Functional colour genes and signals of selection in colour polymorphic salamanders

Coloration has been associated with multiple biologically relevant traits that drive adaptation and diversification in many taxa. However, despite the great diversity of colour patterns present in amphibians the underlying molecular basis is largely unknown. Here, we use insight from a highly colour-variable lineage of the European fire salamander (Salamandra salamandra bernardezi) to identify functional associations with striking variation in colour morph and pattern. The three focal colour morphs—ancestral black-yellow striped, fully yellow and fully brown—differed in pattern, visible coloration and cellular composition. From population genomic analyses of up to 4,702 loci, we found no correlations of neutral population genetic structure with colour morph. However, we identified 21 loci with genotype–phenotype associations, several of which relate to known colour genes. Furthermore, we inferred response to selection at up to 142 loci between the colour morphs, again including several that relate to coloration genes. By transcriptomic analysis across all different combinations, we found 196 differentially expressed genes between yellow, brown and black skin, 63 of which are candidate genes involved in animal coloration. The concordance across different statistical approaches and ‘omic data sets provide several lines of evidence for loci linked to functional differences between colour morphs, including TYR, CAMK1 and PMEL. We found little association between colour morph and the metabolomic profile of its toxic compounds from the skin secretions. Our research suggests that current ecological and evolutionary hypotheses for the origins and maintenance of these striking colour morphs may need to be revisited.This research was supported by a Natural Environment Research Council; a Royal Society Research Grant; a Glasgow Natural History Society grant; a Wellcome Trust ISSF Catalyst Grant and a Spanish Ministry of Science Grant

Space Universities Network - supporting Space Science and Engineering Higher Education Community in the UK

The world space economy is expected to grow to $400 billion by 2030 and to provide 100,000 jobs. In the UK we currently have 38,500 directly employed with a further 70000 jobs dependent on the space sector. By 2030 the UK aims to have a further 100,000 new people employed within the sector. Training space engineers and scientists is critical to fulfilling this need. The UK-based “Space Universities Network” (SUN) was formed in 2016 with the aim of enhancing the quality of learning and teaching by providing support and resources to the Space science and engineering higher education community. SUN’s objectives are to facilitate the creation of a skilled workforce of graduates who can meet the challenges of future scientific and commercial exploitation of space. The network addresses this need by helping to inspire students to join the space sector and ensuring they are well equipped at University to contribute. SUN enables the developing, sharing and promotion of effective practice and innovation in the delivery of university-level space science and engineering curricula. It does this through workshops, offering opportunities for networking to support the space teaching community and a web-based repository of resources. This paper describes the process that led to the foundation of SUN, its objectives, modes of operation, prime activities, evaluation and future projects. Once firmly established, it is hoped to expand the network through partnerships with similar organisations in other countries

Development of in-situ trap characterisation techniques for EMCCDs

The "trap pumping" technique has seen considerable use over recent years as a means to probe the intrinsic properties of silicon defects that can impact charge transfer performance within CCD-based technologies. While the theory behind the technique is reasonably well understood, it has to date only been applied to relatively simple pixel designs where the motion of charge between pixel phases is fairly easy to predict. For some devices, the intrinsic pixel architecture is more complex and can consist of unequal phase sizes and additional implants that deform the electronic potential. Here, we present the implementation of the trap pumping technique for the CCD201-20, a 2-phase Teledyne e2v EMCCD. Clocking schemes are presented that can provide the location of silicon defects to sub-micron resolution. Experimental techniques that allow determination of trap energy levels and emission cross sections are presented. These are then implemented on an irradiated CCD201-20 to determine the energy level and emission cross section for defects thought to be the double acceptor state of the silicon divacancy (VV--) and carbon-phosphorus (CiPs) pairs. An improvement in charge transfer performance through optimised parallel clock delay is demonstrated and found to correlate with the properties of defects found using the trap pumping technique

Development of in-situ trap characterisation techniques for EMCCDs

The "trap pumping" technique has seen considerable use over recent years as a means to probe the intrinsic properties of silicon defects that can impact charge transfer performance within CCD-based technologies. While the theory behind the technique is reasonably well understood, it has to date only been applied to relatively simple pixel designs where the motion of charge between pixel phases is fairly easy to predict. For some devices, the intrinsic pixel architecture is more complex and can consist of unequal phase sizes and additional implants that deform the electronic potential. Here, we present the implementation of the trap pumping technique for the CCD201-20, a 2-phase Teledyne e2v EMCCD. Clocking schemes are presented that can provide the location of silicon defects to sub-micron resolution. Experimental techniques that allow determination of trap energy levels and emission cross sections are presented. These are then implemented on an irradiated CCD201-20 to determine the energy level and emission cross section for defects thought to be the double acceptor state of the silicon divacancy (VV--) and carbon-phosphorus (CiPs) pairs. An improvement in charge transfer performance through optimised parallel clock delay is demonstrated and found to correlate with the properties of defects found using the trap pumping technique

Compact CMOS camera demonstrator (C3D) for Ukube-1

The Open University, in collaboration with e2v technologies and XCAM Ltd, have been selected to fly an EO (Earth Observation) technology demonstrator and in-orbit radiation damage characterisation instrument on board the UK Space Agency's UKube-1 pilot Cubesat programme. Cubesat payloads offer a unique opportunity to rapidly build and fly space hardware for minimal cost, providing easy access to the space environment. Based around the e2v 1.3 MPixel 0.18 micron process eye-on-Si CMOS devices, the instrument consists of a radiation characterisation imager as well as a narrow field imager (NFI) and a wide field imager (WFI). The narrow and wide field imagers are expected to achieve resolutions of 25 m and 350 m respectively from a 650 km orbit, providing sufficient swathe width to view the southern UK with the WFI and London with the NFI. The radiation characterisation experiment has been designed to verify and reinforce ground based testing that has been conducted on the e2v eye-on-Si family of devices and includes TEC temperature control circuitry as well as RADFET in-orbit dosimetry. Of particular interest are SEU and SEL effects. The novel instrument design allows for a wide range of capabilities within highly constrained mass, power and space budgets providing a model for future use on similarly constrained missions, such as planetary rovers. Scheduled for launch in December 2011, this 1 year low cost programme should not only provide valuable data and outreach opportunities but also help to prove flight heritage for future missions

A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism

Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection