A novel RNA motif based on the structure of unusually stable 2',5'-linked r(UUCG) loops

We have recently shown that hairpins containing 2',5'-linked RNA loops exhibit superior thermodynamic stability compared to native hairpins comprised of 3',5'-RNA loops [Hannoush, R. N.; Damha, M. J. J. Am. Chem. Soc. 2001, 123, 12368-12374]. A remarkable feature of the 2',5'-r(UUCG) tetraloop is that, unlike the corresponding 3',5'-linked tetraloop, its stability is virtually independent of the hairpin stem composition. Here, we determine the solution structure of unusually stable hairpins of the sequence 5'-G(1)G(2)A(3)C(4)-(U(5)U(6)C(7)G(8))-G(9)(U/T(10))C(11)C(12)-3' containing a 2',5'-linked RNA (UUCG) loop and either an RNA or a DNA stem. The 2',5'-linked RNA loop adopts a new fold that is completely different from that previously observed for the native 3',5'-linked RNA loop. The 2',5'-RNA loop is stabilized by (a). U5.G8 wobble base pairing, with both nucleotide residues in the anti-conformation, (b). extensive base stacking, and (c). sugar-base and sugar-sugar contacts, all of which contribute to the extra stability of this hairpin structure. The U5:G8 base pair stacks on top of the C4:G9 loop-closing base pair and thus appears as a continuation of the stem. The loop uracil U6 base stacks above U5 base, while the cytosine C7 base protrudes out into the solvent and does not participate in any of the stabilizing interactions. The different sugar pucker and intrinsic bonding interactions within the 2',5'-linked ribonucleotides help explain the unusual stability and conformational properties displayed by 2',5'-RNA tetraloops. These findings are relevant for the design of more effective RNA-based aptamers, ribozymes, and antisense agents and identify the 2',5'-RNA loop as a novel structural motif.     

Some Isoperimetric Inequalities in Electrochemistry and Hele Shaw Flows

Isoperimetric inequalities are applied to a moving-boundaryproblem for doubly-connected domains. This problem occurs forexample in electrochemistry, in which case the domains in questionare the electrolyte of an electrolytic cell. The two electrodessurrounding the electrolyte are assumed to grow or dissolve,at different rates in general, by electrochemical reaction.We obtain optimal estimates showing, for example, that the leastchange in volume of each electrode always occurs in sphericalsymmetry.     

Remarkable stability of hairpins containing 2',5'-linked RNA loops.

We report here the results of a comparative study of hairpin loops that differ in the connectivity of phosphodiester linkages (3',5'- versus 2',5'-linkages). In addition, we have studied the effect of changing the stem composition on the thermodynamic stability of hairpin loops. Specifically, we constructed hairpins containing one of six stem duplex combinations, i.e., DNA:DNA ("DD"), RNA:RNA ("RR"), DNA:RNA ("DR"), 2',5'-RNA:RNA ("RR"), 2',5'-RNA:DNA ("RD"), and 2',5'-RNA:2',5'-RNA ("RR"), and one of three tetraloop compositions, i.e., 2',5'-RNA ("R"), RNA ("R"), and DNA ("D"). All hairpins contained the conserved and well-studied loop sequence 5'-...C(UUCG)G...-3' [Cheong et al. Nature 1990, 346, 680-682]. We show that the 2',5'-linked loop C(UUCG)G, i.e.,...C(3'p5')U(2'p5')U(2'p5')C(2'p5')G(2'p5')G(3'p5')..., like its "normal" RNA counterpart, forms an unusually stable tetraloop structure. We also show that the stability imparted by 2',5'-RNA loops is dependent on base sequence, a property that is shared with the regioisomeric 3',5'-RNA loops. Remarkably, we find that the stability of the UUCG tetraloop is virtually independent of the hairpin stem composition (DD, RR, RR, etc.), whereas the native RNA tetraloop exerts extra stability only when the stem is duplex RNA (R:R). As a result, the relative stabilities of hairpins with a 2',5'-linked tetraloop, e.g. ggac(UUCG)gtcc (T(m) = 61.4 degrees C), are often superior to those with RNA tetraloops, e.g. ggac(UUCG)gtcc (T(m) = 54.6 degrees C). In fact, it has been possible to observe the formation of a 2',5'-RNA:DNA hybrid duplex by linking the hybrid's strands to a (UUCG) loop. These duplexes (RD), which are not stable enough to form in an intermolecular complex [Wasner et al. Biochemistry 1998, 37, 7478-7486], were stable at room temperature (T(m) approximately 50 degrees C). Thus, 2',5'-loops have potentially important implications in the study of nucleic acid complexes where structural data are not yet available. Furthermore, they may be particularly useful as structural motifs for synthetic ribozymes and nucleic acid "aptamers".     

MODELING CLIMATE CHANGE AND THE EFFECT ON THE NORWEGIAN SALMON FARMING INDUSTRY

Abstract Global warming is expected to affect the ecosystem in the Northeast Atlantic, and substantial changes will also affect the aquaculture industry. Farming of salmon and trout is the biggest aquaculture industry in Norway, with an export value of about 3 billion US dollars in 2007. The objective of the paper is to analyze the potential economic effect a general increase in sea temperature can have on the Norwegian salmon aquaculture industry. The assessment of the economic impact of global warming is made possible by estimating a growth function, which explicitly includes sea water temperature. The analysis compares the economic effect of a climate change on fish farming plants in the south and the north of Norway. The scenarios are based on a model with monthly seasonal variation in temperature.     

Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors

Split-and-pool synthesis of a 10,000-membered library of molecules resembling the natural product carpanone has been achieved. The synthesis features development of solid-phase multicomponent reactions between nitrogen nucleophiles, enones, and hydroxylamines, and a solid-phase application of the Huisgen cycloaddition affording substituted triazoles. The synthesis was performed in high-capacity (500 microm) polystyrene beads using a one bead-one stock solution strategy that enabled phenotypic screens of the resulting library. Using whole-cell fluorescence imaging, we discovered a series of molecules from the carpanone-based library that inhibit exocytosis from the Golgi apparatus. The most potent member of this series has an IC(50) of 14 microM. We also report structure-activity relationships for the molecules exhibiting this interesting phenotype. These inhibitors of exocytosis may be useful reagents for the study of vesicular traffic.     

A theoretical analysis of the excited states in 2-benzoylthiophene

The lower excited states of 2-benzoylthiophene have been studied using ab initio quantum chemical methods based on multiconfigurational wave functions. Six singlet and six triplet excited states have been characterized. The geometry has been optimized for the two lowest triplet states, which are responsible for the photoreactivity of the chromophore in the photosensitizing drug tiaprofenic acid. The T¹(π → π?) and T₂(n → π?) states have been found to be close in energy with the π → π? state slightly lower. The excited states have been characterized using density difference and spin density plots. The different photochemical behaviour of the two triplet states can be rationalized from the theoretical data.     

II: PROPERTIES OF DIATOMIC AND TRIATOMIC MOLECULES

Results are presented from a theoretical study of the × ⁶Σ⁺, A ⁶Σ⁺ and ⁶Δ electronic states of CrH using multiconfiguration second-order perturbation theory in the multi-state formalism (MS-CASPT2). It is shown that the results for the spectroscopic constants and radiative lifetimes for the A state are in agreement with experiment and an earlier multireference configuration interaction study only if the two close lying × and A states are allowed to interact at a level of approximation that includes dynamic correlation.     

PHOTOINACTIVATION OF CATALASES FROM MAMMAL LIVER, PLANT LEAVES AND BACTERIA. COMPARISON OF INACTIVATION CROSS SECTIONS AND QUANTUM YIELDS AT 406 nm

Abstract— Photoinactivation in vitro at pH 7.0 of catalases from different sources (bovine liver, spinach leaves, and Micrococcus lysodeikticus) was studied. The wavelength of the inactivating light was close to the Soret peak of catalase. No great difference in light sensitivity between soluble catalases were found; the inactivation cross sections found ranged from 3.8.10^-4 to 5.0. 10^-4Ų/molecule. The inactivation quantum yield is 2.2. 10^-5 for bovine liver catalase and 3.110^-5 for Micrococcus catalase. The quantum yield for soluble spinach catalase is of a similar order of magnitude. There are some indications of a greater resistance to photodestruction of the spinach leaf catalase activity associated with small particles.     

Unpolarized structure functions and the parton distributions for nucleon in an independent quark model

Considering the nucleon as consisting entirely of its valence quarks confined independently in a scalar-vector harmonic potential; unpolarized structure functions F ₁(x, μ ²) and F ₂(x, μ ²) are derived in the Bjorken limit under certain simplifying assumptions; from which valence quark distribution functions u _v(x, μ ²) and d _v(x, μ ²) are appropriately extracted satisfying the normalization constraints. QCD-evolution of these input distributions from a model scale of μ ²=0.07 GeV² to a higher Q ² scale of Q ₀ ² =15 GeV² yields xu _v(x, Q ₀ ² ) and xd _v(x, Q ₀ ² ) in good agreement with experimental data. The gluon and sea-quark distributions such as G(x, Q ₀ ² ) and q _s(x, Q ₀ ² ) are dynamically generated with a reasonable qualitative agreement with the available data; using the leading order renormalization group equations with appropriate valence-quark distributions as the input.     

High scale parity invariance as a solution to the SUSY CP problem and an explanation of small ε′/ε

It is shown that if the supersymmetric Standard Model (MSSM) emerges as the low energy limit of a high scale left-right symmetric gauge structure, the number of uncontrollable CP violating phases of MSSM are drastically reduced. In particular it guarantees the vanishing of the dangerous phases that were at the root of the so called SUSY CP problem. Such a symmetric gauge structure is independently motivated by the smallness of neutrino masses that arise via seesaw mechanism automatic in the theory. The minimal version of this theory also provides an explanation of the smallness of ε′/ε as a consequence of the high scale parity invariance. This talk is based on work done in collaboration with K S Babu and B Dutta.