Differential Hox expression in murine embryonic stem cell models of normal and malignant hematopoiesis

The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFR;2. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFR;2) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis

Organophosphorus Pesticides Decrease M2 Muscarinic Receptor Function in Guinea Pig Airway Nerves via Indirect Mechanisms

BACKGROUND: Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Intravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS)-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. CONCLUSIONS/SIGNIFICANCE: These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity

A Six-Planet System Around the Star HD 34445

We present a new precision radial velocity dataset that reveals a multi-planet system orbiting the G0V star HD 34445. Our 18-year span consists of 333 precision radial velocity observations, 56 of which were previously published, and 277 which are new data from Keck Observatory, Magellan at Las Campanas Observatory, and the Automated Planet Finder at Lick Observatory. These data indicate the presence of six planet candidates in Keplerian motion about the host star with periods of 1057, 215, 118, 49, 677, and 5700 days, and minimum masses of 0.63, 0.17, 0.1, 0.05, 0.12 and 0.38 Jupiter masses respectively. The HD 34445 planetary system, with its high degree of multiplicity, its long orbital periods, and its induced stellar radial velocity half-amplitudes in the range $2 \,{\rm m\, s^{-1}} \lesssim K \lesssim 5\,{\rm m\, s^{-1}}$ is fundamentally unlike either our own solar system (in which only Jupiter and Saturn induce significant reflex velocities for the Sun), or the Kepler multiple-transiting systems (which tend to have much more compact orbital configurations)Comment: 10 pages, 11 figure

The test case of HD26965: difficulties disentangling weak Doppler signals from stellar activity

We report the discovery of a radial velocity signal that can be interpreted as a planetary-mass candidate orbiting the K dwarf HD26965, with an orbital period of 42.364$\pm$0.015 days, or alternatively, as the presence of residual, uncorrected rotational activity in the data. Observations include data from HIRES, PFS, CHIRON, and HARPS, where 1,111 measurements were made over 16 years. Our best solution for HD26965 $b$ is consistent with a super-Earth that has a minimum mass of 6.92$\pm$0.79 M$_{\oplus}$ orbiting at a distance of 0.215$\pm$0.008 AU from its host star. We have analyzed the correlation between spectral activity indicators and the radial velocities from each instrument, showing moderate correlations that we include in our model. From this analysis, we recover a $\sim$38 day signal, which matches some literature values of the stellar rotation period. However, from independent Mt. Wilson HK data for this star, we find evidence for a significant 42 day signal after subtraction of longer period magnetic cycles, casting doubt on the planetary hypothesis for this period. Although our statistical model strongly suggests that the 42-day signal is Doppler in origin, we conclude that the residual effects of stellar rotation are difficult to fully model and remove from this dataset, highlighting the difficulties to disentangle small planetary signals and photospheric noise, particularly when the orbital periods are close to the rotation period of the star. This study serves as an excellent test case for future works that aim to detect small planets orbiting `Sun-like' stars using radial velocity measurements.Comment: 16 pages, 10 figures, 13 tables, accepted for publication in A

NMFS / Interagency Working Group Evaluation of CITES Criteria and Guidelines.

EXECUTIVE SUMMARY: At present, the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) criteria used to assess whether a population qualifies for inclusion in the CITES Appendices relate to (A) size of the population, (B) area of distribution of the population, and (C) declines in the size of the population. Numeric guidelines are provided as indicators of a small population (less than 5,000 individuals), a small subpopulation (less than 500 individuals), a restricted area of distribution for a population (less than 10,000 km2), a restricted area of distribution for a subpopula-tion (less than 500 km2), a high rate of decline (a decrease of 50% or more in total within 5 years or two generations whichever is longer or, for a small wild population, a decline of 20% or more in total within ten years or three generations whichever is longer), large fluctuations (population size or area of distribution varies widely, rapidly and frequently, with a variation greater than one order of magnitude), and a short-term fluctuation (one of two years or less). The Working Group discussed several broad issues of relevance to the CITES criteria and guidelines. These included the importance of the historical extent of decline versus the recent rate of decline; the utility and validity of incorporating relative population productivity into decline criteria; the utility of absolute numbers for defining small populations or small areas; the appropriateness of generation times as time frames for examining declines; the importance of the magnitude and frequency of fluctuations as factors affecting risk of extinction; and the overall utility of numeric thresh-olds or guidelines

MagAO Imaging of Long-period Objects (MILO). I. A Benchmark M Dwarf Companion Exciting a Massive Planet around the Sun-like Star HD 7449

We present high-contrast Magellan adaptive optics (MagAO) images of HD 7449, a Sun-like star with one planet and a long-term radial velocity (RV) trend. We unambiguously detect the source of the long-term trend from 0.6-2.15 \microns ~at a separation of \about 0\fasec 54. We use the object's colors and spectral energy distribution to show that it is most likely an M4-M5 dwarf (mass \about 0.1-0.2 \msun) at the same distance as the primary and is therefore likely bound. We also present new RVs measured with the Magellan/MIKE and PFS spectrometers and compile these with archival data from CORALIE and HARPS. We use a new Markov chain Monte Carlo procedure to constrain both the mass ($> 0.17$ \msun ~at 99$\%$ confidence) and semimajor axis (\about 18 AU) of the M dwarf companion (HD 7449B). We also refine the parameters of the known massive planet (HD 7449Ab), finding that its minimum mass is $1.09^{+0.52}_{-0.19}$ \mj, its semimajor axis is $2.33^{+0.01}_{-0.02}$ AU, and its eccentricity is $0.8^{+0.08}_{-0.06}$. We use N-body simulations to constrain the eccentricity of HD 7449B to $\lesssim$ 0.5. The M dwarf may be inducing Kozai oscillations on the planet, explaining its high eccentricity. If this is the case and its orbit was initially circular, the mass of the planet would need to be $\lesssim$ 1.5 \mj. This demonstrates that strong constraints on known planets can be made using direct observations of otherwise undetectable long-period companions.Comment: Corrected planet mass error (7.8 Mj --> 1.09 Mj, in agreement with previous studies

DOPPLER MONITORING OF THE WASP-47 MULTIPLANET SYSTEM

We present precise Doppler observations of WASP-47, a transiting planetary system featuring a hot Jupiter with both inner and outer planetary companions. This system has an unusual architecture and also provides a rare opportunity to measure planet masses in two different ways: the Doppler method, and the analysis of transit-timing variations (TTV). Based on the new Doppler data, obtained with the Planet Finder Spectrograph on the Magellan/Clay 6.5 m telescope, the mass of the hot Jupiter is 370 ± 29[subscript ⊕]. This is consistent with the previous Doppler determination as well as the TTV determination. For the inner planet WASP-47e, the Doppler data lead to a mass of 12.2 ± 3.7[subscript ⊕], in agreement with the TTV-based upper limit of <22 M[subscript ⊕] (95% confidence). For the outer planet WASP-47d, the Doppler mass constraint of 10.4 ± 8.4[subscript ⊕] is consistent with the TTV-based measurement of $15.2[+6.7 over -7.6] M[subscript ⊕].United States. National Aeronautics and Space Administration (Origins Program Grant NNX11AG85G

Doppler monitoring of the WASP-47 multiplanet system

We present precise Doppler observations of WASP-47, a transiting planetary system featuring a hot Jupiter with both inner and outer planetary companions. This system has an unusual architecture and also provides a rare opportunity to measure planet masses in two different ways: the Doppler method, and the analysis of transit-timing variations (TTV). Based on the new Doppler data, obtained with the Planet Finder Spectrograph on the Magellan/Clay 6.5 m telescope, the mass of the hot Jupiter is 370+/- 29M⊕. This is consistent with the previous Doppler determination as well as the TTV determination. For the inner planet WASP-47e, the Doppler data lead to a mass of 12.2 +/-3.7 M⊕ in agreement with the TTV-based upper limit of <22 M⊕ (95% confidence). For the outer planet WASP-47d, the Doppler mass constraint of 10.4 +/- 8.4 M⊕ is consistent with the TTV-based measurement of 15.2 -7.6 to +6.7 M