86 research outputs found

    The Effects Of Post-Natal Hyperthyroidism on Coronal Suture Fusion and Calvarial Growth in Rabbits with Familial, Delayed-Onset Synostosis: Testing a Gene/Environmental Causal Mechanism of Variable Phenotypic Expression of Craniosynostosis

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    Early fusion of craniosynostosis may occur prior to birth or afterwards during cranial vault growth. The cause of craniosynostosis may be due to genetic maturations and/or environmental influences. Many reports show environmental influences increasing the penetrance or expression of craniosynostosis. The purpose of this study is to identify the environmental influences of post-natal administration of tri-iodothyronine (T3) in rabbits that demonstrate familial delayed onset craniosynostosis, and identify a possible gene/environment interaction. A total of 65 New Zealand white rabbits (Oryctolagus cuniculus) were used. Forty one (41) rabbits with delayed onset craniosynostosis were obtained, as well as 24 in-colony normal rabbits from a similar colony, but who did not display phenotypic expression of craniosynostosis. Both phenotypic groups were divided into 3 treatments groups: post-natal injections of tri-iodothyronine (T3), vehicle sham, or control no-treatment group. A 2x3x3 (phenotype x treatment x age) design was used. Amalgam markers were placed around frontonasal, coronal and anterior lambdoid suture. Lateral and dorsoventral cephalograms were taken at 10, 25 and 42 days. Lateral cephalograms were traced, 13 anatomic landmarks identified, and both linear and angular measurements were made. Correlation between treatment group and coronal suture marker measurement was made. Results showed statistically increased blood T3 levels (F = 5.96, p<0.005) and decreased blood T4 levels (F = 41.07; p<0.000) in T3 treated groups. Coronal suture marker separation decreased in treated rabbits but was not significant (F=2.07; p NS). Mean changes in body weight were significant in T3 treated groups (F=6.91; p<0.002). Mean changes in total craniofacial length, cranial vault and length, and cranial base angle were not significant. Mean changes in cranial vault shape index were significant (F=5.837; p<0.006). Mean changes in palatal angle were significant for delayed on-set rabbits as well as T3 treated groups (F=4.535; p<0.05; and F=3.333; p<0.05). In conclusion, the effect of T3 on cranial development showed changes in cranial vault shape index and palatal plane angle. Decreased coronal suture marker separation was observed in T3 treated rabbits but not statistically significant. No gene/environment interaction was observed in this study and other factors affecting variable phenotypic expression should be explored

    Evidence for metapopulation structure in seep-dwelling amphipods

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    Twelve seepage springs in a 3 km2 area of the Goldmine Tract in the C&amp;amp;O Canal National Historical Park in Montgomery County, Maryland, USA were sampled in 1994–1995 and again in 2023 for three amphipod species: Stygobromus tenuis potomacus, Stygobromus pizzinii, and Crangonyx shoemakeri. During that time interval, there were 11 colonizations and 1 exinction. Three populations persisted. These results are consistent with the proposed metapopulation hypothesis of population structure

    Common structure in the heterogeneity of plant-matter decay

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    Carbon removed from the atmosphere by photosynthesis is released back by respiration. Although some organic carbon is degraded quickly, older carbon persists; consequently carbon stocks are much larger than predicted by initial decomposition rates. This disparity can be traced to a wide range of first-order decay-rate constants, but the rate distributions and the mechanisms that determine them are unknown. Here, we pose and solve an inverse problem to find the rate distributions corresponding to the decomposition of plant matter throughout North America. We find that rate distributions are lognormal, with a mean and variance that depend on climatic conditions and substrate. Changes in temperature and precipitation scale all rates similarly, whereas the initial substrate composition sets the time scale of faster rates. These findings probably result from the interplay of stochastic processes and biochemical kinetics, suggesting that the intrinsic variability of decomposers, substrate and environment results in a predictable distribution of rates. Within this framework, turnover times increase exponentially with the kinetic heterogeneity of rates, thereby providing a theoretical expression for the persistence of recalcitrant organic carbon in the natural environment

    Colours and pigments in late ukiyo-e art works: A preliminary non-invasive study of Japanese woodblock prints to interpret hyperspectral images using in-situ point-by-point diffuse reflectance spectroscopy

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    Dyes and pigments have been used in traditional Japanese woodblock printings in the ukiyo-e style for several centuries. However, the possible introduction of new European pigments and the extraordinary quality of the works of the later period led to take a keen interest in the analytical study of these ukiyo-e prints manufactured at the end of the 19th century. The present research discusses the analytical results of the series Bijin juni kagetsu (“Beauties in the Twelve Months”) by Shuntei, dated in 1898–1899. Due to the characteristics of this type of artworks, diffuse reflectance spectroscopy (DRS) has been chosen as a portable, non-invasive analytical technique to identify pigments and colorants used in the woodblock prints. The analytical possibilities offered by the in-situ point-by-point DRS as a preliminary tool to better interpret hyperspectral imaging (HSI) data were highlighted. Reflectance spectra of more than 190 points sampled throughout the artwork were recorded between 360 and 740 nm, and characterised. Throughout an statistical classification of the spectral data using unsupervised pattern recognition methods, twenty-two different colour composition was confirmed. These groups of reflectance spectra were then identified according the presence of characteristic maxima, minima and inflection points in every spectrum. Some micro-samples extracted from the pigments still remained in a woodblock (used for a 20th century print) were analysed by FESEM-EDS to better interpret some reflectance spectra. Traditional Japanese pigments (like vermilion, red lead, and indigo) and synthetic materials introduced in the 18th and 19th centuries (Prussian blue, synthetic arsenic sulphides, eosin, and methyl violet or crystal violet) were identified in the Shuntei''s series colours, together with some mixtures of pigments to prepare blue, green, orange and purple. Based on these twenty-two reflectance patterns, the point-by-point spectra make easier the task of interpreting the very complex HSI data, and reduce the time of treatment and interpretation required by HSI

    HVAD to HeartMate 3 left ventricular assist device exchange: Best practices recommendations

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    The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices

    Computational Analysis of Phosphopeptide Binding to the Polo-Box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation

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    The Polo-Like Kinase 1 (PLK1) acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD). The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors

    Origins Space Telescope: Baseline mission concept

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    The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins\u27 natural background-limited sensitivity
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