Single muscle fiber proteomics reveals unexpected mitochondrial specialization

Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity

Pharmacogenetic GWAS meta-analysis of LDL cholesterol response to statins

Cardiolog

Star formation in galaxies at z~4-5 from the SMUVS survey: a clear starburst/main-sequence bimodality for Halpha emitters on the SFR-M* plane

We study a large galaxy sample from the Spitzer Matching Survey of the UltraVISTA ultra-deep Stripes (SMUVS) to search for sources with enhanced 3.6 micron fluxes indicative of strong Halpha emission at z=3.9-4.9. We find that the percentage of "Halpha excess" sources reaches 37-40% for galaxies with stellar masses log10(M*/Msun) ~ 9-10, and decreases to <20% at log10(M*/Msun) ~ 10.7. At higher stellar masses, however, the trend reverses, although this is likely due to AGN contamination. We derive star formation rates (SFR) and specific SFR (sSFR) from the inferred Halpha equivalent widths (EW) of our "Halpha excess" galaxies. We show, for the first time, that the "Halpha excess" galaxies clearly have a bimodal distribution on the SFR-M* plane: they lie on the main sequence of star formation (with log10(sSFR/yr^{-1})<-8.05) or in a starburst cloud (with log10(sSFR/yr^{-1}) >-7.60). The latter contains ~15% of all the objects in our sample and accounts for >50% of the cosmic SFR density at z=3.9-4.9, for which we derive a robust lower limit of 0.066 Msun yr^{-1} Mpc^{-3}. Finally, we identify an unusual >50sigma overdensity of z=3.9-4.9 galaxies within a 0.20 x 0.20 sq. arcmin region. We conclude that the SMUVS unique combination of area and depth at mid-IR wavelengths provides an unprecedented level of statistics and dynamic range which are fundamental to reveal new aspects of galaxy evolution in the young Universe.Comment: 18 pages, 11 figures, 1 table. Re-submitted to the ApJ, after addressing referee report. Main changes with respect to v1: a new section and a new appendix have been added to investigate further the origin and robustness of the sSFR bimodality. No conclusion change

Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons

Although apoptosis has been extensively studied in developing neurons, the dynamic changes in this pathway after neuronal maturation remain largely unexplored. We show that as neurons mature, cytochrome c– mediated apoptosis progresses from inhibitor of apoptosis protein–dependent to –independent regulation because of a complete loss of Apaf-1 expression. However, after DNA damage, mature neurons resynthesize Apaf-1 through the cell cycle–related E2F1 pathway and restore their apoptotic potential. Surprisingly, we find that E2F1 is sufficient to induce Apaf-1 expression in developing but not mature neurons. Rather, Apaf-1 up-regulation in mature neurons requires both chromatin derepression and E2F1 transcriptional activity. This differential capacity of E2F1 to induce Apaf-1 transcription is because of the association of the Apaf-1 promoter with active chromatin in developing neurons and repressed chromatin in mature neurons. These data specifically illustrate how the apoptotic pathway in mature neurons becomes increasingly restricted by a novel mechanism involving the regulation of chromatin structure

A nuclear magnetic resonance study of the metal-nonmetal transition in arsenic-doped germanium

An investigation of the metal-nonmetal transition in arsenic-doped germanium (Ge;As) has been performed using the technique of nuclear magnetic resonance. The host Ge⁷³ resonance has been observed in twelve, single crystal, uncompensated specimens with room-temperature carrier concentrations from 7.10¹⁶-1.75.10¹⁹cm⁻³. Measurements of the nuclear spin-lattice relaxation time T₁, Knight shift K and the nuclear linewidth △B for Ge⁷³ are reported. Specifically, data are given at and below liquid helium temperatures for an applied magnetic field of 1. 44T and at 4.2K alone at a field of 5T. The Knight shifts have been measured at 4.2K at 5T and values of △B are given for both fields at 4.2K. The T₁ measurements at low field (1.44T) and Knight shift results show donor density dependences of free-electron type. A strong field dependence of T₁ has however been observed which is inexplicable by free-electron theory. The resonance linewidths are greater than the nuclear dipolar value, even for non-metallic samples, and increase with doping density and magnetic field. At the critical concentration for transition to metallic behaviour K shows an abrupt change from zero to a finite value. The low-field T₁'s are in contrast continuous across the transition but the high-field T₁'s do show a sharp increase below the critical doping density. A calculation shows spin diffusion to be unimportant for the samples and other mechanisms which can generate a field-dependent relaxation time are discussed. Firstly, assuming that the electrons form a homogeneous system and are confined to a narrow impurity band parameterised by an appropriate Bohr radius leads to a field dependence of T₁ in order of magnitude agreement with the data. A second qualitative model in line with recent ideas on the origin of negative magnetoresistance in doped semiconductors invokes the presence of nearly-free moments or Kondo centres in addition to the itinerant electron system. The fluctuation of the moments can furnish a relaxation process in addition to that due to Fermi contact between band electrons and nuclei. An increase in magnetic field inhibits the moment fluctuation rate and thus increases with field. Moreover the presence of moments will lead to resonance line broadening as we have observed. Finally, the magnetic properties of an Anderson transition are discussed and the abrupt appearance of K is shown to be consistent with Mott's interpretation of an Anderson transition. An important overall result is that the electron-electron effects observed in Si:P are absent in the Ge:As system. Simple estimates show that the intra-atomic correlation energy is smaller in n-Ge than n-Si and it is concluded that the metal-nonmetal transition in Ge:As is of Anderson-type and that correlation plays no essential role. This proposal is shown to be in agreement with the results of other experiments in heavily-doped Ge

