NF-κB Mediates FGF Signal Regulation of msx-1 Expression

AbstractThe nuclear factor-κB (NF-κB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-κB activity is necessary for both chicken and mouse limb development. We report here that the NF-κB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-κB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential κB-binding sites similar to the interferon-γ (IFN-γ) κB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-κB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-κB mediates the FGF-2/-4 signal regulation of msx-1 gene expression

Synthesis, structural studies, and redox chemistry of bimetallic [Mn(CO)₃] and [Re(CO)₃] complexes

Manganese ([Mn(CO)₃]) and rhenium tricarbonyl ([Re(CO)₃]) complexes represent a workhorse family of compounds with applications in a variety of fields. Here, the coordination, structural, and electrochemical properties of a family of mono- and bimetallic [Mn(CO)₃] and [Re(CO)₃] complexes are explored. In particular, a novel heterobimetallic complex featuring both [Mn(CO)₃] and [Re(CO)₃] units supported by 2,2′-bipyrimidine (bpm) has been synthesized, structurally characterized, and compared to the analogous monomeric and homobimetallic complexes. To enable a comprehensive structural analysis for the series of complexes, we have carried out new single crystal X-ray diffraction studies of seven compounds: Re(CO)₃Cl(bpm), anti-[{Re(CO₃)Cl}₂(bpm)], Mn(CO)₃Br(bpz) (bpz = 2,2′-bipyrazine), Mn(CO)₃Br(bpm), syn- and anti-[{Mn(CO3)Br}₂(bpm)], and syn-[Mn(CO₃)Br(bpm)Re(CO)₃Br]. Electrochemical studies reveal that the bimetallic complexes are reduced at much more positive potentials (ΔE ≥ 380 mV) compared to their monometallic analogues. This redox behavior is consistent with introduction of the second tricarbonyl unit which inductively withdraws electron density from the bridging, redox-active bpm ligand, resulting in more positive reduction potentials. [Re(CO₃)Cl]₂(bpm) was reduced with cobaltocene; the electron paramagnetic resonance spectrum of the product exhibits an isotropic signal (near g = 2) characteristic of a ligand-centered bpm radical. Our findings highlight the facile synthesis as well as the structural characteristics and unique electrochemical behavior of this family of complexes

Gaussian process regression bootstrapping: exploring the effects of uncertainty in time course data

Motivation: Although widely accepted that high-throughput biological data are typically highly noisy, the effects that this uncertainty has upon the conclusions we draw from these data are often overlooked. However, in order to assign any degree of confidence to our conclusions, we must quantify these effects. Bootstrap resampling is one method by which this may be achieved. Here, we present a parametric bootstrapping approach for time-course data, in which Gaussian process regression (GPR) is used to fit a probabilistic model from which replicates may then be drawn. This approach implicitly allows the time dependence of the data to be taken into account, and is applicable to a wide range of problems

UKIRT under new management: status and plans

The United Kingdom Infrared Telescope (UKIRT) observatory has been transferred to the ownership of the University of Hawaii (UH) and is now being managed by UH. We have established partnerships with several organizations to utilize the UKIRT for science projects and to support its operation. Our main partners are the U.S. Naval Observatory (USNO), the East Asian Observatory (EAO), and the UKIRT microlensing team (JPL/IPAC/OSU/Vanderbilt). The USNO is working on deep northern hemisphere surveys in the H and K bands and the UKIRT microlensing team is running a monitoring campaign of the Galactic bulge. EAO, UH, and USNO have individual P.I. research programs. Most of the observations are using the Wide Field Camera (WFCAM), but the older suite of cassegrain instruments are still fully operational. Data processing and archiving continue to be done CASU and WSA in the UK. We are working on a concept to upgrade the WFCAM with new larger infrared detector arrays for substantially improved survey efficiency

Physical activity in relation to urban environments in 14 cities worldwide: a cross-sectional study

Background Physical inactivity is a global pandemic responsible for over 5 million deaths annually through its effects on multiple non-communicable diseases. We aimed to document how objectively measured attributes of the urban environment are related to objectively measured physical activity, in an international sample of adults. Methods We based our analyses on the International Physical activity and Environment Network (IPEN) adult study, which was a coordinated, international, cross-sectional study. Participants were sampled from neighbourhoods with varied levels of walkability and socioeconomic status. The present analyses of data from the IPEN adult study included 6822 adults aged 18–66 years from 14 cities in ten countries on five continents. Indicators of walkability, public transport access, and park access were assessed in 1·0 km and 0·5 km street network buffers around each participant's residential address with geographic information systems. Mean daily minutes of moderate-to-vigorous-intensity physical activity were measured with 4–7 days of accelerometer monitoring. Associations between environmental attributes and physical activity were estimated using generalised additive mixed models with gamma variance and logarithmic link functions. Results Four of six environmental attributes were significantly, positively, and linearly related to physical activity in the single variable models: net residential density (exp[b] 1·006 [95% CI 1·003–1·009]; p=0·001), intersection density (1·069 [1·011–1·130]; p=0·019), public transport density (1·037 [1·018–1·056]; p=0·0007), and number of parks (1·146 [1·033–1·272]; p=0·010). Mixed land use and distance to nearest public transport point were not related to physical activity. The difference in physical activity between participants living in the most and least activity-friendly neighbourhoods ranged from 68 min/week to 89 min/week, which represents 45–59% of the 150 min/week recommended by guidelines. Interpretation Design of urban environments has the potential to contribute substantially to physical activity. Similarity of findings across cities suggests the promise of engaging urban planning, transportation, and parks sectors in efforts to reduce the health burden of the global physical inactivity pandemic. Funding Funding for coordination of the IPEN adult study, including the present analysis, was provided by the National Cancer Institute of National Institutes of Health (CA127296) with studies in each country funded by different sources

