Multicolour correlative imaging using phosphor probes

Correlative light and electron microscopy exploits the advantages of optical methods, such as multicolour probes and their use in hydrated live biological samples, to locate functional units, which are then correlated with structural details that can be revealed by the superior resolution of electron microscopes. One difficulty is locating the area imaged by the electron beam in the much larger optical field of view. Multifunctional probes that can be imaged in both modalities and thus register the two images are required. Phosphor materials give cathodoluminescence (CL) optical emissions under electron excitation. Lanthanum phosphate containing thulium or terbium or europium emits narrow bands in the blue, green and red regions of the CL spectrum; they may be synthesised with very uniform-sized crystals in the 10- to 50-nm range. Such crystals can be imaged by CL in the electron microscope, at resolutions limited by the particle size, and with colour discrimination to identify different probes. These materials also give emissions in the optical microscope, by multiphoton excitation. They have been deposited on the surface of glioblastoma cells and imaged by CL. Gadolinium oxysulphide doped with terbium emits green photons by either ultraviolet or electron excitation. Sixty-nanometre crystals of this phosphor have been imaged in the atmospheric scanning electron microscope (JEOL ClairScope). This probe and microscope combination allow correlative imaging in hydrated samples. Phosphor probes should prove to be very useful in correlative light and electron microscopy, as fiducial markers to assist in image registration, and in high/super resolution imaging studies

Discovery of the Transiting Planet Kepler-5B

We present 44 days of high duty cycle, ultra precise photometry of the 13th magnitude star Kepler-5 (KIC 8191672, T(eff) = 6300 K, log g = 4.1), which exhibits periodic transits with a depth of 0.7%. Detailed modeling of the transit is consistent with a planetary companion with an orbital period of 3.548460 +/- 0.000032 days and a radius of 1.431(-0.052)(+0.041) R(J). Follow-up radial velocity measurements with the Keck HIRES spectrograph on nine separate nights demonstrate that the planet is more than twice as massive as Jupiter with a mass of 2.114(-0.059)(+0.056) M(J) and a mean density of 0.894 +/- 0.079 g cm(-3).NASA's Science Mission DirectorateAstronom

Patterns of Failure after IMRT in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage

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Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Improving pregnancy outcomes in humans through studies in sheep

Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus

The trend of disruption in the functional brain network topology of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

Silicic volcanism on Mars evidenced by tridymite in high-SiO2 sedimentary rock at Gale crater

Tridymite, a SiO2 mineral that crystallizes at low pressures and high temperatures (>870 °C) from high-SiO2 materials, was detected at high concentrations in a sedimentary mudstone in Gale crater, Mars. Mineralogy and abundance were determined by X-ray diffraction using the Chemistry and Mineralogy instrument on the Mars Science Laboratory rover Curiosity. Terrestrial tridymite is commonly associated with silicic volcanism where high temperatures and high-silica magmas prevail, so this occurrence is the first in situ mineralogical evidence for martian silicic volcanism. Multistep processes, including high-temperature alteration of silica-rich residues of acid sulfate leaching, are alternate formation pathways for martian tridymite but are less likely. The unexpected discovery of tridymite is further evidence of the complexity of igneous petrogenesis on Mars, with igneous evolution to high-SiO2 compositions

Stable Isotope Composition of Fatty Acids in Organisms of Different Trophic Levels in the Yenisei River

We studied four-link food chain, periphytic microalgae and water moss (producers), trichopteran larvae (consumers I), gammarids (omnivorous – consumers II) and Siberian grayling (consumers III) at a littoral site of the Yenisei River on the basis of three years monthly sampling. Analysis of bulk carbon stable isotopes and compound specific isotope analysis of fatty acids (FA) were done. As found, there was a gradual depletion in 13C contents of fatty acids, including essential FA upward the food chain. In all the trophic levels a parabolic dependence of δ13C values of fatty acids on their degree of unsaturation/chain length occurred, with 18:2n-6 and 18:3n-3 in its lowest point. The pattern in the δ13C differences between individual fatty acids was quite similar to that reported in literature for marine pelagic food webs. Hypotheses on isotope fractionation were suggested to explain the findings