Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library

The utility of blue fluorescent protein (BFP) has been limited by its low quantum yield and rapid photobleaching. A library targeting residues neighboring the chromophore yielded a variant with enhanced quantum yield (0.55 versus 0.34), reduced pH sensitivity and a 40-fold increase in photobleaching half-life. This BFP, named Azurite, is well expressed in bacterial and mammalian cells and extends the palette of fluorescent proteins that can be used for imaging

β-Aminopropionitrile-Induced Aortic Aneurysm and Dissection in Mice

The mechanistic basis for the formation of aortic aneurysms and dissection needs to be elucidated to facilitate the development of effective medications. β-Aminopropionitrile administration in mice has been used frequently to study the pathologic features and mechanisms of aortic aneurysm and dissection. This mouse model mimics several facets of the pathology of human aortic aneurysms and dissection, although many variables exist in the experimental design and protocols that must be resolved to determine its application to the human disease. In the present brief review, we have introduced the development of this mouse model and provided insights into understanding its pathologic features

Circadian Disruption with Constant Light Exposure Exacerbates Atherosclerosis in Male \u3cem\u3eApolipoproteinE\u3c/em\u3e-Deficient Mice

Disruption of the circadian system caused by disordered exposure to light is pervasive in modern society and increases the risk of cardiovascular disease. The mechanisms by which this happens are largely unknown. ApolipoproteinE-deficient (ApoE−/−) mice are studied commonly to elucidate mechanisms of atherosclerosis. In this study, we determined the effects of light-induced circadian disruption on atherosclerosis in ApoE−/− mice. We first characterized circadian rhythms of behavior, light responsiveness, and molecular timekeeping in tissues from ApoE−/− mice that were indistinguishable from rhythms in ApoE+/+ mice. These data showed that ApoE−/− mice had no inherent circadian disruption and therefore were an appropriate model for our study. We next induced severe disruption of circadian rhythms by exposing ApoE−/− mice to constant light for 12 weeks. Constant light exposure exacerbated atherosclerosis in male, but not female, ApoE−/− mice. Male ApoE−/− mice exposed to constant light had increased serum cholesterol concentrations due to increased VLDL/LDL fractions. Taken together, these data suggest that ApoE−/− mice are an appropriate model for studying light-induced circadian disruption and that exacerbated dyslipidemia may mediate atherosclerotic lesion formation caused by constant light exposure

Mathematical models of bipolar disorder

We use limit cycle oscillators to model bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about 1% of the United States adult population. We consider two non-linear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individuals using weakly-coupled, weakly-damped harmonic oscillators. We discuss how the proposed models can be used as a framework for refined models that incorporate additional biological data. We conclude with a discussion of possible generalizations of our work, as there are several biologically-motivated extensions that can be readily incorporated into the series of models presented here

BL Lac X-ray Spectra: simpler than we thought

We report results from {\it XMM-Newton} observations of thirteen X-ray bright BL Lacertae objects, selected from the {\it Einstein} Slew Survey sample. The spectra are generally well fit by power-law models, with four objects having hard ($\alpha<1; F_\nu \propto \nu^{-\alpha}$) spectra that indicates synchrotron peaks at $>5$ keV. None of our spectra show line features, indicating that soft X-ray absorption ``notches'' must be rare amongst BL Lacs, rather than common or ubiquitous as had previously been asserted. We find significant curvature in most of the spectra. This curvature is almost certainly intrinsic, as it appears nearly constant from 0.5 to 6 keV, an observation which is inconsistent with the small columns seen in these sources.Comment: 4 pages, 1 figure; to be published in proceedings of the Cozumel meeting on "Multiwavelength Surveys for AGN", Cozumel 200

Hypercholesterolemia Accelerates Both the Initiation and Progression of Angiotensin II-induced Abdominal Aortic Aneurysms

Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice. Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups achieved comparable luminal dilation on week 2 through week 6 of AngII infusion as monitored by ultrasound. To determine whether hypercholesterolemia contributed to the progression of established AAAs, male LDL receptor -/- mice were fed Western diet and infused with AngII for 4 weeks. Mice with established AAAs were then stratified into two groups based on luminal diameters measured by ultrasound. While AngII infusion was continued for another 8 weeks in both groups, mice in one group were continuously fed Western diet, but diet in the other group was switched to normal laboratory diet. In the latter group, plasma cholesterol concentrations were reduced rapidly to approximately 500 mg/dl within one week after the diet was switched from Western diet to normal laboratory diet. Luminal expansion progressed constantly in mice continuously fed Western diet, whereas no continuous expansion was detected in mice that were switched to normal laboratory diet. Conclusion: Hypercholesterolemia accelerates both the initiation of AAAs and progression of established AAAs in AngII-infused male LDL receptor -/- mice. Clinical Relevance: Hypercholesterolemia is modestly associated with AAAs in observational or retrospective clinical studies. It is not feasible to study whether hypercholesterolemia contributes to the initiation of AAAs or progression of established AAAs in human. This study using AngII-induced AAA mouse model provides solid evidence that hypercholesterolemia contributes to both the initiation and progression of AAAs, supporting that statin therapy at any stage of AAA development may be beneficial to hypercholesterolemic patients with AAAs

Very-high-energy gamma radiation associated with the unshocked wind of the Crab pulsar

We show that the relativistic wind in the Crab pulsar, which is commonly thought to be invisible in the region upstream of the termination shock at R < 0.1 pc, in fact could be directly observed through its inverse Compton gamm-ray emission. The search for such specific component of radiation in the gamma-ray spectrum of the Crab can provide unique information about the unshocked pulsar wind that is not accessible at other wavelengths.Comment: 11 pages, 11 figures, to appear in one of the April issues of MNRA

Scattering of Low-Frequency Radiation by a Gyrating Electron

The scattering of electromagnetic radiation by the particle gyrating in an external magnetic field is considered. Particular attention is paid to the low-frequency case, when the frequencies of incident radiation are much less than the electron gyrofrequency. The spectral and polarization features of the scattering cross-section are analyzed in detail. It is found that the scattering transfers the low-frequency photons to high harmonics of the gyrofrequency, into the range of the synchrotron emission of the electron. The total scattering cross-section appears much larger than that for the particle at rest. The problem studied is directly applicable to the radio wave scattering in the magnetosphere of a pulsar. The particles acquire relativistic rotational energies as a result of resonant absorption of the high-frequency radio waves and concurrently scatter the low-frequency radio waves, which are still below the resonance. It is shown that the scattering can affect the radio intensity and polarization at the lowest frequencies and can compete with the resonant absorption in contributing to the low-frequency turnover in the pulsar spectrum. Moreover, the scattering can be an efficient mechanism of the pulsar high-energy emission, in addition to the synchrotron re-emission of the particles. Other astrophysical applications of the scattering by gyrating particles are pointed out as well.Comment: 13 pages, no figures. Accepted for publication in MNRA

On possibility of measurement of the electron beam energy using absorption of radiation by electrons in a magnetic field

The possibility of the precise measurement of the electron beam energy using absorption of radiation by electrons in a static and homogeneous magnetic field in a range up to a few hundred GeV energies, was considered in [1]. With the purpose of experimental checking of this method in a range of several tens MeV energies, the possibility of measurement of absolute energy of the electron beam energy with relative accuracy up to 10^{-4} is examined in details.Comment: 14 pages, 10 figure