223 research outputs found
Exoplanetary Geophysics -- An Emerging Discipline
Thousands of extrasolar planets have been discovered, and it is clear that
the galactic planetary census draws on a diversity greatly exceeding that
exhibited by the solar system's planets. We review significant landmarks in the
chronology of extrasolar planet detection, and we give an overview of the
varied observational techniques that are brought to bear. We then discuss the
properties of the currently known distribution, using the mass-period diagram
as a guide to delineating hot Jupiters, eccentric giant planets, and a third,
highly populous, category that we term "ungiants", planets having masses less
than 30 Earth masses and orbital periods less than 100 days. We then move to a
discussion of the bulk compositions of the extrasolar planets. We discuss the
long-standing problem of radius anomalies among giant planets, as well as
issues posed by the unexpectedly large range in sizes observed for planets with
masses somewhat greater than Earth's. We discuss the use of transit
observations to probe the atmospheres of extrasolar planets; various
measurements taken during primary transit, secondary eclipse, and through the
full orbital period, can give clues to the atmospheric compositions,
structures, and meteorologies. The extrasolar planet catalog, along with the
details of our solar system and observations of star-forming regions and
protoplanetary disks, provide a backdrop for a discussion of planet formation
in which we review the elements of the favored pictures for how the terrestrial
and giant planets were assembled. We conclude by listing several research
questions that are relevant to the next ten years and beyond.Comment: Review chapter to appear in Treatise on Geophysics, 2nd Editio
Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations
Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy
Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo
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