HDX-guided EPR spectroscopy to interrogate membrane protein dynamics

This project was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/S018069/1) to C.P., who also acknowledges support from the Wellcome Trust (WT) (219999/Z/19/Z) and the Chinese Scholarship Council (CSC) in the form of studentships for B.J.L. and B.W., respectively. A.N.C. is a Sir Henry Dale Fellow jointly funded by the WT and the Royal Society (220628/Z/20/Z). Funding from the BBSRC (BB/M012573/1) enabled the purchase of mass spectrometry equipment.Solvent accessibilities of and distances between protein residues measured by pulsed-EPR approaches provide high-resolution information on dynamic protein motions. We describe protocols for the purification and site-directed spin labeling of integral membrane proteins. In our protocol, peptide-level HDX-MS is used as a precursor to guide single-residue resolution ESEEM accessibility measurements and spin labeling strategies for EPR applications. Exploiting the pentameric MscL channel as a model, we discuss the use of cwEPR, DEER/PELDOR, and ESEEM spectroscopies to interrogate membrane protein dynamics. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).Publisher PDFPeer reviewe

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Spin states of asteroids in the Eos collisional family

Eos family was created during a catastrophic impact about 1.3 Gyr ago. Rotation states of individual family members contain information about the history of the whole population. We aim to increase the number of asteroid shape models and rotation states within the Eos collision family, as well as to revise previously published shape models from the literature. Such results can be used to constrain theoretical collisional and evolution models of the family, or to estimate other physical parameters by a thermophysical modeling of the thermal infrared data. We use all available disk-integrated optical data (i.e., classical dense-in-time photometry obtained from public databases and through a large collaboration network as well as sparse-in-time individual measurements from a few sky surveys) as input for the convex inversion method, and derive 3D shape models of asteroids together with their rotation periods and orientations of rotation axes. We present updated shape models for 15 asteroids and new shape model determinations for 16 asteroids. Together with the already published models from the publicly available DAMIT database, we compiled a sample of 56 Eos family members with known shape models that we used in our analysis of physical properties within the family. Rotation states of asteroids smaller than ~20 km are heavily influenced by the YORP effect, whilst the large objects more or less retained their rotation state properties since the family creation. Moreover, we also present a shape model and bulk density of asteroid (423) Diotima, an interloper in the Eos family, based on the disk-resolved data obtained by the Near InfraRed Camera (Nirc2) mounted on the W.M. Keck II telescope.Comment: Accepted for publication in ICARUS Special Issue - Asteroids: Origin, Evolution & Characterizatio

Environmental impact of wind energy:Synthesis and Review

One purpose of wind turbines is to provide pollution-free electric power at a reasonable price in an environmentally sound way. In this focus issue the latest research on the environmental impact of wind farms is presented. Offshore wind farms affect the marine fauna in both positive and negative ways. For example, some farms are safe havens for porpoises while other farms show fewer harbor porpoises even after ten years. Atmospheric computer experiments are carried out to investigate the possible impact and resource of future massive installations of wind turbines. The following questions are treated. What is the global capacity for energy production by the wind? Will the added turbulence and reduced wind speeds generated by massive wind farms cool or heat the surface? Can wind farms affect precipitation? It is also shown through life-cycle analysis how wind energy can reduce the atmospheric emission of eight air pollutants. Finally, noise generation and its impact on humans are studied

Palomar discovery and initial characterization of naked-eye long period comet C/2022 E3 (ZTF)

Long-period comets are planetesimal remnants constraining the environment and volatiles of the protoplanetary disc. We report the discovery of hyperbolic long-period comet C/2022 E3 (ZTF), which has a perihelion $\sim$1.11 au, an eccentricity $\gtrsim$1 and an inclination $\sim$109$^{\circ}$, from images taken with the Palomar 48-inch telescope during morning twilight on 2022 Mar 2. Additionally, we report the characterization of C/2022 E3 (ZTF) from observations taken with the Palomar 200-inch, the Palomar 60-inch, and the NASA Infrared Telescope Facility in early 2023 February to 2023 March when the comet passed within $\sim$0.28 au of the Earth and reached a visible magnitude of $\sim$5. We measure g-r = 0.70$\pm$0.01, r-i = 0.20$\pm$0.01, i-z = 0.06$\pm$0.01, z-J = 0.90$\pm$0.01, J-H = 0.38$\pm$0.01 and H-K = 0.15$\pm$0.01 colours for the comet from observations. We measure the A(0$^\circ$)f$\rho$ (0.8~$\mu$m) in a 6500~km radius from the nucleus of 1483$\pm$40~cm, and CN, C$_3$, and C$_2$ production of 5.43$\pm0.11\times$10$^{25}$~mol/s, 2.01$\pm0.04\times$10$^{24}$, and 3.08$\pm0.5\times$10$^{25}$~mol/s, similar to other long period comets. We additionally observe the appearance of jet-like structures at a scale of $\sim$4,000 km in wide-field g-band images, which may be caused by the presence of CN gas in the near-nucleus coma.Comment: Accepted for publication in MNRAS:L, 9 pages, 6 figures, 2 table

An interdisciplinary system dynamics model for post-disaster housing recovery

Many previous disasters have demonstrated the need for extensive personal, public, and governmental expenditures for housing recovery highlighting the importance of studying housing recovery. Yet, much research is still needed to fully understand the multi-faceted and complex nature of housing recovery. The goal of this paper is to present a holistic model to further the understanding of the dynamic processes and interdependencies of housing recovery. The impetus for this work is that inequalities in housing recovery could be addressed more effectively if we better understood interconnected factors and dynamic processes that slow down recovery for some. Currently, there is a lack of understanding about such factors and processes. Literature from engineering and social sciences was reviewed to develop an integrated system dynamics model for post-disaster housing recovery. While it is beyond current capabilities to quantify such complexities, the presented model takes a major stride toward articulating the complex phenomenon that is housing recovery

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a non-physical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains >99.5% efficient at detecting objects on a single night but drops to 80% efficiency at producing orbits for objects detected on multiple nights. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table

Media events and cosmopolitan fandom:"Playful nationalism' in the Eurovision Song Contest

Academic literature on media events is increasingly concerned with their global dimensions and the applicability of Dayan and Katz's (1992) theoretical concept in a post-national context. This paper contributes to this debate by exploring the Eurovision Song Contest as a global media event. In particular, we employ a perspective from 'inside the media event', drawing upon empirical material collected during the 2014 Eurovision final in Copenhagen and focusing on the experiences of fans attending the contest. We argue that the ESC as a media event is experienced by its fans as a cosmopolitan space, open and diverse, whereas national belonging is expressed in a playful way tied to the overall visual aesthetics of the contest. However, the bounded and narrow character of participation render this cosmopolitan space rather limited