Radio recombination lines from the largest bound atoms in space

In this paper, we report the detection of a series of radio recombination lines (RRLs) in absorption near 26 MHz arising from the largest bound carbon atoms detected in space. These atoms, which are more than a million times larger than the ground state atoms are undergoing delta transitions (n~1009, Delta n=4) in the cool tenuous medium located in the Perseus arm in front of the supernova remnant, Cassiopeia A. Theoretical estimates had shown that atoms which recombined in tenuous media are stable up to quantum levels n~1500. Our data indicates that we have detected radiation from atoms in states very close to this theoretical limit. We also report high signal-to-noise detections of alpha, beta and gamma transitions in carbon atoms arising in the same clouds. In these data, we find that the increase in line widths with quantum number (proportional to n^5) due to pressure and radiation broadening of lines is much gentler than expected from existing models which assume a power law background radiation field. This discrepancy had also been noted earlier. The model line widths had been overestimated since the turnover in radiation field of Cassiopeia A at low frequencies had been ignored. In this paper, we show that, once the spectral turnover is included in the modeling, the slower increase in line width with quantum number is naturally explained.Comment: 5 pages, 4 figures, accepted for publication in MNRA

PS Booster Orbit Correction

At the end of the 2007 run, orbit measurements were carried out in the 4 rings of the PS Booster (PSB) for different working points and beam energies. The aim of these measurements was to provide the necessary input data for a PSB realignment campaign during the 2007/2008 shutdown. Currently, only very few corrector magnets can be operated reliably in the PSB; therefore the orbit correction has to be achieved by displacing (horizontally and vertically) and/or tilting some of the defocusing quadrupoles (QDs). In this report we first describe the orbit measurements, followed by a detailed explanation of the orbit correction strategy. Results and conclusions are presented in the last section

Control genético de la floculación de Saccharomyces cerevisiae en proceso de fermentación industrial

La floculación es una característica muy importante de las cepas industriales de Saccharomyces cerevisiae, que facilita las operaciones de clarificación del producto y recuperación de levadura. Sin embargo se desconocen los genes que controlan la floculación bajo condiciones de operación industrial. En el presente trabajo se determinó el número y tipo de genes relacionados con la floculación (FLO) por la reacción en cadena de la polimerasa (PCR) de punto final, así como sus niveles de expresión en diferentes cepas de levaduras industriales, mediante PCR cuantitativa (qPCR), bajo condiciones de proceso que afectan la floculación (alta presión osmótica, presión hidrostática, represión catabólica, restricción calórica y edad generacional). Por otra parte se analizó la expresión global a nivel transcripcional por microarreglos de ADN. La capacidad floculante fue disminuida de forma específica por alto contenido de glucosa en el medio (represión catabólica); pero incrementada con la edad generacional. El contenido de genes FLO fue variable (de 3 a 6 genes por cepa), siendo más conservados los genes Lg-FLO1, FLO8 y FLO11. En los resultados de qPCR se determinó que sólo la expresión de Lg-FLO1 se correlacionó con la floculación. Finalmente, el análisis de microarreglos reveló que la regulación de floculación esta sujeta principalmente a un mecanismo de silenciamiento epigenético por modificación de la arquitectura de la cromatina en genes subteloméricos

Insights into Activation Mechanisms of Store-Operated TRPC1 Channels in Vascular Smooth Muscle.

In vascular smooth muscle cells (VMSCs), the stimulation of store-operated channels (SOCs) mediate Ca2+ influx pathways which regulate important cellular functions including contraction, proliferation, migration, and growth that are associated with the development of vascular diseases. It is therefore important that we understand the biophysical, molecular composition, activation pathways, and physiological significance of SOCs in VSMCs as these maybe future therapeutic targets for conditions such as hypertension and atherosclerosis. Archetypal SOCs called calcium release-activated channels (CRACs) are composed of Orai1 proteins and are stimulated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) following store depletion. In contrast, this review focuses on proposals that canonical transient receptor potential (TRPC) channels composed of a heteromeric TRPC1/C5 molecular template, with TRPC1 conferring activation by store depletion, mediate SOCs in native contractile VSMCs. In particular, it summarizes our recent findings which describe a novel activation pathway of these TRPC1-based SOCs, in which protein kinase C (PKC)-dependent TRPC1 phosphorylation and phosphatidylinositol 4,5-bisphosphate (PIP2) are obligatory for channel opening. This PKC- and PIP2-mediated gating mechanism is regulated by the PIP2-binding protein myristoylated alanine-rich C kinase (MARCKS) and is coupled to store depletion by TRPC1-STIM1 interactions which induce Gq/PLCβ1 activity. Interestingly, the biophysical properties and activation mechanisms of TRPC1-based SOCs in native contractile VSMCs are unlikely to involve Orai1

Stress responsive miR-23a attenuates skeletal muscle atrophy by targeting MAFbx /atrogin-1

Muscle atrophy occurs in many pathological states and results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. We used dexamethasone to induce muscle wasting and investigated the role of a microRNA (miRNA) in the control of muscle-specific E3 ubiquitin ligase MAFbx/atrogin-1. Here we show that miR-23a suppresses MAFbx/atrogin-1 translation by binding to 3'UTR of the mRNA. Furthermore, ectopic expression of miR-23a is sufficient to protect myocytes from atrophy in vitro and in vivo in response to dexamethasone treatment, and heat stress-induced miR-23a protects muscle from dexamethasone-induced muscle atrophy. Our surprising discovery of the physiological role of miR-23a in preventing the atrophy program should lay the basis not only for further understanding of the mechanisms of muscle wasting in diverse diseases, but also for developing novel therapies for these debilitating conditions

Fundamental studies on a heat driven lamp

A detailed theoretical study of a heat-driven lamp has been performed. This lamp uses a plasma produced in a thermionic diode. The light is produced by the resonance transition of cesium. An important result of this study is that up to 30% of the input heat is predicted to be converted to light in this device. This is a major improvement over ordinary thermionic energy converters in which only approx. 1% is converted to resonance radiation. Efficiencies and optimum inter-electrode spacings have been found as a function of cathode temperature and the radiative escape factor. The theory developed explains the operating limits of the device

Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms, including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single mRNA transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work, we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during its biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamics simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results indicate that cotranslational folding of this viral protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent polypeptide chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding or binding events may also stimulate PRF

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems—imidazopurinones. The adduct derived from methylglyoxal-3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers—was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2′-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity

Transcriptional delay stabilizes bistable gene networks

Transcriptional delay can significantly impact the dynamics of gene networks. Here we examine how such delay affects bistable systems. We investigate several stochastic models of bistable gene networks and find that increasing delay dramatically increases the mean residence times near stable states. To explain this, we introduce a non-Markovian, analytically tractable reduced model. The model shows that stabilization is the consequence of an increased number of failed transitions between stable states. Each of the bistable systems that we simulate behaves in this manner