The blocking of mid-latitude westerly winds by stationary anticyclones

Imperial Users onl

Click Worthy: Stories Encourage Emergency Physicians to Learn More About Opioid Prescribing Guidelines

Narrative vignettes outperform standard summaries in promoting engagement with opioid prescription guidelines among a national sample of emergency physicians

Structure-guided SCHEMA recombination generates diverse chimeric channelrhodopsins

Integral membrane proteins (MPs) are key engineering targets due to their critical roles in regulating cell function. In engineering MPs, it can be extremely challenging to retain membrane localization capability while changing other desired properties. We have used structure-guided SCHEMA recombination to create a large set of functionally diverse chimeras from three sequence-diverse channelrhodopsins (ChRs). We chose 218 ChR chimeras from two SCHEMA libraries and assayed them for expression and plasma membrane localization in human embryonic kidney cells. The majority of the chimeras express, with 89% of the tested chimeras outperforming the lowest-expressing parent; 12% of the tested chimeras express at even higher levels than any of the parents. A significant fraction (23%) also localize to the membrane better than the lowest-performing parent ChR. Most (93%) of these well-localizing chimeras are also functional light-gated channels. Many chimeras have stronger light-activated inward currents than the three parents, and some have unique off-kinetics and spectral properties relative to the parents. An effective method for generating protein sequence and functional diversity, SCHEMA recombination can be used to gain insights into sequence–function relationships in MPs

The upstream Cymru story: a tale of international exchange, collaboration and persistence

2017 was a memorable year. The End Youth Homelessness Cymru (EYHC) coalition was launched with a goal of ending youth homelessness in Wales within 10 years. The Coalition's goals were supported by the First Minister of Wales at the time, Carwyn Jones, who stated: 'We believe we have a wonderful opportunity here in Wales to deliver real change. If we can put a man on the moon, we can surely end youth homelessness in Wales'. There was a collective will to rethink responses to youth homelessness in Wales by prioritising prevention and a real appetite for new approaches. In 2018, news about the success of The Geelong Project (TGP) in Australia reached Wales and by 2020 Upstream Cymru had been launched. This brief article tells the story of the development and implementation of the initiative

Synthesis and study of novel multifunctional cyclodextrin‐deferasirox hybrids

Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal‐selective chelation therapy. Deferasirox, 4‐[(3Z,5E)‐3,5‐bis(6‐oxo‐1‐cyclohexa‐2,4‐dienylidene)‐1,2,4‐triazolidin‐1‐yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann Pick C or for hypervitaminosis. We have conjugated deferasirox, via an amide coupling reaction, to both 6A‐amino‐6A‐deoxy‐β‐cyclodextrin and 3A‐amino‐3A‐deoxy‐2A(S),3A(R)‐β‐cyclodextrin, at the upper and lower rim respectively creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of β‐cyclodextrin with deferasirox to significantly improve the biological properties and reduce the cytotoxicity of this drug

Respiratory Infection in Institutions during Early Stages of Pandemic (H1N1) 2009, Canada

Outbreaks of respiratory infection in institutions in Ontario, Canada were studied from April 20 to June 12, 2009, during the early stages of the emergence of influenza A pandemic (H1N1) 2009. Despite widespread presence of influenza in the general population, only 2 of 83 outbreaks evaluated by molecular methods were associated with pandemic (H1N1) 2009

Participatory politics, environmental journalism and newspaper campaigns

This is an Author's Accepted Manuscript of an article published in Journalism Studies, 13(2), 210 - 225, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/1461670X.2011.646398.This article explores the extent to which approaches to participatory politics might offer a more useful alternative to understanding the role of environmental journalism in a society where the old certainties have collapsed, only to be replaced by acute uncertainty. This uncertainty not only generates acute public anxiety about risks, it has also undermined confidence in the validity of long-standing premises about the ideal role of the media in society and journalistic professionalism. The consequence, this article argues, is that aspirations of objective reportage are outdated and ill-equipped to deal with many of the new risk stories environmental journalism covers. It is not a redrawing of boundaries that is needed but a wholesale relocation of our frameworks into approaches better suited to the socio-political conditions and uncertainties of late modernity. The exploration of participatory approaches is an attempt to suggest one way this might be done

Directed Evolution of a Bright Near-Infrared Fluorescent Rhodopsin Using a Synthetic Chromophore

By engineering a microbial rhodopsin, Archaerhodopsin-3 (Arch), to bind a synthetic chromophore, merocyanine retinal, in place of the natural chromophore all-trans-retinal (ATR), we generated a protein with exceptionally bright and unprecedentedly red-shifted near-infrared (NIR) fluorescence. We show that chromophore substitution generates a fluorescent Arch complex with a 200-nm bathochromic excitation shift relative to ATR-bound wild-type Arch and an emission maximum at 772 nm. Directed evolution of this complex produced variants with pH-sensitive NIR fluorescence and molecular brightness 8.5-fold greater than the brightest ATR-bound Arch variant. The resulting proteins are well suited to bacterial imaging; expression and stability have not been optimized for mammalian cell imaging. By targeting both the protein and its chromophore, we overcome inherent challenges associated with engineering bright NIR fluorescence into Archaerhodopsin. This work demonstrates an efficient strategy for engineering non-natural, tailored properties into microbial opsins, properties relevant for imaging and interrogating biological systems

Rhinovirus Outbreaks in Long-term Care Facilities, Ontario, Canada

Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza