The isotopic ratio of nitrogen measured in primitive Solar System bodies shows a broad range of values, the origin of which remains unknown. One key question is whether these isotopic reservoirs of ...nitrogen predate the comet formation stage or are posterior to it. Another central question is elucidating the processes that can produce the observed variations in the 14N/15N isotopic ratio. Disks that orbit pre-main-sequence (T Tauri) stars provide unique opportunities for observing the chemical content of analogs of the protosolar nebula and therefore for building a comprehensive scenario that can explain the origin of nitrogen in the Solar System and in planet-forming disks. With ALMA, it has become possible to measure isotopic ratios of nitrogen-bearing species in such environments. We present spectrally and spatially resolved observations of the hyperfine structure of the 4−3 rotational transition of HCN and its main isotopologs H13CN and HC15N in the disk orbiting the 8 Myr old T Tauri star TW Hya. The sensitivity allows directly measuring the HCN/H13CN and HCN/HC15N abundance ratios with minimal assumptions. Averaged spatially over the disks, the ratios are 86 ± 4 and 223 ± 21, respectively. The latter value is significantly lower than the CN/C15N ratio of 323 ± 30 in this disk and thus provides the first evidence that two isotopic reservoirs of nitrogen are present in a disk at the stage of giant planet and comet formation. Furthermore, we find clear evidence for an increase in the ratio of HCN to HC15N with radius. The ratio in the outer disk, at 45 au, is 339 ± 28, in excellent agreement with direct measurements in the local interstellar medium, and with the bulk nitrogen isotopic ratio predicted from galactic evolution calculations. In the comet formation region at r = 20 au, the ratio is a factor ≈3 lower, 121 ± 11. This radial increase qualitatively agrees with the scenario in which selective photodissociation of N2 is the dominant fractionation process. However, our isotopic ratios and kinetic temperature of the HCN-emitting layers quantitatively disagree with models of nitrogen chemistry in disks.
The thickness and refractive index of 1,2-dipalmitoyl-
sn
-glycero-3-phosphatidyl choline (DPPC) and 1,2-dipalmitoyl-
sn
-glycero-3-phosphoethanolamine (DPPE) monolayers Langmuir--Blodgett (LB) ...deposited on mica were measured in dry air and bulk water using multiple-beam interferometry (MBI). Measurements of thickness using atomic force microscopy (AFM) of identical monolayers, and X-ray reflectivity (XRR) of the monolayers on quartz were taken for comparison. The measurement of the properties of solid-supported monolayers in dry air allows lipid optical properties to be determined free from solvent effects. The thickness and refractive index measured by MBI were 25.5 ± 0.6 Å and 1.485 ± 0.007 for DPPE monolayers, and 23.9 ± 0.5 Å and 1.478 ± 0.006 for DPPC monolayers in dry air. These thicknesses are consistent with the other techniques used in this work as well as other measurements in the literature. The refractive indices of solid-supported lipid monolayers have not been previously measured. The values are higher than previous measurements on black lipid films done by reflectometry, which is attributed to increased lipid packing density and the absence of hydrocarbon solvents. Applying water to the monolayers had no measurable effect on their properties, indicating that any change in hydration was below detection.
Figure
ᅟ
Thoracostomopsidae is a family of free-living marine nematodes that has three subfamilies (Thoracostomopsinae, Trileptiinae and Enoplolaiminae). Most species descriptions within this family are very ...old and lack indication of important morphological details, so this article aims to fill this gap in the literature. This taxonomic review provides a list of all valid species, as well as species inquirenda, nomina nuda and synonyms, for each genus. Our review recognizes 16 valid genera, 193 valid species, 47 species inquirendae and three species as nomen nudum. Additionally, taxonomic dichotomous keys were constructed, modified or updated for each genus, as well to the subfamilies, using the most important diagnostic characters.
Abstract
Despite their very close structural similarity, CxxC/S-type (class I) glutaredoxins (Grxs) act as oxidoreductases, while CGFS-type (class II) Grxs act as FeS cluster transferases. Here we ...show that the key determinant of Grx function is a distinct loop structure adjacent to the active site. Engineering of a CxxC/S-type Grx with a CGFS-type loop switched its function from oxidoreductase to FeS transferase. Engineering of a CGFS-type Grx with a CxxC/S-type loop abolished FeS transferase activity and activated the oxidative half reaction of the oxidoreductase. The reductive half-reaction, requiring the interaction with a second GSH molecule, was enabled by switching additional residues in the active site. We explain how subtle structural differences, mostly depending on the structure of one particular loop, act in concert to determine Grx function.
Bioactivities from marine algae of the genus Gracilaria de Almeida, Cynthia Layse F; Falcão, Heloina de S; Lima, Gedson R de M ...
International Journal of Molecular Sciences,
07/2011, Letnik:
12, Številka:
7
Journal Article, Book Review
Recenzirano
Odprti dostop
Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired ...immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted.
Cosolvent Molecular Dynamics (MD) simulations are increasingly popular techniques developed for prediction and characterization of allosteric and cryptic binding sites, which can be rendered ..."druggable" by small molecule ligands. Despite their conceptual simplicity and effectiveness, the analysis of cosolvent MD trajectories relies on pocket volume data, which requires a high level of manual investigation and may introduce a bias. In this work, we present CAT (Cosolvent Analysis Toolkit): an open-source, freely accessible analytical tool, suitable for automated analysis of cosolvent MD trajectories. CAT is compatible with commonly used molecular graphics software packages such as UCSF Chimera and VMD. Using a novel hybrid empirical force field scoring function, CAT accurately ranks the dynamic interactions between the macromolecular target and cosolvent molecules. To benchmark, CAT was used for three validated protein targets with allosteric and orthosteric binding sites, using five chemically distinct cosolvent molecules. For all systems, CAT has accurately identified all known sites. CAT can thus assist in computational studies aiming at identification of protein "hotspots" in a wide range of systems. As an easy-to-use computational tool, we expect that CAT will contribute to an increase in the size of the potentially 'druggable' human proteome.
In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term 'inflammageing', which was used for the first time by Franceschi and co-workers in ...2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be 'druggable' by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the 'druggability' of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.
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