Geodynamics of synconvergent extension and tectonic mode switching: Constraints from the Sevier-Laramide orogen

Many orogenic belts experience alternations in shortening and extension (tectonic mode switches) during continuous plate convergence. The geodynamics of such alternations are not well understood. We present a record of Late Cretaceous to Eocene alternations of shortening and extension from the interior of the retroarc Sevier-Laramide orogen of the western United States. We integrate new Lu-Hf garnet geochronometry with revised PT paths utilizing differential thermobarometry combined with isochemical G-minimization plots, and monazite Th-Pb inclusion geochronometry to produce a well-constrained “M” shaped PTt path. Two burial events (86 and 65 Ma) are separated by ∼3 kbar of decompression. The first burial episode is Late Cretaceous, records a 2 kbar pressure increase at ∼515–550 °C and is dated by a Lu-Hf garnet isochron age of 85.5 ± 1.9 Ma (2σ); the second burial episode records ∼1 kbar of pressure increase at ∼585–615 °C, and is dated by radially decreasing Th-Pb ages of monazite inclusions in garnet between ∼65 and 45 Ma. We propose a synconvergent lithospheric delamination cycle, superimposed on a dynamic orogenic wedge, as a viable mechanism. Wedge tapers may evolve from critical to subcritical (amplification), to supercritical (separation), and back to subcritical (re-equilibration) owing to elevation changes resulting from isostatic adjustments during the amplification and separation of Rayleigh-Taylor instabilities, and post-separation thermal and rheological re-equilibration. For the Sevier-Laramide hinterland, the sequence of Late Cretaceous delamination, low-angle subduction, and slab rollback/foundering during continued plate convergence explains the burial-exhumation-burial-exhumation record and the “M-shaped” PTt path

Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1-Deficient Mice

AbstractMutations in the EXT1 gene are responsible for human hereditary multiple exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog diffusion and signaling, which play an important role in tissue patterning during both invertebrate and vertebrate development. The EXT1 protein is also required for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous mutants fail to gastrulate and generally lack organized mesoderm and extraembryonic tissues, resulting in smaller embryos compared to normal littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm development indicates the delayed and abnormal development of both of these tissues. Immunohistochemical staining revealed a visceral endoderm pattern of Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient embryos and wild-type embryos treated with heparitinase I, Ihh failed to associate with the cells. The effect of the EXT1 deletion on heparan sulfate formation was tested by HPLC and cellular glycosyltransferase activity assays. Heparan sulfate synthesis was abolished in EXT1 −/− ES cells and decreased to less than 50% in +/− cell lines. These results indicate that EXT1 is essential for both gastrulation and heparan sulfate biosynthesis in early embryonic development

Prospective, randomized study of one, two, or three trabecular bypass stents in open-angle glaucoma subjects on topical hypotensive medication

PURPOSE: To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG) not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively. MATERIALS AND METHODS: Subjects with medicated intraocular pressure (IOP) 18–30 mmHg and postmedication-washout baseline IOP 22–38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg. RESULTS: A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96–2.73) for three-stent vs two-stent groups and 1.73 mmHg (95% confidence interval 0.83–2.64) for two-stent vs one-stent groups. Adverse events through 18 months were limited to cataract progression with best-corrected visual acuity loss and subsequent cataract surgery. CONCLUSION: In this series, implantation of each additional stent resulted in significantly greater IOP reduction with reduced medication use. Titratability of stents as a sole procedure was shown to be effective and safe, with sustained effect through 18 months postoperatively in OAG not controlled with medication

Fish assemblages associated with artificial reefs assessed using multiple gear types in the northwest Gulf of Mexico

Quantitative surveys of fishes associated with artificial reefs in the northwest Gulf of Mexico were conducted over a 4-yr period (2014-2017). Artificial reefs surveyed were comprised of three types: concrete structures, rig jackets, and decommissioned ships. All reefs were surveyed using vertical long line ( VLL), fish traps, and Adaptive Resolution Imaging Sonar (ARIS 1800). Mean fish abundance did not significantly differ using VLL [1.7 ind set(-1) (SD 2.2)] among the three reef types. However, relative abundance among all fishes collected was significantly highest on rig reefs using traps [6.2 ind soak(-1) (SD 3.8)], while results from sonar surveys indicated that the mean relative fish density was highest on concrete reefs [15.3 fish frame(-1) (SD 26.8)]. Red snapper (n = 792), followed by gray triggerfish (n = 130), pigfish (n = 70), tomtate (n = 69), and hardhead catfish (n = 57) were the most numerically abundant species using VLL and traps; red snapper comprised 90.7% of total catch using VLL and 43.9% using traps. Mean Brillouin\u27s diversity (HB) was highest on ships using VLL [0.41 (SD 0.14)] and highest on rigs using traps [0.87 (SD 0.58)] compared to the lowest diversity found on concrete [VLL 0.07 (SD 0.11); traps 0.36 (SD 0.32)]. Findings from this study can be used to inform the planning of future artificial reefs and their effect on the assemblages of reef-associated fishes. Additionally, these results highlight the value of using multiple gear types to survey reef fish assemblages associated with artificial reefs

Mediators of Monocyte Migration in Response to Recovery Modalities following Resistance Exercise

