scholarly journals Electron Bio-Imaging Centre (eBIC): the UK national research facility for biological electron microscopy

2017 ◽  
Vol 73 (6) ◽  
pp. 488-495 ◽  
Author(s):  
Daniel K. Clare ◽  
C. Alistair Siebert ◽  
Corey Hecksel ◽  
Christoph Hagen ◽  
Valerie Mordhorst ◽  
...  

The recent resolution revolution in cryo-EM has led to a massive increase in demand for both time on high-end cryo-electron microscopes and access to cryo-electron microscopy expertise. In anticipation of this demand, eBIC was set up at Diamond Light Source in collaboration with Birkbeck College London and the University of Oxford, and funded by the Wellcome Trust, the UK Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC) to provide access to high-end equipment through peer review. eBIC is currently in its start-up phase and began by offering time on a single FEI Titan Krios microscope equipped with the latest generation of direct electron detectors from two manufacturers. Here, the current status and modes of access for potential users of eBIC are outlined. In the first year of operation, 222 d of microscope time were delivered to external research groups, with 95 visits in total, of which 53 were from unique groups. The data collected have generated multiple high- to intermediate-resolution structures (2.8–8 Å), ten of which have been published. A second Krios microscope is now in operation, with two more due to come online in 2017. In the next phase of growth of eBIC, in addition to more microscope time, new data-collection strategies and sample-preparation techniques will be made available to external user groups. Finally, all raw data are archived, and a metadata catalogue and automated pipelines for data analysis are being developed.

Author(s):  
Kim Aumann ◽  
Angie Hart ◽  
Sophie Duncan

Following an observed need to build community partner infrastructure and support to enhance community-university partnerships, a successful bid was made to the UK Arts and Humanities Research Council. This funding provided an opportunity for community partners to come together with engaged academics at the first ever UK Community Partner Summit. They resolved to set up a community partner network to help build capacity for effective community-university partnerships, and to influence the policy environment which supports this work. This article reflects on the activity of the working group in seeking to establish the network, and introduces some of the concepts that have proved critical to its development. Drawing on a wealth of perspectives from a range of sources including academic and grey literature, community partner experiences, and international work, we open up some of the challenges that we have faced, and explore some of the implications of our first year’s work together. We reflect on the time it takes to establish any form of network, the need to be clear about definitions and boundaries, and the challenge of changing cultures. We conclude that the progress with the network to date is encouraging, and we look forward to building on our learning thus far, to develop stronger community-university partnerships of the future.Keywords: community partner infrastructure and networks, partnership resilience, community-university partnership


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Claudio Ortolani ◽  
Elide A. Pastorello

Abstract Background On June 30, 2020, the WHO reported over 10 millions of COVID-19 cases worldwide with over half a million deaths. In severe cases the disease progresses into an Acute Respiratory Distress Syndrome (ARDS), which in turn depends on an overproduction of cytokines (IL-6, TNFα, IL-12, IL-8, CCL-2 and IL1) that causes alveolar and vascular lung damage. Clearly, it is essential to find an immunological treatment that controls the “cytokine storm”. In the meantime, however, it is essential to have effective antiviral and anti-inflammatory drugs available immediately. Pharmacologic therapy for COVID-19 Hydroxychloroquine or chloroquine have been widely adopted worldwide for the treatment of SARS-CoV-2 pneumonia. However, the choice of this treatment was based on low quality of evidence, i.e. retrospective, non-randomized controlled studies. Recently, four large Randomized Controlled Trials (RCTs) have been performed in record time delivering reliable data: (1) the National Institutes of Health (NIH) RCT included 60 hospitals participating all over the world and showed the efficacy of remdesivir in reducing the recovery time in hospitalized adults with COVID-19 pneumonia; (2) three large RCTs already completed, for hydroxychloroquine, dexamethasone and Lopinavir and Ritonavir respectively. These trials were done under the umbrella of the 'Recovery' project, headed by the University of Oxford. The project includes 176 participating hospitals in the UK and was set up to verify the efficacy of some of the treatments used for COVID-19. These three ‘Recovery’ RCTs concluded definitely: (a) that treatment with hydroxychloroquine provides no benefits in patients hospitalized with COVID-19; (b) that treatment with dexamethasone reduced deaths by one-third in COVID-19 patients that were mechanically ventilated, and by one-fifth in patients receiving oxygen only; (c) that the combination of Lopinavir and Ritonavir is not effective in reducing mortality in COVID-19 hospitalized patients. Conclusions The results of these four large RCTs have provided sound indications to doctors for the treatment of patients with COVID-19 and prompted the correction of many institutional provisions and guidelines on COVID-19 treatments (i.e. FDA, NIH, UK Health Service, etc.). Even though a definitive treatment for COVID-19 has not yet been found, large RCTs stand as the Gold Standards for COVID-19 therapy and offer a solid scientific base on which to base treatment decisions.


Author(s):  
James Herbert

This chapter discusses the antagonism and resistance directed against the ARHB. When the Dearing Report first appeared, the University of Oxford stood against the establishment of a separate Research Council for humanities. It expressed doubts about the new public funding of such a new organization and on the transfer of control of expenditure away from the universities to a council envisaged as the instrument of a national policy for research in arts and humanities. Cambridge University also expressed, albeit not as adamantly as Oxford, their disapproval of a Humanities Research Council. Adding to these disapprovals were the conflicts it had caused in the contemporary UK political life, particularly with devolution. In the devolution process of the UK government, one of the devolved powers was education, which created adverse effects on the formulation of Humanities Research Council. The AHRB also met with criticism from other councils including the journals and newspapers of the UK.


