Sex Dimorphism in the Myocardial Response to Aortic Stenosis

OBJECTIVES: The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. BACKGROUND: AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. METHODS: This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro-brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). CONCLUSIONS: CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471.)

Awesome SOSS: atmospheric characterization of WASP-96 b using the JWST early release observations

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData availability: All data used in this study are publicly available from the Barbara A. Mikulski Archive for Space Telescopes; https://mast.stsci.edu/portal/Mashup/Clients/Mast/Portal.html. The models generated in this paper can be made available on request.The newly operational JWST offers the potential to study the atmospheres of distant worlds with precision that has not been achieved before. One of the first exoplanets observed by JWST in the summer of 2022 was WASP-96 b, a hot Saturn orbiting a G8 star. As a part of the Early Release Observations programme, one transit of WASP-96 b was observed with NIRISS/SOSS to capture its transmission spectrum from 0.6 to 2.85 μm. In this work, we utilize four retrieval frameworks to report precise and robust measurements of WASP-96 b's atmospheric composition. We constrain the logarithmic volume mixing ratios of multiple chemical species in its atmosphere, including: H2O =, CO2 =, and K =, thus generally consistent with 1× solar (with the exception of CO2). Notably, our results offer a first abundance constraint on potassium in WASP-96 b's atmosphere and important inferences on carbon-bearing species such as CO2 and CO. Our short wavelength NIRISS/SOSS data are best explained by the presence of an enhanced Rayleigh scattering slope, despite previous inferences of a clear atmosphere - although we find no evidence for a grey cloud deck. Finally, we explore the data resolution required to appropriately interpret observations using NIRISS/SOSS. We find that our inferences are robust against different binning schemes. That is, from low R = 125 to the native resolution of the instrument, the bulk atmospheric properties of the planet are consistent. Our systematic analysis of these exquisite observations demonstrates the power of NIRISS/SOSS to detect and constrain multiple molecular and atomic species in the atmospheres of hot giant planets

Shared Decision Making Tools for People Facing Stroke Prevention Strategies in Atrial Fibrillation: A Systematic Review and Environmental Scan.

OBJECTIVE: Shared decision making (SDM) tools can help implement guideline recommendations for patients with atrial fibrillation (AF) considering stroke prevention strategies. We sought to characterize all available SDM tools for this purpose and examine their quality and clinical impact. METHODS: We searched through multiple bibliographic databases, social media, and an SDM tool repository from inception to May 2020 and contacted authors of identified SDM tools. Eligible tools had to offer information about warfarin and ≥1 direct oral anticoagulant. We extracted tool characteristics, assessed their adherence to the International Patient Decision Aids Standards, and obtained information about their efficacy in promoting SDM. RESULTS: We found 14 SDM tools. Most tools provided up-to-date information about the options, but very few included practical considerations (e.g., out-of-pocket cost). Five of these SDM tools, all used by patients prior to the encounter, were tested in trials at high risk of bias and were found to produce small improvements in patient knowledge and reductions in decisional conflict. CONCLUSION: Several SDM tools for stroke prevention in AF are available, but whether they promote high-quality SDM is yet to be known. The implementation of guidelines for SDM in this context requires user-centered development and evaluation of SDM tools that can effectively promote high-quality SDM and improve stroke prevention in patients with AF

Atomic-Level Characterization of the Activation Mechanism of SERCA by Calcium

We have performed molecular dynamics (MD) simulations to elucidate, in atomic detail, the mechanism by which the sarcoplasmic reticulum Ca2+-ATPase (SERCA) is activated by Ca2+. Crystal structures suggest that activation of SERCA occurs when the cytoplasmic head-piece, in an open (E1) conformation stabilized by Ca2+, undergoes a large-scale open-to-closed (E1 to E2) transition that is induced by ATP binding. However, spectroscopic measurements in solution suggest that these structural states (E1 and E2) are not tightly coupled to biochemical states (defined by bound ligands); the closed E2 state predominates even in the absence of ATP, in both the presence and absence of Ca2+. How is this loose coupling consistent with the high efficiency of energy transduction in the Ca2+-ATPase? To provide insight into this question, we performed long (500 ns) all-atom MD simulations starting from the open crystal structure, including a lipid bilayer and water. In both the presence and absence of Ca2+, we observed a large-scale open-to-closed conformational transition within 400 ns, supporting the weak coupling between structural and biochemical states. However, upon closer inspection, it is clear that Ca2+ is necessary and sufficient for SERCA to reach the precise geometrical arrangement necessary for activation of ATP hydrolysis. Contrary to suggestions from crystal structures, but in agreement with solution spectroscopy, the presence of ATP is not required for this activating transition. Principal component analysis showed that Ca2+ reshapes the free energy landscape of SERCA to create a path between the open conformation and the activated closed conformation. Thus the malleability of the free energy landscape is essential for SERCA efficiency, ensuring that ATP hydrolysis is tightly coupled to Ca2+ transport. These results demonstrate the importance of real-time dynamics in the formation of catalytically competent conformations of SERCA, with broad implications for understanding enzymatic catalysis in atomic detail

