406 research outputs found
Delineating the role of FANCA in glucose-stimulated insulin secretion in β cells through its protein interactome
Hyperinsulinemia affects 72% of Fanconi anemia (FA) patients and an additional 25% experience lowered glucose tolerance or frank diabetes. The underlying molecular mechanisms contributing to the dysfunction of FA pancreas β cells is unknown. Therefore, we sought to evaluate the functional role of FANCA, the most commonly mutated gene in FA, in glucosestimulated insulin secretion (GSIS). This study reveals that FANCA or FANCB knockdown impairs GSIS in human pancreas β cell line EndoC-βH3. To identify potential pathways by which FANCA might regulate GSIS, we employed a proteomics approach to identify FANCA protein interactions in EndoC-βH3 differentially regulated in response to elevated glucose levels. Glucose-dependent changes in the FANCA interaction network were observed, including increased association with other FA family proteins, suggesting an activation of the DNA damage response in response to elevated glucose levels. Reactive oxygen species increase in response to glucose stimulation and are necessary for GSIS in EndoC-βH3 cells. Glucose-induced activation of the DNA damage response was also observed as an increase in the DNA damage foci marker γ-H2AX and dependent upon the presence of reactive oxygen species. These results illuminate the role of FANCA in GSIS and its protein interactions regulated by glucose stimulation that may explain the prevalence of β cell-specific endocrinopathies in FA patients
Source contributions to Northern Hemisphere CO and black carbon during spring and summer 2008 from POLARCAT and START08/preHIPPO observations and MOZART-4
International audienceAnthropogenic pollution and wildfires are main producers of carbon monoxide (CO) and black carbon (BC) in the Northern Hemisphere. High concentrations of these compounds are transported into the Arctic troposphere, influencing the ecosystem in high northern latitudes and the global climate. The global chemical transport model MOZART-4 is used to quantify the seasonal evolution of the contribution of CO and BC from different source regions in spring and summer 2008 by tagging their emissions. Aircraft observations from the POLARCAT experiments, in particular NASA ARCTAS, NOAA ARCPAC, POLARCAT-France, DLR GRACE and YAK-AEROSIB, as well as the NSF START08/preHIPPO experiments during Spring-Summer 2008 are combined to quantify the representation of simulated tracer characteristics in anthropogenic and fire plumes. In general, the model reproduces CO and BC well. Based on aircraft measurements and FLEXPART back-trajectories, the altitude contribution of emissions coming from different source regions is well captured in the model. Uncertainties of the MOZART-4 model are identified by comparing the data with model results on the flight tracks and using MOPITT satellite observations. Anthropogenic emissions are underestimated by about 10% in high northern latitudes in spring, and shortcomings exist in simulating fire plumes. The remote impact of East-Siberian fire emissions is underestimated for spring, whereas the impact of Southeast Asian fire emissions to mid-latitude CO values is overestimated by the model. In summer, mid-latitude CO values agree well between model and observations, whereas summer high latitude East-Siberian fire emissions in the model are overestimated by 20% in comparison to observations in the region. On the other hand, CO concentrations are underestimated by about 30% over Alaska and Canada at altitudes above 4 km. BC values are overestimated by the model at altitudes above 4 km in summer. Based on MOZART-4, with tagged CO and BC tracers, anthropogenic emissions of Asia, Europe and the US have the largest contribution to the CO and BC in mid- and high latitudes in spring and summer. Southeast Asian, Chinese and Indian fires have a large impact on CO pollution in spring in low latitudes with a maximum between 20° and 30°, whereas Siberian fires contribute largely to the pollution in high latitudes, up to 10% in spring and up to 30% in summer. The largest contributions to BC values in high latitudes are from anthropogenic emissions (about 70%). CO and BC have larger mass loadings in April than in July, as a result of photochemistry and dynamics
Galaxy Zoo: CANDELS barred discs and bar fractions
