49 research outputs found
Autoimmune and autoinflammatory mechanisms in uveitis
The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
Kepler Eclipsing Binary Stars. Vii. The Catalog Of Eclipsing Binaries Found In The Entire Kepler Data Set
The Kepler mission has provided unprecedented, nearly continuous photometric data of ~200,000 objects in the ~105 deg2 field of view (FOV) from the beginning of science operations in May of 2009 until the loss of the second reaction wheel in May of 2013. The Kepler Eclipsing Binary Catalog contains information including but not limited to ephemerides, stellar parameters, and analytical approximation fits for every known eclipsing binary system in the Kepler FOV. Using target pixel level data collected from Kepler in conjunction with the Kepler Eclipsing Binary Catalog, we identify false positives among eclipsing binaries, i.e., targets that are not eclipsing binaries themselves, but are instead contaminated by eclipsing binary sources nearby on the sky and show eclipsing binary signatures in their light curves. We present methods for identifying these false positives and for extracting new light curves for the true source of the observed binary signal. For each source, we extract three separate light curves for each quarter of available data by optimizing the signal-to-noise ratio, the relative percent eclipse depth, and the flux eclipse depth. We present 289 new eclipsing binaries in the Kepler FOV that were not targets for observation, and these have been added to the catalog
The centrosome and spindle as a ribonucleoprotein complex
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosome Research 19 (2011): 367-376, doi:10.1007/s10577-011-9186-7.The presence of nucleic acids in centrosomes and the spindle have been proposed,
observed, and reported since the 1950s. Why did the subject remain, perhaps even until
today, such a controversial issue? The explanation is manifold, and includes legitimate
concern over contamination from other cellular compartments in biochemical
preparations. With a typically high background of cytoplasmic ribosomes, even
microscopic images of stained intact cells could be difficult to interpret. Also, evidence
for RNA and DNA in centrosomes accumulated for approximately 40 years but was
interspersed with contradictory studies, primarily regarding the presence of DNA
(reviewed in Johnson and Rosenbaum, 1991; Marshall and Rosenbaum, 2000). Perhaps
less tangible but still a likely cause for lingering controversy is that the presence of
nucleic acids in the spindle or centrosomes will require us to look differently at these
structures from a functional, and more to the point, evolutionary standpoint.This work was supported by grants from the NIH (GM088503) and NSF (MCB0843092)
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ANCA-associated vasculitis.
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients
Low-mass and sub-stellar eclipsing binaries in stellar clusters
We highlight the importance of eclipsing double-line binaries in our
understanding on star formation and evolution. We review the recent discoveries
of low-mass and sub-stellar eclipsing binaries belonging to star-forming
regions, open clusters, and globular clusters identified by ground-based
surveys and space missions with high-resolution spectroscopic follow-up. These
discoveries provide benchmark systems with known distances, metallicities, and
ages to calibrate masses and radii predicted by state-of-the-art evolutionary
models to a few percent. We report their density and discuss current
limitations on the accuracy of the physical parameters. We discuss future
opportunities and highlight future guidelines to fill gaps in age and
metallicity to improve further our knowledge of low-mass stars and brown
dwarfs.Comment: 30 pages, 5 figures, no table. Review pape