The structure of Rph, an exoribonuclease from Bacillus anthracis, at 1.7 angstrom resolution

Maturation of tRNA precursors into functional tRNA molecules requires trimming of the primary transcript at both the 5' and 3' ends. Cleavage of nucleotides from the 3' stem of tRNA precursors, releasing nucleotide diphosphates, is accomplished in Bacillus by a phosphate-dependent exoribonuclease, Rph. The crystal structure of this enzyme from B. anthracis has been solved by molecular replacement to a resolution of 1.7 angstrom and refined to an R factor of 19.3%. There is one molecule in the asymmetric unit; the crystal packing reveals the assembly of the protein into a hexamer arranged as a trimer of dimers. The structure shows two sulfate ions bound in the active-site pocket, probably mimicking the phosphate substrate and the phosphate of the 3'-terminal nucleotide of the tRNA precursor. Three other bound sulfate ions point to likely RNA-binding sites

The debris disk - terrestrial planet connection

The eccentric orbits of the known extrasolar giant planets provide evidence that most planet-forming environments undergo violent dynamical instabilities. Here, we numerically simulate the impact of giant planet instabilities on planetary systems as a whole. We find that populations of inner rocky and outer icy bodies are both shaped by the giant planet dynamics and are naturally correlated. Strong instabilities -- those with very eccentric surviving giant planets -- completely clear out their inner and outer regions. In contrast, systems with stable or low-mass giant planets form terrestrial planets in their inner regions and outer icy bodies produce dust that is observable as debris disks at mid-infrared wavelengths. Fifteen to twenty percent of old stars are observed to have bright debris disks (at wavelengths of ~70 microns) and we predict that these signpost dynamically calm environments that should contain terrestrial planets.Comment: Contribution to proceedings of IAU 276: Astrophysics of Planetary System

Racial Differences in the Human Endogenous Circadian Period

The length of the endogenous period of the human circadian clock (tau) is slightly greater than 24 hours. There are individual differences in tau, which influence the phase angle of entrainment to the light/dark (LD) cycle, and in doing so contribute to morningness-eveningness. We have recently reported that tau measured in subjects living on an ultradian LD cycle averaged 24.2 hours, and is similar to tau measured using different experimental methods. Here we report racial differences in tau. Subjects lived on an ultradian LD cycle (1.5 hours sleep, 2.5 hours wake) for 3 days. Circadian phase assessments were conducted before and after the ultradian days to determine the change in circadian phase, which was attributed to tau. African American subjects had a significantly shorter tau than subjects of other races. We also tested for racial differences in our previous circadian phase advancing and phase delaying studies. In the phase advancing study, subjects underwent 4 days of a gradually advancing sleep schedule combined with a bright light pulse upon awakening each morning. In the phase delaying study, subjects underwent 4 days of a gradually delaying sleep schedule combined with evening light pulses before bedtime. African American subjects had larger phase advances and smaller phase delays, relative to Caucasian subjects. The racial differences in tau and circadian phase shifting have important implications for understanding normal phase differences between individuals, for developing solutions to the problems of jet lag and shift work, and for the diagnosis and treatment of circadian rhythm based sleep disorders such as advanced and delayed sleep phase disorder

Tensile properties of the transverse carpal ligament and carpal tunnel complex

A new sophisticated method that uses video analysis techniques together with a Maillon Rapide Delta to determine the tensile properties of the transverse carpal ligament–carpal tunnel complex has been developed. Six embalmed cadaveric specimens amputated at the mid-forearm and aged (mean (SD)): 82 (6.29) years were tested. The six hands were from three males (four hands) and one female (two hands). Using trigonometry and geometry the elongation and strain of the transverse carpal ligament and carpal arch were calculated. The cross-sectional area of the transverse carpal ligament was determined. Tensile properties of the transverse carpal ligament–carpal tunnel complex and Load–Displacement data were also obtained. Descriptive statistics, one-way ANOVA together with a post-hoc analysis (Tukey) and t-tests were incorporated. A transverse carpal ligament–carpal tunnel complex novel testing method has been developed. The results suggest that there were no significant differences between the original transverse carpal ligament width and transverse carpal ligament at peak elongation (P= 0.108). There were significant differences between the original carpal arch width and carpal arch width at peak elongation (P=0.002). The transverse carpal ligament failed either at the mid-substance or at their bony attachments. At maximum deformation the peak load and maximum transverse carpal ligament displacements ranged from 285.74 N to 1369.66 N and 7.09 mm to 18.55 mm respectively. The transverse carpal ligament cross-sectional area mean (SD) was 27.21 (3.41)mm2. Using this method the results provide useful biomechanical information and data about the tensile properties of the transverse carpal ligament–carpal tunnel complex

Multi-instrument observations of the effects of a solar wind pressure pulse on the high latitude ionosphere : a detailed case study of a geomagnetic sudden impulse

