The Role of Nonconserved Residues of Archaeoglobus fulgidus Ferritin on Its Unique Structure and Biophysical Properties

Archaeoglobus fulgidus ferritin (AfFtn) is the only tetracosameric ferritin known to form a tetrahedral cage, a structure that remains unique in structural biology. As a result of the tetrahedral (2-3) symmetry, four openings (∼45 Å in diameter) are formed in the cage. This open tetrahedral assembly contradicts the paradigm of a typical ferritin cage: a closed assembly having octahedral (4-3-2) symmetry. To investigate the molecular mechanism affecting this atypical assembly, amino acid residues Lys-150 and Arg-151 were replaced by alanine. The data presented here shed light on the role that these residues play in shaping the unique structural features and biophysical properties of the AfFtn. The x-ray crystal structure of the K150A/R151A mutant, solved at 2.1 Å resolution, indicates that replacement of these key residues flips a “symmetry switch.” The engineered molecule no longer assembles with tetrahedral symmetry but forms a typical closed octahedral ferritin cage. Small angle x-ray scattering reveals that the overall shape and size of AfFtn and AfFtn-AA in solution are consistent with those observed in their respective crystal structures. Iron binding and release kinetics of the AfFtn and AfFtn-AA were investigated to assess the contribution of cage openings to the kinetics of iron oxidation, mineralization, or reductive iron release. Identical iron binding kinetics for AfFtn and AfFtn-AA suggest that Fe^2+ ions do not utilize the triangular pores for access to the catalytic site. In contrast, relatively slow reductive iron release was observed for the closed AfFtn-AA, demonstrating involvement of the large pores in the pathway for iron release

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Structural characterization of Methanococcus adenylate kinases

The crystal structures of adenylate kinases from the mesophile Methanococcus voltae (37°C) and the thermophile M. thermolithotrophicus (65°C) have been solved to 2.5 A resolution using molecular replacement methods. These adenylate kinases share 78% primary sequence identity, yet exhibit significantly different thermal stabilities and optimal activity ranges. Analyses of these archaeal structures reveal possible details regarding their disparate thermostabilities. In this study, we perform a comparative structural analysis of the mesophilic and thermophilic adenylate kinases and draw four general conclusions. First, we find correlation between thermostability and ionic interactions and identify a unique ionic network in the thermophilic enzyme. Second, we find beta-branched residues incorporated within alpha-helices of the thermophilic enzyme with significantly greater frequency. Third, we find examples of tighter packing within the CORE domain of the thermophilic enzyme. Last, most of the mutations in the thermophile occur very near the surface resulting in greater negative surface potential. In additional to the comparative thermostability study, we also analyze these two methanococcal structures with respect to their apparent lack of an essential lysine residue, which is present within the P-loop of previously characterized adenylate kinases. Previous modeling experiments proposed that, if protonated, His92 could participate in a similar manner as the lysine residue present in homologous adenylate kinases. From our investigation, we conclude that, as in the case of the homologous Sulfolobus acidocaldarius adenylate kinase structure, His92 is involved in interactions with the terminal phosphate group of AMP. Structural alignments of Methanococcus and homologous enzymes demonstrate that Gly14 is structurally equivalent to Lys14, indicating that an amino acid outside of the canonical P-loop must compensate for the essential lysine deficiency. We propose that this compensatory role is filled either by Arg138 or Arg140, each of which are LID domain residues conserved among the archaeal enzymes

Cognitive control dysfunction in workers exposed to manganese-containing welding fume

BACKGROUND: Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. METHODS: We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15.5 years) of exposure to welding fume. We performed linear regression to assess the association between exposure to Mn-containing welding fume and cognitive control tasks. RESULTS: Overall performance was inversely related to intensity of welding exposure (P = 0.009) and was driven by the Two-Back and Letter Number Sequencing tests that assess working memory (both P = 0.02). CONCLUSIONS: Occupational exposure to Mn-containing welding fume may be associated with poorer working memory performance, and workers may benefit from practices that reduce exposure intensity. Am. J. Ind. Med. 60:181-188, 2017. © 2016 Wiley Periodicals, Inc

Effects of parkinsonism on health status in welding exposed workers

BACKGROUND: Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. METHODS: Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was ≥15. All subjects completed a Parkinson\u27s disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. RESULTS: Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL\u27s). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. CONCLUSION: Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD

Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study

BACKGROUND: Manganese (Mn) is a common component of welding fume. Exposure to Mn fume has been associated with parkinsonism. A simple and reliable screening tool to evaluate Mn exposed workers for neurotoxic injury would have broad occupational health application. METHODS: This study investigated 490 occupational welders recruited from a trade union list. Subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism, intermediate, and normal groups were defined as UPDRS3 score ≥ 15, 6-15, and \u3c6, respectively. Workers completed a health status questionnaire (PDQ39) and a Parkinson disease (PD) Symptoms Questionnaire. Areas under receiver operator curve (AUC) were analyzed based on these scores, adjusted for age, smoking, race, gender, and neurologist, using normal as the reference. RESULTS: The AUC was 0.79 (95% confidence interval [CI]=0.73-0.84) for PDQ39 and 0.78 (95% CI=0.72-0.85) for PD Symptoms Questionnaire score. At 70% sensitivity, the specificity for PDQ39 score and PD Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and 80.1%, respectively. CONCLUSIONS: These results suggest the questionnaires have reasonably good sensitivity and specificity to predict parkinsonism in Mn exposed workers. These questionnaires could be a valuable first step in a tiered screening approach for Mn exposed workers