The Periodic Spectroscopic Variability of FU Orionis

FU Orionis systems are young stars undergoing outbursts of disc accretion and where the optical spectrum contains lines associated with both the disc photosphere and a wind component. Previous observations of the prototype FU Orionis have suggested that the wind lines and the photospheric lines are modulated with periods of 14.54 and 3.54 days respectively (Herbig et al. 2003). We have re-observed the system at higher spectral resolution, by monitoring variations of optical line profiles over 21 nights in 2007 and have found periods of 13.48 and 3.6 days in the wind and disc components consistent with the above: this implies variability mechanisms that are stable over at least a decade. In addition we have found: i) that the variations in the photospheric absorption lines are confined to the blue wing of the line (around -9km/s): we tentatively ascribe this to an orbiting hotspot in the disc which is obscured by a disc warp during its receding phase. ii) The wind period is manifested not only in blue-shifted Halpha absorption, but also in red-shifted emission of Halpha and Hbeta, as well as in blue-shifted absorption of Na I D, Li I and Fe II. iii) We find that the periodic modulation of blue-shifted Halpha absorption at around -100km/s, is phase lagged with respect to variations in the other lines by ~1.8days. This is consistent with a picture in which variations at the wind base first affect chromospheric emission and then low velocity blue-shifted absorption, followed - after a lag equal to the propagation time of disturbances across the wind's acceleration region - by a response in high velocity blue-shifted absorption. Such arguments constrain the size of the acceleration region to ~10^12cm. We discuss possible mechanisms for periodic variations within the innermost 0.1AU of the disc, including the possibility that these variations indicate the presence of an embedded hot Jupiter.Comment: 20 pages, 23 figures. Accepted for publication in MNRAS. See http://www.ast.cam.ac.uk/~slp65/FUOripaperHRes.pdf for a pdf version of the paper with high-resolution images; footnote added to the titl

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function

Inborn errors of immunity (IEI) are a genetically heterogeneous group of disorders with a broad clinical spectrum. Identification of molecular and functional bases of these disorders is important for diagnosis, treatment, and an understanding of the human immune response. We identified 6 unrelated males with neutropenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure associated with 3 different variants in the X-linked gene TLR8, encoding the endosomal Toll-like receptor 8 (TLR8). Interestingly, 5 patients had somatic variants in TLR8 with <30% mosaicism, suggesting a dominant mechanism responsible for the clinical phenotype. Mosaicism was also detected in skin-derived fibroblasts in 3 patients, demonstrating that mutations were not limited to the hematopoietic compartment. All patients had refractory chronic neutropenia, and 3 patients underwent allogeneic hematopoietic cell transplantation. All variants conferred gain of function to TLR8 protein, and immune phenotyping demonstrated a proinflammatory phenotype with activated T cells and elevated serum cytokines associated with impaired B-cell maturation. Differentiation of myeloid cells from patient-derived induced pluripotent stem cells demonstrated increased responsiveness to TLR8. Together, these findings demonstrate that gain-of-function variants in TLR8 lead to a novel childhood-onset IEI with lymphoproliferation, neutropenia, infectious susceptibility, B- and T-cell defects, and in some cases, bone marrow failure. Somatic mosaicism is a prominent molecular mechanism of this new disease