2007 ◽  
Vol 29 (5) ◽  
pp. 24-26
Author(s):  
Clare Sansom

Systems biology is certainly fashionable. In the UK, the Biotechnology and Biological Sciences Research Council has put forward the majority of an investment of well over £70 million to set up six university-based ‘centres of integrative systems biology’. Other countries are making similar investments. A few years ago, however, as with ‘bioinformatics’ a decade or so earlier, it seemed that there were almost as many definitions of systems biology as there were practitioners. It is not too much of an exaggeration to say that almost any computer analysis of a biological problem might have been badged in that way.


Author(s):  
M. Ellisman ◽  
T. Hutton ◽  
A. Kirkland ◽  
A. Lin ◽  
C. Lin ◽  
...  

The OptIPuter microscopy demonstrator project has been designed to enable concurrent and remote usage of world-class electron microscopes located in Oxford and San Diego. The project has constructed a network consisting of microscopes and computational and data resources that are all connected by a dedicated network infrastructure using the UK Lightpath and US Starlight systems. Key science drivers include examples from both materials and biological science. The resulting system is now a permanent link between the Oxford and San Diego microscopy centres. This will form the basis of further projects between the sites and expansion of the types of systems that can be remotely controlled, including optical, as well as electron, microscopy. Other improvements will include the updating of the Microsoft cluster software to the high performance computing (HPC) server 2008, which includes the HPC basic profile implementation that will enable the development of interoperable clients.


Author(s):  
Nakazo Watari ◽  
Yasuaki Hotta ◽  
Yoshio Mabuchi

It is very useful if we can observe the identical cell elements within the same sections by light microscopy (LM), transmission electron microscopy (TEM) and/or scanning electron microscopy (SEM) sequentially, because, the cell fine structure can not be indicated by LM, while the color is; on the other hand, the cell fine structure can be very easily observed by EM, although its color properties may not. However, there is one problem in that LM requires thick sections of over 1 μm, while EM needs very thin sections of under 100 nm. Recently, we have developed a new method to observe the same cell elements within the same plastic sections using both light and transmission (conventional or high-voltage) electron microscopes.In this paper, we have developed two new observation methods for the identical cell elements within the same sections, both plastic-embedded and paraffin-embedded, using light microscopy, transmission electron microscopy and/or scanning electron microscopy (Fig. 1).


Author(s):  
J. A. Hugo ◽  
V. A. Phillips

A continuing problem in high resolution electron microscopy is that the level of detail visible to the microscopist while he is taking a picture is inferior to that obtainable by the microscope, readily readable on a photographic emulsion and visible in an enlargement made from the plate. Line resolutions, of 2Å or better are now achievable with top of the line 100kv microscopes. Taking the resolution of the human eye as 0.2mm, this indicates a need for a direct viewing magnification of at least one million. However, 0.2mm refers to optimum viewing conditions in daylight or the equivalent, and certainly does not apply to a (colored) image of low contrast and illumination level viewed on a fluorescent screen through a glass window by the dark-adapted eye. Experience indicates that an additional factor of 5 to 10 magnification is needed in order to view lattice images with line spacings of 2 to 4Å. Fortunately this is provided by the normal viewing telescope supplied with most electron microscopes.


Author(s):  
P. A. Madden ◽  
W. R. Anderson

The intestinal roundworm of swine is pinkish in color and about the diameter of a lead pencil. Adult worms, taken from parasitized swine, frequently were observed with macroscopic lesions on their cuticule. Those possessing such lesions were rinsed in distilled water, and cylindrical segments of the affected areas were removed. Some of the segments were fixed in buffered formalin before freeze-drying; others were freeze-dried immediately. Initially, specimens were quenched in liquid freon followed by immersion in liquid nitrogen. They were then placed in ampuoles in a freezer at −45C and sublimated by vacuum until dry. After the specimens appeared dry, the freezer was allowed to come to room temperature slowly while the vacuum was maintained. The dried specimens were attached to metal pegs with conductive silver paint and placed in a vacuum evaporator on a rotating tilting stage. They were then coated by evaporating an alloy of 20% palladium and 80% gold to a thickness of approximately 300 A°. The specimens were examined by secondary electron emmission in a scanning electron microscope.


Author(s):  
Robert M. Fisher

By 1940, a half dozen or so commercial or home-built transmission electron microscopes were in use for studies of the ultrastructure of matter. These operated at 30-60 kV and most pioneering microscopists were preoccupied with their search for electron transparent substrates to support dispersions of particulates or bacteria for TEM examination and did not contemplate studies of bulk materials. Metallurgist H. Mahl and other physical scientists, accustomed to examining etched, deformed or machined specimens by reflected light in the optical microscope, were also highly motivated to capitalize on the superior resolution of the electron microscope. Mahl originated several methods of preparing thin oxide or lacquer impressions of surfaces that were transparent in his 50 kV TEM. The utility of replication was recognized immediately and many variations on the theme, including two-step negative-positive replicas, soon appeared. Intense development of replica techniques slowed after 1955 but important advances still occur. The availability of 100 kV instruments, advent of thin film methods for metals and ceramics and microtoming of thin sections for biological specimens largely eliminated any need to resort to replicas.


Author(s):  
F. Sachs ◽  
M. J. Song

Cellular electrophysiology has been revolutionized by the introduction of patch clamp techniques. The patch clamp records current from a small patch of the cell membrane which has been sucked into a glass pipette. The membrane patch, a few micons in diameter, is attached to the glass by a seal which is electrically, diffusionally and mechanically tight. Because of the tight electrical seal, the noise level is low enough to record the activity of single ion channels over a time scale extending from 10μs to days. However, although the patch technique is over ten years old, the patch structure is unknown. The patch is inside a glass pipette where it has been impossible to see with standard electron microscopes. We show here that at 1 Mev the glass pipette is transparent and the membrane within can be seen with a resolution of about 30 A.


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