•Olivine+metal spectra affected by olivine composition, metal content, grain size, nanophase iron.•Different spectral metrics can be used to constrain these properties.•Olivine±metal-bearing ...asteroids show spectral variations indicating diverse mineralogy.
Olivine-rich asteroids appear to be common in the main asteroid belt as well as present in the near-Earth asteroid population. There are a number of meteorite classes that are dominated by olivine±metal. To determine whether relationships exist between these asteroids and meteorites, we spectrally characterized a number of olivine+meteoritic metal powder intimate and areal mixtures, pallasite slabs, and olivine powders on a metal slab. Our goal is to understand the spectral characteristics of olivine+metal assemblages and develop spectral metrics that can be used to analyze reflectance spectra of olivine-dominated asteroids. We found that the major olivine absorption band in the 1μm region is resolvable in intimate mixtures for metal abundances as high as ∼90wt.%. The wavelength position of the 1μm region olivine absorption band center is sensitive to Fa content but insensitive to other variables. However, the band minimum position moves to shorter wavelengths with increasing metal abundance due to changes in spectral slope. The full width at half maximum (FWHM) of this band and reflectance at 1.8μm are both most sensitive to olivine Fa content, metal abundance, and grain size, and much less to the presence of nanophase iron that reddens spectra. Reflectance at 0.56μm and the 1.8/0.56μm reflectance ratio are sensitive to these same parameters as well as to nanophase iron-associated spectral reddening. The wavelength position of the local reflectance maximum in the 0.7μm region moves to longer wavelengths with increasing metal abundance and is most useful for constraining metal abundance in high metal-content mixtures. Pallasite slab spectra differ in a number of respects from powdered assemblages and multiple spectral parameters can be used to discriminate them. The spectra of increasingly fine-grained olivine+metal assemblages and those involving low-Fa olivine show increasing spectral dominance by metal. Systematic application of multiple spectral metrics allows olivine+metal assemblage properties such as Fa content, olivine/metal ratio, and grain size to be quantified or constrained. Analysis of reflectance spectra of 22 presumed olivine±metal-rich asteroids indicates that most of them possess low- to medium-Fa content olivine (Fa<∼67), with variable abundances of macroscopic metal. A number exhibit visible region absorption bands that are indicative of some fraction of coarser-grained olivine (>45μm). Most asteroid spectra can be plausibly linked to specific olivine±metal-bearing meteorite classes. Most of the asteroid spectra examined exhibit some degree of spectral reddening below ∼1.8μm which is most consistent with the presence of fine-grained nanophase iron, likely produced by space weathering.
First light of the Gemini Planet Imager Macintosh, Bruce; Graham, James R.; Ingraham, Patrick ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Volume:
111, Issue:
35
Journal Article
Peer reviewed
Open access
The Gemini Planet Imager is a dedicated facility for directly imaging and spectroscopically characterizing extrasolar planets. It combines a very high-order adaptive optics system, a ...diffraction-suppressing coronagraph, and an integral field spectrograph with low spectral resolution but high spatial resolution. Every aspect of the Gemini Planet Imager has been tuned for maximum sensitivity to faint planets near bright stars. During first-light observations, we achieved an estimated H band Strehl ratio of 0.89 and a 5-σ contrast of 10 ⁶ at 0.75 arcseconds and 10 ⁵ at 0.35 arcseconds. Observations of Beta Pictoris clearly detect the planet, Beta Pictoris b, in a single 60-s exposure with minimal postprocessing. Beta Pictoris b is observed at a separation of 434 ± 6 milliarcseconds (mas) and position angle 211.8 ± 0.5°. Fitting the Keplerian orbit of Beta Pic b using the new position together with previous astrometry gives a factor of 3 improvement in most parameters over previous solutions. The planet orbits at a semimajor axis of Formula near the 3:2 resonance with the previously known 6-AU asteroidal belt and is aligned with the inner warped disk. The observations give a 4% probability of a transit of the planet in late 2017.