The formation of bars in disc galaxies is a tracer of the dynamical maturity of the population. Previous studies have found that the incidence of bars in discs decreases from the local Universe to z ~ 1, and by z > 1 simulations predict that bar features in dynamically mature discs should be extremely rare. Here, we report the discovery of strong barred structures in massive disc galaxies at z ~ 1.5 in deep rest-frame optical images from the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. From within a sample of 876 disc galaxies identified by visual classification in Galaxy Zoo, we identify 123 barred galaxies. Selecting a subsample within the same region of the evolving galaxy luminosity function (brighter than L*), we find that the bar fraction across the redshift range 0.5 ≤ z ≤ 2 (fbar = 10.7+6.3 -3.5 per cent after correcting for incompleteness) does not significantly evolve.We discuss the implications of this discovery in the context of existing simulations and our current understanding of the way disc galaxies have evolved over the last 11 billion yearsPeer reviewedFinal Accepted Versio
Taking the Measure of the Universe: Precision Astrometry with SIM PlanetQuest
Precision astrometry at microarcsecond accuracy has application to a wide
range of astrophysical problems. This paper is a study of the science questions
that can be addressed using an instrument that delivers parallaxes at about 4
microarcsec on targets as faint as V = 20, differential accuracy of 0.6
microarcsec on bright targets, and with flexible scheduling. The science topics
are drawn primarily from the Team Key Projects, selected in 2000, for the Space
Interferometry Mission PlanetQuest (SIM PlanetQuest). We use the capabilities
of this mission to illustrate the importance of the next level of astrometric
precision in modern astrophysics. SIM PlanetQuest is currently in the detailed
design phase, having completed all of the enabling technologies needed for the
flight instrument in 2005. It will be the first space-based long baseline
Michelson interferometer designed for precision astrometry. SIM will contribute
strongly to many astronomical fields including stellar and galactic
astrophysics, planetary systems around nearby stars, and the study of quasar
and AGN nuclei. SIM will search for planets with masses as small as an Earth
orbiting in the `habitable zone' around the nearest stars using differential
astrometry, and could discover many dozen if Earth-like planets are common. It
will be the most capable instrument for detecting planets around young stars,
thereby providing insights into how planetary systems are born and how they
evolve with time. SIM will observe significant numbers of very high- and
low-mass stars, providing stellar masses to 1%, the accuracy needed to
challenge physical models. Using precision proper motion measurements, SIM will
probe the galactic mass distribution and the formation and evolution of the
Galactic halo. (abridged)Comment: 54 pages, 28 figures, uses emulateapj. Submitted to PAS
15th Annual Environmental Law Institute
Materials from the 15th Annual Environmental Law Institute held by UK/CLE in March 1999
Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence
To assess the capability of perfusion MRI to differentiate between necrosis and tumor recurrence in patients showing radiological progression of cerebral metastases treated with stereotactic radiosurgery (SRS). From 2004 to 2006 dynamic susceptibility-weighted contrast-enhanced perfusion MRI scans were performed on patients with cerebral metastasis showing radiological progression after SRS during follow-up. Several perfusion MRI characteristics were examined: a subjective visual score of the relative cerebral blood volume (rCBV) map and quantitative rCBV measurements of the contrast-enhanced areas of maximal perfusion. For a total of 34 lesions in 31 patients a perfusion MRI was performed. Diagnoses were based on histology, definite radiological decrease or a combination of radiological and clinical follow-up. The diagnosis of tumor recurrence was obtained in 20 of 34 lesions, and tumor necrosis in 14 of 34. Regression analyses for all measures proved statistically significant (χ2 = 11.6–21.6, P < 0.001–0.0001). Visual inspection of the rCBV map yielded a sensitivity and specificity of 70.0 respectively 92.9%. The optimal cutoff point for maximal tumor rCBV relative to white matter was 2.00 (improving the sensibility to 85.0%) and 1.85 relative to grey matter (GM), improving the specificity to 100%, with a corresponding sensitivity of 70.0%. Perfusion MRI seems to be a useful tool in the differentiation of necrosis and tumor recurrence after SRS. For the patients displaying a rCBV-GM greater than 1.85, the diagnosis of necrosis was excluded. Salvage treatment can be initiated for these patients in an attempt to prolong survival
A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms
We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases
Consumer Bankruptcy Update
Materials from the Consumer Bankruptcy Update presentations held by UK/CLE in December 2000
Hot and Cool Forms of Inhibitory Control and Externalizing Behavior in Children of Mothers who Smoked during Pregnancy: An Exploratory Study
This study examined whether children exposed to prenatal smoking show deficits in “hot” and/or “cool” executive functioning (EF). Hot EF is involved in regulation of affect and motivation, whereas cool EF is involved in handling abstract, decontextualized problems. Forty 7 to 9-year-old children (15 exposed to prenatal smoking, 25 non-exposed) performed two computerized tasks. The Sustained Attention Dots (SA-Dots) Task (as a measure of “cool” inhibitory control) requires 400 non-dominant hand and 200 dominant hand responses. Inhibitory control of the prepotent response is required for dominant hand responses. The Delay Frustration Task (DeFT) (as a measure of “hot” inhibitory control) consists of 55 simple maths exercises. On a number of trials delays are introduced before the next question appears on the screen. The extent of response-button pressing during delays indicates frustration-induced inhibitory control. Prenatally exposed children showed poorer inhibitory control in the DeFT than non-exposed children. A dose–response relationship was also observed. In addition, prenatally exposed children had significantly higher (dose-dependent) conduct problem- and hyperactivity-inattention scores. There were no significant group differences in inhibitory control scores from the SA-Dots. These results indicate that children exposed to prenatal smoking are at higher risk of hot but not cool executive function deficits
Current systematic carbon-cycle observations and the need for implementing a policy-relevant carbon observing system
A globally integrated carbon observation and analysis system is needed to
improve the fundamental understanding of the global carbon cycle, to improve
our ability to project future changes, and to verify the effectiveness of
policies aiming to reduce greenhouse gas emissions and increase carbon
sequestration. Building an integrated carbon observation system requires
transformational advances from the existing sparse, exploratory framework
towards a dense, robust, and sustained system in all components:
anthropogenic emissions, the atmosphere, the ocean, and the terrestrial
biosphere. The paper is addressed to scientists, policymakers, and funding
agencies who need to have a global picture of the current state of the
(diverse) carbon observations. We identify the current state of carbon
observations, and the needs and notional requirements for a global integrated
carbon observation system that can be built in the next decade. A key
conclusion is the substantial expansion of the ground-based observation
networks required to reach the high spatial resolution for CO<sub>2</sub> and
CH<sub>4</sub> fluxes, and for carbon stocks for addressing policy-relevant
objectives, and attributing flux changes to underlying processes in each
region. In order to establish flux and stock diagnostics over areas such as
the southern oceans, tropical forests, and the Arctic, in situ observations
will have to be complemented with remote-sensing measurements. Remote sensing
offers the advantage of dense spatial coverage and frequent revisit. A key
challenge is to bring remote-sensing measurements to a level of long-term
consistency and accuracy so that they can be efficiently combined in models
to reduce uncertainties, in synergy with ground-based data. Bringing tight
observational constraints on fossil fuel and land use change emissions will
be the biggest challenge for deployment of a policy-relevant integrated
carbon observation system. This will require in situ and remotely sensed data
at much higher resolution and density than currently achieved for natural
fluxes, although over a small land area (cities, industrial sites, power
plants), as well as the inclusion of fossil fuel CO<sub>2</sub> proxy measurements
such as radiocarbon in CO<sub>2</sub> and carbon-fuel combustion tracers.
Additionally, a policy-relevant carbon monitoring system should also provide
mechanisms for reconciling regional top-down (atmosphere-based) and bottom-up
(surface-based) flux estimates across the range of spatial and temporal
scales relevant to mitigation policies. In addition, uncertainties for each
observation data-stream should be assessed. The success of the system will
rely on long-term commitments to monitoring, on improved international
collaboration to fill gaps in the current observations, on sustained efforts
to improve access to the different data streams and make databases
interoperable, and on the calibration of each component of the system to
agreed-upon international scales
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