Mol. Syst. Biol.

We report a proteomic analysis of microdissected material from formalin-fixed and paraffin-embedded colorectal cancer, quantifying >7500 proteins between patient matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels of 1808 proteins changed significantly between normal and cancer tissues, a much larger fraction than that reported in transcript-based studies. Tumor cells exhibit extensive alterations in the cell-surface and nuclear proteomes. Functionally similar changes in the proteome were observed comparing rapidly growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic remodeling between primary cancer and metastases, suggesting that no drastic proteome changes are necessary for the tumor to propagate in a different tissue context. Additionally, we introduce a new way to determine protein copy numbers per cell without protein standards. Copy numbers estimated in enterocytes and cancer cells are in good agreement with CaCo-2 and HeLa cells and with the literature data. Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer

Measurement of ambient aerosol hydration state at Great Smoky Mountains National Park in the southeastern United States

We present results from two field deployments of a unique tandem differential mobility analyzer (TDMA) configuration with two primary capabilities: identifying alternative stable or meta-stable ambient aerosol hydration states associated with hysteresis in aerosol hydration behavior and determining the actual Ambient hydration State (AS-TDMA). This data set is the first to fully classify the ambient hydration state of aerosols despite recognition that hydration state significantly impacts the roles of aerosols in climate, visibility and heterogeneous chemistry. The AS-TDMA was installed at a site in eastern Tennessee on the border of Great Smoky Mountains National Park for projects during the summer of 2006 and winter of 2007–2008. During the summer, 12% of the aerosols sampled in continuous AS-TDMA measurements were found to posses two possible hydration states under ambient conditions. In every case, the more hydrated of the possible states was occupied. The remaining 88% did not posses multiple possible states. In continuous measurements during the winter, 49% of the aerosols sampled possessed two possible ambient hydration states; the remainder possessed only one. Of those aerosols with multiple possible ambient hydration states, 65% occupied the more hydrated state; 35% occupied the less hydrated state. This seasonal contrast is supported by differences in the fine particulate (PM<sub>2.5</sub>) composition and ambient RH as measured during the two study periods. In addition to seasonal summaries, this work includes case studies depicting the variation of hydration state with changing atmospheric conditions

100 Hz ROCS microscopy correlated with fluorescence reveals cellular dynamics on different spatiotemporal scales

Fluorescence techniques dominate the field of live-cell microscopy, but bleaching and motion blur from too long integration times limit dynamic investigations of small objects. High contrast, label-free life-cell imaging of thousands of acquisitions at 160 nm resolution and 100 Hz is possible by Rotating Coherent Scattering (ROCS) microscopy, where intensity speckle patterns from all azimuthal illumination directions are added up within 10 ms. In combination with fluorescence, we demonstrate the performance of improved Total Internal Reflection (TIR)-ROCS with variable illumination including timescale decomposition and activity mapping at five different examples: millisecond reorganization of macrophage actin cortex structures, fast degranulation and pore opening in mast cells, nanotube dynamics between cardiomyocytes and fibroblasts, thermal noise driven binding behavior of virus-sized particles at cells, and, bacterial lectin dynamics at the cortex of lung cells. Using analysis methods we present here, we decipher how motion blur hides cellular structures and how slow structure motions cover decisive fast motions

Rb-37(97)60 : The Cornerstone of the Region of Deformation around A similar to 100

Excited states of the neutron-rich nuclei Rb-97,Rb- 99 were populated for the first time using the multistep Coulomb excitation of radioactive beams. Comparisons of the results with particle-rotor model calculations provide clear identification for the ground-state rotational band of Rb-97 as being built on the pi g(9/2) [431] 3/2(+) Nilsson-model configuration. The ground-state excitation spectra of the Rb isotopes show a marked distinction between single-particle-like structures below N = 60 and rotational bands above. The present study defines the limits of the deformed region around A similar to 100 and indicates that the deformation of Rb-97 is essentially the same as that observed well inside the deformed region. It further highlights the power of the Coulomb-excitation technique for obtaining spectroscopic information far from stability. The Rb-99 case demonstrates the challenges of studies with very short-lived postaccelerated radioactive beams.Peer reviewe

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in 74^{74}Zn: Suggestion for a Northern Extension of the N=40N=40 Island of Inversion

The excited states of $N=44$ $^{74}$Zn were investigated via $\gamma$-ray spectroscopy following $^{74}$Cu $\beta$ decay. By exploiting $\gamma$-$\gamma$ angular correlation analysis, the $2_2^+$, $3_1^+$, $0_2^+$ and $2_3^+$ states in $^{74}$Zn were firmly established. The $\gamma$-ray branching and $E2/M1$ mixing ratios for transitions de-exciting the $2_2^+$, $3_1^+$ and $2_3^+$ states were measured, allowing for the extraction of relative $B(E2)$ values. In particular, the $2_3^+ \to 0_2^+$ and $2_3^+ \to 4_1^+$ transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the $N=40$ gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize $^{74}$Zn in its ground state. Furthermore, an excited $K=0$ band with a significantly larger softness in its shape is identified. A shore of the $N=40$ ``island of inversion'' appears to manifest above $Z=26$, previously thought as its northern limit in the chart of the nuclides

Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α

Glucocorticoid levels rise dramatically in late gestation to mature foetal organs in readiness for postnatal life. Immature heart function may compromise survival. Cardiomyocyte glucocorticoid receptor (GR) is required for the structural and functional maturation of the foetal heart in vivo, yet the molecular mechanisms are largely unknown. Here we asked if GR activation in foetal cardiomyocytes in vitro elicits similar maturational changes. We show that physiologically relevant glucocorticoid levels improve contractility of primary-mouse-foetal cardiomyocytes, promote Z-disc assembly and the appearance of mature myofibrils, and increase mitochondrial activity. Genes induced in vitro mimic those induced in vivo and include PGC-1α, a critical regulator of cardiac mitochondrial capacity. SiRNA-mediated abrogation of the glucocorticoid induction of PGC-1α in vitro abolished the effect of glucocorticoid on myofibril structure and mitochondrial oxygen consumption. Using RNA sequencing we identified a number of transcriptional regulators, including PGC-1α, induced as primary targets of GR in foetal cardiomyocytes. These data demonstrate that PGC-1α is a key mediator of glucocorticoid-induced maturation of foetal cardiomyocyte structure and identify other candidate transcriptional regulators that may play critical roles in the transition of the foetal to neonatal heart