Structural basis of initial RNA polymerase II transcription

Several RNA polymerase II–nucleic acid crystal structures reveal the transition of the initiating polymerase from the open complex (OC) state to the initially transcribing complex (ITC) containing several RNA nucleotides

Copyright Law, Readers and Authors in Colonial Australia

This article explores the impact of imperial and domestic copyright law on Australian readers, authors and literary culture throughout the nineteenth century.  It investigates the effects of the Copyright Act 1842 on colonial readers, in terms of the cost and availability of books and the circulation of ideas, and uncovers Australian responses to the Foreign Reprints Act 1847.  It further explores the creation of domestic colonial copyright legislation and its links to an increase in the number of novels published as books in the 1870s and 1880s.  Drawing on recent empirical research exploring relationships between book publishing and the growth of a national literature, it argues that copyright law and policy are important considerations in fostering such histories of Australian literary culture

The structure of a reduced form of OxyR from Neisseria meningitidis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - © 2010 Sainsbury et al; licensee BioMed Central Ltd.Background: Survival of the human pathogen, Neisseria meningitidis, requires an effective response to oxidative stress resulting from the release of hydrogen peroxide by cells of the human immune system. In N. meningitidis, expression of catalase, which is responsible for detoxifying hydrogen peroxide, is controlled by OxyR, a redox responsive LysR-type regulator. OxyR responds directly to intracellular hydrogen peroxide through the reversible formation of a disulphide bond between C199 and C208 in the regulatory domain of the protein. Results: We report the first crystal structure of the regulatory domain of an OxyR protein (NMB0173 from N. meningitidis) in the reduced state i.e. with cysteines at positions 199 and 208. The protein was crystallized under reducing conditions and the structure determined to a resolution of 2.4 Å. The overall fold of the Neisseria OxyR shows a high degree of similarity to the structure of a C199S mutant OxyR from E. coli, which cannot form the redox sensitive disulphide. In the neisserial structure, C199 is located at the start of helix α3, separated by 18 Å from C208, which is positioned between helices α3 and α4. In common with other LysR-type regulators, full length OxyR proteins are known to assemble into tetramers. Modelling of the full length neisserial OxyR as a tetramer indicated that C199 and C208 are located close to the dimer-dimer interface in the assembled tetramer. The formation of the C199-C208 disulphide may thus affect the quaternary structure of the protein. Conclusion: Given the high level of structural similarity between OxyR from N. meningitidis and E. coli, we conclude that the redox response mechanism is likely to be similar in both species, involving the reversible formation of a disulphide between C199-C208. Modelling suggests that disulphide formation would directly affect the interface between regulatory domains in an OxyR tetramer which in turn may lead to an alteration in the spacing/orientation of the DNA-binding domains and hence the interaction of OxyR with its DNA binding sites.This work was supported by UK Medical Research Council, the Biotechnology Biological Research Council, and by a MRC Research Studentship

Structure of the PII signal transduction protein of Neisseria meningitidis at 1.85 Å resolution

The structure of the PII signal transduction protein of N. meningitidis at 1.85 Å resolution is described

A versatile ligation-independent cloning method suitable for high-throughput expression screening applications

This article describes the construction of a set of versatile expression vectors based on the In-Fusion™ cloning enzyme and their use for high-throughput cloning and expression screening. Modifications to commonly used vectors rendering them compatible with In-Fusion™ has produced a ligation-independent cloning system that is (1) insert sequence independent (2) capable of cloning large PCR fragments (3) efficient over a wide (20-fold) insert concentration range and (4) applicable to expression in multiple hosts. The system enables the precise engineering of (His6-) tagged constructs with no undesirable vector or restriction-site-derived amino acids added to the expressed protein. The use of a multiple host-enabled vector allows rapid screening in both E. coli and eukaryotic hosts (HEK293T cells and insect cell hosts, e.g. Sf9 cells). These high-throughput screening activities have prompted the development and validation of automated protocols for transfection of mammalian cells and Ni-NTA protein purification

Terrestrial Mammal Conservation: Global Evidence for the Effects of Interventions for terrestrial mammals excluding bats and primates

Terrestrial Mammal Conservation provides a thorough summary of the available scientific evidence of what is known, or not known, about the effectiveness of all of the conservation actions for wild terrestrial mammals across the world (excluding bats and primates, which are covered in separate synopses). Actions are organized into categories based on the International Union for Conservation of Nature classifications of direct threats and conservation actions. Over the course of fifteen chapters, the authors consider interventions as wide ranging as creating uncultivated margins around fields, prescribed burning, setting hunting quotas and removing non-native mammals.This book is written in an accessible style and is designed to be an invaluable resource for anyone concerned with the practical conservation of terrestrial mammals.The authors consulted an international group of terrestrial mammal experts and conservationists to produce this synopsis. Funding was provided by the MAVA Foundation, Arcadia and National Geographic Big Cats Initiative.Terrestrial Mammal Conservation is the seventeenth publication in the Conservation Evidence Series, linked to the online resource www.ConservationEvidence.com. Conservation Evidence Synopses are designed to promote a more evidence-based approach to biodiversity conservation. Others in the series include Bat Conservation, Primate Conservation, Bird Conservation and Forest Conservation and more are in preparation. Expert assessment of the evidence summarised within synopses is provided online and within the annual publication What Works in Conservation

Mental health and the criminal justice system: The role of interagency training to promote practitioner understanding of the diversion agenda

Historically there has been a significant under-recognition of mental health problems among people in the criminal justice system, and little research exploring the issues encountered by those with mental health problems who come into contact with the criminal justice system. Recent policy has highlighted the importance of early identification of mental health needs in criminal cases, and the role of diversion of offenders into appropriate mental health services. However research suggests that currently the provision of mental health services for offenders is patchy, and it has been suggested that improved interagency communication and training is required to improve the diversion of offenders with mental health problems into more appropriate mental health provision.The aim of this paper is to consider the current position of those with mental health conditions within the criminal justice system in England, and discuss how joint interagency training can improve understanding of the diversion agenda for the range of practitioners that come into contact with offenders with mental health problems. The perspectives of a range of practitioners who attended a joint interagency training day will be discussed, and recommendations for future training will be offered. © 2014 Taylor & Francis

The importance of concepts

Words change meaning over time. Some meaning shift is accompanied by a corresponding change in subject matter; some meaning shift is not. In this paper I argue that an account of linguistic meaning can accommodate the first kind of case, but that a theory of concepts is required to accommodate the second. Where there is stability of subject matter through linguistic change, it is concepts that provide the stability. The stability provided by concepts allows for genuine disagreement and ameliorative change in the context of conceptual engineering

Terrestrial Mammal Conservation

"Terrestrial Mammal Conservation provides a thorough summary of the available scientific evidence of what is known, or not known, about the effectiveness of all of the conservation actions for wild terrestrial mammals across the world (excluding bats and primates, which are covered in separate synopses). Actions are organized into categories based on the International Union for Conservation of Nature classifications of direct threats and conservation actions. Over the course of fifteen chapters, the authors consider interventions as wide ranging as creating uncultivated margins around fields, prescribed burning, setting hunting quotas and removing non-native mammals. This book is written in an accessible style and is designed to be an invaluable resource for anyone concerned with the practical conservation of terrestrial mammals. The authors consulted an international group of terrestrial mammal experts and conservationists to produce this synopsis. Funding was provided by the MAVA Foundation, Arcadia and National Geographic Big Cats Initiative. Terrestrial Mammal Conservation is the seventeenth publication in the Conservation Evidence Series, linked to the online resource www.ConservationEvidence.com. Conservation Evidence Synopses are designed to promote a more evidence-based approach to biodiversity conservation. Others in the series include Bat Conservation, Primate Conservation, Bird Conservation and Forest Conservation and more are in preparation. Expert assessment of the evidence summarised within synopses is provided online and within the annual publication What Works in Conservation.

The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators

LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upregulated during bacterial–host cell contact. Here, we report the crystal structures of both regulatory domain and full-length CrgA, the first of a novel subclass of LTTRs that form octameric rings. Non-denaturing mass spectrometry analysis and analytical ultracentrifugation established that the octameric form of CrgA is the predominant species in solution in both the presence and absence of an oligonucleotide encompassing the CrgA-binding sequence. Furthermore, analysis of the isolated CrgA–DNA complex by mass spectrometry showed stabilization of a double octamer species upon DNA binding. Based on the observed structure and the mass spectrometry findings, a model is proposed in which a hexadecameric array of two CrgA oligomers binds to its DNA target site