Differences in adolescent activity and dietary behaviors across home, school, and other locations warrant location-specific intervention approaches

Background Investigation of physical activity and dietary behaviors across locations can inform “setting-specific” health behavior interventions and improve understanding of contextual vulnerabilities to poor health. This study examined how physical activity, sedentary time, and dietary behaviors differed across home, school, and other locations in young adolescents. Methods Participants were adolescents aged 12–16 years from the Baltimore-Washington, DC and the Seattle areas from a larger cross-sectional study. Participants (n = 472) wore an accelerometer and Global Positioning Systems (GPS) tracker (Mean days = 5.12, SD = 1.62) to collect location-based physical activity and sedentary data. Participants (n = 789) completed 24-h dietary recalls to assess dietary behaviors and eating locations. Spatial analyses were performed to classify daily physical activity, sedentary time patterns, and dietary behaviors by location, categorized as home, school, and “other” locations. Results Adolescents were least physically active at home (2.5 min/hour of wear time) and school (2.9 min/hour of wear time) compared to “other” locations (5.9 min/hour of wear time). Participants spent a slightly greater proportion of wear time in sedentary time when at school (41 min/hour of wear time) than at home (39 min/hour of wear time), and time in bouts lasting ≥30 min (10 min/hour of wear time) and mean sedentary bout duration (5 min) were highest at school. About 61% of daily energy intake occurred at home, 25% at school, and 14% at “other” locations. Proportionately to energy intake, daily added sugar intake (5 g/100 kcal), fruits and vegetables (0.16 servings/100 kcal), high calorie beverages (0.09 beverages/100 kcal), whole grains (0.04 servings/100 kcal), grams of fiber (0.65 g/100 kcal), and calories of fat (33 kcal/100 kcal) and saturated fat (12 kcal/100 kcal) consumed were nutritionally least favorable at “other” locations. Daily sweet and savory snacks consumed was highest at school (0.14 snacks/100 kcal). Conclusions Adolescents’ health behaviors differed based on the location/environment they were in. Although dietary behaviors were generally more favorable in the home and school locations, physical activity was generally low and sedentary time was higher in these locations. Health behavior interventions that address the multiple locations in which adolescents spend time and use location-specific behavior change strategies should be explored to optimize health behaviors in each location

Associations of built environment and proximity of food outlets with weight status:Analysis from 14 cities in 10 countries

The study aimed to examine associations of neighborhood built environments and proximity of food outlets (BE measures) with body weight status using pooled data from an international study (IPEN Adult). Objective BE measures were calculated using geographic information systems for 10,008 participants (4463 male, 45%) aged 16-66 years in 14 cities. Participants self-reported proximity to three types of food outlets. Outcomes were body mass index (BMI) and overweight/obesity status. Male and female weight status associations with BE measures were estimated by generalized additive mixed models. Proportion (95% CI) of overweight (BMI 25 to = 30) from 2.9% (1.3, 4.4) to 31.3% (27.7, 34.7), with Hong Kong being the lowest and Cuernavaca, Mexico highest for both proportions. Results differed by sex. Greater street intersection density, public transport density and perceived proximity to restaurants (males) were associated with lower odds of overweight/obesity (BMI >= 25). Proximity to public transport stops (females) was associated with higher odds of overweight/obesity. Composite BE measures were more strongly related to BMI and overweight/obesity status than single variables among men but not women. One standard deviation improvement in the composite measures of BE was associated with small reductions of 0.1-0.5% in BMI but meaningful reductions of 2.5-5.3% in the odds of overweight/obesity. Effects were linear and generalizable across cities. Neighborhoods designed to support public transport, with food outlets within walking distance, may contribute to global obesity control

Precision orbital dynamics from interstellar scintillation arcs for PSR J0437-4715

Intensity scintillations of radio pulsars are known to originate from interference between waves scattered by the electron density irregularities of interstellar plasma, often leading to parabolic arcs in the two-dimensional power spectrum of the recorded dynamic spectrum. The degree of arc curvature depends on the distance to the scattering plasma and its transverse velocity with respect to the line-of-sight. We report the observation of annual and orbital variations in the curvature of scintillation arcs over a period of 16 years for the bright millisecond pulsar, PSR J0437-4715. These variations are the signature of the relative transverse motions of the Earth, pulsar, and scattering medium, which we model to obtain precise measurements of parameters of the pulsar's binary orbit and the scattering medium itself. We observe two clear scintillation arcs in most of our $>$5000 observations and we show that they originate from scattering by thin screens located at distances $D_1 = 89.8 \pm 0.4$ pc and $D_2 = 124 \pm 3$ pc from Earth. The best-fit scattering model we derive for the brightest arc yields the pulsar's orbital inclination angle $i = 137.1 \pm 0.3^\circ$, and longitude of ascending node, $\Omega=206.3\pm0.4^\circ$. Using scintillation arcs for precise astrometry and orbital dynamics can be superior to modelling variations in the diffractive scintillation timescale, because the arc curvature is independent of variations in the level of turbulence of interstellar plasma. This technique can be used in combination with pulsar timing to determine the full three-dimensional orbital geometries of binary pulsars, and provides parameters essential for testing theories of gravity and constraining neutron star masses.Comment: 19 pages, 10 figures. Accepted for publication in Ap