Dynamics of Symbiont Abundance in Bathymodiolin Deep-sea Symbioses

Deep-sea hydrothermal vents and cold seeps are widespread throughout the world's oceans and represent `oases of life' in a dark and hostile environment. These chemosynthetic habitats are often dominated by mussels of the genus Bathymodiolus. The bivalves harbor bacterial symbionts in their gills that use methane and reduced inorganic compounds such as sulfide and hydrogen as energy sources for chemosynthetic primary production. It is well known that the spatial and temporal gradients of these energy sources can be extremely steep at vents and seeps, and some studies have shown that differences in energy source availability affect symbiont abundance in Bathymodiolus mussels. However, in-depth analyses of physico-chemical gradients and their effect on symbiont abundance are lacking. One of the basic requirements for these analyses is a reliable quantification method for the symbionts. The goal of my thesis was therefore to develop an accurate and efficient protocol for determining symbiont abundance in bathymodiolin mussels

Kdo Hydrolase Is Required for Francisella tularensis Virulence and Evasion of TLR2-Mediated Innate Immunity

ABSTRACT The highly virulent Francisella tularensis subsp. tularensis has been classified as a category A bioterrorism agent. A live vaccine strain (LVS) has been developed but remains unlicensed in the United States because of an incomplete understanding of its attenuation. Lipopolysaccharide (LPS) modification is a common strategy employed by bacterial pathogens to avoid innate immunity. A novel modification enzyme has recently been identified in F. tularensis and Helicobacter pylori. This enzyme, a two-component Kdo (3-deoxy-d-manno-octulosonic acid) hydrolase, catalyzes the removal of a side chain Kdo sugar from LPS precursors. The biological significance of this modification has not yet been studied. To address the role of the two-component Kdo hydrolase KdhAB in F. tularensis pathogenesis, a ΔkdhAB deletion mutant was constructed from the LVS strain. In intranasal infection of mice, the ΔkdhAB mutant strain had a 50% lethal dose (LD50) 2 log10 units higher than that of the parental LVS strain. The levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid were significantly higher (2-fold) in mice infected with the ΔkdhAB mutant than in mice infected with LVS. In vitro stimulation of bone marrow-derived macrophages with the ΔkdhAB mutant induced higher levels of TNF-α and IL-1β in a TLR2-dependent manner. In addition, TLR2−/− mice were more susceptible than wild-type mice to ΔkdhAB bacterial infection. Finally, immunization of mice with ΔkdhAB bacteria elicited a high level of protection against the highly virulent F. tularensis subsp. tularensis strain Schu S4. These findings suggest an important role for the Francisella Kdo hydrolase system in virulence and offer a novel mutant as a candidate vaccine

Neuro-explicit semantic segmentation of the diffusion cloud chamber

For decades, in diffusion cloud chambers, different types of subatomic particle tracks from radioactive sources or cosmic radiation had to be identified with the naked eye which limited the amount of data that could be processed. In order to allow these classical particle detectors to enter the digital era, we successfully developed a neuro-explicit artificial intelligence model that, given an image from the cloud chamber, automatically annotates most of the particle tracks visible in the image according to the type of particle or process that created it. To achieve this goal, we combined the attention U-Net neural network architecture with methods that model the shape of the detected particle tracks. Our experiments show that the model effectively detects particle tracks and that the neuro-explicit approach decreases the misclassification rate of rare particles by 73% compared with solely using the attention U-Net

Lasagne : a static binary translator for weak memory model architectures

Funding: This work was supported by a UK RISE Grant.The emergence of new architectures create a recurring challenge to ensure that existing programs still work on them. Manually porting legacy code is often impractical. Static binary translation (SBT) is a process where a program’s binary is automatically translated from one architecture to another, while preserving their original semantics. However, these SBT tools have limited support to various advanced architectural features. Importantly, they are currently unable to translate concurrent binaries. The main challenge arises from the mismatches of the memory consistency model specified by the different architectures, especially when porting existing binaries to a weak memory model architecture. In this paper, we propose Lasagne, an end-to-end static binary translator with precise translation rules between x86 and Arm concurrency semantics. First, we propose a concurrency model for Lasagne’s intermediate representation (IR) and formally proved mappings between the IR and the two architectures. The memory ordering is preserved by introducing fences in the translated code. Finally, we propose optimizations focused on raising the level of abstraction of memory address calculations and reducing the number offences. Our evaluation shows that Lasagne reduces the number of fences by up to about 65%, with an average reduction of 45.5%, significantly reducing their runtime overhead.Postprin

Acute Haemodynamic Changes During Haemodialysis Do Not Exacerbate Gut Hyperpermeability

© 2019 The Author(s)Introduction: The gastrointestinal tract is a potential source of inflammation in dialysis patients. In-vitro studies suggest breakdown of the gut barrier in uraemia leading to increased intestinal permeability and it is hypothesised that haemodialysis exacerbates this problem due to mesenteric ischemia induced by blood volume changes during treatment. Method: The effect of haemodialysis on intestinal permeability was studied in ten haemodialysis patients and compared with five controls. Intestinal permeability was assessed by measuring the differential absorption of four orally administered sugar probes which provides an index of small and whole bowel permeability. A multi-sugar solution (containing lactulose, rhamnose, sucralose and erythritol) was orally administered after an overnight fast. Plasma levels of all sugar probes were measured hourly for 10hrs post-administration. In haemodialysis patients, the procedure was carried out twice – once on a non-dialysis day and once immediately after haemodialysis. Results: Area under curve (AUC) for lactulose: rhamnose (L:R) ratio and sucralose: erythritol (S:E) ratio was similar post-dialysis and on non-dialysis days. AUC for L:R was higher in haemodialysis patients compared to controls (0.071 vs. 0.034,p=0.001), AUC for S:E ratio was not significantly different. Levels of lactulose, sucralose and erythritol were elevated and retained for longer in haemodialysis patients compared to controls due to dependence of sugars on kidney function for clearance. Conclusion: We found no significant acute changes in intestinal permeability in relation to the haemodialysis procedure. Valid comparison of intestinal permeability between controls and haemodialysis patients was not possible due to the strong influence of kidney function on sugar levels.Peer reviewedFinal Published versio

At the crossroads of biomacromolecular research: highlighting the interdisciplinary nature of the field

Due to their complexity and wide-ranging utility, biomacromolecular research is an especially interdisciplinary branch of chemistry. It is my goal that the Biomacromolecules subject area of Chemistry Central Journal will parallel this richness and diversity. In this inaugural commentary, I attempt to set the stage for achieving this by highlighting several areas where biomacromolecular research overlaps more traditional chemistry sub-disciplines. Specifically, it is discussed how Materials Science and Biotechnology, Analytical Chemistry, Cell Biology and Chemical Theory are each integral to modern biomacromolecular research. Investigators with reports in any of these areas, or any other dealing with biomacromolecules, are encouraged to submit their research papers to Chemistry Central Journal

Technology use, adoption and behaviour in older adults: results from the iStoppFalls Project

Technology use is a common constituent of modern life. However, little is known about older adults’ use of technology. This article presents a subset of data collected via the technology deployed in the iStoppFalls randomized control trial. The primary focus lies on questions about digital device/Internet use, ownership, length, and frequency as well as social networking. Data was collected from participants aged 65 years or older. Seventy-eight participants completed a specifically developed technology survey as part of the baseline assessment. Results showed that the majority of subjects owned a computer with men being its main user. Participants used technological devices on a daily basis for more than 1 year. The main reason for using technology was e-mail communication, search engines, text processing, and online shopping. Only a few participants used social network applications, with Google+ and Facebook being the most popular ones. Future work should consider an in-depth qualitative approach to further increase understanding of technology use in older adults

Early Interactions of Murine Macrophages with Francisella tularensis Map to Mouse Chromosome 19

ABSTRACT Differences among individuals in susceptibility to infectious diseases can be modulated by host genetics. Much of the research in this field has aimed to identify loci within the host genome that are associated with these differences. In mice, A/J (AJ) and C57BL/6J (B6) mice show differential susceptibilities to various pathogens, including the intracellular pathogen Francisella tularensis. Because macrophages are the main initial target during F. tularensis infection, we explored early interactions of macrophages from these two mouse strains with F. tularensis as well as the genetic factors underlying these interactions. Our results indicate that bacterial interactions with bone marrow-derived macrophages (BMDMs) during early stages of infection are different in the AJ and B6 strains. During these early stages, bacteria are more numerous in B6 than in AJ macrophages and display differences in trafficking and early transcriptional response within these macrophages. To determine the genetic basis for these differences, we infected BMDMs isolated from recombinant inbred (RI) mice derived from reciprocal crosses between AJ and B6, and we followed early bacterial counts within these macrophages. Quantitative trait locus (QTL) analysis revealed a locus on chromosome 19 that is associated with early differences in bacterial counts in AJ versus B6 macrophages. QTL analysis of published data that measured the differential susceptibilities of the same RI mice to an in vivo challenge with F. tularensis confirmed the F. tularensis susceptibility QTL on chromosome 19. Overall, our results show that early interactions of macrophages with F. tularensis are dependent on the macrophage genetic background