Transcriptome analysis of Listeria monocytogenes exposed to biocide stress reveals a multi-system response involving cell wall synthesis, sugar uptake, and motility

peer-reviewedListeria monocytogenes is a virulent food-borne pathogen most often associated with the consumption of “ready-to-eat” foods. The organism is a common contaminant of food processing plants where it may persist for extended periods of time. A commonly used approach for the control of Listeria monocytogenes in the processing environment is the application of biocides such as quaternary ammonium compounds. In this study, the transcriptomic response of a persistent strain of L. monocytogenes (strain 6179) on exposure to a sub-lethal concentration of the quaternary ammonium compound benzethonium chloride (BZT) was assessed. Using RNA-Seq, gene expression levels were quantified by sequencing the transcriptome of L. monocytogenes 6179 in the presence (4 ppm) and absence of BZT, and mapping each data set to the sequenced genome of strain 6179. Hundreds of differentially expressed genes were identified, and subsequent analysis suggested that many biological processes such as peptidoglycan biosynthesis, bacterial chemotaxis and motility, and carbohydrate uptake, were involved in the response of L. monocyotogenes to the presence of BZT. The information generated in this study further contributes to our understanding of the response of bacteria to environmental stress. In addition, this study demonstrates the importance of using the bacterium's own genome as a reference when analysing RNA-Seq data.This work was supported by the E.U.7th framework projects PROMISE (project number 265877)and FOODSEG(project number 266061).Aidan Casey was supported by the Teagasc Walsh Fellowship programme

Enabling non-engineers to use engineering tools: introducing product development to pupils using knowledge-integrating systems

Many engineering tasks are supported by tools based on innovative technologies. Powerful tools for computer aided design, simulations or programming permit a wide range of possibilities for engineers in solving complex problems. However, using these tools commonly requires extensive training or specific skills. Specialized systems that enable tool and technology usage could support novices in solving engineering tasks using embedded knowledge, lowering the hurdle of expertise required for operation. In the presented case study, knowledge-integrating systems inspired by knowledge-based engineering were developed to allow pupils to solve an engineering challenge without existing skills or prior training. To provide a realistic application context, a teaching module was developed, introducing high school students to product engineering in the form of a conceive-design-implement-operate experience with the learning goal to engage them in the STEM field. Solving the included engineering challenge required the creation, test and iteration of designs for laser cut and additive manufacturing, and code processing sensor signals for motor actuation. To evaluate the knowledge-integrating systems in their use qualitatively, a trial run was conducted. Participants were enabled to fulfil basic product engineering tasks and expressed engagement in product development and overall satisfaction. The module’s key element is an educational exoskeleton that can be controlled by electromyography signals. It is modified to eventually support a fictional character suffering from monoplegia. The module was realized accompanying the CYBATHLON, a championship for people with physical disabilities in solving everyday tasks assisted by state-of-the-art technical systems

High precision modeling at the 10^{-20} level

The requirements for accurate numerical simulation are increasing constantly. Modern high precision physics experiments now exceed the achievable numerical accuracy of standard commercial and scientific simulation tools. One example are optical resonators for which changes in the optical length are now commonly measured to 10^{-15} precision. The achievable measurement accuracy for resonators and cavities is directly influenced by changes in the distances between the optical components. If deformations in the range of 10^{-15} occur, those effects cannot be modeled and analysed any more with standard methods based on double precision data types. New experimental approaches point out that the achievable experimental accuracies may improve down to the level of 10^{-17} in the near future. For the development and improvement of high precision resonators and the analysis of experimental data, new methods have to be developed which enable the needed level of simulation accuracy. Therefore we plan the development of new high precision algorithms for the simulation and modeling of thermo-mechanical effects with an achievable accuracy of 10^{-20}. In this paper we analyse a test case and identify the problems on the way to this goal.Comment: 7 pages, 10 figure

