Publications

Abstract:
What can the brand manager expect from Facebook?.

Managers cannot afford to ignore social media and have stepped up their involvement in the belief that social media activities extend the brand’s reach and engagement with consumers. Facebook is the preeminent social medium with an ever increasing branded content. One hundred brands selected from the Interbrand “Best Global Brand Report” form the basis of this study to test research propositions about the ability of branded Facebook pages to expand and engage users. Data captured from branded Facebook pages was supplemented with socialbaker’s data. No correlation is found between the size of a brand and the number of Facebook fans, and there is no consistent relationship with user engagement and brand size.
The authors discuss broadening reach, improving engagement, interaction and activity and the implications for social media strategies and make recommendations for managing Facebook presence. Paid advertising is required to increase brand reach to all potential category users. 

Abstract:
A highly attenuating and frequency tailorable annular hole phononic crystal for surface acoustic waves.

© 2017 the Author(s). Surface acoustic wave (SAW) devices are widely used for signal processing, sensing and increasingly for lab-on-a-chip applications. Phononic crystals can control the propagation of SAW, analogous to photonic crystals, enabling components such as waveguides and cavities. Here we present an approach for the realisation of robust, tailorable SAW phononic crystals, based on annular holes patterned in a SAW substrate. Using simulations and experiments, we show that this geometry supports local resonances which create highly attenuating phononic bandgaps at frequencies with negligible coupling of SAWs into other modes, even for relatively shallow features. The enormous bandgap attenuation is up to an order-of-magnitude larger than that achieved with a pillar phononic crystal of the same size, enabling effective phononic crystals to be made up of smaller numbers of elements. This work transforms the ability to exploit phononic crystals for developing novel SAW device concepts, mirroring contemporary progress in photonic crystals. 

Abstract:
AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner.

© 2017 John Wiley. &. Sons Ltd Aim: to test the hypothesis that, given the role of AMP-activated protein kinase (AMPK) in regulating intracellular ATP levels, AMPK may alter ATP release from astrocytes, the main sources of extracellular ATP (eATP) within the brain. Materials and Methods: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild-type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs). Cells were treated with drugs known to modulate AMPK activity: A-769662, AICAR and metformin, for up to 3 hours. Intracellular calcium was measured using Fluo4 and Fura-2 calcium-sensitive fluorescent dyes. Results: in U373 cells, A-769662 (100 μM) increased AMPK phosphorylation, whereas AICAR and metformin (1 mM) induced a modest increase or had no effect, respectively. Only A-769662 increased eATP levels, and this was partially blocked by AMPK inhibitor Compound C. A-769662-induced increases in eATP were preserved in AMPK α1/α2 null MEF cells. A-769662 increased intracellular calcium in U373, HTAS and CRTAS cells and chelation of intracellular calcium using BAPTA-AM reduced A-769662-induced eATP levels. A-769662 also increased ATP release from a number of other central and peripheral endocrine cell types. Conclusions: AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. 

Abstract:
Constrained evolution of the sex comb in Drosophila simulans.

Male fitness is dependent on sexual traits that influence mate acquisition (precopulatory sexual selection) and paternity (post-copulatory sexual selection), and although many studies have documented the form of selection in one or the other of these arenas, fewer have done it for both. Nonetheless, it appears that the dominant form of sexual selection is directional, although theoretically, populations should converge on peaks in the fitness surface, where selection is stabilizing. Many factors, however, can prevent populations from reaching adaptive peaks. Genetic constraints can be important if they prevent the development of highest fitness phenotypes, as can the direction of selection if it reverses across episodes of selection. In this study, we examine the evidence that these processes influence the evolution of the multivariate sex comb morphology of male Drosophila simulans. To do this, we conduct a quantitative genetic study together with a multivariate selection analysis to infer how the genetic architecture and selection interact. We find abundant genetic variance and covariance in elements of the sex comb. However, there was little evidence for directional selection in either arena. Significant nonlinear selection was detected prior to copulation when males were mated to nonvirgin females, and post-copulation during sperm offence (again with males mated to nonvirgins). Thus, contrary to our predictions, the evolution of the D. simulans sex comb is limited neither by genetic constraints nor by antagonistic selection between pre- and post-copulatory arenas, but nonlinear selection on the multivariate phenotype may prevent sex combs from evolving to reach some fitness maximizing optima. 

Abstract:
Dynamic in-situ sensing of fluid-dispersed 2D materials integrated on microfluidic Si chip.

In this work, we propose a novel approach for wafer-scale integration of 2D materials on CMOS photonics chip utilising methods of synthetic chemistry and microfluidics technology. We have successfully demonstrated that this approach can be used for integration of any fluid-dispersed 2D nano-objects on silicon-on-insulator photonics platform. We demonstrate for the first time that the design of an optofluidic waveguide system can be optimised to enable simultaneous in-situ Raman spectroscopy monitoring of 2D dispersed flakes during the device operation. Moreover, for the first time, we have successfully demonstrated the possibility of label-free 2D flake detection via selective enhancement of the Stokes Raman signal at specific wavelengths. We discovered an ultra-high signal sensitivity to the xyz alignment of 2D flakes within the optofluidic waveguide, which in turn enables precise in-situ alignment detection for the first practicable realisation of 3D photonic microstructure shaping based on 2D-fluid composites and CMOS photonics platform while also representing a useful technological tool for the control of liquid phase deposition of 2D materials. 

Abstract:
Inspiring a ‘Fourth Revolution’? the Modern Revolutionary Tradition and the Problems Surrounding the Commemoration of 1917 in 2017 in Russia.

© 2017 Institute of Historical Research.There has been much written about the official commemorations of 1917 in Soviet Russia, but after 1991 the revolution became a contentious event and it is unclear how the state will commemorate the centenary. It is too big to ignore, but potentially dangerous politically. After the ‘colour revolutions’ and the Arab Spring, revolution has been associated with instability, violence and terror, and is used to justify increasingly authoritarian and interventionist domestic and foreign policies. This article examines Putin’s speeches and the state’s actions to suggest that the state may try to recast 1917 as a celebration of former imperial and Soviet power rather than as a short-lived democratic revolution. 

Abstract:
Time-dependent spectral analysis of interactions within groups of walking pedestrians and vertical structural motion using wavelets.

