Buckling without bending: a new paradigm in morphogenesis

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out-of-phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in-phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2d morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluid-like film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential". Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale-invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bio-inspired applications, and address how our model is and is not unique to the developing nervous system.Comment: version accepted by Physical Review

Biodesalination: an emerging technology for targeted removal of Na+and Cl−from seawater by cyanobacteria

Although desalination by membrane processes is a possible solution to the problem of freshwater supply, related cost and energy demands prohibit its use on a global scale. Hence, there is an emerging necessity for alternative, energy and cost-efficient methods for water desalination. Cyanobacteria are oxygen-producing, photosynthetic bacteria that actively grow in vast blooms both in fresh and seawater bodies. Moreover, cyanobacteria can grow with minimal nutrient requirements and under natural sunlight. Taking these observations together, a consortium of five British Universities was formed to test the principle of using cyanobacteria as ion exchangers, for the specific removal of Na+ and Cl− from seawater. This project consisted of the isolation and characterisation of candidate strains, with central focus on their potential to be osmotically and ionically adaptable. The selection panel resulted in the identification of two Euryhaline strains, one of freshwater (Synechocystis sp. Strain PCC 6803) and one of marine origin (Synechococcus sp. Strain PCC 7002) (Robert Gordon University, Aberdeen). Other work packages were as follows. Genetic manipulations potentially allowed for the expression of a light-driven, Cl−-selective pump in both strains, therefore, enhancing the bioaccumulation of specific ions within the cell (University of Glasgow). Characterisation of surface properties under different salinities (University of Sheffield), ensured that cell–liquid separation efficiency would be maximised post-treatment, as well as monitoring the secretion of mucopolysaccharides in the medium during cell growth. Work at Newcastle University is focused on the social acceptance of this scenario, together with an assessment of the potential risks through the generation and application of a Hazard Analysis and Critical Control Points plan. Finally, researchers in Imperial College (London) designed the process, from biomass production to water treatment and generation of a model photobioreactor. This multimodal approach has produced promising first results, and further optimisation is expected to result in mass scaling of this process

Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications

Parkinson's disease subtypes in the Oxford Parkinson disease centre (OPDC) discovery cohort

Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s

Globalisation, neo-liberalism and vocational learning: the case of English further education colleges

Further education (FE) has traditionally been a rather unspectacular activity. Lacking the visibility of schools or the prestige of universities, for the vast majority of its existence FE has had a relatively low profile on the margins of English education. Over recent years this situation has altered significantly and further education has undergone profound change. This paper argues that a combination of related factors – neo-liberalism, globalisation, and dominant discourses of the knowledge economy – has acted in synergy to transform FE into a highly performative and marketised sector. Against this backdrop, further education has been assigned a particular role based upon certain narrow and instrumental understandings of skill, employment and economic competitiveness. The paper argues that, although it has always been predominantly working class in nature, FE is now, more than ever, positioned firmly at the lower end of the institutional hierarchy in the highly class-stratified terrain of English education

Dust Emission from Evolved and Unevolved HII Regions in the Large Magellanic Cloud

We present a study of the dust properties of 12 classical and superbubble HII regions in the Large Magellanic Cloud. We use infrared photometry from Spitzer (8, 24, 70, and 160 \mum bands), obtained as part of the Surveying the Agents of a Galaxy's Evolution (SAGE) program, along with archival spectroscopic classifications of the ionizing stars to examine the role of stellar sources on dust heating and processing. Our infrared observations show surprisingly little correlation between the emission properties of the dust and the effective temperatures or bolometric magnitudes of stars in the HII regions, suggesting that the HII region evolutionary timescale is not on the order of the dust processing timescale. We find that the infrared emission of superbubbles and classical HII regions shows little differentiation between the two classes, despite the significant differences in age and morphology. We do detect a correlation of the 24 \mum emission from hot dust with the ratio of 70 to 160 \mum flux. This correlation can be modeled as a trend in the temperature of a minority hot dust component, while a majority of the dust remains significantly cooler.Comment: 15 pages, 5 figures. Accepted to Ap

Identification of a major causative agent of human cercarial dermatitis, Trichobilharzia franki (Muller and Kimmig 1994), in southern England and its evolutionary relationships with other European populations.