Cell surface pili are polymeric protein assemblies that enable bacteria to adhere to surfaces and to specific host tissues. The pili expressed by Gram-positive bacteria constitute a unique paradigm ...in which sortase-mediated covalent linkages join successive pilin subunits like beads on a string. These pili are formed from two or three distinct types of pilin subunit, typically encoded in small gene clusters, often with their cognate sortases. In Group A streptococci (GAS), a major pilin forms the polymeric backbone, whereas two minor pilins are located at the tip and the base. Here, we report the 1.9-Å resolution crystal structure of the GAS basal pilin FctB, revealing an immunoglobulin (Ig)-like N-terminal domain with an extended proline-rich tail. Unexpected structural homology between the FctB Ig-like domain and the N-terminal domain of the GAS shaft pilin helps explain the use of the same sortase for polymerization of the shaft and its attachment to FctB. It also enabled the identification, from mass spectral data, of the lysine residue involved in the covalent linkage of FctB to the shaft. The proline-rich tail forms a polyproline-II helix that appears to be a common feature of the basal (cell wall-anchoring) pilins. Together, our results indicate distinct structural elements in the pilin proteins that play a role in selecting for the appropriate sortases and thereby help orchestrate the ordered assembly of the pilus.
T‐cell receptor (TCR) usage has an important role in determining the outcome of CD8+ cytotoxic T‐lymphocyte responses to viruses and other pathogens. However, the characterization of TCR usage from ...which such conclusions are drawn is based on exclusive analysis of either the TCRα chain or, more commonly, the TCRβ chain. Here, we have used a multiplexed reverse transcription‐PCR protocol to analyse the CDR3 regions of both TCRα and β chains from single naive or immune epitope‐specific cells to provide a comprehensive picture of epitope‐specific TCR usage and selection into the immune response. Analysis of TCR repertoires specific for three influenza‐derived epitopes (DbNP366, DbPA224 and DbPB1‐F262) showed preferential usage of particular TCRαβ proteins in the immune repertoire relative to the naive repertoire, in some cases, resulting in a complete shift in TRBV preference or CDR3 length, and restricted repertoire diversity. The NP366‐specific TCRαβ repertoire, previously defined as clonally restricted based on TCRβ analysis, was similarly diverse as the PA224‐ and PB1‐F262‐specific repertoires. Intriguingly, preferred TCR characteristics (variable gene usage, CDR3 length and junctional gene usage) appeared to be able to confer specificity either independently or in concert with one another, depending on the epitope specificity. These data have implications for established correlations between the nature of the TCR repertoire and response outcomes after infection, and suggest that analysis of a subset of cells or a single TCR chain does not accurately depict the nature of the antigen‐specific TCRαβ repertoire.
When 22 members of the BrainNet Europe (BNE) consortium assessed 31 cases with α-synuclein (αS) immunoreactive (IR) pathology applying the consensus protocol described by McKeith and colleagues in ...2005, the inter-observer agreement was 80%, being lowest in the limbic category (73%). When applying the staging protocol described by Braak and colleagues in 2003, agreement was only 65%, and in some cases as low as 36%. When modifications of these strategies, i.e., McKeith’s protocol by Leverenz and colleagues from 2009, Braak’s staging by Müller and colleagues from 2005 were applied then the agreement increased to 78 and 82%, respectively. In both of these modifications, a reduced number of anatomical regions/blocks are assessed and still in a substantial number of cases, the inter-observer agreement differed significantly. Over 80% agreement in both typing and staging of αS pathology could be achieved when applying a new protocol, jointly designed by the BNE consortium. The BNE-protocol assessing αS-IR lesions in nine blocks offered advantages over the previous modified protocols because the agreement between the 22 observers was over 80% in most cases. Furthermore, in the BNE-protocol, the αS pathology is assessed as being present or absent and thus the quality of staining and the assessment of the severity of αS-IR pathology do not alter the inter-observer agreement, contrary to other assessment strategies. To reach these high agreement rates an entity of amygdala-predominant category was incorporated. In conclusion, here we report a protocol for assessing αS pathology that can achieve a high inter-observer agreement for both the assignment to brainstem, limbic, neocortical and amygdala-predominant categories of synucleinopathy and the Braak stages.
Group A
(GAS) (
) is an important human pathogen associated with significant global morbidity and mortality for which there is no safe and efficacious vaccine. The T antigen, a protein that ...polymerizes to form the backbone of the GAS pilus structure, is a potential vaccine candidate. Previous surveys of the
gene, which encodes the T antigen, have identified 21 different
types and subtypes such that any T antigen-based vaccine must be multivalent and carefully designed to provide broad strain coverage. In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The existence of shared epitopes between T antigens, combined with the remarkably conserved structure and high level of surface sequence divergence, has important implications for the design of multivalent T antigen-based vaccines.
Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially ...understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesity's impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.
Epstein‐Barr virus (EBV) is one of the most common viruses in humans, capable of causing life‐threatening infections and cancers in immunocompromised individuals. Although CD8+ T cells provide key ...protection against EBV, the persistence and dynamics of specific T‐cell receptor (TCR) clones during immunosuppression in transplant patients is largely unknown. For the first time, we used a novel single‐cell TCRαβ multiplex‐nested reverse transcriptase PCR to dissect TCRαβ clonal diversity within GLCTLVAML (GLC)‐specific CD8+ T cells in healthy individuals and immunocompromised lung transplant recipients. The GLC peptide presented by HLA‐A*02:01 is one of the most immunogenic T‐cell targets from the EBV proteome. We found that the GLC‐specific TCRαβ repertoire was heavily biased toward TRAV5 and encompassed five classes of public TCRαβs, suggesting that these clonotypes are preferentially utilized following infection. We identified that a common TRAV5 was diversely paired with different TRAJ and TRBV/TRBJ genes, in both immunocompetent and immunocompromised individuals, with an average of 12 different TCRαβ clonotypes/donor. Moreover, pre‐transplant GLC‐specific TCRαβ repertoires were relatively stable over 1 year post transplant under immunosuppression in the absence or presence of EBV reactivation. In addition, we provide the first evidence of early GLC‐specific CD8+ T cells at 87 days post transplant, which preceded clinical EBV detection at 242 days in an EBV‐seronegative patient receiving a lung allograft from an EBV‐seropositive donor. This was associated with a relatively stable TCRαβ repertoire after CD8+ T‐cell expansion. Our findings provide insights into the composition and temporal dynamics of the EBV‐specific TCRαβ repertoire in immunocompromised transplant patients and suggest that the early detection of EBV‐specific T cells might be a predictor of ensuing EBV blood viremia.
Mycobacterium tuberculosis (MTb) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the ...structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure–activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies. The compounds were inactivated by glutathione-dependent adduct formation as well as quinazolinone oxidation in microsomes. Pharmacokinetic studies demonstrated modest bioavailability and compound exposures. Resistance to the compounds in MTb was conferred by promoter mutations in the alternative nonessential NDH-2 encoded by ndhA in MTb. Bioenergetic analyses revealed a decrease in oxygen consumption rates in response to inhibitor in cells in which membrane potential was uncoupled from ATP production, while inverted membrane vesicles showed mercapto-quinazolinone-dependent inhibition of ATP production when NADH was the electron donor to the respiratory chain. Enzyme kinetic studies further demonstrated noncompetitive inhibition, suggesting binding of this scaffold to an allosteric site. In summary, while the initial MTb SAR showed limited improvement in potency, these results, combined with structural information on the bacterial protein, will aid in the future discovery of new and improved NDH-2 inhibitors.
This article gives an overview of research into psychological treatments for concurrent posttraumatic stress disorder (PTSD) and substance used disorder (SUD), with a special focus on the ...effectiveness of treatments addressing both disorders compared to treatments addressing one of the disorders alone. In addition, a distinction is made between trauma-focused versus non-trauma-focused therapies for concurrent PTSD and SUD. The databases Embase, Psychinfo, Medline and Web of science were searched for relevant articles. In total, seventeen studies were identified evaluating ten treatments protocols (six trauma-focused and four non-trauma-focused treatment approaches). In general, the studies showed pre–post reductions for PTSD and/or SUD symptoms. Although most treatments for concurrent PTSD and SUD did not prove to be superior to regular SUD treatments, there are some promising preliminary results suggesting that some patients might benefit from trauma-focused interventions. However, the lack of methodologically sound treatment trials makes it difficult to draw firm conclusions. Methodological limitations are discussed, along with recommendations for future research.
► Prevalence of PTSD is high in individuals suffering from substance use disorders. ► Ten protocols for the combined treatment of PTSD and SUD have been evaluated. ► Non-trauma-focused interventions showed significant effects on SUD and PTSD. ► Non-trauma-focused interventions did not perform superior to SUD treatment alone. ► Some patients may benefit from trauma-focused interventions.
PDF
