A Survey of UK Healthcare Workers’ Attitudes on Volunteering to Help with the Ebola Outbreak in West Africa

Objective

To understand the barriers and enablers for UK healthcare workers who are considering going to work in the current Ebola outbreak in West Africa, but have not yet volunteered.

Design

After focus group discussions, and a pilot questionnaire, an anonymous survey was conducted using SurveyMonkey to determine whether people had considered going to West Africa, what factors might make them more or less likely to volunteer, and whether any of these were modifiable factors.

Participants

The survey was publicised among doctors, nurses, laboratory staff and allied health professionals. 3109 people answered the survey, of whom 472 (15%) were considering going to work in the epidemic but had not yet volunteered. 1791 (57.6%) had not considered going, 704 (22.6%) had considered going but decided not to, 53 (1.7%) had volunteered to go and 14 (0.45%) had already been and worked in the epidemic.

Results

For those considering going to West Africa, the most important factor preventing them from volunteering was a lack of information to help them decide; fear of getting Ebola and partners’ concerns came next. Uncertainty about their potential role, current work commitments and inability to get agreement from their employer were also important barriers, whereas clarity over training would be an important enabler. In contrast, for those who were not considering going, or who had decided against going, family considerations and partner concerns were the most important factors.

Conclusions

More UK healthcare workers would volunteer to help tackle Ebola in West Africa if there was better information available, including clarity about roles, cover arrangements, and training. This could be achieved with a well-publicised high quality portal of reliable information.     

GAPDH mediates nitrosylation of nuclear proteins

S-nitrosylation of proteins by nitric oxide is a major mode of signalling in cells. S-nitrosylation can mediate the regulation of a range of proteins, including prominent nuclear proteins, such as HDAC2 (ref. 2) and PARP1 (ref. 3). The high reactivity of the nitric oxide group with protein thiols, but the selective nature of nitrosylation within the cell, implies the existence of targeting mechanisms. Specificity of nitric oxide signalling is often achieved by the binding of nitric oxide synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 (ref. 5) and CAPON. As the three principal isoforms of NOS--neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)--are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys 150 residue. Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1, which possesses a nuclear localization signal, and is transported to the nucleus. Here, we show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme sirtuin-1 (SIRT1), histone deacetylase-2 (HDAC2) and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of nitric oxide groups may be a general mechanism in cellular signal transduction.     

Action of Brefeldin A on Amphibian Neurons: Passage of Newly Synthesized Proteins Through the Golgi Complex Is Not Required for Continued Fast Organelle Transport in Axons

Abstract: The relation between the availability of newly synthesized protein and lipid and the axonal transport of optically detectable organelles was examined in peripheral nerve preparations of amphibia (Rana catesbeiana and Xenopus laevis) in which intracellular traffic from the endo-plasmic reticulum to the Golgi complex was inhibited with brefeldin A (BFA). Accumulation of fast-transported radio-labeled protein or phospholipid proximal to a sciatic nerve ligature was monitored in vitro in preparations of dorsal root ganglia and sciatic nerve. Organelle transport was examined by computer-enhanced video microscopy of single myelinated axons. BFA reduced the amount of radiolabeled protein and lipid entering the fast-transport system of the axon without affecting either the synthesis or the transport rate of these molecules. The time course of the effect of BFA on axonal transport is consistent with an action at an early step in the intrasomal pathway, and with its action being related to the observed rapid (<1 h) disassembly of the Golgi complex. At a concentration of BFA that reduced fast-transported protein by >95%, no effect was observed on the flux or velocity of anterograde or retrograde organelle transport in axons for at least 20 h. Bidirectional axonal transport of organelles was similarly unaffected following suppression of protein synthesis by >99%. The findings suggest that the anterograde flux of transport organelles is not critically dependent on a supply of newly synthesized membrane precursors. The possibilities are considered that anterograde organelles normally arise from membrane components supplied from a post-Golgi storage pool, as well as from recycled retrograde organelles.     

