JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis

Background The V617F mutation, which causes the substitution of phenylalanine for valine at position 617 of the Janus kinase (JAK) 2 gene (JAK2), is often present in patients with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. However, the molecular basis of these myeloproliferative disorders in patients without the V617F mutation is unclear. Methods We searched for new mutations in members of the JAK and signal transducer and activator of transcription (STAT) gene families in patients with V617F-negative polycythemia vera or idiopathic erythrocytosis. The mutations were characterized biochemically and in a murine model of bone marrow transplantation. Results We identified four somatic gain-of-function mutations affecting JAK2 exon 12 in 10 V617F-negative patients. Those with a JAK2 exon 12 mutation presented with an isolated erythrocytosis and distinctive bone marrow morphology, and several also had reduced serum erythropoietin levels. Erythroid colonies could be grown from their blood samples in the absence of exogenous erythropoietin. All such erythroid colonies were heterozygous for the mutation, whereas colonies homozygous for the mutation occur in most patients with V617F-positive polycythemia vera. BaF3 cells expressing the murine erythropoietin receptor and also carrying exon 12 mutations could proliferate without added interleukin-3. They also exhibited increased phosphorylation of JAK2 and extracellular regulated kinase 1 and 2, as compared with cells transduced by wild-type JAK2 or V617F JAK2. Three of the exon 12 mutations included a substitution of leucine for lysine at position 539 of JAK2. This mutation resulted in a myeloproliferative phenotype, including erythrocytosis, in a murine model of retroviral bone marrow transplantation. Conclusions JAK2 exon 12 mutations define a distinctive myeloproliferative syndrome that affects patients who currently receive a diagnosis of polycythemia vera or idiopathic erythrocytosis.

The 2003 November 14 occultation by Titan of TYC 1343-1865-1

We observed a stellar occultation by Titan on 2003 November 14 from La Palma Observatory using ULTRACAM with three Sloan filters: u, g, and i (358, 487, and 758 nm, respectively). The occultation probed latitudes 2°?S and 1°?N during immersion and emersion, respectively. A prominent central flash was present in only the i filter, indicating wavelength-dependent atmospheric extinction. We inverted the light curves to obtain six lower-limit temperature profiles between 335 and 485 km (0.04 and 0.003 mb) altitude. The i profiles agreed with the temperature measured by the Huygens Atmospheric Structure Instrument [Fulchignoni, M., and 43 colleagues, 2005. Nature 438, 785 791] above 415 km (0.01 mb). The profiles obtained from different wavelength filters systematically diverge as altitude decreases, which implies significant extinction in the light curves. Applying an extinction model [Elliot, J.L., Young, L.A., 1992. Astron. J. 103, 991 1015] gave the altitudes of line of sight optical depth equal to unity: 396±7 and 401±20 km (u immersion and emersion); 354±7 and 387±7 km (g immersion and emersion); and 336±5 and 318±4 km (i immersion and emersion). Further analysis showed that the optical depth follows a power law in wavelength with index 1.3±0.2. We present a new method for determining temperature from scintillation spikes in the occulting body's atmosphere. Temperatures derived with this method are equal to or warmer than those measured by the Huygens Atmospheric Structure Instrument. Using the highly structured, three-peaked central flash, we confirmed the shape of Titan's middle atmosphere using a model originally derived for a previous Titan occultation [Hubbard, W.B., and 45 colleagues, 1993. Astron. Astrophys. 269, 541 563].

Body size in ecological networks

Body size determines a host of species traits that can affect the structure and dynamics of food webs, and other ecological networks, across multiple scales of organization. Measuring body size provides a relatively simple means of encapsulating and condensing a large amount of the biological information embedded within an ecological network. Recently, important advances have been made by incorporating body size into theoretical models that explore food web stability, the patterning of energy fluxes, and responses to perturbations. Because metabolic constraints underpin bodysize scaling relationships, metabolic theory offers a potentially useful new framework within which to develop novel models to describe the structure and functioning of ecological networks and to assess the probable consequences of biodiversity change.