Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding ‘big data’ that is conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

dizinc(II)

The centrosymmetric [Zn-2{CH3OC6H4P(OC5H9)S-2}(4)], features an eight-membered Zn2S4P2 ring as a result of two bidentate bridging thiolate ligands; the remaining ligands are chelating. Copyright (c) 2005 John Wiley & Sons, Ltd.C1 Pamukkale Univ, Fac Arts & Sci, Dept Chem, TR-20017 Denizli, Turkey.Ankara Univ, Fac Sci, Dept Chem, TR-06100 Ankara, Turkey.Bogazici Univ, Dept Chem, TR-34000 Istanbul, Turkey.Univ Leipzig, Fac Chem & Minerol, Dept Chem, D-04103 Leipzig, Germany

Disentangling UV photodesorption and photoconversion rates of H

Context. The nondissociative ultraviolet photodesorption of water ice is a nonthermal desorption mechanism required to account for detected abundances of gas-phase water toward cold regions within the interstellar medium. Previous experimental and theoretical studies provide a range of photodesorption rates for H2O ice and point to a convoluted competition with other molecular processes following the absorption of a UV photon in the ice. Ultraviolet irradiation also induces photodissociation, resulting in the formation of radicals that may directly desorb triggering gas-phase reactions or recombine in surface reactions. Aims. In this work, we aim to quantify the effects of photodesorption and investigate photoconversion upon UV photolysis of an H2O ice. Methods. We irradiated a porous amorphous H2O ice at 20 K with UV photons in the 7–10.2 eV range and compared the measurements to a nearly identical experiment that included a layer of argon coating on top of the water ice. The purpose of the argon coating is to quench any type of photon-triggered desorption. To trace ice composition and thickness, laser desorption post ionization time-of-flight mass spectrometry was utilized. This method is independent of the (non)dissociative character of a process and provides a diagnostic tool different from earlier studies that allows an independent check. Results. The total photodesorption rate for a porous amorphous H2O ice at 20 K we derive is (1.0 ± 0.2) × 10−3 per incident UV photon (7–10.2 eV), which is in agreement with the available literature. This rate is based on the elemental balance of oxygen-bearing species. As a result, we placed an upper limit on the intact (H2O) and dissociative (OH) desorption rates equal to 1.0 × 10−3 per incident UV photon, while for the reactive desorption (O2), this limit is equal to 0.5 × 10−3 per incident UV photon. Photoconversion depletes the H2O ice at a rate of (2.3 ± 0.2) × 10−3 per incident UV photon. At low UV fluence (9.0 × 1017 photons cm−2), the loss of H2O is balanced by photoproduct formation (O2 and H2O2). At high UV fluence (4.5 × 1018 photons cm−2), about 50% of the initial H2O molecules are depleted. This amount is not matched by the registered O-bearing products, which points to an additional, unaccounted loss channel of H2O

Gas-phase infrared spectroscopy of the rubicene cation (C_26H_14^+). A case study for interstellar pentagons

Laboratory astrophysics and astrochemistr

Stabilization of {runo}(6) and {runo}(7) states in [ru(ii)(trpy)(bik)(no)](n+) {trpy=2,2 ':6 ',2 ''-terpyridine, bik=2,2 '-bis(1-methylimidazolyl) ketone} - formation, reactivity, and photorelease of metal-bound nitrosyl

Ruthenium nitrosyl complexes have been isolated in the {RuNO}(6) and {RuNO}(7) configurations, employing the following reaction pathway for [Ru(trpy)(bik)(X)](n+): X = Cl(-), [1](ClO(4)) -> X = CH(3)CN, [2](ClO(4))(2) -> X = NO(2)(-), [3](ClO(4)) -> X = NO(+), [4](ClO(4))(3) -> X = NO(center dot), [4](ClO(4))(2). The single- crystal X-ray structures of [1](ClO(4))center dot(C(6)H(6))center dot H(2)O, [2](ClO(4))(2)center dot H(2)O, and [3](ClO(4))center dot H(2)O have been determined. The successive NO(+)/NO(-) (reversible) and NO(center dot)/NO(-) (irreversible) reduction processes of [4](3+) appear at +0.36 and -0.40 V vs. SCE, respectively. While the nu(C=O) frequency of the bik ligand at about 1630 cm(-1) is largely invariant on complexation and reduction, the nu(NO) frequency for the (RuNO)(6) state in [4](3+) at 1950 cm(-1) shifts to about 1640 cm(-1) on one-electron reduction to the {RuNO}(7) form in [4](2+), reflecting the predominant NO(+)-> NO(center dot) character of this electron transfer. However, a sizeable contribution from ruthenium with its high spin-orbit coupling constant to the singly occupied molecular or bital (SOMO) is apparent from the enhanced g anisotropy in the EPR spectrum [4](2+) (g(1) = 2.015, g(2) = 1.995, g(3) = 1.881; g(av) = 1.965; Delta g = 0.134). The {RuNO}(6) unit in [4](3+) reacts with OH(-) via an associatively activated process (Delta S(#) = -126.5 +/- 2JK(-l) mol(-1)) with a second-order rate constant of k = 3.3 X 10(-2) M(-1) s(-1), leading to the corresponding nitro complex [3](+). On exposure to light both {RuNO}(6) and {RuNO}(7) in [4](3+) and [4](2+) undergo Ru-NO photocleavage in CH(3)CN via the formation of [Ru(trpy)(bik)(CH(3)CN)](2+), [2](2+). The rate of photocleavage of the Ru(II)-NO(+) bond in [4](3+) (k(NO), 8.57 x 10(-1) s(-1), t(1/2) = 0-80 s) is found to be much faster than that of the Ru(II)-NO(center dot) bond in [4](2+), [k(NO center dot), 5.45 x 10 s(-1), t(1/2) = 21.2 min (= 1272 s)]. The photoreleased nitrosyl can be trapped as an Mb-NO adduct. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009

Effect of molecular structure on the infrared signatures of astronomically relevant PAHs

Emission bands from polycyclic aromatic hydrocarbons (PAHs) dominate the mid-infrared spectra of a wide variety of astronomical sources, encompassing nearly all stages of stellar evolution. Despite their similarities, details in band positions and shapes have allowed a classification of PAH emission to be developed. It has been suggested that this classification is in turn associated with the degree of photoprocessing of PAHs. Over the past decade, a more complete picture of the PAH interstellar life-cycle has emerged, in which a wide range of PAH species are formed during the later stages of stellar evolution. After this they are photoprocessed, increasing the relative abundance of the more stable (typically larger and compact) PAHs. For this work we have tested the effect of the symmetry, size, and structure of PAHs on their fragmentation pattern and infrared spectra by combining experiments at the free electron laser for infrared experiments (FELIX) and quantum chemical computations. Applying this approach to the cations of four molecular species, perylene (C20H12), peropyrene (C26H14), ovalene (C32H14) and isoviolanthrene (C34H18), we find that a reduction of molecular symmetry causes the activation of vibrational modes in the 7–9 μm range. We show that the IR characteristics of less symmetric PAHs can help explain the broad band observed in the class D spectra, which are typically associated with a low degree of photoprocessing. Such large, nonsymmetrical irregular PAHs are currently largely missing from the NASA Ames PAH database. The band positions and shapes of the largest more symmetric PAH measured here, show the best resemblance with class A and B sources, representative of regions with high radiation fields and thus heavier photoprocessing. Furthermore, the dissociation patterns observed in the mass spectra hint to an enhanced stability of the carbon skeleton in more symmetric PAHs with respect to the irregular and less symmetric species, which tend to loose carbon containing units. Although not a direct proof, these findings are fully in line with the grandPAH hypothesis, which claims that symmetric large PAHs can survive as the radiation field increases, while their less symmetric counterparts are destroyed or converted to symmetric PAHs