© 2017 the Authors a multi-scale and multi-object interaction phenomena can arise when a group of walking pedestrians crosses a structure capable of exhibiting dynamic response. This is because each pedestrian is an autonomous dynamic system capable of displaying intricate behaviour affected by social, psychological, biomechanical and environmental factors, including adaptations to the structural motion. Despite a wealth of mathematical models attempting to describe and simulate coupled crowd-structure system, their applicability can generally be considered uncertain. This can be assigned to a number of assumptions made in their development and the scarcity or unavailability of data suitable for their validation, in particular those associated with pedestrian-pedestrian and pedestrian-structure interaction. To alleviate this problem, data on behaviour of individual pedestrians within groups of six walkers with different spatial arrangements are gathered simultaneously with data on dynamic structural response of a footbridge, from a series of measurements utilising wireless motion monitors. Unlike in previous studies on coordination of pedestrian behaviour, the collected data can serve as a proxy for pedestrian vertical force, which is of critical importance from the point of view of structural stability. A bivariate analysis framework is proposed and applied to these data, encompassing wavelet transform, synchronisation measures based on Shannon entropy and circular statistics. A topological pedestrian map is contrived showing the strength and directionality of between-subjects interactions. It is found that the coordination in pedestrians’ vertical force depends on the spatial collocation within a group, but it is generally weak. The relationship between the bridge and pedestrian behaviour is also analysed, revealing stronger propensity for pedestrians to coordinate their force with the structural motion rather than with each other. 

Abstract:
Wild small mammals as sentinels for the environmental transmission of antimicrobial resistance.

© 2016 the Authors Antimicrobial resistance (AMR) represents a serious threat to human health worldwide. We have tested the use of free-living small mammals (mice, voles and shrews) as sentinels of variation in the distribution of AMR in the environment and the potential for transmission from the natural environment to animal hosts. Escherichia coli isolated from the faeces of small mammals trapped at paired coastal and inland sites were tested for resistance to four antibiotics: trimethoprim, ampicillin, ciprofloxacin and cefotaxime. Coastal individuals were over twice as likely to carry AMR E. coli than inland individuals (79% and 35% respectively), and both between-site and between-species variation was observed. Animals from coastal populations also excreted increased numbers of AMR E. coli and a greater diversity of E. coli phylotypes, including human-associated pathogenic strains. Small mammals appear to be useful bioindicators of fine-scale spatial variation in the distribution of AMR and, potentially, of the risks of AMR transmission to mammalian hosts, including humans. 

Abstract:
A framework for experimental determination of localised vertical pedestrian forces on full-scale structures using wireless attitude and heading reference systems.

© 2016 the Authors a major weakness among loading models for pedestrians walking on flexible structures proposed in recent years is the various uncorroborated assumptions made in their development. This applies to spatio-temporal characteristics of pedestrian loading and the nature of multi-object interactions. To alleviate this problem, a framework for the determination of localised pedestrian forces on full-scale structures is presented using a wireless attitude and heading reference systems (AHRS). An AHRS comprises a triad of tri-axial accelerometers, gyroscopes and magnetometers managed by a dedicated data processing unit, allowing motion in three-dimensional space to be reconstructed. A pedestrian loading model based on a single point inertial measurement from an AHRS is derived and shown to perform well against benchmark data collected on an instrumented treadmill. Unlike other models, the current model does not take any predefined form nor does it require any extrapolations as to the timing and amplitude of pedestrian loading. In order to assess correctly the influence of the moving pedestrian on behaviour of a structure, an algorithm for tracking the point of application of pedestrian force is developed based on data from a single AHRS attached to a foot. A set of controlled walking tests with a single pedestrian is conducted on a real footbridge for validation purposes. A remarkably good match between the measured and simulated bridge response is found, indeed confirming applicability of the proposed framework. 

Abstract:
Dietary choice for a balanced nutrient intake increases the mean and reduces the variance in the reproductive performance of male and female cockroaches.

© 2016 the Authors. Ecology and Evolution published by John Wiley. &. Sons Ltd. Sexual selection may cause dietary requirements for reproduction to diverge across the sexes and promote the evolution of different foraging strategies in males and females. However, our understanding of how the sexes regulate their nutrition and the effects that this has on sex-specific fitness is limited. We quantified how protein (P) and carbohydrate (C) intakes affect reproductive traits in male (pheromone expression) and female (clutch size and gestation time) cockroaches (Nauphoeta cinerea). We then determined how the sexes regulate their intake of nutrients when restricted to a single diet and when given dietary choice and how this affected expression of these important reproductive traits. Pheromone levels that improve male attractiveness, female clutch size and gestation time all peaked at a high daily intake of P:C in a 1:8 ratio. This is surprising because female insects typically require more P than males to maximize reproduction. The relatively low P requirement of females may reflect the action of cockroach endosymbionts that help recycle stored nitrogen for protein synthesis. When constrained to a single diet, both sexes prioritized regulating their daily intake of P over C, although this prioritization was stronger in females than males. When given the choice between diets, both sexes actively regulated their intake of nutrients at a 1:4.8 P:C ratio. The P:C ratio did not overlap exactly with the intake of nutrients that optimized reproductive trait expression. Despite this, cockroaches of both sexes that were given dietary choice generally improved the mean and reduced the variance in all reproductive traits we measured relative to animals fed a single diet from the diet choice pair. This pattern was not as strong when compared to the single best diet in our geometric array, suggesting that the relationship between nutrient balancing and reproduction is complex in this species. 

Abstract:
Hypoxia Suppressed Copper Toxicity during Early Development in Zebrafish Embryos in a Process Mediated by the Activation of the HIF Signaling Pathway.

Hypoxia is a global and increasingly important stressor in aquatic ecosystems, with major impacts on biodiversity worldwide. Hypoxic waters are often contaminated with a wide range of chemicals but little is known about the interactions between these stressors. We investigated the effects of hypoxia on the responses of zebrafish (Danio rerio) embryos to copper, a widespread aquatic contaminant. We showed that during continuous exposures copper toxicity was reduced by over 2-fold under hypoxia compared to normoxia. When exposures were conducted during 24 h windows, hypoxia reduced copper toxicity during early development and increased its toxicity in hatched larvae. To investigate the role of the hypoxia signaling pathway on the suppression of copper toxicity during early development, we stabilized the hypoxia inducible factor (HIF) pathway under normoxia using a prolyl-4-hydroxylase inhibitor, dimethyloxalylglycine (DMOG) and demonstrated that HIF activation results in a strong reduction in copper toxicity. We also established that the reduction in copper toxicity during early development was independent of copper uptake, while after hatching, copper uptake was increased under hypoxia, corresponding to an increase in copper toxicity. These findings change our understanding of the current and future impacts of worldwide oxygen depletion on fish communities challenged by anthropogenic toxicants. 

Abstract:
Lack of aggression and apparent altruism towards intruders in a primitive termite.

In eusocial insects, the ability to discriminate nestmates from non-nestmates is widespread and ensures that altruistic actions are directed towards kin and agonistic actions are directed towards non-relatives. Most tests of nestmate recognition have focused on hymenopterans, and suggest that cooperation typically evolves in tandem with strong antagonism towards non-nestmates. Here we present evidence from a phylogenetically and behaviourally basal termite species that workers discriminate members of foreign colonies. However, contrary to our expectations, foreign intruders were the recipients of more rather than less cooperative behaviour, and were not subjected to elevated aggression. We suggest that relations between groups may be much more peaceable in basal termites compared to eusocial hymenoptera, owing to energetic and temporal constraints on colony growth, and the reduced incentive that totipotent workers (who may inherit breeding status) have to contribute to self-sacrificial intergroup conflict. 