Solving rate equations for electron tunneling via discrete quantum states

We consider the form of the current-voltage curves generated when tunneling spectroscopy is used to measure the energies of individual electronic energy levels in nanometer-scale systems. We point out that the voltage positions of the tunneling resonances can undergo temperature-dependent shifts, leading to errors in spectroscopic measurements that are proportional to temperature. We do this by solving the set of rate equations that can be used to describe electron tunneling via discrete quantum states, for a number of cases important for comparison to experiments, including (1) when just one spin-degenerate level is accessible for transport, (2) when 2 spin-degenerate levels are accessible, with no variation in electron-electron interactions between eigenstates, and (3) when 2 spin-degenerate levels are accessible, but with variations in electron-electron interactions. We also comment on the general case with an arbitrary number of accessible levels. In each case we analyze the voltage-positions, amplitudes, and widths of the current steps due to the quantum states.Comment: REVTeX 4, 10 pages, 12 figures, submitted to Phys. Rev. B. Associated programs available at http://www.ccmr.cornell.edu/~ralph

Skull Evolution Method and Analysis in The Rhinocerotidae: Phylogeny of Early Rhinocerotoids

After phylogeny is measurably disposed of, cranial elements utilized essentially for rumination ought to change most with hypsodonty (high-delegated cheek teeth). These structures should be least phylogenetically restricted. Corollary: structures with significant common ancestry will integrate more morphologically. All living rhinoceroses and many extinct European Plio-Pleistocene species We examined skull, mandible, and upper tooth row form in the dorsal, lateral, and occlusal perspectives using two-dimensional geometric morphometrics. Hypsodonty index was employed to represent eating behaviours. We divided form variation into function, phylogeny, and size using phylogenetically independent comparisons and variation partitioning. We used Escoufier's RV coefficient to evaluate morphological reconciliation. The mandible and upper tooth column covariate most with hypsodonty and least with phylogeny. Skull morphology corresponds least with hypsodonty and most with phylogeny. Low morphological joining between the top tooth line and different parts recommends it is the least phylogenetically restricted. As predicted, the chewing area is confined by function rather than phylogeny, unlike others

Wound healing activity of topical application of Aloe vera gel in experimental animal models

Aloe vera gel of 50% and 96.4% were tested for its wound healing activity by topical application in experimental rats. The effect of Aloe vera gel on wound healing was evaluated by wound excision model and histopathology was used to study the effect on wound healing. The effect produced by Aloe vera gel with reference to wound contraction, wound closure, decrease in surface area of wound, tissue regeneration at the wound site and histopathological characteristics were significant in treated rats. The effect of Aloe vera gel on biochemical studies revealed significant increase in collagen and decreased hexosamine content and malondialdehyde levels when compared with control. The present study thus provided scientific rationale for the traditional use of Aloe vera gel for management of wounds

Single muscle fiber proteomics reveals unexpected mitochondrial specialization.

Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity

The Spitzer Matching Survey of the UltraVISTA Ultra-deep Stripes (SMUVS):The Evolution of Dusty and Nondusty Galaxies with Stellar Mass at z = 2–6

The Spitzer Matching Survey of the UltraVISTA Ultra-deep Stripes (SMUVS) has obtained the largest ultradeep Spitzer maps to date in a single field of the sky. We considered the sample of about 66,000 SMUVS sources at z = 2–6 to investigate the evolution of dusty and nondusty galaxies with stellar mass through the analysis of the galaxy stellar mass function (GSMF), extending previous analyses about one decade in stellar mass and up to z = 6. We further divide our nondusty galaxy sample with rest-frame optical colors to isolate red quiescent (“passive”) galaxies. At each redshift, we identify a characteristic stellar mass in the GSMF above which dusty galaxies dominate, or are at least as important as nondusty galaxies. Below that stellar mass, nondusty galaxies compose about 80% of all sources, at all redshifts except at z = 4–5. The percentage of dusty galaxies at z = 4–5 is unusually high: 30%–40% for {M}* ={10}9{--}{10}10.5 {M}ȯ and &gt;80% at M * &gt; 1011 M ⊙, which indicates that dust obscuration is of major importance in this cosmic period. The overall percentage of massive ({log}}10({M}* /{M}ȯ )&gt; 10.6) galaxies that are quiescent increases with decreasing redshift, reaching &gt;30% at z ∼ 2. Instead, the quiescent percentage among intermediate-mass galaxies (with {log}}10({M}* /{M}ȯ )=9.7{--}10.6) stays roughly constant at a ∼10% level. Our results indicate that massive and intermediate-mass galaxies clearly have different evolutionary paths in the young universe and are consistent with the scenario of galaxy downsizing