Ireland’s unseen majority – microbial diversity of the seabed

Despite their size, prokaryote (bacteria and archaea) biomass is estimated to represent between 15 and 30% of total living biomass1,2. Prokaryotes play major roles in marine ecosystems and in global biogeochemical cycling3,4. Molecular phylogenetic approaches have revolutionised microbiology and have revealed that the complexity of microbial life is orders of magnitude greater than previous estimates based on cultivation-based approaches5. This highlights how little we currently know about the microbial world and the clear potential of this vast untapped resource for human application. Here we present the first in-depth analysis of microbial community diversity and composition in the Irish Sea. The western Irish Sea is characterised by distinct hydrographic conditions, resulting in summer stratified offshore deeper waters and settling of fine mud, while well-mixed waters and coarser sediment type dominate in the south and coastal regions. We wished to assess whether these factors play a role in prokaryote abundance and diversity

Hydrographic controls on marine organic matter fate and microbial diversity in the western Irish Sea

Cycling of organic matter (OM) is the key biological process in the marine environment and knowledge of the sources and the reactivity of OM, in addition to factors controlling its distribution in estuarine, coastal and shelf sediments are of key importance for understanding global biogeochemical cycles. With recent advances in cultivation-independent molecular approaches to microbial ecology, the key role of prokaryotes in global biogeochemical cycling in marine ecosystems has been emphasised. However, spatial studies combining the distribution and fate of OM with microbial community abundance and diversity remain rare. Here, a combined spatial lipid biomarker and 16S rRNA tagged pyrosequencing study was conducted in surface sediments and particulate matter across hydrographically distinct zones associated with the seasonal western Irish Sea gyre. The aim was to assess the spatial variation of, and factors controlling, marine organic cycling and sedimentary microbial communities across these distinct zones. The distribution of phospholipid fatty acids, source-specific sterols, wax esters and C25 highly branched isoprenoids indicate that diatoms, dinoflagellates and green algae were the major contributors of marine organic matter, while the distribution of cholesterol, wax esters and C20 and C22 polyunsaturated fatty acids have highlighted the importance of copepod grazing for mineralizing organic matter in the water column5. This marine OM production and mineralisation was greatest in well-mixed waters compared to offshore stratified waters. Lipid analysis and 16S rRNA PCR-DGGE profiling also suggests that sedimentary bacterial abundance increases while community diversity decreases in offshore stratified waters. The major bacterial classes are the Deltaproteobacteria, Clostridia, Flavobacteriia, Gammaproteobactera and Bacteroiidia. At the family/genus level most groups appear to be associated with organoheterotrophic processing of sedimentary OM, ranging from degradation of complex organic matter (e.g. Tepidibacter sp.) to sulfur-dependent utilisation of simple organic molecules (e.g. Desulfobulbaceae and Desulfuromonadaceae)

A new approach to high resolution, high contrast electron microscopy of macromolecular block copolymer assemblies

Determining the structure of macromolecular samples is vital for understanding and adapting their function. Transmission electron microscopy (TEM) is widely used to achieve this, but, owing to the weak electron scattering cross-section of carbon, TEM images of macromolecular samples are generally low contrast and low resolution. Here we implement a fast and practically simple routine to achieve high-contrast imaging of macromolecular samples using exit wave reconstruction (EWR), revealing a new level of structural detail. This is only possible using ultra-low contrast supports such as the graphene oxide (GO) used here and as such represents a novel application of these substrates. We apply EWR on GO membranes to study self-assembled block copolymer structures, distinguishing not only the general morphology or nanostructure, but also evidence for the substructure (i.e. the polymer chains) which gives insight into their formation mechanisms and functional properties

Immune-derived PD-L1 gene expression defines a subgroup of stage II/III colorectal cancer patients with favorable prognosis that may be harmed by adjuvant chemotherapy

Abstract A recent phase II study of patients with metastatic colorectal carcinoma showed that mismatch repair gene status was predictive of clinical response to PD-1–targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV colorectal carcinoma, suggesting that the amount of PD-L1 protein expression could identify late-stage patients who might benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic colorectal carcinoma are also present in stage II/III colorectal carcinoma, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a statistically significant association of PD-L1 gene expression with MSI in early-stage colorectal carcinoma (P &amp;lt; 0.001) and show that, unlike in non–colorectal carcinoma tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low vs. PD-L1high HR = 9.09; CI, 2.11–39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI, 1.10–22.35). Building on the promising results from the metastatic colorectal carcinoma PD-1–targeting trial, we provide compelling evidence that patients with PD-L1high/MSI/immunehigh stage II/III colorectal carcinoma should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment. Cancer Immunol Res; 4(7); 582–91. ©2016 AACR.</jats:p

The multi-layered nature of the internet-based democratization of brand management

The evolution of the internet, including developments such as Web 2.0, has led to new relationship realities between organizations and their stakeholders. One manifestation of these complex new realities has been the emergence of an internet-based democratization of brand management. Research about this phenomenon has so far mainly focused on investigating just one or more individual themes and thereby disregarded the inherent multi-layered nature of the internet-based democratization of brand management as a holistic, socio-technological phenomenon. The aim of this paper is to address this limitation through an investigation of the various socio-technological democratization developments of the phenomenon. To achieve this aim, a balanced and stakeholder-oriented perspective on brand management has been adopted to conduct an integrative literature review. The review reveals three key developments, which together form the essential parts of the phenomenon: (I) the democratization of internet technology, (II) the democratization of information, and (III) the democratization of social capital. The insights gained help to clarify the basic structures of the multi-layered phenomenon. The findings contribute also to the substantiation of a call for a new brand management paradigm: one that takes not only company-initiated but also stakeholder-initiated brand management activities into accoun

Integrating incremental learning and episodic memory models of the hippocampal region.

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition

Triangulation of gravitational wave sources with a network of detectors

There is significant benefit to be gained by pursuing multi-messenger astronomy with gravitational wave and electromagnetic observations. In order to undertake electromagnetic follow-ups of gravitational wave signals, it will be necessary to accurately localize them in the sky. Since gravitational wave detectors are not inherently pointing instruments, localization will occur primarily through triangulation with a network of detectors. We investigate the expected timing accuracy for observed signals and the consequences for localization. In addition, we discuss the effect of systematic uncertainties in the waveform and calibration of the instruments on the localization of sources. We provide illustrative results of timing and localization accuracy as well as systematic effects for coalescing binary waveforms.Comment: 20 pages, 5 figure

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure