24 research outputs found
Exploring the effect of baryons on the radial distribution of satellite galaxies with GAMA and IllustrisTNG
We explore the radial distribution of satellite galaxies in groups in the Galaxy and Mass Assembly (GAMA) survey and the IllustrisTNG simulations. Considering groups with masses 12.0≤log10(Mh/h−1M⊙)\u3c14.8 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3e12.0≤log10(Mh/h−1M⊙)\u3c14.812.0≤log10(Mh/h−1M⊙)\u3c14.8 at z \u3c 0.267, we find a good agreement between GAMA and a sample of TNG300 groups and galaxies designed to match the GAMA selection. Both display a flat profile in the centre of groups, followed by a decline that becomes steeper towards the group edge, and normalized profiles show no dependence on group mass. Using matched satellites from TNG and dark matter-only TNG-Dark runs we investigate the effect of baryons on satellite radial location. At z = 0, we find that the matched subhaloes from the TNG-Dark runs display a much flatter radial profile: namely, satellites selected above a minimum stellar mass exhibit both smaller halocentric distances and longer survival times in the full-physics simulations compared to their dark-matter only analogues. We then divide the TNG satellites into those which possess TNG-Dark counterparts and those which do not, and develop models for the radial positions of each. We find the satellites with TNG-Dark counterparts are displaced towards the halo centre in the full-physics simulations, and this difference has a power-law behaviour with radius. For the ‘orphan’ galaxies without TNG-Dark counterparts, we consider the shape of their radial distribution and provide a model for their motion over time, which can be used to improve the treatment of satellite galaxies in semi-analytic and semi-empirical models of galaxy formation
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Spontaneous Isomerization of Long-Lived Proteins Provides a Molecular Mechanism for the Lysosomal Failure Observed in Alzheimer's Disease.
Proteinaceous aggregation is a well-known observable in Alzheimer's disease (AD), but failure and storage of lysosomal bodies within neurons is equally ubiquitous and actually precedes bulk accumulation of extracellular amyloid plaque. In fact, AD shares many similarities with certain lysosomal storage disorders though establishing a biochemical connection has proven difficult. Herein, we demonstrate that isomerization and epimerization, which are spontaneous chemical modifications that occur in long-lived proteins, prevent digestion by the proteases in the lysosome (namely, the cathepsins). For example, isomerization of aspartic acid into l-isoAsp prevents digestion of the N-terminal portion of Aβ by cathepsin L, one of the most aggressive lysosomal proteases. Similar results were obtained after examination of various target peptides with a full series of cathepsins, including endo-, amino-, and carboxy-peptidases. In all cases peptide fragments too long for transporter recognition or release from the lysosome persisted after treatment, providing a mechanism for eventual lysosomal storage and bridging the gap between AD and lysosomal storage disorders. Additional experiments with microglial cells confirmed that isomerization disrupts proteolysis in active lysosomes. These results are easily rationalized in terms of protease active sites, which are engineered to precisely orient the peptide backbone and cannot accommodate the backbone shift caused by isoaspartic acid or side chain dislocation resulting from epimerization. Although Aβ is known to be isomerized and epimerized in plaques present in AD brains, we further establish that the rates of modification for aspartic acid in positions 1 and 7 are fast and could accrue prior to plaque formation. Spontaneous chemistry can therefore provide modified substrates capable of inducing gradual lysosomal failure, which may play an important role in the cascade of events leading to the disrupted proteostasis, amyloid formation, and tauopathies associated with AD
Exploring the effect of baryons on the radial distribution of satellite galaxies with GAMA and IllustrisTNG
We explore the radial distribution of satellite galaxies in groups in the Galaxy and Mass Assembly (GAMA) survey and the IllustrisTNG simulations. Considering groups with masses 12.0 ≤ log10(M/−1M) < 14.8 at < 0.267, we find a good agreement between GAMA and a sample of TNG300 groups and galaxies designed to match the GAMA selection. Both display a flat profile in the centre of groups, followed by a decline that becomes steeper towards the group edge, and normalised profiles show no dependence on group mass. Using matched satellites from TNG and dark matter-only TNG-Dark runs we investigate the effect of baryons on satellite radial location. At = 0, we find that the matched subhaloes from the TNG-Dark runs display a much flatter radial profile: namely, satellites selected above a minimum stellar mass exhibit both smaller halo-centric distances and longer survival times in the full-physics simulations compared to their dark-matter only analogues. We then divide the TNG satellites into those which possess TNG-Dark counterparts and those which do not, and develop models for the radial positions of each. Wefindthesatellites with TNG-Dark counterparts are displaced towards the halo centre in the full-physics simulations, and this difference has a power-law behaviour with radius. For the ‘orphan’ galaxies without TNG-Dark counterparts, we consider the shape of their radial distribution and provide a model for their motion over time, which can be used to improve the treatment of satellite galaxies in semi-analytic and semi-empirical models of galaxy formation
Herbert Hoover Elementary / Charleston Complete Corridor Plan
Completed as a part of CRP 425 bicycle and pedestrian planning, led by Dr. William Riggs, this planning project assessed the Herbert Hoover Elementary site and Charleston corridor in the City of Palo Alto with an aim to bring a complete streets strategy to the area. The plans recommend improved accessibility for bicycles and pedestrians along Charleston Road including modal separation between bicyclists and pedestians, improved vehicular flows to mitigate vehicular traffic congestion during peak hours and increased innovation in safety features to prevent pedestrian-vehicle conflicts
Shining the Light on Aging and Isomers Using Photodissociation and Radical Chemistry
Biological aging is a complex and nuanced chemical process that proceeds along numerous routes at the molecular level. Spontaneous deamidation of asparagine and isomerization of aspartic acid are among the most prevalent age-related chemical modifications and are associated with a growing list of human diseases. Although both degradation pathways are common throughout the body, they are often unnoticed because the resulting chemical modification is relatively minor and is exceptionally difficult to detect. Structural characterization is further complicated because both deamidation and isomerization produce four isomers of aspartic acid (L-Asp, D-Asp, L-isoAsp, and D-isoAsp). To better understand the aging process, we utilized radical directed dissociation (RDD) in conjunction with mass spectrometry to identify and quantify the products of deamidation and isomerization. We began by outlining intrinsic factors that govern the deamidation rate, and external factors that influence product outcomes to develop models of peptide and protein aging. Subsequent studies revealed the specific structural and functional perturbations associated with the unnatural isomers present in aged proteins. To further expand our isomer detection capabilities, we applied our radical based fragmentation method to the glutamine deamidation, which exhibits several parallels to asparagine deamidation, but has remained largely uncharacterized. Importantly, we demonstrate that radical chemistry generated diagnostic and informative fragment ions for both glutamic acid and isoglutamic acid. We apply this technique in a manner that is amenable to shotgun proteomics and reveal several key differences between the two aging processes. Finally, we tailor our radical based analytical methodology toward the analysis of isomeric glycans. After successfully discriminating a comprehensive family of isomeric glycans with RDD, we demonstrate similar capabilities with 213 nm ultraviolet photodissociation, and outline how such a versatile approach may unify the closely related fields of glycomics and proteomics
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Sequence and Solution Effects on the Prevalence of d-Isomers Produced by Deamidation.
Deamidation of asparagine is a spontaneous and irreversible post-translational modification associated with a growing list of human diseases. While pervasive, deamidation is often overlooked because it represents a relatively minor chemical change. Structural and functional characterization of this modification is complicated because deamidation of asparagine yields four isomeric forms of Asp. Herein, radical directed dissociation (RDD), in conjunction with mass spectrometry, is used to identify and quantify all four isomers in a series of model peptides that were subjected to various deamidation conditions. Although primary sequence significantly influences the rate of deamidation, it has little impact on the relative proportions of the product isomers. Furthermore, the addition of ammonia can be used to increase the rate of deamidation without significantly perturbing isomer populations. Conversely, external factors such as buffer conditions and temperature alter product distributions but exhibit less dramatic effects on the deamidation rate. Strikingly, the common laboratory and biologically significant bicarbonate buffer is found to strongly promote racemization, yielding increased amounts of d-Asp and d-isoAsp. These outcomes following deamidation have broad implications in human aging and should be considered during the development of protein-based therapeutics
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Statistical Framework for Identifying Differences in Similar Mass Spectra: Expanding Possibilities for Isomer Identification
Isomeric molecules are important analytes in many biological and chemical arenas, yet their similarity poses challenges for many analytical methods, including mass spectrometry (MS). Tandem-MS provides significantly more information about isomers than intact mass analysis, but highly similar fragmentation patterns are common and include cases where no unique m/z peaks are generated between isomeric pairs. However, even in such situations, differences in peak intensity can exist and potentially contain additional information. Herein, we present a framework for comparing mass spectra that differ only in terms of peak intensity and include calculation of a statistical probability that the spectra derive from different analytes. This framework allows for confident identification of peptide isomers by collision-induced dissociation, higher-energy collisional dissociation, electron-transfer dissociation, and radical-directed dissociation. The method successfully identified many types of isomers including various d/l amino acid substitutions, Leu/Ile, and Asp/IsoAsp. The method can accommodate a wide range of changes in instrumental settings including source voltages, isolation widths, and resolution without influencing the analysis. It is shown that quantification of the composition of isomeric mixtures can be enabled with calibration curves, which were found to be highly linear and reproducible. The analysis can be implemented with data collected by either direct infusion or liquid-chromatography MS. Although this framework is presented in the context of isomer characterization, it should also prove useful in many other contexts where similar mass spectra are generated