Aeroecology meets aviation safety: early warning systems in Europe and the Middle East prevent collisions between birds and aircraft

The aerosphere is utilized by billions of birds, moving for different reasons and from short to great distances spanning tens of thousands of kilometres. The aerosphere, however, is also utilized by aviation which leads to increasing conflicts in and around airfields as well as en‐route. Collisions between birds and aircraft cost billions of euros annually and, in some cases, result in the loss of human lives. Simultaneously, aviation has diverse negative impacts on wildlife. During avian migration, due to the sheer numbers of birds in the air, the risk of bird strikes becomes particularly acute for low‐flying aircraft, especially during military training flights. Over the last few decades, air forces across Europe and the Middle East have been developing solutions that integrate ecological research and aviation policy to reduce mutual negative interactions between birds and aircraft. In this paper we 1) provide a brief overview of the systems currently used in military aviation to monitor bird migration movements in the aerosphere, 2) provide a brief overview of the impact of bird strikes on military low‐level operations, and 3) estimate the effectiveness of migration monitoring systems in bird strike avoidance. We compare systems from the Netherlands, Belgium, Germany, Poland and Israel, which are all areas that Palearctic migrants cross twice a year in huge numbers. We show that the en‐route bird strikes have decreased considerably in countries where avoidance systems have been implemented, and that consequently bird strikes are on average 45% less frequent in countries with implemented avoidance systems in place. We conclude by showing the roles of operational weather radar networks, forecast models and international and interdisciplinary collaboration to create safer skies for aviation and birds.     

Short distance migrants travel as far as long distance migrants in lesser black‐backed gulls Larus fuscus

Migration strategies differ greatly among and within avian populations. The associated trade‐offs and fitness consequences of diverse strategies and how they persist are pertinent questions in migration research. Migration is a costly endeavour, presumably compensated for by better survival conditions in the non‐breeding area. One way to assess the cost of alternative strategies is to investigate the investment in movement across the entire annual cycle, an assessment made increasingly feasible with improvements in tracking technology. Our study focuses on lesser black‐backed gulls, generalist seabirds that exploit a broad range of resources, exhibit diverse migration strategies and have potentially altered migration strategies in response to human activities and climate change. We used GPS tracking to quantify lesser black‐backed gulls’ movement throughout their annual cycle and compare trade‐offs among four migration strategies. The annual cumulative distance travelled by long distance migrants wintering in west Africa, over 4000 km from their breeding colony, did not differ significantly from individuals of the same breeding colony wintering only a few hundred kilometres away in Great Britain. Short distance migrants returned to the colony first, and long distance migrants returned last. Sex and wing length were not correlated with maximum range, cumulative distance travelled or timing. Individuals spent only a small proportion of their time in flight and spent on average 17% of their time at sea throughout an annual cycle, suggesting a reliance on inland resources for many individuals. Analysing movement throughout the annual cycle can change our perspective and understanding of consequences of different migration strategies. Our study shows that a range of migration strategies coexists and we propose that the long term costs and benefits of these strategies balance out. Diversity in migration strategies may contribute to the resilience of this species in the face of ongoing anthropogenic impact on the environment.     

In search of cellular immunophenotypes in the blood of children with autism

Background

Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism.

Methods

We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4–6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ≥68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry.

Results

There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls.

Conclusions

These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed.     

Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability

Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/C(Cdh1) (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division.     

Arabidopsis has two redundant Cullin3 proteins that are essential for embryo development and that interact with RBX1 and BTB proteins to form multisubunit E3 ubiquitin ligase complexes in vivo

Cullin-based E3 ubiquitin ligases play important roles in the regulation of diverse developmental processes and environmental responses in eukaryotic organisms. Recently, it was shown in Schizosaccharomyces pombe, Caenorhabditis elegans, and mammals that Cullin3 (CUL3) directly associates with RBX1 and BTB domain proteins in vivo to form a new family of E3 ligases, with the BTB protein subunit functioning in substrate recognition. Here, we demonstrate that Arabidopsis thaliana has two redundant CUL3 (AtCUL3) genes that are essential for embryo development. Besides supporting anticipated specific AtCUL3 interactions with the RING protein AtRBX1 and representative Arabidopsis proteins containing a BTB domain in vitro, we show that AtCUL3 cofractionates and specifically associates with AtRBX1 and a representative BTB protein in vivo. Similar to the AtCUL1 subunit of the SKP1-CUL1-F-box protein-type E3 ligases, the AtCUL3 subunit of the BTB-containing E3 ligase complexes is subjected to modification and possible regulation by the ubiquitin-like protein Related to Ubiquitin in vivo. Together with the presence of large numbers of BTB proteins with diverse structural features and expression patterns, our data suggest that Arabidopsis has conserved AtCUL3-RBX1-BTB protein E3 ubiquitin ligases to target diverse protein substrates for degradation by the ubiquitin/proteasome pathway.