Structure of the regulatory domain of the LysR family regulator NMB2055 (MetR-like protein) from Neisseria meningitidis

Copyright @ 2012 International Union of CrystallographyThe crystal structure of the regulatory domain of NMB2055, a putative MetR regulator from Neisseria meningitidis, is reported at 2.5 Å resolution. The structure revealed that there is a disulfide bond inside the predicted effector-binding pocket of the regulatory domain. Mutation of the cysteines (Cys103 and Cys106) that form the disulfide bond to serines resulted in significant changes to the structure of the effector pocket. Taken together with the high degree of conservation of these cysteine residues within MetR-related transcription factors, it is suggested that the Cys103 and Cys106 residues play an important role in the function of MetR regulators.This study is funded by the Medical Research Council, with additional finance from the Biotechnology and Biological Science Research Council

Haemorrhagic pleural effusion in acute pancreatitis

The literature contains very few reports of haemorrhage remote from the pancreas in acute pancreatitis. This is probably not a true reflection of its incidence and 2 cases are recorded here drawing attention to this feature of the disease

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

The utility of MAS5 expression summary and detection call algorithms

<p>Abstract</p> <p>Background</p> <p>Used alone, the MAS5.0 algorithm for generating expression summaries has been criticized for high False Positive rates resulting from exaggerated variance at low intensities.</p> <p>Results</p> <p>Here we show, with replicated cell line data, that, when used alongside detection calls, MAS5 can be both selective and sensitive. A set of differentially expressed transcripts were identified that were found to be changing by MAS5, but unchanging by RMA and GCRMA. Subsequent analysis by real time PCR confirmed these changes. In addition, with the Latin square datasets often used to assess expression summary algorithms, filtered MAS5.0 was found to have performance approaching that of its peers.</p> <p>Conclusion</p> <p>When used alongside detection calls, MAS5 is a sensitive and selective algorithm for identifying differentially expressed genes.</p

Raymond (Bill) Hoffenberg

N/

Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high &lt;sup&gt;3&lt;/sup&gt;He/&lt;sup&gt;4&lt;/sup&gt;He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic &lt;sup&gt;3&lt;/sup&gt;He/&lt;sup&gt;4&lt;/sup&gt;He ratios yet recorded. A strong correlation between &lt;sup&gt;3&lt;/sup&gt;He/&lt;sup&gt;4&lt;/sup&gt;He and &lt;sup&gt;87&lt;/sup&gt;Sr/&lt;sup&gt;86&lt;/sup&gt;Sr, &lt;sup&gt;143&lt;/sup&gt;Nd/&lt;sup&gt;144&lt;/sup&gt;Nd and trace element ratios demonstrate that the &lt;sup&gt;3&lt;/sup&gt;He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest &lt;sup&gt;3&lt;/sup&gt;He/&lt;sup&gt;4&lt;/sup&gt;He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a &lt;sup&gt;3&lt;/sup&gt;He-recharged depleted mantle (HRDM) reservoir may be the principal source of high &lt;sup&gt;3&lt;/sup&gt;He/&lt;sup&gt;4&lt;/sup&gt;He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Spatial and temporal variability of seagrass at Lizard Island, Great Barrier Reef

Increasing threats to natural ecosystems from local and global stressors are reinforcing the need for baseline data on the distribution and abundance of organisms. We quantified spatial and/or temporal patterns of seagrass distribution, shoot density, leaf area index, biomass, productivity, and sediment carbon content in shallow water (0-5 m) at Lizard Island, Great Barrier Reef, Australia, in field surveys conducted in December 2011 and October 2012. Seagrass meadows were mapped using satellite imagery and field validation. A total of 18.3 ha of seagrass, composed primarily of Thalassia hemprichii and Halodule uninervis, was mapped in shallow water. This was 46% less than the area of seagrass in the same region reported in 1995, although variations in mapping methods may have influenced the magnitude of change detected. There was inter-annual variability in shoot density and length, with values for both higher in 2011 than in 2012. Seagrass properties and sediment carbon content were representative of shallow-water seagrass meadows on a mid-shelf Great Barrier Reef island. The data can be used to evaluate change, to parameterize models of the impact of anthropogenic or environmental variability on seagrass distribution and abundance, and to assess the success of management actions

Foreword

In 2014, four of Emeritus Prof. Peter (fondly known as PB) Beighton’s past PhD students decided that they would like to honour him for his leadership and the influence that he had on their professional lives, and collaborated on a project to compile a Festschrift in his honour. They are Prof. Michael Hayden, now living in Canada, the first PhD graduate that PB supervised in 1979, together with Profs Jacquie Greenberg from the University of Cape Town (UCT), Alan Bryer from UCT and Groote Schuur Hospital (GSH), and Lawrence Stephen from the University of the Western Cape (UWC). Prof. Lawrence Stephen was the last PhD graduate that Prof. Beighton supervised before he officially retired in 1999.Many colleagues who have worked over the past 5 decades and who continue to work with him were invited to contribute to this supplement to the SAMJ. The Festschrift includes the history behind Peter Beighton, who was born, grew up and trained in the UK and came to UCT in 1972. His legacy includes the impact that he made on those who trained under him in SA, as well as throughout the world. The Festschrift includes the history of genetics and current genetic practice in South Africa, as well as the influence that he has had on medical genetics in general, dental genetics and now genomics going into the new millennium. Tributes have been received from people all over the world, attesting to his outstanding leadership and mentorship, and highlight how he influenced the climate, growth and development of genetics at UCT, and scientific and technological fields in genetics and genomics over the past few decades.This Foreword includes a message from Emeritus Prof. Stuart Saunders – former Head of Department (HoD) of Medicine at GSH in the 1970s when PB arrived at UCT – followed by some words from Emeritus Prof. J P van Niekerk, former Dean of the UCT Faculty of Health Sciences in the 1980s. Profs Greenberg, Bryer and Stephen conclude the Foreword, while Prof. Hayden introduces the legacy that Prof. Beighton has passed on

Promoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: Randomised controlled trial protocol

Introduction: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%–90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in nonmetropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA. Methods and analysis: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention. Ethics and dissemination: Ethics approval hasbeen obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences. Trial registration number: ACTRN12618001743257; pre-results, U1111-1222-569