Abstract:
Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2). During this process, sFRP2 promotes Ror2 signal transduction by stabilizing Wnt5a-Ror2 complexes at the membrane, whereas it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis. The cysteine-rich domain of sFRP2 is sufficient for Ror2 activation, and related sFRPs can substitute for this function. Notably, direct interaction of the two receptors via their cysteine-rich domains also promotes Ror2-mediated papc expression but inhibits Fz7 signaling. We propose that sFRPs can act as a molecular switch, channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation. 

Abstract:
Taxonomic distinctness in the diet of two sympatric marine turtle species.

� 2016 Blackwell Verlag GmbH Marine turtles are considered keystone consumers in tropical coastal ecosystems and their decline through overexploitation has been implicated in the deterioration of reefs and seagrass pastures in the Caribbean. In the present study, we analysed stomach contents of green (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) harvested in the legal turtle fishery of the Turks and Caicos Islands (Caribbean) during 2008–2010. Small juveniles to adult-sized turtles were sampled. Together with data from habitat surveys, we assessed diet composition and the taxonomic distinctness (and other species diversity measures) in the diets of these sympatric marine turtle species. The diet of green turtles (n�=�92) consisted of a total of 47 taxa: including three species of seagrass (present in 99% of individuals), 29 species of algae and eight sponge species. Hawksbill turtles (n�=�45) consumed 73 taxa and were largely spongivorous (16 species; sponges present in 100% of individuals) but also foraged on 50 species of algae (present in 73% of individuals) and three species of seagrass. Plastics were found in trace amounts in 4% of green turtle and 9% of hawksbill turtle stomach samples. We expected to find changes in diet that might reflect ontogenetic shifts from small (oceanic-pelagic) turtles to larger (coastal-benthic) turtles. Dietary composition (abundance and biomass), however, did not change significantly with turtle size, although average taxonomic distinctness was lower in larger green turtles. There was little overlap in prey between the two turtle species, suggesting niche separation. Taxonomic distinctness routines indicated that green turtles had the most selective diet, whereas hawksbill turtles were less selective than expected when compared with the relative frequency and biomass of diet items. We discuss these findings in relation to the likely important trophic roles that these sympatric turtle species play in reef and seagrass habitats. 

Abstract:
Theoretical limits on magnetic field strengths in low-mass stars.

Observations have suggested that some low-mass stars have larger radii than
predicted by 1-D structure models. Some theoretical models have invoked very
strong interior magnetic fields (of order 1 MG or more) as a possible cause of
such large radii. Whether fields of that strength could in principle by
generated by dynamo action in these objects is unclear, and we do not address
the matter directly. Instead, we examine whether such fields could remain in
the interior of a low mass object for a significant time, and whether they
would have any other obvious signatures. First, we estimate timescales for the
loss of strong fields by magnetic buoyancy instabilities. We consider a range
of field strengths and simple morphologies, including both idealized flux tubes
and smooth layers of field. We confirm some of our analytical estimates using
thin flux tube magnetohydrodynamic (MHD) simulations of the rise of buoyant
fields in a fully-convective M-dwarf. Separately, we consider the Ohmic
dissipation of such fields. We find that dissipation provides a complementary
constraint to buoyancy: while small-scale, fibril fields might be regenerated
faster than they rise, the dissipative heating associated with such fields
would in some cases greatly exceed the luminosity of the star. We show how
these constraints combine to yield limits on the internal field strength and
morphology in low-mass stars. In particular, we find that for stars of 0.3
solar masses, no fields in flux tubes stronger than about 800 kG are
simultaneously consistent with both constraints. 

Abstract:
Artificial nighttime light changes aphid-parasitoid population dynamics.

Artificial light at night (ALAN) is recognized as a widespread and increasingly important anthropogenic environmental pressure on wild species and their interactions. Understanding of how these impacts translate into changes in population dynamics of communities with multiple trophic levels is, however, severely lacking. In an outdoor mesocosm experiment we tested the effect of ALAN on the population dynamics of a plant-aphid-parasitoid community with one plant species, three aphid species and their specialist parasitoids. The light treatment reduced the abundance of two aphid species by 20% over five generations, most likely as a consequence of bottom-up effects, with reductions in bean plant biomass being observed. For the aphid Megoura viciae this effect was reversed under autumn conditions with the light treatment promoting continuous reproduction through asexuals. All three parasitoid species were negatively affected by the light treatment, through reduced host numbers and we discuss induced possible behavioural changes. These results suggest that, in addition to direct impacts on species behaviour, the impacts of ALAN can cascade through food webs with potentially far reaching effects on the wider ecosystem.  

Abstract:
Filopodia-based Wnt transport during vertebrate tissue patterning.

Paracrine Wnt/β-catenin signalling is important during developmental processes, tissue regeneration and stem cell regulation. Wnt proteins are morphogens, which form concentration gradients across responsive tissues. Little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates. Here we show that Wnt8a is transported on actin-based filopodia to contact responding cells and activate signalling during neural plate formation in zebrafish. Cdc42/N-Wasp regulates the formation of these Wnt-positive filopodia. Enhanced formation of filopodia increases the effective signalling range of Wnt by facilitating spreading. Consistently, reduction in filopodia leads to a restricted distribution of the ligand and a limited signalling range. Using a simulation, we provide evidence that such a short-range transport system for Wnt has a long-range signalling function. Indeed, we show that a filopodia-based transport system for Wnt8a controls anteroposterior patterning of the neural plate during vertebrate gastrulation.  

Abstract:
Ingestion of Plastic Microfibers by the Crab Carcinus maenas and its Effect on Food Consumption and Energy Balance.

Microscopic plastic fragments ( 

Abstract:
Photolithographic patterning of 3D-formed polycarbonate films for targeted cell guiding.

A facile photolithographic platform for the design of cell-guiding polymeric substrates is introduced. Specific areas of the substrate are photo-deactivated for the subsequent growth of bioresistant polymer brushes, creating zones for cell proliferation, and protein adhesion. 

Abstract:
Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.

The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.  

Abstract:
Rearing the scuttle fly Megaselia scalaris (Diptera: Phoridae) on industrial compounds: implications on size and lifespan.

Megaselia scalaris (Loew, 1866) (Diptera, phoridae) is a cosmopolitan fly species used in forensic science, and has been developed as a laboratory model species. They feed on decaying corpses as well as a wide variety of organic matter, and previous studies have even found them feeding on liquid paint or shoe polish, suggesting the possibility that they could breakdown industrial compounds. To test this possibility, we fed M. scalaris on a variety of industrially obtained materials and found that it was unable to complete its life cycle, dying at the larval stage, with the majority of compounds tested. However, when fed on modeling clay, a substrate that contains starch and inedible compounds, it was able to complete its life cycle. On this diet we observed increased larval development time, decreased pupal development time and a shortened adult life span. Additionally, pupae and adult flies were smaller than control flies. Contrary to previous reports, we find no evidence that M. scalaris is able to survive on modern formulations of liquid paint.  

Abstract:
Stopping to food can reduce intake. Effects of stimulus-specificity and individual differences in dietary restraint.

Overeating in our food-rich environment is a key contributor to obesity. Computerised response-inhibition training could improve self-control in individuals who overeat. Evidence suggests that training people to inhibit motor responses to specific food pictures can reduce the subsequent choice and consumption of those foods. Here we undertook three experiments using the stop-signal task to examine the effects of food and non-food related stop-training on immediate snack food consumption. The experiments examined whether training effects were stimulus-specific, whether they were influenced by the comparator (control) group, and whether they were moderated by individual differences in dietary restraint. Experiment 1 revealed lower intake of one food following stop- vs. double- (two key-presses) response training to food pictures. Experiment 2 offered two foods, one of which was not associated with stopping, to enable within- and between-subjects comparisons of intake. A second control condition required participants to ignore signals and respond with one key-press to all pictures. There was no overall effect of training on intake in Experiment 2, but there was a marginally significant moderation by dietary restraint: Restrained eaters ate significantly less signal-food following stop- relative to double-response training. Experiment 3 revealed that stop- vs. double-response training to non-food pictures had no effect on food intake. Taken together with previous findings, these results suggest some stimulus-specific effects of stop-training on food intake that may be moderated by individual differences in dietary restraint.  

Abstract:
Targeted allelic expression profiling in human islets identifies cis-regulatory effects for multiple variants identified by type 2 diabetes genome-wide association studies.

Genome-wide association studies (GWAS) have identified variation at >65 genomic loci associated with susceptibility to type 2 diabetes, but little progress has been made in elucidating the molecular mechanisms behind most of these associations. Using samples heterozygous for transcribed single nucleotide polymorphisms (SNPs), allelic expression profiling is a powerful technique for identifying cis-regulatory variants controlling gene expression. In this study, exonic SNPs, suitable for measuring mature mRNA levels and in high linkage disequilibrium with 65 lead type 2 diabetes GWAS SNPs, were identified and allelic expression determined by real-time PCR using RNA and DNA isolated from islets of 36 white nondiabetic donors. A significant allelic expression imbalance (AEI) was identified for 7/14 (50%) genes tested (ANPEP, CAMK2B, HMG20A, KCNJ11, NOTCH2, SLC30A8, and WFS1), with significant AEI confirmed for five of these genes using other linked exonic SNPs. Lastly, results of a targeted islet expression quantitative trait loci experiment support the AEI findings for ANPEP, further implicating ANPEP as the causative gene at its locus. The results of this study support the hypothesis that changes to cis-regulation of gene expression are involved in a large proportion of SNP associations with type 2 diabetes susceptibility.  

Abstract:
Towards graded-index magnonics: Steering spin waves in magnonic networks.

© 2015 American Physical Society. ©2015 American Physical Society. Magnonics explores precessional excitations of ordered spins in magnetic materials - so-called spin waves - and their use as information and signal carriers within networks of magnonic waveguides. Here, we demonstrate that the nonuniformity of the internal magnetic field and magnetization inherent to magnetic structures creates a medium of graded refractive index for propagating magnetostatic waves and can be used to steer their propagation. The character of the nonuniformity can be tuned and potentially programmed using the applied magnetic field, which opens exciting prospects for the field of graded-index magnonics. 

Abstract:
A staging scheme for the development of the moth midge Clogmia albipunctata.

Model organisms, such as Drosophila melanogaster, allow us to address a wide range of biological questions with experimental rigour. However, studies in model species need to be complemented by comparative studies if we are to fully understand the functional properties and evolutionary history of developmental processes. The establishment of new model organisms is crucial for this purpose. One of the first essential steps to establish a species as an experimental model is to carefully describe its life cycle and development. The resulting staging scheme serves as a framework for molecular studies, and allows us to homologise developmental processes between species. In this paper, we have characterised the life cycle and development of an emerging non-drosophilid dipteran model system: the moth midge Clogmia albipunctata. In particular, we focus on early embryogenesis (cleavage and blastoderm cycles before gastrulation), on formation and retraction of extraembryonic tissues, and on formation of the germ line. Considering the large evolutionary distance between the two species (approximately 250 million years), we find that the development of C. albipunctata is remarkably conserved compared to D. melanogaster. On the other hand, we detect significant differences in morphology and timing affecting the development of extraembryonic tissues and the germ line. Moreover, C. albipunctata shows several heterochronic shifts, and lacks head involution and associated processes during late stages of development.  

Abstract:
A staging scheme for the development of the scuttle fly Megaselia abdita.

Model organisms, such as Drosophila melanogaster, provide powerful experimental tools for the study of development. However, approaches using model systems need to be complemented by comparative studies for us to gain a deeper understanding of the functional properties and evolution of developmental processes. New model organisms need to be established to enable such comparative work. The establishment of new model system requires a detailed description of its life cycle and development. The resulting staging scheme is essential for providing morphological context for molecular studies, and allows us to homologise developmental processes between species. In this paper, we provide a staging scheme and morphological characterisation of the life cycle for an emerging non-drosophilid dipteran model system: the scuttle fly Megaselia abdita. We pay particular attention to early embryogenesis (cleavage and blastoderm stages up to gastrulation), the formation and retraction of extraembryonic tissues, and the determination and formation of germ (pole) cells. Despite the large evolutionary distance between the two species (approximately 150 million years), we find that M. abdita development is remarkably similar to D. melanogaster in terms of developmental landmarks and their relative timing.  

Abstract:
Bioinformatic analysis of ciliary transition zone proteins reveals insights into the evolution of ciliopathy networks.

BACKGROUND: Cilia are critical for diverse functions, from motility to signal transduction, and ciliary dysfunction causes inherited diseases termed ciliopathies. Several ciliopathy proteins influence developmental signalling and aberrant signalling explains many ciliopathy phenotypes. Ciliary compartmentalisation is essential for function, and the transition zone (TZ), found at the proximal end of the cilium, has recently emerged as a key player in regulating this process. Ciliary compartmentalisation is linked to two protein complexes, the MKS and NPHP complexes, at the TZ that consist largely of ciliopathy proteins, leading to the hypothesis that ciliopathy proteins affect signalling by regulating ciliary content. However, there is no consensus on complex composition, formation, or the contribution of each component. RESULTS: Using bioinformatics, we examined the evolutionary patterns of TZ complex proteins across the extant eukaryotic supergroups, in both ciliated and non-ciliated organisms. We show that TZ complex proteins are restricted to the proteomes of ciliated organisms and identify a core conserved group (TMEM67, CC2D2A, B9D1, B9D2, AHI1 and a single TCTN, plus perhaps MKS1) which are present in >50% of all ciliate/flagellate organisms analysed in each supergroup. The smaller NPHP complex apparently evolved later than the larger MKS complex; this result may explain why RPGRIP1L, which forms the linker between the two complexes, is not one of the core conserved proteins. We also uncovered a striking correlation between lack of TZ proteins in non-seed land plants and loss of TZ-specific ciliary Y-links that link microtubule doublets to the membrane, consistent with the interpretation that these proteins are structural components of Y-links, or regulators of their formation. CONCLUSIONS: This bioinformatic analysis represents the first systematic analysis of the cohort of TZ complex proteins across eukaryotic evolution. Given the near-ubiquity of only 6 proteins across ciliated eukaryotes, we propose that the MKS complex represents a dynamic complex built around these 6 proteins and implicated in Y-link formation and ciliary permeability. 

Abstract:
Dietary nitrate supplementation: effects on plasma nitrite and pulmonary O2 uptake dynamics during exercise in hypoxia and normoxia.

We investigated the effects of dietary nitrate (NO3 (-)) supplementation on the concentration of plasma nitrite ([NO2 (-)]), oxygen uptake (V̇o2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a double-blind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO3 (-)-rich beetroot juice (8.4 mmol NO3; BR) or NO3 (-)-depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO2 (-)] was significantly elevated in H-BR and N-BR compared with H-PL (P < 0.01) and N-PL (P < 0.01). The rate of decline in plasma [NO2 (-)] was greater during severe-intensity exercise in H-BR [-30 ± 22 nM/min, 95% confidence interval (CI); -44, -16] compared with H-PL (-7 ± 10 nM/min, 95% CI; -13, -1; P < 0.01) and in N-BR (-26 ± 19 nM/min, 95% CI; -38, -14) compared with N-PL (-1 ± 6 nM/min, 95% CI; -5, 2; P < 0.01). During moderate-intensity exercise, steady-state pulmonary V̇o2 was lower in H-BR (1.91 ± 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 ± 0.25 l/min, 95% CI; 1.93, 2.26; P = 0.02), and V̇o2 kinetics was faster in H-BR (τ: 24 ± 13 s, 95% CI; 15, 32) compared with H-PL (31 ± 11 s, 95% CI; 23, 38; P = 0.04). NO3 (-) supplementation had no significant effect on V̇o2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO3 (-) in hypoxia (H-PL: 197 ± 28; 95% CI; 173, 220 vs. H-BR: 214 ± 43 s, 95% CI; 177, 249; P = 0.04) but not normoxia. The metabolism of NO2 (-) during exercise is altered by NO3 (-) supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO3 (-) supplementation enhances V̇o2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude. 

Abstract:
Effects of glyphosate and its formulation, roundup, on reproduction in zebrafish (Danio rerio).

Roundup and its active ingredient glyphosate are among the most widely used herbicides worldwide and may contaminate surface waters. Research suggests both Roundup and glyphosate induce oxidative stress in fish and may also cause reproductive toxicity in mammalian systems. We aimed to investigate the reproductive effects of Roundup and glyphosate in fish and the potential associated mechanisms of toxicity. To do this, we conducted a 21-day exposure of breeding zebrafish (Danio rerio) to 0.01, 0.5, and 10 mg/L (glyphosate acid equivalent) Roundup and 10 mg/L glyphosate. 10 mg/L glyphosate reduced egg production but not fertilization rate in breeding colonies. Both 10 mg/L Roundup and glyphosate increased early stage embryo mortalities and premature hatching. However, exposure during embryogenesis alone did not increase embryo mortality, suggesting that this effect was caused primarily by exposure during gametogenesis. Transcript profiling of the gonads revealed 10 mg/L Roundup and glyphosate induced changes in the expression of cyp19a1 and esr1 in the ovary and hsd3b2, cat, and sod1 in the testis. Our results demonstrate that these chemicals cause reproductive toxicity in zebrafish, although only at high concentrations unlikely to occur in the environment, and likely mechanisms of toxicity include disruption of the steroidogenic biosynthesis pathway and oxidative stress.  

Abstract:
Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling.

Tightly controlled concentration gradients of morphogens provide positional information and thus regulate tissue differentiation and morphogenesis in multicellular organisms. However, how such morphogenetic fields are formed and maintained remains debated. Here we show that fibroblast growth factor 8 (Fgf8) morphogen gradients in zebrafish embryos are established and maintained by two essential mechanisms. Firstly, Fgf8 is taken up into the cell by clathrin-mediated endocytosis. The speed of the uptake rate defines the range of the morphogenetic gradient of Fgf8. Secondly, our data demonstrate that after endocytosis the routing of Fgf8 from the early endosome to the late endosome shuts down signaling. Therefore, intracellular endocytic transport regulates the intensity and duration of Fgf8 signaling. We show that internalization of Fgf8 into the early endosome and subsequent transport towards the late endosome are two independent processes. Therefore, we hypothesize that Fgf8 receiving cells control both, the propagation width and the signal strength of the morphogen.  

Abstract:
Environmental heterogeneity, multivariate sexual selection and genetic constraints on cuticular hydrocarbons in Drosophila simulans.

Sexual selection is responsible for the evolution of many elaborate traits, but sexual trait evolution could be influenced by opposing natural selection as well as genetic constraints. As such, the evolution of sexual traits could depend heavily on the environment if trait expression and attractiveness vary between environments. Here, male Drosophila simulans were reared across a range of diets and temperatures, and we examined differences between these environments in terms of (i) the expression of male cuticular hydrocarbons (CHCs) and (ii) which male CHC profiles were most attractive to females. Temperature had a strong effect on male CHC expression, whereas the effect of diet was weaker. Male CHCs were subject to complex patterns of directional, quadratic and correlational sexual selection, and we found differences between environments in the combination of male CHCs that were most attractive to females, with clearer differences between diets than between temperatures. We also show that genetic covariance between environments is likely to cause a constraint on independent CHC evolution between environments. Our results demonstrate that even across the narrow range of environmental variation studied here, predicting the outcome of sexual selection can be extremely complicated, suggesting that studies ignoring multiple traits or environments may provide an over-simplified view of the evolution of sexual traits. © 2014 European Society for Evolutionary Biology. 

Abstract:
Exploring the utility of analogies in motor learning after stroke: a feasibility study.

