Inverse folding of RNA pseudoknot structures

Background: RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and \pairGU-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, {\tt RNAinverse}, {\tt RNA-SSD} as well as {\tt INFO-RNA} are limited to RNA secondary structures, we present in this paper the inverse folding algorithm {\tt Inv} which can deal with 3-noncrossing, canonical pseudoknot structures. Results: In this paper we present the inverse folding algorithm {\tt Inv}. We give a detailed analysis of {\tt Inv}, including pseudocodes. We show that {\tt Inv} allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. {\tt Inv} is freely available at \url{http://www.combinatorics.cn/cbpc/inv.html}. Conclusions: The algorithm {\tt Inv} extends inverse folding capabilities to RNA pseudoknot structures. In comparison with {\tt RNAinverse} it uses new ideas, for instance by considering sets of competing structures. As a result, {\tt Inv} is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.Comment: 20 pages, 26 figure

Off-shell effects in dilepton production from hot interacting mesons

The production of dielectrons in reactions involving a_1 mesons and pions is studied. We compare results obtained with different phenomenological Lagrangians that have been used in connection with hadronic matter and finite nuclei. We insist on the necessity for those interactions to satisfy known empirical properties of the strong interaction. Large off-shell effects in dielectron production are found and some consequences for the interpretation of heavy ion data are outlined. We also compare with results obtained using experimentally-extracted spectral functions.Comment: 14 pages, LaTeX2e, 2 figure

Engineering a C-Phase quantum gate: optical design and experimental realization

A two qubit quantum gate, namely the C-Phase, has been realized by exploiting the longitudinal momentum (i.e. the optical path) degree of freedom of a single photon. The experimental setup used to engineer this quantum gate represents an advanced version of the high stability closed-loop interferometric setup adopted to generate and characterize 2-photon 4-qubit Phased Dicke states. Some experimental results, dealing with the characterization of multipartite entanglement of the Phased Dicke states are also discussed in detail.Comment: accepted for publication on EPJ

Twistor Strings with Flavour

We explore the tree-level description of a class of N=2 UV-finite SYM theories with fundamental flavour within a topological B-model twistor string framework. In particular, we identify the twistor dual of the Sp(N) gauge theory with one antisymmetric and four fundamental hypermultiplets, as well as that of the SU(N) theory with 2N hypermultiplets. This is achieved by suitably orientifolding/orbifolding the original N=4 setup of Witten and adding a certain number of new topological 'flavour'-branes at the orientifold/orbifold fixed planes to provide the fundamental matter. We further comment on the appearance of these objects in the B-model on CP(3|4). An interesting aspect of our construction is that, unlike the IIB description of these theories in terms of D3 and D7-branes, on the twistor side part of the global flavour symmetry is realised geometrically. We provide evidence for this correspondence by calculating and matching amplitudes on both sides.Comment: 38+12 pages; uses axodraw.sty. v2: References added, minor clarification

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

Allelic variants of the amylose extender mutation of maize demonstrate phenotypic variation in starch structure resulting from modified protein–protein interactions

amylose extender (ae−) starches characteristically have modified starch granule morphology resulting from amylopectin with reduced branch frequency and longer glucan chains in clusters, caused by the loss of activity of the major starch branching enzyme (SBE), which in maize endosperm is SBEIIb. A recent study with ae− maize lacking the SBEIIb protein (termed ae1.1 herein) showed that novel protein–protein interactions between enzymes of starch biosynthesis in the amyloplast could explain the starch phenotype of the ae1.1 mutant. The present study examined an allelic variant of the ae− mutation, ae1.2, which expresses a catalytically inactive form of SBEIIb. The catalytically inactive SBEIIb in ae1.2 lacks a 28 amino acid peptide (Val272–Pro299) and is unable to bind to amylopectin. Analysis of starch from ae1.2 revealed altered granule morphology and physicochemical characteristics distinct from those of the ae1.1 mutant as well as the wild-type, including altered apparent amylose content and gelatinization properties. Starch from ae1.2 had fewer intermediate length glucan chains (degree of polymerization 16–20) than ae1.1. Biochemical analysis of ae1.2 showed that there were differences in the organization and assembly of protein complexes of starch biosynthetic enzymes in comparison with ae1.1 (and wild-type) amyloplasts, which were also reflected in the composition of starch granule-bound proteins. The formation of stromal protein complexes in the wild-type and ae1.2 was strongly enhanced by ATP, and broken by phosphatase treatment, indicating a role for protein phosphorylation in their assembly. Labelling experiments with [γ-32P]ATP showed that the inactive form of SBEIIb in ae1.2 was phosphorylated, both in the monomeric form and in association with starch synthase isoforms. Although the inactive SBEIIb was unable to bind starch directly, it was strongly associated with the starch granule, reinforcing the conclusion that its presence in the granules is a result of physical association with other enzymes of starch synthesis. In addition, an Mn2+-based affinity ligand, specific for phosphoproteins, was used to show that the granule-bound forms of SBEIIb in the wild-type and ae1.2 were phosphorylated, as was the granule-bound form of SBEI found in ae1.2 starch. The data strongly support the hypothesis that the complement of heteromeric complexes of proteins involved in amylopectin synthesis contributes to the fine structure and architecture of the starch granule

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Search for Gamma Ray Bursts with the Argo-YBJ Detector in Scaler Mode

We report on the search for Gamma Ray Bursts (GRBs) in the energy range 1-100 GeV in coincidence with the prompt emission detected by satellites using the Astrophysical Radiation with Ground-based Observatory at YangBaJing (ARGO-YBJ) air shower detector. Thanks to its mountain location (Yangbajing, Tibet, P.R. China, 4300 m a.s.l.), active surface (about 6700 m**2 of Resistive Plate Chambers), and large field of view (about 2 sr, limited only by the atmospheric absorption), the ARGO-YBJ air shower detector is particularly suitable for the detection of unpredictable and short duration events such as GRBs. The search is carried out using the "single particle technique", i.e. counting all the particles hitting the detector without measurement of the energy and arrival direction of the primary gamma rays. Between 2004 December 17 and 2009 April 7, 81 GRBs detected by satellites occurred within the field of view of ARGO-YBJ (zenith angle < 45 deg). It was possible to examine 62 of these for >1 GeV counterpart in the ARGO-YBJ data finding no statistically significant emission. With a lack of detected spectra in this energy range fluence upper limits are profitable, especially when the redshift is known and the correction for the extragalactic absorption can be considered. The obtained fluence upper limits reach values as low as 10**{-5} erg cm**{-2} in the 1-100 GeV energy region. Besides this individual search for a higher energy counterpart, a statistical study of the stack of all the GRBs both in time and in phase was made, looking for a common feature in the GRB high energy emission. No significant signal has been detected.Comment: accepted for publication in Ap

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

High Altitude test of RPCs for the ARGO-YBJ experiment

A 50 m**2 RPC carpet was operated at the YangBaJing Cosmic Ray Laboratory (Tibet) located 4300 m a.s.l. The performance of RPCs in detecting Extensive Air Showers was studied. Efficiency and time resolution measurements at the pressure and temperature conditions typical of high mountain laboratories, are reported.Comment: 16 pages, 10 figures, submitted to Nucl. Instr. Met