A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self- assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered beta-sheets as their size increases

Student engagement and perceptions of blended-learning of a clinical module in a veterinary degree program.

Blended learning has received much interest in higher education as a way to increase learning efficiency and effectiveness. By combining face-to-face teaching with technology-enhanced learning through online resources, students can manage their own learning. Blended methods are of particular interest in professional degree programs such as veterinary medicine in which students need the flexibility to undertake intra- and extramural activities to develop the range of competencies required to achieve professional qualification. Yet how veterinary students engage with blended learning activities and whether they perceive the approach as beneficial is unclear. We evaluated blended learning through review of student feedback on a 4-week clinical module in a veterinary degree program. The module combined face-to-face sessions with online resources. Feedback was collected by means of a structured online questionnaire at the end of the module and log data collected as part of a routine teaching audit. The features of blended learning that support and detract from students’ learning experience were explored using quantitative and qualitative methods. Students perceived a benefit from aspects of face-to-face teaching and technology-enhanced learning resources. Face-to-face teaching was appreciated for practical activities, whereas online resources were considered effective for facilitating module organization and allowing flexible access to learning materials. The blended approach was particularly appreciated for clinical skills in which students valued a combination of visual resources and practical activities. Although we identified several limitations with online resources that need to be addressed when constructing blended courses, blended learning shows potential to enhance student-led learning in clinical courses

Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis

Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity

Spatial differences in East Scotia Ridge hydrothermal vent food webs: influences of chemistry, microbiology and predation on trophodynamics

The hydrothermal vents on the East Scotia Ridge are the first to be explored in the Antarctic and are dominated by large peltospiroid gastropods, stalked barnacles (Vulcanolepas sp.) and anomuran crabs (Kiwa sp.) but their food webs are unknown. Vent fluid and macroconsumer samples were collected at three vent sites (E2, E9N and E9S) at distances of tens of metres to hundreds of kilometres apart with contrasting vent fluid chemistries to describe trophic interactions and identify potential carbon fixation pathways using stable isotopes. δ13C of dissolved inorganic carbon from vent fluids ranged from −4.6‰ to 0.8‰ at E2 and from −4.4‰ to 1.5‰ at E9. The lowest macroconsumer δ13C was observed in peltospiroid gastropods (−30.0‰ to −31.1‰) and indicated carbon fixation via the Calvin-Benson-Bassham (CBB) cycle by endosymbiotic gamma-Proteobacteria. Highest δ13C occurred in Kiwa sp. (−19.0‰ to −10.5‰), similar to that of the epibionts sampled from their ventral setae. Kiwa sp. δ13C differed among sites, which were attributed to spatial differences in the epibiont community and the relative contribution of carbon fixed via the reductive tricarboxylic acid (rTCA) and CBB cycles assimilated by Kiwa sp. Site differences in carbon fixation pathways were traced into higher trophic levels e.g. a stichasterid asteroid that predates on Kiwa sp. Sponges and anemones at the periphery of E2 assimilated a proportion of epipelagic photosynthetic primary production but this was not observed at E9N. Differences in the δ13C and δ34S values of vent macroconsumers between E2 and E9 sites suggest the relative contributions of photosynthetic and chemoautotrophic carbon fixation (rTCA v CBB) entering the hydrothermal vent food webs vary between the sites

Effects of brooding and broadcasting reproductive modes on the population genetic structure of two Antarctic gastropod molluscs

Life-history characteristics exert a profound influence upon the population structure of many marine organisms. However, relatively few genetic studies have compared direct with indirect-developing species in the same ecosystem or geographical region, and none to our knowledge within an Antarctic setting. To address this issue, we have collected novel amplified fragment length polymorphism (AFLP) data from the direct-developing top shell Margarella antarctica to form a comparison with previously published data for the broadcast-spawning Antarctic limpet Nacella concinna. We scored 270 loci in 240 M. antarctica individuals sampled from five populations spanning the full length of the Antarctic Peninsula. Profound differences were identified in the strength and pattern of population structure between the two species, consistent with gene flow being highly restricted in M. antarctica relative to N. concinna

Hierarchical Population Genetic Structure in a Direct Developing Antarctic Marine Invertebrate

Hoffman J, Clarke A, Clark MS, Peck LS. Hierarchical Population Genetic Structure in a Direct Developing Antarctic Marine Invertebrate. PLoS ONE. 2013;8(5): e63954.Understanding the relationship between life-history variation and population structure in marine invertebrates is not straightforward. This is particularly true of polar species due to the difficulty of obtaining samples and a paucity of genomic resources from which to develop nuclear genetic markers. Such knowledge, however, is essential for understanding how different taxa may respond to climate change in the most rapidly warming regions of the planet. We therefore used over two hundred polymorphic Amplified Fragment Length Polymorphisms (AFLPs) to explore population connectivity at three hierachical spatial scales in the direct developing Antarctic topshell Margarella antarctica. To previously published data from five populations spanning a 1500 km transect along the length of the Western Antarctic Peninsula, we added new AFLP data for four populations separated by up to 6 km within Ryder Bay, Adelaide Island. Overall, we found a nonlinear isolation-by-distance pattern, suggestive of weaker population structure within Ryder Bay than is present over larger spatial scales. Nevertheless, significantly positive Fst values were obtained in all but two of ten pairwise population comparisons within the bay following Bonferroni correction for multiple tests. This is in contrast to a previous study of the broadcast spawner Nacella concinna that found no significant genetic differences among several of the same sites. By implication, the topshell's direct-developing lifestyle may constrain its ability to disperse even over relatively small geographic scales

An unusual hermaphrodite reproductive trait in the Antarctic brooding bivalve Lissarca miliaris (Philobryidae) from the Scotia Sea, Southern Ocean

The Antarctic marine environment is extreme in its low temperatures and short periods of primary productivity. Invertebrates must therefore adapt to maximise reproductive output where low temperature and limited food slows larval development. Brooding is a common reproductive trait in Antarctic marine bivalves; larval development occurs within the mantle cavity, and larvae are released as fully developed young. Lissarca miliaris is a small, short lived, shallow-water brooding bivalve of circum-Antarctic distribution and found most abundant in the sub-Antarctic Magellan Region and islands of the Scotia Arc. Here, an unusual hermaphrodite reproductive trait is described for L. miliaris from King George Island (62?14’S, 58?38’W) and Signy Island (60?42’S, 45?36’W), Antarctica, using histological and dissection techniques. Specimens demonstrate simultaneous and sequential hermaphrodite traits; male and female gonads develop simultaneously but the production of oocytes is reduced while testes are ripe. Functional females are more abundant in specimens above 3mm shell length, although male reproductive tissue persists and functional males are found in all size classes. The number of previtellogenic oocytes produced by far exceeds the number of oocytes extruded and brooded, which may indicate an ancestral link to a planktotrophic past. Hermaphroditism in L. miliaris maximises reproductive efficiency in a short-lived species in which the female’s capacity to brood its young is limited, and demonstrates a specialised adaptation to a cold stenothermal and food limited environment prevailing in the Southern Ocean