Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors

Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study

Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD

Stochastic Species Turnover and Stable Coexistence in a Species-Rich, Fire-Prone Plant Community

Understanding the mechanisms that maintain diversity is important for managing ecosystems for species persistence. Here we used a long-term data set to understand mechanisms of coexistence at the local and regional scales in the Cape Floristic Region, a global hotspot of plant diversity. We used a dataset comprising 81 monitoring sites, sampled in 1966 and again in 1996, and containing 422 species for which growth form, regeneration mode, dispersal distance and abundances at both the local (site) and meta-community scales are known. We found that species presence and abundance were stable at the meta-community scale over the 30 year period but highly unstable at the local scale, and were not influenced by species' biological attributes. Moreover, rare species were no more likely to go extinct at the local scale than common species, and that alpha diversity in local communities was strongly influenced by habitat. We conclude that stochastic environmental fluctuations associated with recurrent fire buffer populations from extinction, thereby ensuring stable coexistence at the meta-community scale by creating a “neutral-like” pattern maintained by niche-differentiation

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

<p>Abstract</p> <p>Background</p> <p>Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein.</p> <p>Findings</p> <p><it>De novo </it>modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins.</p> <p>Conclusions</p> <p>Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.</p

What's wrong with John? A randomised controlled trial of Mental Health First Aid (MHFA) training with nursing students

BACKGROUND: The prevalence of mental health problems have been found to be higher among university students compared to their non-student peers. Nursing students in particular face a range of additional stressors which may impact their undergraduate performance and their careers. Mental Health First Aid (MHFA) aims to increase mental health literacy and to reduce stigma and may positively impact on the student population. This paper describes a MHFA randomised controlled trial targeting nursing students at a large Australian university. This study aimed to measure the impact of the MHFA course on mental health literacy, mental health first aid intentions, confidence in helping someone with a mental health problem and stigmatising attitudes including social distance. METHODS: Participants were first year nursing students (n = 181) randomly allocated to the intervention (n = 92) or control (n = 89) group. Intervention group participants received the standardised MHFA course for nursing students. Online self-report questionnaires were completed at three time intervals: baseline (one week prior to the intervention: T1) (n = 140), post intervention (T2) (n = 120), and two months post intervention (T3) (n = 109). Measures included demographics, mental health knowledge, recognition of depression, confidence in helping, mental health first aid intentions and stigmatising attitudes including social distance. Repeated measures ANOVA was computed to measure if the impact of time (T1, T2, T3) and group (intervention and control) on the outcome variables. RESULTS: There was a significant improvement among intervention compared to control group participants across the three time periods for knowledge scores (p &lt; 0.001), confidence in helping (p &lt; 0.001), mental health first aid intentions (p &lt; 0.001), total personal stigma (p &lt; 0.05), personal dangerous/unpredictable stigma (p &lt; 0.05) and social distance (p &lt; 0.05) scores. CONCLUSION: MHFA is useful training to embed in university courses and has the potential to enhance mental health literacy and reduce stigmatising attitudes and social distance. While this course has particular salience for nursing and other health science students, there are broader benefits to the general university population that should be considered and opportunities accordingly explored for all students to complete the course. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000861651 . Retrospectively registered 11 August 2014

Climate Change, Habitat Loss, Protected Areas and the Climate Adaptation Potential of Species in Mediterranean Ecosystems Worldwide

Mediterranean climate is found on five continents and supports five global biodiversity hotspots. Based on combined downscaled results from 23 atmosphere-ocean general circulation models (AOGCMs) for three emissions scenarios, we determined the projected spatial shifts in the mediterranean climate extent (MCE) over the next century. Although most AOGCMs project a moderate expansion in the global MCE, regional impacts are large and uneven. The median AOGCM simulation output for the three emissions scenarios project the MCE at the end of the 21st century in Chile will range from 129–153% of its current size, while in Australia, it will contract to only 77–49% of its current size losing an area equivalent to over twice the size of Portugal. Only 4% of the land area within the current MCE worldwide is in protected status (compared to a global average of 12% for all biome types), and, depending on the emissions scenario, only 50–60% of these protected areas are likely to be in the future MCE. To exacerbate the climate impact, nearly one third (29–31%) of the land where the MCE is projected to remain stable has already been converted to human use, limiting the size of the potential climate refuges and diminishing the adaptation potential of native biota. High conversion and low protection in projected stable areas make Australia the highest priority region for investment in climate-adaptation strategies to reduce the threat of climate change to the rich biodiversity of the mediterranean biome

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199