scholarly journals The Impact of Retinal Configuration on the Protein–Chromophore Interactions in Bistable Jumping Spider Rhodopsin-1

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 71
Author(s):  
Jonathan R. Church ◽  
Jógvan Magnus Haugaard Olsen ◽  
Igor Schapiro

Bistable rhodopsins have two stable forms that can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applications such as optogenetics. In this work, we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We performed hybrid QM/MM simulations to study three isomers of the retinal chromophore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from QM/MM molecular dynamics trajectories and compared to their experimental counterparts. The chromophore–protein interactions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto the chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted, including a structural change in the polyene chain of the chromophore, as well as changes in the nearby hydrogen bonding network.

Author(s):  
Jonathan Richard Church ◽  
Jógvan Magnus Haugaard Olsen ◽  
Igor Schapiro

Bistable rhodopsins have two stable forms which can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applica-tions such as optogenetics. In this work we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We have performed hybrid QM/MM simulations to study three isomers of the retinal chromo-phore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from a QM/MM molecular dy-namics trajectory and compared to experimental counterparts. The chromophore-protein in-teractions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted including a structural change in the polyene chain of the chromophore as well as changes in the nearby hydrogen bond network.


Sexualities ◽  
2020 ◽  
pp. 136346072098169
Author(s):  
Aidan McKearney

This article focuses on the experiences of gay men in the rural west and northwest region of Ireland, during a period of transformational social and political change in Irish society. These changes have helped facilitate new forms of LGBTQI visibility, and local radicalism in the region. Same-sex weddings, establishment of rural LGBT groups and marching under an LGBT banner at St Patricks Day parades would have been unthinkable in the recent past; but they are now becoming a reality. The men report continuing challenges in their lives as gay men in the nonmetropolitan space, but the emergence of new visibility, voice and cultural acceptance of LGBT people is helping change their lived experiences. The study demonstrates the impact of local activist LGBT citizens. Through their testimonies we can gain an insight into the many, varied and interwoven factors that have interplayed to create the conditions necessary for the men to: increasingly define themselves as gay to greater numbers of people in their localities; to embrace greater visibility and eschew strategies of silence; and aspire to a host of legal, political, cultural and social rights including same-sex marriage. Organic forms of visibility and local radicalism have emerged in the region and through an analysis of their testimonies we can see how the men continue to be transformed by an ever-changing landscape.


2021 ◽  
pp. 026975802110106
Author(s):  
Raoul Notté ◽  
E.R. Leukfeldt ◽  
Marijke Malsch

This article explores the impact of online crime victimisation. A literature review and 41 interviews – 19 with victims and 22 with experts – were carried out to gain insight into this. The interviews show that most impacts of online offences correspond to the impacts of traditional offline offences. There are also differences with offline crime victimisation. Several forms of impact seem to be specific to victims of online crime: the substantial scale and visibility of victimhood, victimisation that does not stop in time, the interwovenness of online and offline, and victim blaming. Victims suffer from double, triple or even quadruple hits; it is the accumulation of different types of impact, enforced by the limitlessness in time and space, which makes online crime victimisation so extremely invasive. Furthermore, the characteristics of online crime victimisation greatly complicate the fight against and prevention of online crime. Finally, the high prevalence of cybercrime victimisation combined with the severe impact of these crimes seems contradictory with public opinion – and associated moral judgments – on victims. Further research into the dominant public discourse on victimisation and how this affects the functioning of the police and victim support would be valuable.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Bimandra A. Djaafara ◽  
Charles Whittaker ◽  
Oliver J. Watson ◽  
Robert Verity ◽  
Nicholas F. Brazeau ◽  
...  

Abstract Background As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. Methods We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine rollout. Results C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. Conclusions Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.


2021 ◽  
Vol 11 (11) ◽  
pp. 4723
Author(s):  
Rosaria Scudiero ◽  
Chiara Maria Motta ◽  
Palma Simoniello

The cleidoic eggs of oviparous reptiles are protected from the external environment by membranes and a parchment shell permeable to water and dissolved molecules. As a consequence, not only physical but also chemical insults can reach the developing embryos, interfering with gene expression. This review provides information on the impact of the exposure to cadmium contamination or thermal stress on gene expression during the development of Italian wall lizards of the genus Podarcis. The results obtained by transcriptomic analysis, although not exhaustive, allowed to identify some stress-reactive genes and, consequently, the molecular pathways in which these genes are involved. Cadmium-responsive genes encode proteins involved in cellular protection, metabolism and proliferation, membrane trafficking, protein interactions, neuronal transmission and plasticity, immune response, and transcription regulatory factors. Cold stress changes the expression of genes involved in transcriptional/translational regulation and chromatin remodeling and inhibits the transcription of a histone methyltransferase with the probable consequence of modifying the epigenetic control of DNA. These findings provide transcriptome-level evidence of how terrestrial vertebrate embryos cope with stress, giving a key to use in population survival and environmental change studies. A better understanding of the genes contributing to stress tolerance in vertebrates would facilitate methodologies and applications aimed at improving resistance to unfavourable environments.


2021 ◽  
Vol 45 (10) ◽  
pp. 4756-4765
Author(s):  
Daoxing Chen ◽  
Liting Zhang ◽  
Yanan Liu ◽  
Jiali Song ◽  
Jingwen Guo ◽  
...  

EGFR L792Y/F/H mutation makes it difficult for Osimertinib to recognize ATP pockets.


Livestock ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 176-179
Author(s):  
Chris Lloyd

The Responsible Use of Medicines in Agriculture Alliance (RUMA) was established to promote the highest standards of food safety, animal health and animal welfare in the British livestock industry. It has a current focus to deliver on the Government objective of identifying sector-specific targets for the reduction, refinement or replacement of antibiotics in animal agriculture. The creation and roll out of sector specific targets in 2017 through the RUMA Targets Task Force, has helped focus activity across the UK livestock sectors to achieve a 50% reduction in antibiotic use since 2014. This has been realised principally through voluntary multi-sector collaboration, cross sector initiatives, codes of practice, industry body support and farm assurance schemes. This article provides an overview of RUMA's work to date providing insight into the methods used to create the targets, why they are so important, the impact they are having and how ongoing support and robust data are vital components in achieving the latest set of targets.


2021 ◽  
Vol 22 (7) ◽  
pp. 3577
Author(s):  
Victor Camberos ◽  
Jonathan Baio ◽  
Ana Mandujano ◽  
Aida F. Martinez ◽  
Leonard Bailey ◽  
...  

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments.


Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Shomeek Chowdhury ◽  
Stephen Hepper ◽  
Mudassir K. Lodi ◽  
Milton H. Saier ◽  
Peter Uetz

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.


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