Intrinsic point defects and volume swelling in ZrSiO4 under irradiation

The effects of high concentration of point defects in crystalline ZrSiO4 as originated by exposure to radiation, have been simulated using first principles density functional calculations. Structural relaxation and vibrational studies were performed for a catalogue of intrinsic point defects, with different charge states and concentrations. The experimental evidence of a large anisotropic volume swelling in natural and artificially irradiated samples is used to select the subset of defects that give similar lattice swelling for the concentrations studied, namely interstitials of O and Si, and the anti-site Zr(Si), Calculated vibrational spectra for the interstitials show additional evidence for the presence of high concentrations of some of these defects in irradiated zircon.Comment: 9 pages, 7 (color) figure

Phylogenetic Origins and Age-Based Proportions of Malacho (Elops smithi) Relative to Ladyfish (Elops saurus): Species on the Move in the Western Gulf of Mexico

Two species of ladyfish occur in the Gulf of Mexico (GOM), Elops saurus and Elops smithi, that are morphologically indistinguishable except for vertebral counts but can also be identified by mitochondrial DNA haplotypes. Here we expand on previous work, most of which has occurred in Florida, and examine the demography, phylogenetics, geographic distribution, and age—structure of ladyfishes in Texas estuaries. Fishery—independent gill net data demonstrated that ladyfishes increase in abundance from north to south along the Texas coast. The abundance of ladyfishes also increased in Texas waters from 1982–2021, which coincides with recent trends of warmer winters. Genetic data confirmed that both E. saurus and E. smithi occur in Texas waters; however, E. smithi was far less common. Contrary to previous research, we observed higher levels of genetic diversity in E. saurus due to larger sample size and thorough sampling of the western portion of its geographic range. Phylogenetic analysis supported the existence of E. saurus as a distinct species but indicated that E. smithi may be paraphyletic with other species of Elops. Otolith analysis showed that the ages of E. saurus and E. smithi ranged from 0–3 years. The lack of individuals \u3e age—3 suggests that ladyfishes migrate to the offshore GOM at age 3 and do not return to coastal areas. This study enhances knowledge of the biology of ladyfishes in inshore waters of the northwestern GOM. Future management would benefit from expanding this research to the entire geographic range of the genus Elops

First observed wild birth and acoustic record of a possible infanticide attempt on a common bottlenose dolphin (Tursiops truncatus)

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Society for Marine Mammalogy for personal use, not for redistribution. The definitive version was published in Marine Mammal Science 32 (2016): 376–385, doi:10.1111/mms.12248.We observed the birth of a common bottlenose dolphin (Tursiops truncatus) followed immediately by a possible infanticide attempt in the estuary near Savannah, Georgia. Our report is unique in several ways: first, we witnessed the birth of the calf; second, we observed infanticidal behavior almost immediately afterward; and third, we obtained acoustic recordings concurrent with the possible infanticidal behavior. Our observations provide insight into aggressive, possible infanticidal, behavior in bottlenose dolphins.Boat time and support was provided by Department of Education/Title VII Award P382G090003. Additional support was provided by EDGE (Enhancing Diversity in Geosciences Education through Costal Research in Port City) NSF award GEO-0194680.2016-07-1

Structure of anhydrotetracycline-bound Tet(X6) reveals the mechanism for inhibition of type 1 tetracycline destructases

Inactivation of tetracycline antibiotics by tetracycline destructases (TDases) remains a clinical and agricultural threat. TDases can be classified as type 1 Tet(X)-like TDases and type 2 soil-derived TDases. Type 1 TDases are widely identified in clinical pathogens. A combination therapy of tetracycline and a TDase inhibitor is much needed to rescue the clinical efficacy of tetracyclines. Anhydrotetracycline is a pan-TDase inhibitor that inhibits both type 1 and type 2 TDases. Here, we present structural, biochemical, and phenotypic evidence that anhydrotetracycline binds in a substrate-like orientation and competitively inhibits the type 1 TDase Tet(X6) to rescue tetracycline antibiotic activity as a sacrificial substrate. Anhydrotetracycline interacting residues of Tet(X6) are conserved within type 1 TDases, indicating a conserved binding mode and mechanism of inhibition. This mode of binding and inhibition is distinct from anhydrotetracycline\u27s inhibition of type 2 TDases. This study forms the framework for development of next-generation therapies to counteract enzymatic tetracycline resistance

Can screening for genetic markers improve peripheral artery bypass patency?

