Structure and Dynamics of Cholesterol-Containing Polyunsaturated Lipid Membranes Studied by Neutron Diffraction and NMR

A direct and quantitative analysis of the internal structure and dynamics of a polyunsaturated lipid bilayer composed of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0-22:6n3-PC) containing 29 mol% cholesterol was carried out by neutron diffraction, 2H-NMR and 13C-MAS NMR. Scattering length distribution functions of cholesterol segments as well as of the sn-1 and sn-2 hydrocarbon chains of 18:0-22:6n3-PC were obtained by conducting experiments with specifically deuterated cholesterol and lipids. Cholesterol orients parallel to the phospholipids, with the A-ring near the lipid glycerol and the terminal methyl groups 3 Å away from the bilayer center. Previously, we reported that the density of polyunsaturated docosahexaenoic acid (DHA, 22:6n3) chains was higher near the lipid–water interface. Addition of cholesterol partially redistributes DHA density from near the lipid–water interface to the center of the hydrocarbon region. Cholesterol raises chain-order parameters of both stearic acid and DHA chains. The fractional order increase for stearic acid methylene carbons C8–C18 is larger, reflecting the redistribution of DHA chain density toward the bilayer center. The correlation times of DHA chain isomerization are short and mostly unperturbed by the presence of cholesterol. The uneven distribution of saturated and polyunsaturated chain densities and the cholesterol-induced balancing of chain distributions may have important implications for the function and integrity of membrane receptors, such as rhodopsin

Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia

To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population

Thermal modelling of gas generation and retention in the Jurassic organic-rich intervals in the Darquain field, Abadan Plain, SW Iran

The petroleum system with Jurassic source rocks is an important part of the hydrocarbons discovered in the Middle East. Limited studies have been done on the Jurassic intervals in the 26,500 km2 Abadan Plain in south-west Iran, mainly due to the deep burial and a limited number of wells that reach the basal Jurassic successions. The goal of this study was to evaluate the Jurassic organic-rich intervals and shale gas play in the Darquain field using organic geochemistry, organic petrography, biomarker analysis, and basin modelling methods. This study showed that organic-rich zones present in the Jurassic intervals of Darquain field could be sources of conventional and unconventional gas reserves. The organic matter content of samples from the organic-rich zones corresponds to medium-to-high-sulphur kerogen Type II-S marine origin. The biomarker characteristics of organic-rich zones indicate carbonate source rocks that contain marine organic matter. The biomarker results also suggest a marine environment with reducing conditions for the source rocks. The constructed thermal model for four pseudo-wells indicates that, in the kitchen area of the Jurassic gas reserve, methane has been generated in the Sargelu and Neyriz source rocks from Early Cretaceous to recent times and the transformation ratio of organic matter is more than 97%. These organic-rich zones with high initial total organic carbon (TOC) are in the gas maturity stage [1.5–2.2% vitrinite reflectance in oil (Ro)] and could be good unconventional gas reserves and gas source rocks. The model also indicates that there is a huge quantity of retained gas within the Jurassic organic-rich intervals

Controlling infectious disease outbreaks: Lessons from mathematical modelling.

Accepted versio

Genome-culture coevolution promotes rapid divergence of killer whale ecotypes.

Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level

Pseudomonas syringae pv. actinidiae (PSA) Isolates from Recent Bacterial Canker of Kiwifruit Outbreaks Belong to the Same Genetic Lineage

Intercontinental spread of emerging plant diseases is one of the most serious threats to world agriculture. One emerging disease is bacterial canker of kiwi fruit (Actinidia deliciosa and A. chinensis) caused by Pseudomonas syringae pv. actinidiae (PSA). The disease first occurred in China and Japan in the 1980s and in Korea and Italy in the 1990s. A more severe form of the disease broke out in Italy in 2008 and in additional countries in 2010 and 2011 threatening the viability of the global kiwi fruit industry. To start investigating the source and routes of international transmission of PSA, genomes of strains from China (the country of origin of the genus Actinidia), Japan, Korea, Italy and Portugal have been sequenced. Strains from China, Italy, and Portugal have been found to belong to the same clonal lineage with only 6 single nucleotide polymorphisms (SNPs) in 3,453,192 bp and one genomic island distinguishing the Chinese strains from the European strains. Not more than two SNPs distinguish each of the Italian and Portuguese strains from each other. The Japanese and Korean strains belong to a separate genetic lineage as previously reported. Analysis of additional European isolates and of New Zealand isolates exploiting genome-derived markers showed that these strains belong to the same lineage as the Italian and Chinese strains. Interestingly, the analyzed New Zealand strains are identical to European strains at the tested SNP loci but test positive for the genomic island present in the sequenced Chinese strains and negative for the genomic island present in the European strains. Results are interpreted in regard to the possible direction of movement of the pathogen between countries and suggest a possible Chinese origin of the European and New Zealand outbreaks

Intracranial injection of dengue virus induces interferon stimulated genes and CD8(+) T cell infiltration by sphingosine kinase 1 independent pathways

We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Car

Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

<p>Abstract</p> <p>Background</p> <p>One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder.</p> <p>Methods and design</p> <p>We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD.</p> <p>The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach.</p> <p>Discussion</p> <p>Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.</p

Ape Conservation Physiology: Fecal Glucocorticoid Responses in Wild Pongo pygmaeus morio following Human Visitation

Nature-based tourism can generate important revenue to support conservation of biodiversity. However, constant exposure to tourists and subsequent chronic activation of stress responses can produce pathological effects, including impaired cognition, growth, reproduction, and immunity in the same animals we are interested in protecting. Utilizing fecal samples (N = 53) from 2 wild habituated orangutans (Pongo pygmaeus morio) (in addition to 26 fecal samples from 4 wild unhabituated orangutans) in the Lower Kinabatangan Wildlife Sanctuary of Sabah, Malaysian Borneo, we predicted that i) fecal glucocorticoid metabolite concentrations would be elevated on the day after tourist visitation (indicative of normal stress response to exposure to tourists on the previous day) compared to samples taken before or during tourist visitation in wild, habituated orangutans, and ii) that samples collected from habituated animals would have lower fecal glucocorticoid metabolites than unhabituated animals not used for tourism. Among the habituated animals used for tourism, fecal glucocorticoid metabolite levels were significantly elevated in samples collected the day after tourist visitation (indicative of elevated cortisol production on the previous day during tourist visitation). Fecal glucocorticoid metabolite levels were also lower in the habituated animals compared to their age-matched unhabituated counterparts. We conclude that the habituated animals used for this singular ecotourism project are not chronically stressed, unlike other species/populations with documented permanent alterations in stress responses. Animal temperament, species, the presence of coping/escape mechanisms, social confounders, and variation in amount of tourism may explain differences among previous experiments. Acute alterations in glucocorticoid measures in wildlife exposed to tourism must be interpreted conservatively. While permanently altered stress responses can be detrimental, preliminary results in these wild habituated orangutans suggest that low levels of predictable disturbance can likely result in low physiological impact on these animals