Background Trichobilharzia is the most species rich and widely distributed genus of schistosomes and is known throughout Europe and North America as an agent of human cercarial dermatitis. The disease is caused by an acute allergic reaction in the skin that develops as a consequence of repeated contact with water containing schistosomatid cercariae. However, despite historical outbreaks of the disease, there are no published records of accurately identified Trichobilharzia species from the UK. Methods Two hundred Radix auricularia (L.) were sampled from a recreational fishing lake in Hampshire and emerging schistosomatid cercariae were collected for microscopy and DNA extraction. General morphological description of the cercariae was performed, alongside sequencing and phylogenetic analysis of the 28S ribosomal DNA for accurate species identification as well as comparisons of ITS1 in order to identify evolutionary affinities with other European populations. All molecular comparisons were performed using published sequences. Results The phylogenetic analysis of 28S sequences identified the cercariae as Trichobilharzia franki. Two unique British ITS1 haplotypes were identified which were most closely related to haplotypes of T. franki populations from France. Haplotype network analysis indicated the mixing of T. franki populations throughout Europe. It is suggested that parasite distribution is the probable result of the movement of migratory waterfowl. Conclusions This is the first accurate record of T. franki in the UK. The movement of T. franki with waterfowl could pose a considerable human health risk, as in mainland Europe, and signifies T. franki-associated human cercarial dermatitis as a re-emerging disease in the UK

Furthering the Growth of Cloud Computing by Providing Privacy as a Service

The evolution of Cloud Computing as a viable business solution for providing hardware and software has created many security concerns. Among these security concerns, privacy is often overlooked. If Cloud Computing is to continue its growth, this privacy concern will need to be addressed. In this work we discuss the current growth of Cloud Computing and the impact the public sector and privacy can have in furthering this growth. To begin to provide privacy protection for Cloud Computing, we introduce privacy constraints that outline privacy preferences. We propose the expansion of Cloud Service Level Agreements (SLAs) to include these privacy constraints as Quality of Service (QoS) levels. This privacy QoS must be agreed upon along with the rest of the QoS terms within the SLA by the Cloud consumer and provider. Finally, we introduce Privacy as a Service (PraaS) to monitor the agreement and provide enforcement if necessary

Policies for new path development: the case of Oxfordshire

This chapter reflects on how evolutionary economic geography (EEG) can be extended to incorporate public policy in its explanations of path development. A weakness of EEG is the poor conceptualisation of the role of the state (central, regional, local) in regional path development. It is therefore argued that a multi-scalar perspective of policy is required and that a large set of policies deserve attention. Oxfordshire in the UK is used to explore the link between public policy and path development

Biotic carbon feedbacks in a materially-closed soil-vegetation-atmosphere system

The magnitude and direction of the coupled feedbacks between the biotic and abiotic components of the terrestrial carbon cycle is a major source of uncertainty in coupled climate–carbon-cycle models1, 2, 3. Materially closed, energetically open biological systems continuously and simultaneously allow the two-way feedback loop between the biotic and abiotic components to take place4, 5, 6, 7, but so far have not been used to their full potential in ecological research, owing to the challenge of achieving sustainable model systems6, 7. We show that using materially closed soil–vegetation–atmosphere systems with pro rata carbon amounts for the main terrestrial carbon pools enables the establishment of conditions that balance plant carbon assimilation, and autotrophic and heterotrophic respiration fluxes over periods suitable to investigate short-term biotic carbon feedbacks. Using this approach, we tested an alternative way of assessing the impact of increased CO2 and temperature on biotic carbon feedbacks. The results show that without nutrient and water limitations, the short-term biotic responses could potentially buffer a temperature increase of 2.3 °C without significant positive feedbacks to atmospheric CO2. We argue that such closed-system research represents an important test-bed platform for model validation and parameterization of plant and soil biotic responses to environmental changes