Individuals who have experienced a stroke need to (re)learn motor skills. Analogy learning has been shown to facilitate motor learning in sports and may also be an attractive alternative to traditional approaches in therapy. The aim of this study was to assess the feasibility and utility of analogies to improve the walking performance in long-term stroke survivors. Three men aged 76, 87 and 70 years who were 6, 1 and 3 years poststroke, respectively, presented with different walking deficits. An analogy, targeted at improving the walking performance was designed with the help of each participant. During a 3-week intervention period, the analogy was practiced once weekly under supervision and daily at home. To assess feasibility, a structured interview was conducted at the end of the intervention period. To assess utility, walking performance was assessed using the 10-Metre Walking Test. All three participants were supportive of the feasibility and benefits of analogy learning. Two of the participants had a meaningful improvement on the 10-Metre Walking Test (0.1 and 0.3 m/s). The third participant did not improve most likely because of medication issues during the week of the retest. Developing analogies in therapy is a creative and challenging process, as analogies must not only guide the correct movement pattern, but also be meaningful to the individual. However, as participants were supportive of the use of analogies, and positive trends were seen in walking speed it seems worthwhile to pursue the use of analogies in future research.  

Abstract:
Human genetic variation and its effect on miRNA biogenesis, activity and function.

miRNAs are small non-coding regulators of gene expression that are estimated to regulate over 60% of all human genes. Each miRNA can target multiple mRNA targets and as such, miRNAs are responsible for some of the 'fine tuning' of gene expression and are implicated in regulation of all cellular processes. miRNAs bind to target genes by sequence complementarity, resulting in target degradation or translational blocking and usually a reduction in target gene expression. Like mRNA, miRNAs are transcribed from genomic DNA and are processed in several steps that are heavily reliant on correct secondary and tertiary structure. Secondary structure is determined by RNA sequence, which is in turn determined by the sequence of the genome. The human genome, however, like most eukaryotes is variable. Large numbers of SNPs (single nucleotide polymorphisms), small insertions and deletions (indels) and CNVs (copy number variants) have been described in our genome. Should this genetic variation occur in regions critical for the correct secondary structure or target binding, it may interfere with normal gene regulation and cause disease. In this review, we outline the consequences of genetic variation involving different aspects of miRNA biosynthesis, processing and regulation, with selected examples of incidences when this has potential to affect human disease.  

Abstract:
In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

After activation by Wnt/β-Catenin ligands, a multi-protein complex assembles at the plasma membrane as membrane-bound receptors and intracellular signal transducers are clustered into the so-called Lrp6-signalosome [Corrected]. However, the mechanism of signalosome formation and dissolution is yet not clear. Our imaging studies of live zebrafish embryos show that the signalosome is a highly dynamic structure. It is continuously assembled by Dvl2-mediated recruitment of the transducer complex to the activated receptors and partially disassembled by endocytosis. We find that, after internalization, the ligand-receptor complex and the transducer complex take separate routes. The Wnt-Fz-Lrp6 complex follows a Rab-positive endocytic path. However, when still bound to the transducer complex, Dvl2 forms intracellular aggregates. We show that this endocytic process is not only essential for ligand-receptor internalization but also for signaling. The μ2-subunit of the endocytic Clathrin adaptor Ap2 interacts with Dvl2 to maintain its stability during endocytosis. Blockage of Ap2μ2 function leads to Dvl2 degradation, inhibiton of signalosome formation at the plasma membrane and, consequently, reduction of signaling. We conclude that Ap2μ2-mediated endocytosis is important to maintain Wnt/β-catenin signaling in vertebrates. 

Abstract:
The effect of thermal variance on the phenotype of marine turtle offspring.

Temperature can have a profound effect on the phenotype of reptilian offspring, yet the bulk of current research considers the effects of constant incubation temperatures on offspring morphology, with few studies examining the natural thermal variance that occurs in the wild. Over two consecutive nesting seasons, we placed temperature data loggers in 57 naturally incubating clutches of loggerhead sea turtles Caretta caretta and found that greater diel thermal variance during incubation significantly reduced offspring mass, potentially reducing survival of hatchlings during their journey from the nest to offshore waters and beyond. With predicted scenarios of climate change, behavioral plasticity in nest site selection may be key for the survival of ectothermic species, particularly those with temperature-dependent sex determination. 

Abstract:
The suitability of VIE tags to assess stock enhancement success in juvenile European lobsters (Homarus gammarus).

Assessments of stock enhancement programmes for European lobsters (Homarus gammarus) require mark-recapture analysis of stocked individuals. However, established tag technology is deemed unsuitable for extensive use by many current lobster hatcheries, particularly upon the early juvenile stages. We tested the suitability of fluorescent Visible Implant Elastomer (VIE) tags for use in 5-month-old juvenile lobsters. Three treatment groups comprising 348 cultured lobsters in total were used to examine survival, growth and tag retention, and to assess mobility, shelter use and moulting behaviours. Tagging had no significant effect on lobster survival, growth, mobility, shelter use or moult frequency. Survival over 7 weeks was 75% among lobsters tagged with two elastomers, 76% in those with one elastomer and 74% among untagged controls. Mortality during moulting did not increase in tagged (6%) compared to untagged lobsters (9%). We found no evidence that VIE tags cause any negative effects that would be expected to inhibit survival upon wild release, but tag loss had reached 12% in both tagged treatments after 7 weeks and showed no sign of abating. Our study suggests that VIEs effectiveness in discerning cultured lobsters long after wild release may be limited when used in smaller juveniles. © 2014 John Wiley & Sons Ltd. 

Abstract:
Evolution and expression of BMP genes in flies.

Bone morphogenetic proteins (BMPs) play key roles in development. In Drosophila melanogaster, there are three BMP-encoding genes: decapentaplegic (dpp), glass bottom boat (gbb) and screw (scw). dpp and gbb are found in all groups of insects. In contrast, the origin of scw via duplication of an ancestral gbb homologue is more recent, with new evidence placing it within the Diptera. Recent studies show that scw appeared basal to the Schizophora, since scw orthologues exist in aschizan cyclorrhaphan flies. In order to further localise the origin of scw, we have utilised new genomic resources for the nematoceran moth midge Clogmia albipunctata (Psychodidae). We identified the BMP subclass members dpp and gbb from an early embryonic transcriptome and show that their expression patterns in the blastoderm differ considerably from those seen in cyclorrhaphan flies. Further searches of the genome of C. albipunctata were unable to identify a scw-like gbb duplicate, but confirm the presence of dpp and gbb. Our phylogenetic analysis shows these to be clear orthologues of dpp and gbb from other non-cyclorrhaphan insects, with C. albipunctata gbb branching ancestrally to the cyclorrhaphan gbb/scw split. Furthermore, our analysis suggests that scw is absent from all Nematocera, including the Bibionomorpha. We conclude that the gbb/scw duplication occurred between the separation of the lineage leading to Brachycera and the origin of cyclorrhaphan flies 200-150 Ma ago.  