Mediators of monocyte migration, complement receptor-3 (CR3), and chemokine ligand-4 (CCL4) were measured in response to recovery modalities following resistance exercise. Thirty resistance-trained men (23.1 +/- 2.9 y; 175.2 +/- 7.1 cm; 82.1 +/- 8.4 kg) were given neuromuscular electric stimulation (NMES), cold water immersion (CWI), or control (CON) treatments immediately following resistance exercise. Blood samples were obtained preexercise (PRE), immediately (IP), 30 minutes (30 P), 24 hours (24 H), and 48 hours (48 H) after exercise for measurement of circulating CCL4 and CR3 expression on CD14+ monocytes, by assay and flow cytometry. Circulating CCL4 showed no consistent changes. Inferential analysis indicated that CR3 expression was likely greater in CON at 30 P than NMES (90.0%) or CWI (86.8%). NMES was likely lower than CON at 24H (92.9%) and very likely lower at 48H (98.7%). Expression of CR3 following CWI was very likely greater than CON (96.5%) at 24H. The proportion of CR3+ monocytes was likely greater following CWI than NMES (85.8%) or CON (85.2%) at 24 H. The change in proportion of CR3+ monocytes was likely (86.4%) greater following NMES than CON from IP to 30 P. The increased expression of CR3 and increased proportion of CR3+ monocytes following CWI at 24 H indicate a potentially improved ability for monocyte adhesion to the endothelium, possibly improving phagocytosis of damaged tissues

Population-Sequencing as a Biomarker of Burkholderia mallei and Burkholderia pseudomallei Evolution through Microbial Forensic Analysis

Large-scale genomics projects are identifying biomarkers to detect human disease. B. pseudomallei and B. mallei are two closely related select agents that cause melioidosis and glanders. Accurate characterization of metagenomic samples is dependent on accurate measurements of genetic variation between isolates with resolution down to strain level. Often single biomarker sensitivity is augmented by use of multiple or panels of biomarkers. In parallel with single biomarker validation, advances in DNA sequencing enable analysis of entire genomes in a single run: population-sequencing. Potentially, direct sequencing could be used to analyze an entire genome to serve as the biomarker for genome identification. However, genome variation and population diversity complicate use of direct sequencing, as well as differences caused by sample preparation protocols including sequencing artifacts and mistakes. As part of a Department of Homeland Security program in bacterial forensics, we examined how to implement whole genome sequencing (WGS) analysis as a judicially defensible forensic method for attributing microbial sample relatedness; and also to determine the strengths and limitations of whole genome sequence analysis in a forensics context. Herein, we demonstrate use of sequencing to provide genetic characterization of populations: direct sequencing of populations

Pathogenesis of bovine spongiform encephalopathy in sheep

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was detected after 6 months in the tonsil and the ileal Peyer’s patches. At 9 months postinfection, PrPSc accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrPSc accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrPSc was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7–L1. At subsequent time points, PrPSc was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrPSc involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord

Projecting hospital utilization during the COVID-19 outbreaks in the United States

Data deposition: The computational system is available in Github (https://github.com/affans/ncov2019odemodel).In the wake of community coronavirus disease 2019 (COVID-19) transmission in the United States, there is a growing public health concern regarding the adequacy of resources to treat infected cases. Hospital beds, intensive care units (ICUs), and ventilators are vital for the treatment of patients with severe illness. To project the timing of the outbreak peak and the number of ICU beds required at peak, we simulated a COVID-19 outbreak parameterized with the US population demographics. In scenario analyses, we varied the delay from symptom onset to self-isolation, the proportion of symptomatic individuals practicing self-isolation, and the basic reproduction number R0. Without self-isolation, when R0 =2.5, treatment of critically ill individuals at the outbreak peak would require 3.8 times more ICU beds than exist in the United States. Self-isolation by 20% of cases 24 h after symptom onset would delay and flatten the outbreak trajectory, reducing the number of ICU beds needed at the peak by 48.4% (interquartile range 46.4-50.3%), although still exceeding existing capacity. When R0 =2, twice as many ICU beds would be required at the peak of outbreak in the absence of self-isolation. In this scenario, the proportional impact of self-isolation within 24 h on reducing the peak number of ICU beds is substantially higher at 73.5% (interquartile range 71.4-75.3%). Our estimates underscore the inadequacy of critical care capacity to handle the burgeoning outbreak. Policies that encourage self-isolation, such as paid sick leave, may delay the epidemic peak, giving a window of time that could facilitate emergency mobilization to expand hospital capacity.S.M.M. acknowledges support from the Canadian Institutes of Health Research (grant OV4-170643; Canadian 2019 Novel Coronavirus Rapid Research), and the Natural Sciences and Engineering Research Council of Canada. A.P.G. gratefully acknowledges funding from the NIH (grant UO1-GM087719), the Burnett and Stender families’ endowment, the Notsew Orm Sands Foundation, NIH grant 1R01AI151176-01, and National Science Foundation grant RAPID-2027755. M.C.F. was supported by the NIH grant K01 AI141576.Integrative Biolog

Ticks produce highly selective chemokine binding proteins with antiinflammatory activity

Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126–1136), and may be therapeutically useful as novel antiinflammatory agents in the future

Spin chirality on a two-dimensional frustrated lattice

The collective behavior of interacting magnetic moments can be strongly influenced by the topology of the underlying lattice. In geometrically frustrated spin systems, interesting chiral correlations may develop that are related to the spin arrangement on triangular plaquettes. We report a study of the spin chirality on a two-dimensional geometrically frustrated lattice. Our new chemical synthesis methods allow us to produce large single crystal samples of KFe3(OH)6(SO4)2, an ideal Kagome lattice antiferromagnet. Combined thermodynamic and neutron scattering measurements reveal that the phase transition to the ordered ground-state is unusual. At low temperatures, application of a magnetic field induces a transition between states with different non-trivial spin-textures.Comment: 7 pages, 4 figure