Diffuse Galactic Gamma Rays from Shock-Accelerated Cosmic Rays

A shock-accelerated particle flux \propto p^-s, where p is the particle momentum, follows from simple theoretical considerations of cosmic-ray acceleration at nonrelativistic shocks followed by rigidity-dependent escape into the Galactic halo. A flux of shock-accelerated cosmic-ray protons with s ~ 2.8 provides an adequate fit to the Fermi-LAT gamma-ray emission spectra of high-latitude and molecular cloud gas when uncertainties in nuclear production models are considered. A break in the spectrum of cosmic-ray protons claimed by Neronov, Semikoz, & Taylor (PRL, 108, 051105, 2012) when fitting the gamma-ray spectra of high-latitude molecular clouds is a consequence of using a cosmic-ray proton flux described by a power law in kinetic energy.Comment: Version to correspond to published letter in PRL; corrected Fig.

Diverse Levels of Sequence Selectivity and Catalytic Efficiency of Protein-Tyrosine Phosphatases

The sequence selectivity of 14 classical protein-tyrosine phosphatases (PTPs) (PTPRA, PTPRB, PTPRC, PTPRD, PTPRO, PTP1B, SHP-1, SHP-2, HePTP, PTP-PEST, TCPTP, PTPH1, PTPD1, and PTPD2) was systematically profiled by screening their catalytic domains against combinatorial peptide libraries. All of the PTPs exhibit similar preference for pY peptides rich in acidic amino acids and disfavor positively charged sequences, but differ vastly in their degrees of preference/disfavor. Some PTPs (PTP-PEST, SHP-1, and SHP-2) are highly selective for acidic over basic (or neutral) peptides (by >105-fold), whereas others (PTPRA and PTPRD) show no to little sequence selectivity. PTPs also have diverse intrinsic catalytic efficiencies (kcat/KM values against optimal substrates), which differ by >105-fold due to different kcat and/or KM values. Moreover, PTPs show little positional preference for the acidic residues relative to the pY residue. Mutation of Arg47 of PTP1B, which is located near the pY-1 and pY-2 residues of a bound substrate, decreased the enzymatic activity by 3–18-fold toward all pY substrates containing acidic residues anywhere within the pY-6 to pY+5 region. Similarly, mutation of Arg24, which is situated near the C-terminus of a bound substrate, adversely affected the kinetic activity of all acidic substrates. A co-crystal structure of PTP1B bound with a nephrin pY1193 peptide suggests that Arg24 engages in electrostatic interactions with acidic residues at the pY+1, pY+2, and likely other positions. These results suggest that long-range electrostatic interactions between positively charged residues near the PTP active site and acidic residues on pY substrates allow a PTP to bind acidic substrates with similar affinities and the varying levels of preference for acidic sequences by different PTPs are likely caused by the different electrostatic potentials near their active sites. The implications of the varying sequence selectivity and intrinsic catalytic activities with respect to PTP in vivo substrate specificity and biological functions are discussed

A DNA methylation signature in the stress driver gene Fkbp5 indicates a neuropathic component in chronic pain

BACKGROUND: Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that contribute to the maintenance of chronic pain and with an epigenetic landscape indicative of the susceptibility to persistent pain. Such genes would provide a novel opportunity for better pain management, as their epigenetic profile could be targeted for the treatment of chronic pain or used as an indication of vulnerability for prevention strategies. Here, we investigated the epigenetic profile of the gene Fkbp5 for this potential, using targeted bisulphite sequencing in rodent pre-clinical models of chronic and latent hypersensitive states. RESULTS: The Fkbp5 promoter DNA methylation (DNAm) signature in the CNS was significantly different between models of persistent pain, and there was a significant correlation between CNS and peripheral blood Fkbp5 DNAm, indicating that further exploration of Fkbp5 promoter DNAm as an indicator of chronic pain pathogenic origin is warranted. We also found that maternal separation, which promotes the persistency of inflammatory pain in adulthood, was accompanied by long-lasting reduction in Fkbp5 DNAm, suggesting that Fkbp5 DNAm profile may indicate the increased vulnerability to chronic pain in individuals exposed to trauma in early life. CONCLUSIONS: Overall, our data demonstrate that the Fkbp5 promoter DNAm landscape brings novel insight into the differing pathogenic origins of chronic pain, may be able to stratify patients and predict the susceptibility to chronic pain

Microarray and pathway analysis reveals decreased CDC25A and increased CDC42 associated with slow growth of BCL2 overexpressing immortalized breast cell line

Bcl-2 is an anti-apoptotic protein that is frequently overex-pressed in cancer cells but its role in carcinogenesis is not clear. We are interested in how Bcl-2 expression affects non-cancerous breast cells and its role in the cell cycle. We prepared an MCF10A breast epithelial cell line that stably overexpressed Bcl-2. We analyzed the cells by flow cytometry after synchronization, and used cDNA microarrays with quantitative reverse-transcription PCR (qRTPCR) to determine differences in gene expression. The microarray data was subjected to two pathway analysis tools, parametric analysis of gene set enrichment (PAGE) and ingenuity pathway analysis (IPA), and western analysis was carried out to determine the correlation between mRNA and protein levels. The MCF10A/Bcl-2 cells exhibited a slow-growth phenotype compared to control MCF10A/Neo cells that we attributed to a slowing of the G1-S cell cycle transition. A total of 363 genes were differentially expressed by at least two-fold, 307 upregulated and 56 downregulated. PAGE identified 22 significantly changed gene sets. The highest ranked network of genes identified by IPA contained 24 genes. Genes that were chosen for further analysis were confirmed by qRT-PCR, however, the western analysis did not always confirm differential expression of the proteins. Downregulation of the phosphatase CDC25A could solely be responsible for the slow growth pheno-type in MCF10A/Bcl-2 cells. Increased levels of GTPase Cdc42 could be adding to this effect. PAGE and IPA are valuable tools for microarray analysis, but protein expression results do not always follow mRNA expression results. Originally published Cell Cycle, Vol. 7, No. 19, Oct. 200

Giant Thermoelectric Effect from Transmission Supernodes

We predict an enormous order-dependent quantum enhancement of thermoelectric effects in the vicinity of a higher-order `supernode' in the transmission spectrum of a nanoscale junction. Single-molecule junctions based on 3,3'-biphenyl and polyphenyl ether (PPE) are investigated in detail. The nonequilibrium thermodynamic efficiency and power output of a thermoelectric heat engine based on a 1,3-benzene junction are calculated using many-body theory, and compared to the predictions of the figure-of-merit ZT.Comment: 5 pages, 6 figure

A Medium-Resolution Near-Infrared Spectral Library of Late Type Stars: I

We present an empirical infrared spectral library of medium resolution (R~2000-3000) H (1.6 micron) and K (2.2 micron) band spectra of 218 red stars, spanning a range of [Fe/H] from ~-2.2 to ~+0.3. The sample includes Galactic disk stars, bulge stars from Baade's window, and red giants from Galactic globular clusters. We report the values of 19 indices covering 12 spectral features measured from the spectra in the library. Finally, we derive calibrations to estimate the effective temperature, and diagnostic relationships to determine the luminosity classes of individual stars from near-infrared spectra. This paper is part of a larger effort aimed at building a near-IR spectral library to be incorporated in population synthesis models, as well as, at testing synthetic stellar spectra.Comment: 34 pages, 12 figures; accepted for publication at ApJS; the spectra are available from the authors upon reques

Timing of Intervention Affects Brain Electrical Activity in Children Exposed to Severe Psychosocial Neglect

Background: Early psychosocial deprivation has profound effects on brain activity in the young child. Previous reports have shown increased power in slow frequencies of the electroencephalogram (EEG), primarily in the theta band, and decreased power in higher alpha and beta band frequencies in infants and children who have experienced institutional care. Methodology/Principal Findings: We assessed the consequences of removing infants from institutions and placing them into a foster care intervention on brain electrical activity when children were 8 years of age. We found the intervention was successful for increasing high frequency EEG alpha power, with effects being most pronounced for children placed into foster care before 24 months of age. Conclusions/Significance: The dependence on age of placement for the effects observed on high frequency EEG alpha power suggests a sensitive period after which brain activity in the face of severe psychosocial deprivation is less amenabl

NLO QCD Corrections to BcB_c-to-Charmonium Form Factors

The $B_c(^1S_0)$ meson to S-wave Charmonia transition form factors are calculated in next-to-leading order(NLO) accuracy of Quantum Chromodynamics(QCD). Our results indicate that the higher order corrections to these form factors are remarkable, and hence are important to the phenomenological study of the corresponding processes. For the convenience of comparison and use, the relevant expressions in asymptotic form at the limit of $m_c\rightarrow0$ for the radiative corrections are presented