Integrating Augmented Reality into bioscience education

Visualisation of 3-dimensional (3D) molecules has traditionally been taught using 2D images, which often fail to convey the intricate complexity of structure-to-function relationships. Augmented Reality provides a platform to bring 3D protein structures into the class to aid biosciences education

Sumoylation of eIF4A2 affects stress granule formation

Regulation of protein synthesis is crucial for cells to maintain viability and to prevent unscheduled proliferation that could lead to tumorigenesis. Exposure to stress results in stalling of translation, with many translation initiation factors, ribosomal subunits and mRNAs being sequestered into stress granules or P bodies. This allows the re-programming of the translation machinery. Many aspects of translation are regulated by post-translational modification. Several proteomic screens have identified translation initiation factors as targets for sumoylation, although in many cases the role of this modification has not been determined. We show here that eIF4A2 is modified by SUMO, with sumoylation occurring on a single residue (K226). We demonstrate that sumoylation of eIF4A2 is modestly increased in response to arsenite and ionising radiation, but decreases in response to heat shock or hippuristanol. In arsenite-treated cells, but not in hippuristanol-treated cells, eIF4A2 is recruited to stress granules, suggesting sumoylation of eIF4A2 correlates with its recruitment to stress granules. Furthermore, we demonstrate that the inability to sumoylate eIF4A2 results in impaired stress granule formation, indicating a new role for sumoylation in the stress response

Evolution-based screening enables genome-wide prioritization and discovery of DNA repair genes

DNA repair is critical for genome stability and is maintained through conserved pathways. Traditional genome-wide mammalian screens are both expensive and laborious. However, computational approaches circumvent these limitations and are a powerful tool to identify new DNA repair factors. By analyzing the evolutionary relationships between genes in the major DNA repair pathways, we uncovered functional relationships between individual genes and identified partners. Here we ranked 17,487 mammalian genes for coevolution with 6 distinct DNA repair pathways. Direct comparison to genetic screens for homologous recombination or Fanconi anemia factors indicates that our evolution-based screen is comparable, if not superior, to traditional screening approaches. Demonstrating the utility of our strategy, we identify a role for the DNA damage-induced apoptosis suppressor (DDIAS) gene in double-strand break repair based on its coevolution with homologous recombination. DDIAS knockdown results in DNA double-strand breaks, indicated by ATM kinase activation and 53BP1 foci induction. Additionally, DDIAS-depleted cells are deficient for homologous recombination. Our results reveal that evolutionary analysis is a powerful tool to uncover novel factors and functional relationships in DNA repair

What is the role of public feeder markets in developing technology-based small firms? An exploration of the motivations for listing on AIM since the GFC

In the aftermath of the 2007 global financial crisis (GFC) stock markets experienced sharp decline in listings and marked reduction in Initial Public Offerings (IPOs). This paper explores the factors determining UK technology based small firm (TBSF) listings on the UK Alternative Investment Market (AIM) and whether this market has a role to play in their future development. A case study approach is used to contrast the experiences of five recent AIM listed TBSFs with five TBSFs approaching private equity investment exit that are considering an IPO. The paper concludes that macro market conditions, rather than managerial resource base or AIM market structural factors were most influential in TBSF pecking order preferences to undertake IPOs. From a resource based management perspective lifelong entrepreneurs were more likely than serial entrepreneurs to favour an IPO exit, as it supported their aims to continue to manage and grow UK-based companies. Additionally, with a more buoyant and sustainable AIM market TBSF investors are more likely to choose IPOs. To conclude, AIM played an important role in listed UK TBSF development. A more buoyant AIM could ease the UK finance escalator’s flow, facilitating more rapid UK TBSF growth

Large herbivores transform plant-pollinator networks in an African savanna

Pollination by animals is a key ecosystem service1,2 and interactions between plants and their pollinators are a model system for studying ecological networks,3,4 yet plant-pollinator networks are typically studied in isolation from the broader ecosystems in which they are embedded. The plants visited by pollinators also interact with other consumer guilds that eat stems, leaves, fruits, or seeds. One such guild, large mammalian herbivores, are well-known ecosystem engineers5, 6, 7 and may have substantial impacts on plant-pollinator networks. Although moderate herbivory can sometimes promote plant diversity,8 potentially benefiting pollinators, large herbivores might alternatively reduce resource availability for pollinators by consuming flowers,9 reducing plant density,10 and promoting somatic regrowth over reproduction.11 The direction and magnitude of such effects may hinge on abiotic context—in particular, rainfall, which modulates the effects of ungulates on vegetation.12 Using a long-term, large-scale experiment replicated across a rainfall gradient in central Kenya, we show that a diverse assemblage of native large herbivores, ranging from 5-kg antelopes to 4,000-kg African elephants, limited resource availability for pollinators by reducing flower abundance and diversity; this in turn resulted in fewer pollinator visits and lower pollinator diversity. Exclusion of large herbivores increased floral-resource abundance and pollinator-assemblage diversity, rendering plant-pollinator networks larger, more functionally redundant, and less vulnerable to pollinator extinction. Our results show that species extrinsic to plant-pollinator interactions can indirectly and strongly alter network structure. Forecasting the effects of environmental change on pollination services and interaction webs more broadly will require accounting for the effects of extrinsic keystone species

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

An assessment of the business impacts of the UK's Enterprise Capital Funds

Recent European studies present persistently critical views of the under performance of government backed venture capital (GVC) schemes when compared to their private sector counterparts. However, they assess the performance of outmoded funding models and fail to contextualise the economic development role of these schemes. This paper provides a contemporary assessment of the business impacts of the UK government’s flagship Enterprise Capital Funds (ECFs) VC scheme in addressing the sub-£2m equity finance gap facing young potential high growth businesses requiring investments. Supply and demand-side evidence is presented from interviews with ECF fund managers, alternative private VCs, industry experts and surveys of successful and unsuccessful scheme applicants. We find that, despite the limitations of mid-scheme evaluation, ECFs are addressing the UK equity gap and delivering business employment, revenue and innovation impacts. However, further progress is required in order to achieve optimal business exits and sustainable early stage private VC system impacts

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease