Urban Design of Bristol Waterfront, Lower Thames Street

The marketplace is going to be one of the highlights on Thames Street, serving as a destination for leisure, shopping and dining. The concept of the project is to have indoor space continue out to the water, providing an outdoor space for dining and leisure, but also giving the boardwalk a resting point. The building is planned as two floors, with the fish market and multipurpose area on the first and an eatery, sitting area, balcony and facilities on the second. The building will be made of a light metal frame with panels to enclose the space and is designed with a folded glass panel that can be opened up to the outside, yet decrease wind pressure in a storm

Disruption of the Zdhhc9 intellectual disability gene leads to behavioural abnormalities in a mouse

Protein S-acylation is a widespread post-translational modification that regulates the trafficking and function of a diverse array of proteins. This modification is catalysed by a family of twenty-three zDHHC enzymes that exhibit both specific and overlapping substrate interactions. Mutations in the gene encoding zDHHC9 cause mild-to-moderate intellectual disability, seizures, speech and language impairment, hypoplasia of the corpus callosum and reduced volume of sub-cortical structures. In this study, we have undertaken behavioural phenotyping, magnetic resonance imaging (MRI) and isolation of S-acylated proteins to investigate the effect of disruption of the Zdhhc9 gene in mice in a C57BL/6 genetic background. Zdhhc9 mutant male mice exhibit a range of abnormalities compared with their wild-type littermates: altered behaviour in the open-field test, elevated plus maze and acoustic startle test that is consistent with a reduced anxiety level; a reduced hang time in the hanging wire test that suggests underlying hypotonia but which may also be linked to reduced anxiety; deficits in the Morris water maze test of hippocampal-dependent spatial learning and memory; and a 36% reduction in corpus callosum volume revealed by MRI. Surprisingly, membrane association and S-acylation of H-Ras was not disrupted in either whole brain or hippocampus of Zdhhc9 mutant mice, suggesting that other substrates of this enzyme are linked to the observed changes. Overall, this study highlights a key role for zDHHC9 in brain development and behaviour, and supports the utility of the Zdhhc9 mutant mouse line to investigate molecular and cellular changes linked to intellectual disability and other deficits in the human population

Environmental forcing by submarine canyons: Evidence between two closely situated cold-water coral mounds (Porcupine Bank Canyon and Western Porcupine Bank, NE Atlantic)

Within the Porcupine Bank Canyon (NE Atlantic), cold-water coral (CWC) mounds are mostly found clustered along the canyon lip, with individual disconnected mounds occurring nearby on the western Porcupine Bank. Remotely operated vehicle-mounted vibrocoring was utilized to acquire cores from both of these sites. This study is the first to employ this novel method when aiming to precisely sample two closely situated areas. Radiometric ages constrain the records from the early to mid-Holocene (9.1 to 5.6 ka BP). The cores were then subjected to 3D segmented computer tomography to capture mound formation stages. The cores were then further examined using stable isotopes and benthic foraminiferal assemblages, to constrain the paleoenvironmental variation that influenced CWC mound formation of each site. In total, mound aggradation rate in the Porcupine Bank Canyon and western Porcupine Bank was comparable to other Holocene CWC mounds situated off western Ireland. Results derived from multiproxy analysis, show that regional climatic shifts define the environmental conditions that allow positive coral mound formation. In addition, the aggradation rate of coral mounds is higher adjacent to the Porcupine Bank Canyon than on the western Porcupine Bank. Benthic foraminifera assemblages and planktic foraminiferal δ13C reveal that higher quality organic matter is more readily available closer to the canyon lip. As such, we hypothesize that coral mound formation in the region is likely controlled by an interplay between enhanced shelf currents and the existence of the Eastern North Atlantic Water-Mediterranean Outflow Water-Transition Zone. The geomorphology of the canyon promotes upwelling of these water masses that are enriched in particles, including food and sediment supply. The higher availability of these particles support the development and succession of ecological hotspots along the canyon lip and adjacent areas of the seafloor. These observations provide a glimpse into the role that submarine canyons play in influencing macro and micro benthic fauna distributions and highlights the importance of their conservation

Using novel methods to track British and Irish Ice Sheet dynamics since the Late Pleistocene, along the west Porcupine Bank, NE Atlantic

