Transcriptional Regulation of the Bmp2 Gene: Retinoic Acid Induction in F9 Embryonal Carcinoma Cells and Saccharomyces Cerevisiae

Bmp2, a highly conserved member of the transforming growth factor-beta gene family, is crucial for normal development. Retinoic acid, combined with cAMP analogs, sharply induces the Bmp2 mRNA during the differentiation of F9 embryonal carcinoma cells into parietal endoderm. Retinoic acid (RA) also induces the Bmp2 gene in chick limb buds. Since normal Bmp2 expression may require an endogenous retinoid signal and aberrant Bmp2 expression may cause some aspects of RA-induced teratogenesis, we studied the mechanism underlying the induction of Bmp2. Measurements of the Bmp2 mRNA half-life and nuclear run-on assays indicated that RA stimulated the transcription rate of the Bmp2 gene. The results of ribonuclease protection and primer extension assays indicated that Bmp2 transcription started 2,127 nucleotides upstream of the translation start site in F9 cells. To identify genetic elements controlling this transcription rate increase, upstream and downstream genomic sequences flanking the Bmp2 gene were screened using chloramphenicol acetyltransferase reporter genes in F9 cells and β-galactosidase reporter genes in Saccharomyces cerevisiae that were cotransformed with retinoic acid receptor and retinoid X receptor expression plasmids. RA-dependent transcriptional activation was detected between base pairs -2,373 and -2,316 relative to the translation start site. We also identified a required Sp1 binding site between -2,308 and -2,298. The data indicate that Bmp2 is directly regulated by retinoic acid-bound receptors and Sp1

Time to revisit the passive overconsumption hypothesis?:Humans show sensitivity to calories in energy-rich meals

BACKGROUND: A possible driver of obesity is insensitivity (passive overconsumption) to food energy density (ED, kcal/g); however, it is unclear whether this insensitivity applies to all meals. OBJECTIVES: We assessed the influence of ED on energy intake (kcal) across a broad and continuous range of EDs comprised of noncovertly manipulated, real-world meals. We also allowed for the possibility that the association between energy intake and ED is nonlinear. METHODS: We completed a secondary analysis of 1519 meals which occurred in a controlled environment as part of a study conducted by Hall and colleagues to assess the effects of food ultra-processing on energy intake. To establish the generalizability of the findings, the analyses were repeated in 32,162 meals collected from free-living humans using data from the UK National Diet and Nutrition Survey (NDNS). Segmented regressions were performed to establish ED “breakpoints” at which the association between consumed meal ED and mean centered meal caloric intake (kcal) changed. RESULTS: Significant breakpoints were found in both the Hall et al. data set (1.41 kcal/g) and the NDNS data set (1.75 and 2.94 kcal/g). Centered meal caloric intake did not increase linearly with consumed meal ED, and this pattern was captured by a 2-component (“volume” and “calorie content” [biologically derived from the sensing of fat, carbohydrate, and protein]) model of physical meal size (g), in which volume is the dominant signal with lower energy-dense foods and calorie content is the dominant signal with higher energy-dense foods. CONCLUSIONS: These analyses reveal that, on some level, humans are sensitive to the energy content of meals and adjust meal size to minimize the acute aversive effects of overconsumption. Future research should consider the relative importance of volume and calorie-content signals, and how individual differences impact everyday dietary behavior and energy balance

A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar Spindle Formation

CLASP is a key regulator of microtubule (MT) dynamics and bipolar mitotic spindle structure with CLASP mutants displaying a distinctive monopolar spindle phenotype. It has been postulated that cryptic TOG domains underlie CLASP’s ability regulate MT dynamics. Here, we report the crystal structure of the first cryptic TOG domain (TOG2) from human CLASP1, revealing the existence of a bona fide TOG array in the CLASP family. Strikingly, CLASP1 TOG2 exhibits a unique, convex architecture across the tubulin-binding surface that contrasts with the flat tubulin-binding surface of XMAP215 family TOG domains. Mutations in key, conserved TOG2 determinants abrogate the ability of CLASP mutants to rescue bipolar spindle formation in Drosophila cells depleted of endogenous CLASP. These findings highlight the common mechanistic use of TOG domains in XMAP215 and CLASP families to regulate MT dynamics, and suggest that differential TOG domain architecture may confer distinct functions to these critical cytoskeletal regulators

Barriers to integrating direct oral anticoagulants into anticoagulation clinic care: A mixedâ methods study

BackgroundOutpatient anticoagulation clinics were initially developed to care for patients taking vitamin K antagonists such as warfarin. There has not been a systematic evaluation of the barriers and facilitators to integrating direct oral anticoagulant (DOAC) care into outpatient anticoagulation clinics.MethodsWe performed a mixed methods study consisting of an online survey of anticoagulation clinic providers and semiâ structured interviews with anticoagulation clinic leaders and managers between March and May of 2017. Interviews were transcribed and coded, exploring for themes around barriers and facilitators to DOAC care within anticoagulation clinics. Survey questions pertaining to the specific themes identified in the interviews were analyzed using summary statistics.ResultsSurvey responses were collected from 159 unique anticoagulation clinics and 20 semiâ structured interviews were conducted. Three primary barriers to DOAC care in the anticoagulation clinic were described by the interviewees: (a) a lack of provider awareness for ongoing monitoring and services provided by the anticoagulation clinic; (b) financial challenges to providing care to DOAC patients in an anticoagulation clinic model; and (c) clinical knowledge versus scope of care by the anticoagulation staff. These themes linked to three key areas of variation, including: (a) the size and hospital affiliation of the anticoagulation clinic; (b) the use of faceâ toâ face versus telephoneâ based care; and (c) the use of nurses or pharmacists in the anticoagulation clinic.ConclusionsAnticoagulation clinics in the United States experience important barriers to integrating DOAC care. These barriers vary based on the clinic size, model for warfarin care, and staff credentials (nursing or pharmacy).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/1/rth212157.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/2/rth212157_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/3/rth212157-sup-0001-Supinfo.pd

Possible thermochemical disequilibrium in the atmosphere of the exoplanet GJ 436b

The nearby extrasolar planet GJ 436b--which has been labelled as a 'hot Neptune'--reveals itself by the dimming of light as it crosses in front of and behind its parent star as seen from Earth. Respectively known as the primary transit and secondary eclipse, the former constrains the planet's radius and mass, and the latter constrains the planet's temperature and, with measurements at multiple wavelengths, its atmospheric composition. Previous work using transmission spectroscopy failed to detect the 1.4-\mu m water vapour band, leaving the planet's atmospheric composition poorly constrained. Here we report the detection of planetary thermal emission from the dayside of GJ 436b at multiple infrared wavelengths during the secondary eclipse. The best-fit compositional models contain a high CO abundance and a substantial methane (CH4) deficiency relative to thermochemical equilibrium models for the predicted hydrogen-dominated atmosphere. Moreover, we report the presence of some H2O and traces of CO2. Because CH4 is expected to be the dominant carbon-bearing species, disequilibrium processes such as vertical mixing and polymerization of methane into substances such as ethylene may be required to explain the hot Neptune's small CH4-to-CO ratio, which is at least 10^5 times smaller than predicted

The Murchison Widefield Array

It is shown that the excellent Murchison Radio-astronomy Observatory site allows the Murchison Widefield Array to employ a simple RFI blanking scheme and still calibrate visibilities and form images in the FM radio band. The techniques described are running autonomously in our calibration and imaging software, which is currently being used to process an FM-band survey of the entire southern sky.Comment: Accepted for publication in Proceedings of Science [PoS(RFI2010)016]. 6 pages and 3 figures. Presented at RFI2010, the Third Workshop on RFI Mitigation in Radio Astronomy, 29-31 March 2010, Groningen, The Netherland

Exile Vol. XL No. 2

38th Year Title Page by Carrie Horner \u2797 i Epigraph by Ezra Pound ii Table of Contents iii-iv Remembering Sundays by Allison Lemieux \u2795 1 Untitled by James Oliver \u2794 2 \u2778 Beige Chevy Malibu by Craig J. McDonough \u2794 3-4 Brushtown Road by Lelei Jennings \u2795 5 In Memoriam: River Phoenix, 1970-93 by Kirstin Rogers \u2794 6 Untitled by Kira Pollack \u2794 7 Checkmate by Kevin Nix \u2794 8 Anywhere in Ohio by Jen Hanysh \u2795 9 Untitled by Nicky Taylor \u2794 10 Under Your Influence by Katherine Anne Campo \u2794 11 Tulips by Tricia B. Swearingen \u2794 12 Untitled by Keith Chapman \u2795 12 December Storm by Erin Lott \u2796 13-19 On Meeting Phil Levine After a Reading at Denison University April 6, 1993 by Christopher Harnish \u2794 20 The 422 Bypass by Joel Husenits \u2795 21 Untitled by Ken Tyburski \u2794 22 Shakespeare\u27s Foreskin by Carey Christie \u2795 23 The Thaw by Chris Iven \u2794 24 The Rockbridge County Fair by Morgan Roper \u2794 25 Let it Drop Through by Carey Christie \u2795 26-27 Aladdin\u27s by Paul Rinkes \u2794 28-29 Untitled by Aileen Jones \u2794 30 The Tango by Hope Layne Morgan \u2794 31 Icarus by Carey Christine \u2795 32-33 fad by Jeremy Aufrance \u2795 34 Untitled by James Oliver \u2794 35 Desert Villanelle by Christopher Harnish \u2794 36 The Skull by Nicky Taylor \u2794 37 Rodeo Bar by Carl Jeffrey Boon \u2796 38 I, Mordred by Carey Christie \u2795 39-43 Between Centuries by Leslie Dana Wells \u2794 44-45 Untitled by Carrie Horner \u2797 45 Untitled by Alex Emmons \u2796 46 Coleridge\u27s Curse by Allison Lemieux \u2795 47 Untitled by Jenny Baker \u2794 48 five by Jeremy Aufrance \u2795 49 Untitled by James Oliver \u2794 50 Lobster Boy by Kirstin Rogers \u2794 51 Fire on the Mountain by Christopher Harnish \u2794 52-53 Yosemite by Morgan Roper \u2794 54 Untitled by Carrie Horner \u2797 54 Untitled by Ken Tyburski \u2794 55 Sleepless Nights Fades to Credits by Allison Lemieux \u2794 56 Dancing Days by Julie McDonald \u2794 57 Immobile by Adrienne Fair \u2796 58-59 Untitled by Kira Pollack \u2794 60 Dorm Fire by Lisa Marie Antonille \u2795 Untitled by Carrie Horner \u2797 61 The Book by Matt Wanat \u2795 62-63 Distance by Carl Jeffrey Boon \u2796 64 Untitled by Jenny Baker \u2794 65 Cover by Ken Tyburski \u2794 Editorial decision is shared equally among the Editorial Board. -6

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

The α(1,3)fucosyltransferases FucT-IV and FucT-VII Exert Collaborative Control over Selectin-Dependent Leukocyte Recruitment and Lymphocyte Homing

AbstractE-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV−/−/FucT-VII−/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII−/− mice is revoked in FucT-IV−/−/FucT-VII−/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing