2,648 research outputs found
Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action
We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity
Prevalence and impacts of self-medication in a disadvantaged setting: the importance of multi-dimensional health interventions
BackgroundSelf-medication is recognized as an effective form of treatment and is increasingly encouraged to treat minor illnesses. However, misuse of self-medication leaves devastating impacts on human health and causes antimicrobial resistance. Using medication without a prescription among farmers could cause more severe effects on their health than non-farm workers since they suffer from several occupational hazards such as excessive exposure to pesticides.MethodsA cross-sectional study was conducted in 197 residents living in Moc Chau from August to September. A structured questionnaire and face-to-face were used to collecting data. The multivariate logistic model was applied to indicate associated factors with the self-medication.ResultsThe prevalence of self-medication among farmers was 67%. Pain relievers (66.7%) and antibiotics (32.5%) were the types of medicines that were the most commonly purchased and used without a medical prescription. Ethnics and health status also significantly affected the self-medication practice as well as the purchase and use of antibiotics. The distance to travel to a medical center and the dangerous or difficult travel, participants with arthritis or inpatient treatment had significantly associated with buying and using the medicine and antibiotics without the medical prescription of farmers.ConclusionOur research highlights a considerably high prevalence of self-medication among farmers residing in the mountainous area of Vietnam. Individual factors such as ethnics, health status, distance to health centers, and dangerous or difficult travel were found to be related to the SM practice as well as the purchase and use of antibiotics. From that, the current study suggests interventions. For instance, official guidelines are needed to raise awareness and minimize the disadvantages of self-medication; and digital health technologies should be applied to reduce the gap in healthcare service between mountainous and other areas of Vietnam
Detection of intrinsic source structure at ~3 Schwarzschild radii with Millimeter-VLBI observations of SAGITTARIUS A*
We report results from very long baseline interferometric (VLBI) observations
of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230
GHz). The observations were performed in 2013 March using six VLBI stations in
Hawaii, California, Arizona, and Chile. Compared to earlier observations, the
addition of the APEX telescope in Chile almost doubles the longest baseline
length in the array, provides additional {\it uv} coverage in the N-S
direction, and leads to a spatial resolution of 30 as (3
Schwarzschild radii) for Sgr A*. The source is detected even at the longest
baselines with visibility amplitudes of 4-13% of the total flux density.
We argue that such flux densities cannot result from interstellar refractive
scattering alone, but indicate the presence of compact intrinsic source
structure on scales of 3 Schwarzschild radii. The measured nonzero
closure phases rule out point-symmetric emission. We discuss our results in the
context of simple geometric models that capture the basic characteristics and
brightness distributions of disk- and jet-dominated models and show that both
can reproduce the observed data. Common to these models are the brightness
asymmetry, the orientation, and characteristic sizes, which are comparable to
the expected size of the black hole shadow. Future 1.3 mm VLBI observations
with an expanded array and better sensitivity will allow a more detailed
imaging of the horizon-scale structure and bear the potential for a deep
insight into the physical processes at the black hole boundary.Comment: 11 pages, 5 figures, accepted to Ap
Induced pseudoscalar coupling of the proton weak interaction
The induced pseudoscalar coupling is the least well known of the weak
coupling constants of the proton's charged--current interaction. Its size is
dictated by chiral symmetry arguments, and its measurement represents an
important test of quantum chromodynamics at low energies. During the past
decade a large body of new data relevant to the coupling has been
accumulated. This data includes measurements of radiative and non radiative
muon capture on targets ranging from hydrogen and few--nucleon systems to
complex nuclei. Herein the authors review the theoretical underpinnings of
, the experimental studies of , and the procedures and uncertainties
in extracting the coupling from data. Current puzzles are highlighted and
future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic
Prime Focus Spectrograph - Subaru's future -
The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and
Redshifts (SuMIRe) project has been endorsed by Japanese community as one of
the main future instruments of the Subaru 8.2-meter telescope at Mauna Kea,
Hawaii. This optical/near-infrared multi-fiber spectrograph targets cosmology
with galaxy surveys, Galactic archaeology, and studies of galaxy/AGN evolution.
Taking advantage of Subaru's wide field of view, which is further extended with
the recently completed Wide Field Corrector, PFS will enable us to carry out
multi-fiber spectroscopy of 2400 targets within 1.3 degree diameter. A
microlens is attached at each fiber entrance for F-ratio transformation into a
larger one so that difficulties of spectrograph design are eased. Fibers are
accurately placed onto target positions by positioners, each of which consists
of two stages of piezo-electric rotary motors, through iterations by using
back-illuminated fiber position measurements with a wide-field metrology
camera. Fibers then carry light to a set of four identical fast-Schmidt
spectrographs with three color arms each: the wavelength ranges from 0.38
{\mu}m to 1.3 {\mu}m will be simultaneously observed with an average resolving
power of 3000. Before and during the era of extremely large telescopes, PFS
will provide the unique capability of obtaining spectra of 2400
cosmological/astrophysical targets simultaneously with an 8-10 meter class
telescope. The PFS collaboration, led by IPMU, consists of USP/LNA in Brazil,
Caltech/JPL, Princeton, & JHU in USA, LAM in France, ASIAA in Taiwan, and
NAOJ/Subaru.Comment: 13 pages, 11 figures, submitted to "Ground-based and Airborne
Instrumentation for Astronomy IV, Ian S. McLean, Suzanne K. Ramsay, Hideki
Takami, Editors, Proc. SPIE 8446 (2012)
Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment
Development of new, antimetastatic drugs from natural products has been substantially constrained by the lack of a reliable in vitro screening system. Such a system should ideally mimic the native, three-dimensional (3D) tumor microenvironment involving different cell types and allow quantitative analysis of cell behavior critical for metastasis. These requirements are largely unmet in the current model systems, leading to poor predictability of the in vitro collected data for in vivo trials, as well as prevailing inconsistency among different in vitro tests. In the present study, we report application of a 3D, microfluidic device for validation of the antimetastatic effects of 12 natural compounds. This system supports co-culture of endothelial and cancer cells in their native 3D morphology as in the tumor microenvironment and provides real-time monitoring of the cells treated with each compound. We found that three compounds, namely sanguinarine, nitidine, and resveratrol, exhibited significant antimetastatic or antiangiogenic effects. Each compound was further examined for its respective activity with separate conventional biological assays, and the outcomes were in agreement with the findings collected from the microfluidic system. In summary, we recommend use of this biomimetic model system as a new engineering tool for high-throughput evaluation of more diverse natural compounds with varying anticancer potentials
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