Undiagnosed dementia in primary care: A record linkage study

BackgroundThe number of people living with dementia is greater than the number with a diagnosis of dementia recorded in primary care. This suggests that a significant number are living with dementia that is undiagnosed. Little is known about this group and there is little quantitative evidence regarding the consequences of diagnosis for people with dementia.ObjectivesThe aims of this study were to (1) describe the population meeting the criteria for dementia but without diagnosis, (2) identify predictors of being diagnosed and (3) estimate the effect of diagnosis on mortality, move to residential care, social participation and well-being.DesignA record linkage study of a subsample of participants (n = 598) from the Cognitive Function and Ageing Study II (CFAS II) (n = 7796), an existing cohort study of the population of England aged ≥ 65 years, with standardised validated assessment of dementia and consent to access medical records.Data sourcesData on dementia diagnoses from each participant’s primary care record and covariate and outcome data from CFAS II.SettingA population-representative cohort of people aged ≥ 65 years from three regions of England between 2008 and 2011.ParticipantsA total of 598 CFAS II participants, which included all those with dementia who consented to medical record linkage (n = 449) and a stratified sample without dementia (n = 149).Main outcome measuresThe main outcome was presence of a diagnosis of dementia in each participant’s primary care record at the time of their CFAS II assessment(s). Other outcomes were date of death, cognitive performance scores, move to residential care, hospital stays and social participation.ResultsAmong people with dementia, the proportion with a diagnosis in primary care was 34% in 2008–11 and 44% in 2011–13. In both periods, a further 21% had a record of a concern or a referral but no diagnosis. The likelihood of having a recorded diagnosis increased with severity of impairment in memory and orientation, but not with other cognitive impairment. In multivariable analysis, those aged ≥ 90 years and those age

Tournaments and colouring

A tournament is a complete graph with its edges directed, and colouring a tournament means partitioning its vertex set into transitive subtournaments. For some tournaments H there exists c such that every tournament not containing H as a subtournament has chromatic number at most c (we call such a tournament H a hero); for instance, all tournaments with at most four vertices are heroes. In this paper we explicitly describe all heroes.Simons Foundation (Fellowship

Cytotoxic and Inflammatory Effects of Electronic and Traditional Cigarettes on Oral Gingival Cells Using a Novel Automated Smoking Instrument: An In Vitro Study

Information about the potential oral health effects of vaping from electronic cigarettes (e-cigs) is still sparse and inconsistent. The purpose of this study was to compare the safety and cytotoxicity of e-cig liquid aerosols versus traditional cigarette (t-cig) smoke on human epithelial oral cells. T-cig smoke and e-cig aerosols were generated by a newly developed automated smoking instrument in order to simulate realistic user puffing behaviors. Air-liquid interface transwell cell cultures were exposed to standardized puff topography (puff duration: 2 s, puff volume: 35 mL, puff frequency: 1 puff every 60 s) of reference t-cigs or commercially available e-cigs at different air dilutions. Cell viability, morphology, and death rate were evaluated with MTT and TUNEL assays. The inflammatory cytokine gene expression of inflammatory genes was assessed by quantitative RT-PCR. E-cigs and t-cigs indicated similar adverse effects by enhancing cytotoxicity and cell death in a dose-dependent manner. E-cig aerosol and t-cig smoke treatment expressed upregulation of inflammatory cytokines up to 3.0-fold (p < 0.05). These results indicate that e-cig smoking may contribute to oral tissue-cell damage and tissue inflammation. Our approach allows the production of e-cig aerosol and t-cig smoke in order to identify harmful effects in oral tissues in vitro

Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks

A New Outlook on Ice Cloud through Sub-Millimetre-Wave Scattering

Scattering by atmospheric ice at sub-mm-wave frequencies is a challenge to both the cloud physics and light scattering communities owing to scattering at these frequencies being dependent on assumptions about the particle size distribution, ice crystal shape, orientation and size. Moreover, the scattering also depends on how the particle density is assumed to evolve with size. As there is as yet no prediction of a universal PSD or mass–dimension or density–dimension relationship, the modelling of ice crystals, so as to conserve the observed scattering and ice mass, is potentially problematic. In this presentation, the challenge presented by sub-mm-wave scattering is explored through the study of an ice cloud case using a new sub-mm spectral-like radiometer that was deployed on board an aircraft. Here, we evaluate the predictive quality of applying members from an ensemble model of cirrus ice crystals to modelling observed sub-millimetre brightness temperatures. The airborne straight and level near-nadir observations used here were from a case of ice cloud, which occurred during a winter period. The airborne microwave observations were obtained using the International Submillimetre Airborne Radiometer (ISMAR) [1], as the observations collected were at near-nadir we do not as yet consider polarisation. The ISMAR instrument has five central frequencies located between 118 and 664 GHz, with a number of sub-channels situated around some of the central frequencies to obtain spectral-like observations. The frequency selected for presentation is the 664 GHz “window” channel. This channel selection reduces uncertainties in modelling the gaseous spectroscopy, thereby enabling the scattering properties of members of the ensemble model to be more directly evaluated at this frequency. This is also the frequency that is most sensitive to assumptions about the ice crystal models and microphysics. The methodologies adopted for the calculation of the single-scattering properties of the ensemble model members at this frequency have been previously peer-reviewed and published [2, 3]. As such, this presentation concentrates on the application of these methodologies to the interpretation of the airborne ISMAR observations using a fast, state-of-the-art line-by-line radiative transfer model [4]. Moreover, state-of-the-art airborne observations of particle size distributions (PSDs) were also collected from the ice cloud case. These in-situ PSDs, as well as an often used database of in-situ PSDs collected during the SPARTICUS campaign in 2010, are applied to the two most compact and spatial hexagonal ice aggregate members of the ensemble model. A further ice aggregate model, called the Voronoi model, forming a chain of polyhedral particles, constructed to follow an observed density–dimension relationship, was also applied so as to simulate the observations. From the in-situ PSDs, geometric optics-based power law relationships have been previously obtained between the ice water content and the bulk extinction coefficient [5]. These same geometric optics-based relationships were estimated using the area–dimension power laws predicted by the ensemble model members and the Voronoi model. The best-fit ensemble model members to the observed power laws, and the Voronoi model, were applied in order to simulate the sub-mm-wave observations. Thus, we demonstrate consistency of model application from the limit of geometric optics (i.e. typically at visible wavelengths) to the sub-mm. In this presentation, we demonstrate a general overlap between the uncertainty in the radiative transfer simulations assuming the ensemble model members and the uncertainty in ISMAR brightness temperature observations at 664 GHz. However, portions of the straight and level runs were either simulated well with the compact aggregate model member or a three-component model, consisting of the two members of the ensemble model and the Voronoi particle, but never with one and the same model. Owing to the Voronoi model being the most spatial of all the models, this model simulated, to within the upper end of the experimental uncertainty, the ISMAR observations, but never the coldest observations at the highest sub-mm-wave frequency. However, if a different density–dimension relationship were to be adopted in the modelling of the Voronoi model that predicted higher mass values, then this should result in an improved agreement with the observations. It is as yet unclear as to which density–dimension relation is best to apply in general. These observations indicate changes in microphysics in terms of the mass–dimension profile and/or the size of the ice crystals and, therefore, represent a challenge to the global retrieval of ice cloud properties using the Ice Cloud Imager (ICI), which is due for launch around 2022. A further uncertainty is the assumed parametrised shape of the PSD. We also show in this presentation that the choice of PSD and ice crystal models are of equal importance in interpreting sub-mm-wave observations. [1] Fox, S et al., 2017: ISMAR: an airborne submillimetre radiometer. Atmos. Meas. Tech., doi:10.5194/ amt-10-477-2017. [2] Baran, A. J., et al., 2018: The applicability of physical optics in the millimetre and sub-millimetre spectral region. Part II: Application to a three-component model of ice cloud and its evaluation against the bulk single-scattering properties of various other aggregate models. JQSRT. 206, 68-80. [3] Baran, A. J., Hesse E., and Sourdeval O., 2017: The applicability of physical optics in the millimetre and sub-millimetre spectral region. Part I: The ray tracing with diffraction on facets method. JQSRT. 190, 83-100. [4] Havemann, S et al., The Havemann-Taylor Fast Radiative Transfer Code (HT-FRTC): a multipurpose code based on Principal Components, submitted to JQSRT (February 2018). [5] Fox, S et al., 2017: ISMAR: an airborne submillimetre radiometer. Atmos. Meas. Tech., doi:10.5194/ amt-10-477-2017.Peer reviewe

COMT Val(158)Met genotypes differentially influence subgenual cingulate functional connectivity in healthy females

Brain imaging studies have cons stently shown subgenual Anterior Cingulate Cortical (sgACC) involvement in emotion processing. catechol-O-methyltransferase (COMT) Val(158) and Met(158) polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI) may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val(158)Met polymorphism (rs4680) on sgACC resting-state functional connectivity (rsFC) in healthy individuals. A homogeneous group of 61 Caucasian right-handed healthy female university students, all within the same age range, underwent isfMRI. Compared to Met158 homozygotes, Val(158) allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus (IFG), and the nucleus accumbens (NAc). On the other hand, compared to Val(158) homozygotes, we found in Met(158) allele carriers stronger sgACC rsFC with the medial frontal gyrus (MEG), more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val(158) and Met(158) allele carriers. Hovvever, the exact nature of these directions remains to be determined