A New Mouse Model to Study Acquired Lymphedema

Schneider and colleagues say that the new model, published in PLoS Medicine, promises to increase our understanding of lymphedema and hopefully accelerate the development and testing of new treatments

A model of top-down gain control in the auditory system

To evaluate a model of top-down gain control in the auditory system, 6 participants were asked to identify 1-kHz pure tones differing only in intensity. There were three 20-session conditions: (1) four soft tones (25, 30, 35, and 40 dB SPL) in the set; (2) those four soft tones plus a 50-dB SPL tone; and (3) the four soft tones plus an 80-dB SPL tone. The results were well described by a top-down, nonlinear gain-control system in which the amplifier’s gain depended on the highest intensity in the stimulus set. Individual participants’ identification judgments were generally compatible with an equal-variance signal-detection model in which the mean locations of the distribution of effects along the decision axis were determined by the operation of this nonlinear amplification system

Waist-to-Height Ratio Is More Predictive of Years of Life Lost than Body Mass Index

Objective: Our aim was to compare the effect of central obesity (measured by waist-to-height ratio, WHtR) and total obesity (measured by body mass index, BMI) on life expectancy expressed as years of life lost (YLL), using data on British adults. Methods: A Cox proportional hazards model was applied to data from the prospective Health and Lifestyle Survey (HALS) and the cross sectional Health Survey for England (HSE). The number of years of life lost (YLL) at three ages (30, 50, 70 years) was found by comparing the life expectancies of obese lives with those of lives at optimum levels of BMI and WHtR. Results: Mortality risk associated with BMI in the British HALS survey was similar to that found in US studies. However, WHtR was a better predictor of mortality risk. For the first time, YLL have been quantified for different values of WHtR. This has been done for both sexes separately and for three representative ages. Conclusion: This study supports the simple message ‘‘Keep your waist circumference to less than half your height’’. The use of WHtR in public health screening, with appropriate action, could help add years to life

Cardiac q-space trajectory imaging by motion-compensated tensor-valued diffusion encoding in human heart in vivo

Purpose Tensor-valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the technical feasibility of tensor-valued diffusion encoding at high b-values with q-space trajectory imaging (QTI) analysis, in the human heart in vivo. Methods Ten healthy volunteers were scanned on a 3T scanner. We designed time-optimal gradient waveforms for tensor-valued diffusion encoding (linear and planar) with second-order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (μFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time. Results QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 μm2/ms, FA = 0.31 ± 0.03, μFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas μFA was insensitive to this effect. Conclusion We demonstrated the first tensor-valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial μFA, MKi, MKa, and Cc. The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Characterizing Structural Transitions Using Localized Free Energy Landscape Analysis

Structural changes in molecules are frequently observed during biological processes like replication, transcription and translation. These structural changes can usually be traced to specific distortions in the backbones of the macromolecules involved. Quantitative energetic characterization of such distortions can greatly advance the atomic-level understanding of the dynamic character of these biological processes.Molecular dynamics simulations combined with a variation of the Weighted Histogram Analysis Method for potential of mean force determination are applied to characterize localized structural changes for the test case of cytosine (underlined) base flipping in a GTCAGCGCATGG DNA duplex. Free energy landscapes for backbone torsion and sugar pucker degrees of freedom in the DNA are used to understand their behavior in response to the base flipping perturbation. By simplifying the base flipping structural change into a two-state model, a free energy difference of upto 14 kcal/mol can be attributed to the flipped state relative to the stacked Watson-Crick base paired state. This two-state classification allows precise evaluation of the effect of base flipping on local backbone degrees of freedom.The calculated free energy landscapes of individual backbone and sugar degrees of freedom expectedly show the greatest change in the vicinity of the flipping base itself, but specific delocalized effects can be discerned upto four nucleotide positions away in both 5' and 3' directions. Free energy landscape analysis thus provides a quantitative method to pinpoint the determinants of structural change on the atomic scale and also delineate the extent of propagation of the perturbation along the molecule. In addition to nucleic acids, this methodology is anticipated to be useful for studying conformational changes in all macromolecules, including carbohydrates, lipids, and proteins

Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

<p>Abstract</p> <p>Background</p> <p>HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns.</p> <p>Methods</p> <p>HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated.</p> <p>Results</p> <p>Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (<it>P </it>< 0.05), but was not an independent prognostic marker of survival <it>(P > 0.05)</it>. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (<it>P </it>< 0.05). The 5-year survival rate in patients with negative and positive VEGF expression was 70.2% and 61.9% respectively; the difference was not statistically significant <it>(P = 0.146)</it>. No correlation between HER-2/neu and VEGF expression was detected (<it>P = </it>0.151).</p> <p>Conclusions</p> <p>HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.</p