Abstract:
Gas loading of graphene-quartz surface acoustic wave devices.

Graphene was transferred to the propagation path of quartz surface acoustic wave devices and the attenuation due to gas loading of air and argon measured at 70 MHz and 210 MHz and compared to devices with no graphene. Under argon loading, there was no significant difference between the graphene and non-graphene device and the values of measured attenuation agree well with those calculated theoretically. Under air loading, at 210 MHz, there was a significant difference between the non-graphene and graphene devices, with the average value of attenuation obtained with the graphene devices being approximately twice that obtained from the bare quartz devices. © 2013 AIP Publishing LLC. 

Abstract:
Inbreeding reveals mode of past selection on male reproductive characters in Drosophila melanogaster.

Directional dominance is a prerequisite of inbreeding depression. Directionality arises when selection drives alleles that increase fitness to fixation and eliminates dominant deleterious alleles, while deleterious recessives are hidden from it and maintained at low frequencies. Traits under directional selection (i.e. fitness traits) are expected to show directional dominance and therefore an increased susceptibility to inbreeding depression. In contrast, traits under stabilizing selection or weakly linked to fitness are predicted to exhibit little-to-no inbreeding depression. Here, we quantify the extent of inbreeding depression in a range of male reproductive characters and then infer the mode of past selection on them. The use of transgenic populations of Drosophila melanogaster with red or green fluorescent-tagged sperm heads permitted in vivo discrimination of sperm from competing males and quantification of characteristics of ejaculate composition, performance, and fate. We found that male attractiveness (mating latency) and competitive fertilization success (P2) both show some inbreeding depression, suggesting they may have been under directional selection, whereas sperm length showed no inbreeding depression suggesting a history of stabilizing selection. However, despite having measured several sperm quality and quantity traits, our data did not allow us to discern the mechanism underlying the lowered competitive fertilization success of inbred (f = 0.50) males.  

Abstract:
Thermal emission from large area chemical vapor deposited graphene devices.

The spatial variation of thermal emission from large area graphene grown by chemical vapor deposition, transferred onto SiO2/Si substrates and fabricated into field effect transistor structures, has been investigated using infra-red microscopy. A peak in thermal emission occurs, the position of which can be altered by reversal of the current direction. The experimental results are compared with a one dimensional finite element model, which accounts for Joule heating and electrostatic effects, and it is found that the thermal emission is governed by the charge distribution in the graphene and maximum Joule heating occurs at the point of minimum charge density. © 2013 AIP Publishing LLC. 

Abstract:
Advancing age is associated with gene expression changes resembling mTOR inhibition: evidence from two human populations.

Interventions which inhibit TOR activity (including rapamycin and caloric restriction) lead to downstream gene expression changes and increased lifespan in laboratory models. However, the role of mTOR signaling in human aging is unclear. We tested the expression of mTOR-related transcripts in two independent study cohorts; the InCHIANTI population study of aging and the San Antonio Family Heart Study (SAFHS). Expression of 27/56 (InCHIANTI) and 19/44 (SAFHS) genes were associated with age after correction for multiple testing. 8 genes were robustly associated with age in both cohorts. Genes involved in insulin signaling (PTEN, PI3K, PDK1), ribosomal biogenesis (S6K), lipid metabolism (SREBF1), cellular apoptosis (SGK1), angiogenesis (VEGFB), insulin production and sensitivity (FOXO), cellular stress response (HIF1A) and cytoskeletal remodeling (PKC) were inversely correlated with age, whereas genes relating to inhibition of ribosomal components (4EBP1) and inflammatory mediators (STAT3) were positively associated with age in one or both datasets. We conclude that the expression of mTOR-related transcripts is associated with advancing age in humans. Changes seen are broadly similar to mTOR inhibition interventions associated with increased lifespan in animals. Work is needed to establish whether these changes are predictive of human longevity and whether further mTOR inhibition would be beneficial in older people. 

Abstract:
Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain.

BACKGROUND: a fundamental requirement for development of diverse brain regions is the function of local organizers at morphological boundaries. These organizers are restricted groups of cells that secrete signaling molecules, which in turn regulate the fate of the adjacent neural tissue. The thalamus is located in the caudal diencephalon and is the central relay station between the sense organs and higher brain areas. The mid-diencephalic organizer (MDO) orchestrates the development of the thalamus by releasing secreted signaling molecules such as Shh. RESULTS: Here we show that canonical Wnt signaling in the caudal forebrain is required for the formation of the Shh-secreting MD organizer in zebrafish. Wnt signaling induces the MDO in a narrow time window of 4 hours - between 10 and 14 hours post fertilization. Loss of Wnt3 and Wnt3a prevents induction of the MDO, a phenotype also observed upon blockage of canonical Wnt signaling per se. Pharmaceutical activation of the canonical Wnt pathways in Wnt3/Wnt3a compound morphant embryos is able to restore the lack of the MDO. After blockage of Wnt signaling or knock-down of Wnt3/Wnt3a we find an increase of apoptotic cells specifically within the organizer primordium. Consistently, blockage of apoptosis restores the thalamus organizer MDO in Wnt deficient embryos. CONCLUSION: We have identified canonical Wnt signaling as a novel pathway, that is required for proper formation of the MDO and consequently for the development of the major relay station of the brain - the thalamus. We propose that Wnt ligands are necessary to maintain the primordial tissue of the organizer during somitogenesis by suppressing Tp53-mediated apoptosis. 

Abstract:
Social preferences based on sexual attractiveness: a female strategy to reduce male sexual attention.

Male sexual harassment of females is common across sexually reproducing species and can result in fitness costs to females. We hypothesized that females can reduce unwanted male attention by constructing a social niche where their female associates are more sexually attractive than themselves, thus influencing the decision-making of males to their advantage. We tested this hypothesis in the Trinidadian guppy (Poecilia reticulata), a species with high levels of male sexual harassment. First, we confirmed that non-receptive females were harassed less when they were paired with a more sexually attractive (receptive) female than with another non-receptive female. We then found that, indeed, females exploit this as a strategy to reduce sexual harassment; non-receptive females actively preferred to associate with receptive over non-receptive females. Importantly, when given access only to chemosensory cues, non-receptive females still showed this preference, suggesting that they use information from chemical cues to assess the sexual attractiveness of potential female partners. Receptive females in contrast showed no such preferences. Our results demonstrate that females can decrease male harassment by associating with females that are more sexually attractive than themselves and that they perform active partner choices based on this relative attractiveness. We propose that this strategy is likely to represent an important pathway by which females can construct social niches that influence the decision-making of others to their advantage; in this case, to reduce the sexual harassment they experience. 

Abstract:
The structure of a Burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development.

Macrophage infectivity potentiators (Mips) are a subset of immunophilins associated with virulence in a range of micro-organisms. These proteins possess prolyl-peptide isomerase activity and are inhibited by drugs including rapamycin and tacrolimus. We determined the structure of the Mip homologue (BpML1) from the human pathogen and biowarfare threat Burkholderia pseudomallei by nuclear magnetic resonance and X-ray crystallography. The crystal structure suggests that key catalytic residues in the BpML1 active site have unexpected conformational flexibility consistent with a role in catalysis. The structure further revealed BpML1 binding to a helical peptide, in a manner resembling the physiological interaction of human TGFβ receptor 1 with the human immunophilin FKBP12. Furthermore, the structure of BpML1 bound to the class inhibitor cycloheximide N-ethylethanoate showed that this inhibitor mimics such a helical peptide, in contrast to the extended prolyl peptide mimicking shown by inhibitors such as tacrolimus. We suggest that Mips, and potentially other bacterial immunophilins, participate in protein-protein interactions in addition to their prolyl-peptide isomerase activity, and that some roles of Mip proteins in virulence are independent of their prolyl-peptide isomerase activity. 

Abstract:
The developmental expression of foxl2 in the dogfish Scyliorhinus canicula.

The FoxL2 genes are a subfamily of the Fox (forkhead box) gene family. FOXL2 is mutated in the disorder Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome (BPES), which is characterized by eyelid malformations, and Premature Ovarian Failure (POF). In the mouse expression is seen in the perioptic mesenchyme, developing eyelids, ovary and pituitary. We have isolated a foxl2 cDNA from the dogfish Scyliorhinus canicula (also known as the lesser spotted catshark), allowing the characterisation of this gene's sequence and expression from a lineage that diverged early in the evolution of gnathostomes. Molecular phylogenetic analysis strongly grouped this sequence with the gnathostomes within the FoxL2 subfamily. We demonstrate the early expression of Scyliorhinus canicula foxl2 in the mandibular head mesoderm and later in continuous populations of mandibular arch cells and mandibular head mesenchyme cells around the developing pituitary. As development proceeds expression decreases in the mesenchyme of the head but is seen in the mesenchyme around the eye and later in the developing eyelids. Additionally expression is seen in regions of pharyngeal arch mesoderm and in ectoderm from which gill buds will form. This expression is maintained in the developing and elongating gill buds. Thus, S. canicula foxl2 is a marker for the mandibular mesoderm and gill buds and its expression is conserved in the perioptic mesenchyme, developing eyelids and pituitary. 

Abstract:
A test of imitative learning in starlings using a two-action method with an enhanced ghost control.

Imitative learning, in which an individual learns to reproduce the behaviour pattern of another, has attracted considerable attention as a potentially powerful form of social learning. Despite extensive research, however, it has proved difficult to demonstrate in nonhuman animals. We investigated the ability of European starlings, Sturnus vulgaris, to imitate the behaviour of a conspecific. Subjects watched a trained conspecific manipulating a plug for access to a food reward, using either a pushing or a pulling action. When later tested with the same apparatus these birds completed the task using the same action they had previously observed. In a second experiment, a separate group of starlings saw the plug move upwards or downwards automatically and a nearby conspecific obtain a food reward. When given access to the task these starlings failed to move the plug in the direction they had seen. Our experiment is an improvement on previous bidirectional control designs and provides strong evidence that starlings are capable of imitation. We advocate further use of this experimental design in attempts to demonstrate imitative learning. © 2002 the Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved. 

Abstract:
Estimating group size and population density of Eurasian badgers Meles meles by quantifying latrine use.

1. Conservation issues and a potential role in disease transmission generate the continued need to census Eurasian badgers Meles meles, but direct counts and sett counts present difficulties. The feasibility of estimating social group size and population density of badgers by quantifying their use of latrines was evaluated. 2. The number of latrines, or preferably the number of separate dung pits, which were known from bait-marking to be used by members of a social group, was positively correlated with adult group size estimated from mark-recapture studies at Woodchester Park and North Nibley (south-west England). In the latter study area both latrine-use measures were also significantly associated with total group size (i.e. including cubs and adults). 3. In spring 1997 and 1998, we quantified latrine use along strip transects, following linear features across four and five areas, respectively, in England, where badger density in summer was known from mark-recapture/resight studies. 4. Seven latrine-use measures were evaluated with regard to their potential to predict badger density. Each measure separately explained between 62% and 91% of the variation in population density in a given year. The simplest measures (latrines km-1 and pits km-1) were most stable between years. 5. For these two simple latrine-use measures, a linear model without an intercept term explained the highest proportion of variation in population density. A stepwise procedure to produce the best model selected only one (latrines km-1) of the two measures as an explanatory variable, indicating that pits km-1 is colinear with the former variable. 6. A badger census technique based on simple measurements of latrine use has great promise but needs to be validated across a wider range of badger populations, habitats, years, seasons and weather conditions. 

Abstract:
Embryonen, Tiermodelle, Chimären. Stammzell-Ethik in Großbritannien und Deutschland.

 

Abstract:
Cyber Security in the Asia-Pacific.

 

Abstract:
Narrating the ‘Arab Spring’: Where Expertise Meets Heuristics in Legislative Hearings.

 

Abstract:
Prediction of manipulation under anaesthesia success using local binary pattern features.

 

Abstract:
Intra- and inter-operator precision measurements of hip migration using projection radiography and dual energy x-ray absorptiometry.

 

Abstract:
Characterisation of transient actions induced by spectators on sport stadia.

 

Abstract:
Vitamin D deficiency and insufficiency in the radiography population: Are we at risk?.

 

Abstract:
The Museum of Contemporary Commodities, online collection and website.

MoCC is neither a building nor a permanent collection of stuff – it’s an invitation. To consider every shop, online store and warehouse full of stuff as if it were a museum, and all the things in it part of our collective future heritage. To create a different kind of imaginary, a new conversation, to ask or answer questions and consider the values we associate with the things and stuff that help to make us who we are, and to shape the places in which we live.

Become one of this museums curators. Add something to our online collection that you think is important, interesting or essential. Something that we can learn from or talk about. Maybe it's something that's part of your daily life? Something throwaway or irreplaceable. Something made specifically for you, or that you share with someone else. Something that was a gift or that you collect. A commodity that's alive, something that's been stolen or lost, something intangible? Why is it important? How do you feel about it?

By adding something to MoCC you are engaging in a data collection and processing exercise that is also an experiment in collective re-valuing. Our use and interpretation of the information in this database will be different from those of online retailers and direct marketing companies. We will not monetize it or use it to predict and manipulate your behaviour. However we will process this data using algorithms which have been written, like all algorithms, to interpret and present information with a specific agenda. How does knowing this affect your experience of the Museum? How does data collection and processing more widely affect our choices and limitations as well as those of other people?