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

Identification of carbon dioxide in an exoplanet atmosphere

Carbon dioxide (CO2) is a key chemical species that is found in a wide range of planetary atmospheres. In the context of exoplanets, CO2 is an indicator of the metal enrichment (that is, elements heavier than helium, also called ‘metallicity’)1–3, and thus the formation processes of the primary atmospheres of hot gas giants4–6. It is also one of the most promising species to detect in the secondary atmospheres of terrestrial exoplanets7–9. Previous photometric measurements of transiting planets with the Spitzer Space Telescope have given hints of the presence of CO2, but have not yielded definitive detections owing to the lack of unambiguous spectroscopic identification10–12. Here we present the detection of CO2 in the atmosphere of the gas giant exoplanet WASP-39b from transmission spectroscopy observations obtained with JWST as part of the Early Release Science programme13,14. The data used in this study span 3.0–5.5 micrometres in wavelength and show a prominent CO2 absorption feature at 4.3 micrometres (26-sigma significance). The overall spectrum is well matched by one-dimensional, ten-times solar metallicity models that assume radiative–convective–thermochemical equilibrium and have moderate cloud opacity. These models predict that the atmosphere should have water, carbon monoxide and hydrogen sulfide in addition to CO2, but little methane. Furthermore, we also tentatively detect a small absorption feature near 4.0 micrometres that is not reproduced by these models

The Relative Role of Perceived Partner Risks in Promoting Condom Use in a Three-City Sample of High-Risk, Low-Income Women

We examined the effect of women’s perceptions of sexual partner risks on condom use. Women from three US cities (n = 1,967) were recruited to provide data on HIV risks. In univariate models, increased odds of condom use were associated with perceiving that partners had concurrent partners and being unaware of partners': (a) HIV status, (b) bisexuality, (c) concurrency; and/or (d) injection drug use. In multivariate models, neither being unaware of the four partner risk factors nor perceiving a partner as being high risk was associated with condom use. Contextual factors associated with decreased odds of condom use were having sex with a main partner, homelessness in the past year, alcohol use during sex, and crack use in the past 30 days. Awareness of a partner’s risks may not be sufficient for increasing condom use. Contextual factors, sex with a main partner in particular, decrease condom use despite awareness of partner risk factors

Awesome SOSS: transmission spectroscopy of WASP-96b with NIRISS/SOSS

This is the final version. Available from Oxford University Press via the DOI in this recordData availability: All data used in this study is publicly available from the Barbara A. Mikulski Archive for Space Telescopes: https://mast.stsci.edu/portal/Mashup/Clients/Mast/Portal.htmlThe future is now - after its long-awaited launch in 2021 December, JWST began science operations in 2022 July and is already revolutionizing exoplanet astronomy. The Early Release Observations (ERO) programme was designed to provide the first images and spectra from JWST, covering a multitude of science cases and using multiple modes of each on-board instrument. Here, we present transmission spectroscopy observations of the hot-Saturn WASP-96 b with the Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph, observed as part of the ERO programme. As the SOSS mode presents some unique data reduction challenges, we provide an in-depth walk-through of the major steps necessary for the reduction of SOSS data: including background subtraction, correction of 1/f noise, and treatment of the trace order overlap. We furthermore offer potential routes to correct for field star contamination, which can occur due to the SOSS mode's slitless nature. By comparing our extracted transmission spectrum with grids of atmosphere models, we find an atmosphere metallicity between 1× and 5× solar, and a solar carbon-to-oxygen ratio. Moreover, our models indicate that no grey cloud deck is required to fit WASP-96 b's transmission spectrum, but find evidence for a slope shortward of 0.9 μm, which could either be caused by enhanced Rayleigh scattering or the red wing of a pressure-broadened Na feature. Our work demonstrates the unique capabilities of the SOSS mode for exoplanet transmission spectroscopy and presents a step-by-step reduction guide for this new and exciting instrument

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Background: Saliva of blood sucking arthropods contains compounds that antagonize their hosts ’ hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding. Methodology/Principal Findings: We have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had.75 % coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function. Conclusions/Significance: This data set of proteins constitutes a mining platform for novel pharmacologically activ