Extensive research has been undertaken to elucidate the glacial history of the British Irish Ice Sheet (BIIS) in the NE Atlantic. BRITICE-CHRONO has compiled terrestrial and marine based evidence, to provide an empirical reconstruction of ice sheet expansion and retreat during the Late Pleistocene. Across the Irish margin, particular focus has been given to seafloor sediments which contain ice-rafted debris (IRD). However, there are few publications on IRD from areas proximal to the maximum extent of the BIIS, which would offer further insights on the behaviour of the ice sheet during (de)glacial events. Previous exploratory surveys of the west Porcupine Bank (wPB) visually identified IRD on the seafloor and these present a new study site to investigate the extent of the BIIS and the course of its icebergs. Moreover, there are uncertainties about the effects of icebergs on the marine life and cold-water corals occupying the nearby Porcupine Bank Canyon. Assessing a sediment core containing an IRD analogue for the wPB would thus, have a dual purpose. In the past however, coring missions of the wPB using traditional coring methods (i.e. piston and gravity cores) were unsuccessful. Here, we utilized a novel ROV-mounted vibrocoring procedure to capture a 0.75 m IRD-bearing sediment core from the wPB. Then further novel analytical methods (computed tomography-based IRD-detection) were used to quantify IRD every 0.02 cm to provide the highest resolution record of BIIS related IRD to date. From this, several fluxes of IRD deposition onto the wPB between 31.6 and 9 ka BP were revealed and corroborated by other published records from across the NE Atlantic. It was shown that the wPB IRD fluxes occur simultaneously with other parts of the margin. The IRD signal also shows that iceberg calving occurred on the wPB during the Younger Dryas. Grain-size analysis of the core allowed for a reconstruction and interpretation of the palaeoenvironmental conditions during these IRD flux events and shows that BIIS-derived glaciers had a major impact on hydrodynamic conditions in the wPB. Subsequently, intensive scouring led to a major hiatus in the core during 27.3â 17.2 ka BP. These results are a useful addition to BIIS literature on this part of the shelf. Furthermore, it shows that bottom currents were influenced by (de)glacial events, an important finding when considering the presence of nearby current-dependant benthos

Transcriptome Prediction Performance Across Machine Learning Models and Diverse Ancestries

Transcriptome prediction methods such as PrediXcan and FUSION have become popular in complex trait mapping. Most transcriptome prediction models have been trained in European populations using methods that make parametric linear assumptions like the elastic net (EN). To potentially further optimize imputation performance of gene expression across global populations, we built transcriptome prediction models using both linear and non-linear machine learning (ML) algorithms and evaluated their performance in comparison to EN. We trained models using genotype and blood monocyte transcriptome data from the Multi-Ethnic Study of Atherosclerosis (MESA) comprising individuals of African, Hispanic, and European ancestries and tested them using genotype and whole-blood transcriptome data from the Modeling the Epidemiology Transition Study (METS) comprising individuals of African ancestries. We show that the prediction performance is highest when the training and the testing population share similar ancestries regardless of the prediction algorithm used. While EN generally outperformed random forest (RF), support vector regression (SVR), and K nearest neighbor (KNN), we found that RF outperformed EN for some genes, particularly between disparate ancestries, suggesting potential robustness and reduced variability of RF imputation performance across global populations. When applied to a high-density lipoprotein (HDL) phenotype, we show including RF prediction models in PrediXcan revealed potential gene associations missed by EN models. Therefore, by integrating other ML modeling into PrediXcan and diversifying our training populations to include more global ancestries, we may uncover new genes associated with complex traits

Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics

Desmoglein 3 (Dsg3), a member of the desmoglein sub-family, serves as an adhesion molecule in desmosomes. Our previous study showed that overexpression of human Dsg3 in several epithelial lines induces formation of membrane protrusions, a phenotype suggestive of Rho GTPase activation. Here we examined the interaction between Dsg3 and actin in detail and showed that endogenous Dsg3 colocalises and interacts with actin, particularly the junctional actin in a Rac1-dependent manner. Ablation of Rac1 activity by dominant negative Rac1 mutant (N17Rac1) or the Rac1 specific inhibitor (NSC23766) directly disrupts the interaction between Dsg3 and actin. Assembly of the junctional actin at the cell borders is accompanied with enhanced levels of Dsg3, while inhibition of Dsg3 by RNAi results in profound changes in the organisation of actin cytoskeleton. In accordance, overexpression of Dsg3 results in a remarkable increase of Rac1 and Cdc42 activities and to a lesser extent, RhoA. The enhancements in Rho GTPases are accompanied by the pronounced actin-based membrane structures such as lamellipodia and filopodia, enhanced rate of actin turnover and cell polarisation. Together, our results reveal an important novel function for Dsg3 in promoting actin dynamics through regulating Rac1 and Cdc42 activation in epithelial cells

Measuring Biodiversity and Extinction – Present and Past

How biodiversity is changing in our time represents a major concern for all organismal biologists. Anthropogenic changes to our planet are decreasing species diversity through the negative effects of pollution, habitat destruction, direct extirpation of species, and climate change. But major biotic changes – including those that have both increased and decreased species diversity – have happened before in Earth’s history. Biodiversity dynamics in past eras provide important context to understand ecological responses to current environmental change. The work of assessing biodiversity is woven into ecology, environmental science, conservation, paleontology, phylogenetics, evolutionary and developmental biology, and many other disciplines; yet, the absolute foundation of how we measure species diversity depends on taxonomy and systematics. The aspiration of this symposium, and complementary contributed talks, was to promote better understanding of our common goals and encourage future interdisciplinary discussion of biodiversity dynamics. The contributions in this collection of papers bring together a diverse group of speakers to confront several important themes. How can biologists best respond to the urgent need to identify and conserve diversity? How can we better communicate the nature of species across scientific disciplines? Where are the major gaps in knowledge about the diversity of living animal and plant groups, and what are the implications for understanding potential diversity loss? How can we effectively use the fossil record of past diversity and extinction to understand current biodiversity loss