages, 11 figure

The role of marine reserves in achieving sustainable fisheries (One contribution of 15 to a Theme Issue 'Fisheries: a Future?')

Many fishery management tools currently in use have conservation value. They are designed to maintain stocks of commercially important species above target levels. However, their limitations are evident from continuing declines in fish stocks throughout the world. We make the case that to reverse fishery declines, safeguard marine life and sustain ecosystem processes, extensive marine reserves that are off limits to fishing must become part of the management strategy. Marine reserves should be incorporated into modern fishery management because they can achieve many things that conventional tools cannot. Only complete and permanent protection from fishing can protect the most sensitive habitats and vulnerable species. Only reserves will allow the development of natural, extended age structures of target species, maintain their genetic variability and prevent deleterious evolutionary change from the effects of fishing. Species with natural age structures will sustain higher rates of reproduction and will be more resilient to environmental variability. Higher stock levels maintained by reserves will provide insurance against management failure, including risk-prone quota setting, provided the broader conservation role of reserves is firmly established and legislatively protected. Fishery management measures outside protected areas are necessary to complement the protection offered by marine reserves, but cannot substitute for it

Spatial distributions of electromagnetic field variations and injection regions during the 20 November 2007 sawtooth event

We report multi-spacecraft and ground-based observations of a &quot;sawtooth&quot; event on 20 November 2007. For this event, data from three THEMIS, two GOES, and four LANL spacecraft are available as well as those from extensively distributed ground magnetometers and all-sky imagers. In the present paper we focus on the spatial extents of the electromagnetic and particle signatures of the first &quot;tooth&quot;. In this event, auroral images and ground magnetic bays showed two activations: a pseudo onset and a major onset (we use the term pseudo onset since the former auroral brightening did not significantly expand poleward). Ground magnetic bay observations indicate that the substorm current wedge (SCW) developed after the major onset in an azimuthally wide region of ~14–3 h MLT. Similarly, broad magnetic bay distribution was observed also for the pseudo onset prior to the major onset. Furthermore, around the pseudo onset, magnetic dipolarisations were observed from 0.5 to 5 h MLT. These observations illustrate that, during sawtooth events, activities following not only the major onset but also the pseudo onset can extend more widely than those during usual substorms. Remarkable electromagnetic field fluctuations embedded in the dipolarisation trend were seen at 0.5 and 2.5 h MLT. In particular, comprehensive plasma and field data from THEMIS showed the presence of a long-excited weak magnetosonic wave and an impulsive large-amplitude Alfvén wave with an earthward Poynting flux at around the eastward edge of the SCW; the latter was sufficiently strong for powering aurora (140 mW/m&lt;sup&gt;2&lt;/sup&gt; when mapped to the ionosphere). These two activations of the electromagnetic wave were identified, corresponding to the pseudo onset and the major onset. On the other hand, the dipolarisation at geosynchronous 0 h MLT was observed only after the major onset, despite its closer location to the centre of the auroral activity in terms of the MLT; this indicates that the inner radial limit of the dipolarisation region at the pseudo onset was tailward of geosynchronous altitude at 0 h MLT. The outer radial limit of the electron injection region was also found at ~10 &lt;I&gt;R&lt;sub&gt;E&lt;/sub&gt;&lt;/I&gt; by conjunction measurements with THEMIS satellites. These radial distributions are not significantly different to those expected for usual substorms

Report of the ICES\NAFO Joint Working Group on Deep-water Ecology (WGDEC), 11–15 March 2013, Floedevigen, Norway.

On 11 February 2013, the joint ICES/NAFO WGDEC, chaired by Francis Neat (UK) and attended by ten members met at the Institute for Marine Research in Floedevi-gen, Norway to consider the terms of reference (ToR) listed in Section 2. WGDEC was requested to update all records of deep-water vulnerable marine eco-systems (VMEs) in the North Atlantic. New data from a range of sources including multibeam echosounder surveys, fisheries surveys, habitat modelling and seabed imagery surveys was provided. For several areas across the North Atlantic, WGDEC makes recommendations for areas to be closed to bottom fisheries for the purposes of conservation of VMEs

Recovery of a temperate reef assemblage in a marine protected area following the exclusion of towed demersal fishing.

Marine Protected Areas MPA have been widely used over the last 2 decades to address human impacts on marine habitats within an ecosystem management context. Few studies have quantified recovery of temperate rocky reef communities following the cessation of scallop dredging or demersal trawling. This is critical information for the future management of these habitats to contribute towards conservation and fisheries targets. The Lyme Bay MPA, in south west UK, has excluded towed demersal fishing gear from 206 km(2) of sensitive reef habitat using a Statutory Instrument since July 2008. To assess benthic recovery in this MPA we used a flying video array to survey macro epi-benthos annually from 2008 to 2011. 4 treatments (the New Closure, previously voluntarily Closed Controls and Near or Far Open to fishing Controls) were sampled to test a recovery hypothesis that was defined as 'the New Closure becoming more similar to the Closed Controls and less similar to the Open Controls'. Following the cessation of towed demersal fishing, within three years positive responses were observed for species richness, total abundance, assemblage composition and seven of 13 indicator taxa. Definitive evidence of recovery was noted for species richness and three of the indicator taxa (Pentapora fascialis, Phallusia mammillata and Pecten maximus). While it is hoped that MPAs, which exclude anthropogenic disturbance, will allow functional restoration of goods and services provided by benthic communities, it is an unknown for temperate reef systems. Establishing the likely timescales for restoration is key to future marine management. We demonstrate the early stages of successful recruitment and link these to the potential wider ecosystem benefits including those to commercial fisheries