Funding: ARF was supported by an STFC studentship, Science Foundation Ireland Grant 18/FRL/6199, and an Irish Research Council Government of Ireland Postdoctoral Fellowship GOIPD/2022/782. ML, TKY, and SEM acknowledge support from the Science and Technology Facilities Council, UKRI, grant no. ST/W00089X/1. JAC is supported by Royal Society grant DHF\R1\211068. HKS was supported by an STFC studentship. TE was supported by a Leverhulme Trust Early Career Fellowship (ECF-2019-155), the University of Leicester and the University of Glasgow. SJW was supported by NERC studentship NE/L002493/1. MKJ was supported by STFC Grant ST/W00089X/1. JML was supported by the Irish Research Council. LJP was supported by AFOSR MURI Award 26-0201-51-62.The effects of a solar wind pressure pulse on the terrestrial magnetosphere have been observed in detail across multiple datasets. The communication of these effects into the magnetosphere is known as a positive geomagnetic sudden impulse (+SI), and are observed across latitudes and different phenomena to characterise the propagation of +SI effects through the magnetosphere. A superposition of Alfvén and compressional propagation modes are observed in magnetometer signatures, with the dominance of these signatures varying with latitude. For the first time, collocated lobe reconnection convection vortices and region 0 field aligned currents are observed preceding the +SI onset, and an enhancement of these signatures is observed as a result of +SI effects. Finally, cusp auroral emission is observed collocated with the convection and current signatures. For the first time, simultaneous observations across multiple phenomena are presented to confirm models of +SI propagation presented previously.Publisher PDFPeer reviewe

A general model of resonance capture in planetary systems: First and second order resonances

Mean motion resonances are a common feature of both our own Solar System and of extrasolar planetary systems. Bodies can be trapped in resonance when their orbital semi-major axes change, for instance when they migrate through a protoplanetary disc. We use a Hamiltonian model to thoroughly investigate the capture behaviour for first and second order resonances. Using this method, all resonances of the same order can be described by one equation, with applications to specific resonances by appropriate scaling. We focus on the limit where one body is a massless test particle and the other a massive planet. We quantify how the the probability of capture into a resonance depends on the relative migration rate of the planet and particle, and the particle's eccentricity. Resonant capture fails for high migration rates, and has decreasing probability for higher eccentricities. More massive planets can capture particles at higher eccentricities and migration rates. We also calculate libration amplitudes and the offset of the libration centres for captured particles, and the change in eccentricity if capture does not occur. Libration amplitudes are higher for larger initial eccentricity. The model allows for a complete description of a particle's behaviour as it successively encounters several resonances. We discuss implications for several scenarios: (i) Planet migration through gas discs trapping other planets or planetesimals in resonances. (ii) Planet migration through a debris disc. (iii) Dust migration through PR drag. The Hamiltonian model will allow quick interpretation of the resonant properties of extrasolar planets and Kuiper Belt Objects, and will allow synthetic images of debris disc structures to be quickly generated, which will be useful for predicting and interpreting disc images made with ALMA, Darwin/TPF or similar missions. [Abridged]Comment: 19 pages, 14 figures; accepted to MNRA

An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

A deimmunised form of the ribotoxin, α-sarcin, lacking CD4+ T cell epitopes and its use as an immunotoxin warhead

Fungal ribotoxins that block protein synthesis can be useful warheads in the context of a targeted immunotoxin. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus that functions by catalytically cleaving a single phosphodiester bond in the sarcin–ricin loop of the large ribosomal subunit, thus making the ribosome unrecognisable to elongation factors and leading to inhibition of protein synthesis. Peptide mapping using an ex vivo human T cell assay determined that α-sarcin contained two T cell epitopes; one in the N-terminal 20 amino acids and the other in the C-terminal 20 amino acids. Various mutations were tested individually within each epitope and then in combination to isolate deimmunised α-sarcin variants that had the desired properties of silencing T cell epitopes and retention of the ability to inhibit protein synthesis (equivalent to wild-type, WT α-sarcin). A deimmunised variant (D9T/Q142T) demonstrated a complete lack of T cell activation in in vitro whole protein human T cell assays using peripheral blood mononuclear cells from donors with diverse HLA allotypes. Generation of an immunotoxin by fusion of the D9T/Q142T variant to a single-chain Fv targeting Her2 demonstrated potent cell killing equivalent to a fusion protein comprising the WT α-sarcin. These results represent the first fungal ribotoxin to be deimmunised with the potential to construct a new generation of deimmunised immunotoxin therapeutics

Identifying risk and mitigating gambling-related harm in online poker

The present paper conducts a critical analysis of the potential for gambling-related harm in relation to online poker participation, and a theoretical evaluation of current responsible gambling strategies employed to mitigate harm in online gambling and applies the evaluation of these strategies specifically to online poker gambling. Theoretically, the primary risk for harm in online poker is the rapid and continuous nature of poker provisions online, and has been demonstrated to be associated with disordered gambling behaviour, including the chasing of monetary losses. The following responsible gambling features were deemed relevant for consideration: informed player choice, voluntary self-exclusion, employee intervention, pre-commitment, in-game feedback, behavioural tracking tools, and age restriction and verification. Although current responsible gambling features are evaluated as theoretically robust, there remains a fundamental need for experimental validation of their effectiveness. Furthermore, despite online poker gamblers perceiving the responsible gambling features as valuable tools, in reality very few players regularly use available responsible gambling features. Ultimately, for the online poker gambling industry to retain market credibility and avoid substantial top-down regulation, it is imperative to demonstrate effectiveness of responsible gambling approaches, and increase customer utilisation of available harm-mitigation features