AbstractObjective: Three genetic mutations have been associated with an increased risk of thromboembolic events: factor V Leiden R506Q, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR) mutations. The aim of this study was to determine the effect of these mutations on patency of peripheral bypass procedures and preoperative and postoperative thromboembolic events. Methods: Two hundred forty-four randomly selected volunteers participating in the Veterans Affairs Cooperative Study #362 were tested for factor V Leiden, prothrombin, or MTHFR mutations with polymerase chain reaction. Patients enrolled in the study were randomized to receive aspirin therapy or aspirin and warfarin therapy after a peripheral bypass procedure. The frequencies of preoperative and postoperative thromboembolic events and primary patency (PP), assisted primary patency (APP), and secondary patency (SP) rates were compared among carriers of the various mutations. Results: Fourteen patients (5.7%) were heterozygous for the factor V Leiden mutation, seven (2.9%) were heterozygous for the prothrombin mutation, and 108 (44.6%) were heterozygous and 15 (6.2%) homozygous for the MTHFR mutation. After surgery, patients homozygous for the MTHFR gene mutation had increased graft thrombosis, compared with patients who were heterozygous (33.3% versus 11.1%; P = .01), and lower PP, APP and SP rates (P < .05). Furthermore, patients heterozygous for the MTHFR mutation had fewer graft thromboses (11.1% versus 24.4%; P = .01), fewer below-knee amputations (0.9% versus 7.6%; P = .02), and higher PP, APP, and SP rates (PP, 79.6%; APP, 88.9%; SP, 90.7%; P < .05) compared with wild-type control subjects (PP, 63%; APP, 75.6%; SP, 76.5%; P < .05). Conclusion: Patients with either factor V Leiden or prothrombin mutations were not at an increased risk for postoperative graft occlusion or thromboembolic events. Patients heterozygous for MTHFR mutation had a lower risk of graft thrombosis and higher graft patency rates compared with both homozygous and wild-type control subjects. Patients homozygous for the MTHFR mutation had lower graft patency rates compared with patients who were heterozygous, and a trend was seen toward lower patency rates compared with wild-type control subjects. Therefore, screening for the MTHFR gene mutation before surgery may identify patients at an increased risk of graft thrombosis. (J Vasc Surg 2002;36:1198-206.

Plutonium stabilization in zircon: Effects of self-radiation

Zircon (ZrSiO4)(ZrSiO4) is the most thoroughly studied of all candidate ceramic phases for the stabilization of plutonium. Self-radiation damage from α-decay of the 239Pu,239Pu, which releases a 5.16 MeV α-particle and a 0.086 MeV 235U235U recoil nucleus, can significantly affect the structure and properties of zircon. Recent computer simulations using energy minimization techniques indicate that the lowest energy configuration occurs for a defect cluster composed of two near-neighbor Pu3+Pu3+ substitutions on Zr4+Zr4+ sites and a neighboring charge-compensating oxygen vacancy. © 2000 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87571/2/18_1.pd

Application of Metapopulation Theory to Northern Bobwhite Conservation

Northern bobwhite (Colinus virginianus) populations have declined throughout the majority of the species’ range, and have experienced the largest declines in fragmented habitats, suggesting landscape scale processes may be responsible for this decline. We used the results from a stochastic population dynamics model of South Texas bobwhites as conceptual justification for use of metapopulation theory in bobwhite management. Annual quasi-extinction probabilities for isolated bobwhite populations were 0.003 (95% CI: 0.001 0.006), 0.105 (95% CI: 0.083 0.126), and 0.773 (95% CI: 0.750 0.796) for simulated populations harvested at 20, 30, and 40% annually. The probability of regional persistence at 30% harvest increased to ~ 100% in scenarios where we modeled 5 occupied hypothetical 800-ha habitat patches; however, at 40% harvest rates, probability of regional metapopulation persistence did not reach 95% until 12 habitat patches were occupied. This suggests bobwhites probably require somewhere from 800 to 9,600 ha of available habitat space to maintain 95% probability of regional metapopulation persistence as harvest varies from 0 to 40% annually. Our results have strong implications for bobwhite harvest management given the high probability of quasi-extinction of isolated populations at rates of harvest 25%. Multiple patches of habitat (where individual patch size is 800 ha) must be available to ensure bobwhite metapopulation persistence

Evolutionary pathways to NS5A inhibitor resistance in genotype 1 hepatitis C virus

Direct-acting antivirals (DAAs) targeting NS5A are broadly effective against hepatitis C virus (HCV) infections, but sustained virological response rates are generally lower in patients infected with genotype (gt)-1a than gt-1b viruses. The explanation for this remains uncertain. Here, we adopted a highly accurate, ultra-deep primer ID sequencing approach to intensively study serial changes in the NS5A-coding region of HCV in gt-1a- and gt-1b-infected subjects receiving a short course of monotherapy with the NS5A inhibitor, elbasvir. Low or undetectable levels of viremia precluded on-treatment analysis in gt-1b-infected subjects, but variants with the resistance-associated substitution (RAS) Y93H in NS5A dominated rebounding virus populations following cessation of treatment. These variants persisted until the end of the study, two months later. In contrast, while Y93H emerged in multiple lineages and became dominant in subjects with gt-1a virus, these haplotypes rapidly decreased in frequency off therapy. Substitutions at Q30 and L31 emerged in distinctly independent lineages at later time points, ultimately coming to dominate the virus population off therapy. Consistent with this, cell culture studies with gt-1a and gt-1b reporter viruses and replicons demonstrated that Y93H confers a much greater loss of replicative fitness in gt-1a than gt-1b virus, and that L31M/V both compensates for the loss of fitness associated with Q30R (but not Y93H) and also boosts drug resistance. These observations show how differences in the impact of RASs on drug resistance and replicative fitness influence the evolution of gt-1a and gt-1b viruses during monotherapy with an antiviral targeting NS5A. © 2018 Elsevier B.V

Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors

Background & Aims All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3. Methods We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production. Results Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly. Conclusions DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis