Kissing loop interaction in adenine riboswitch: insights from umbrella sampling simulations

Introduction: Riboswitches are cis-acting regulatory RNA elements prevalently located in the leader sequences of bacterial mRNA. An adenine sensing riboswitch cis-regulates adeninosine deaminase gene (add) in Vibrio vulnificus. The structural mechanism regulating its conformational changes upon ligand binding mostly remains to be elucidated. In this open framework it has been suggested that the ligand stabilizes the interaction of the distal "kissing loop" complex. Using accurate full-atom molecular dynamics with explicit solvent in combination with enhanced sampling techniques and advanced analysis methods it could be possible to provide a more detailed perspective on the formation of these tertiary contacts. Methods In this work, we used umbrella sampling simulations to study the thermodynamics of the kissing loop complex in the presence and in the absence of the cognate ligand. We enforced the breaking/formation of the loop-loop interaction restraining the distance between the two loops. We also assessed the convergence of the results by using two alternative initialization protocols. A structural analysis was performed using a novel approach to analyze base contacts. Results Contacts between the two loops were progressively lost when larger inter-loop distances were enforced. Inter-loop Watson-Crick contacts survived at larger separation when compared with non-canonical pairing and stacking interactions. Intra-loop stacking contacts remained formed upon loop undocking. Our simulations qualitatively indicated that the ligand could stabilize the kissing loop complex. We also compared with previously published simulation studies. Discussion and Conclusions Kissing complex stabilization given by the ligand was compatible with available experimental data. However, the dependence of its value on the initialization protocol of the umbrella sampling simulations posed some questions on the quantitative interpretation of the results and called for better converged enhanced sampling simulations

Towards de novo RNA 3D Structure Prediction

RNA is a fundamental class of biomolecules that mediate a large variety of molecular processes within the cell. Computational algorithms can be of great help in the understanding of RNA structure-function relationship. One of the main challenges in this field is the development of structure-prediction algorithms, which aim at the prediction of the three-dimensional (3D) native fold from the sole knowledge of the sequence. In a recent paper, we have introduced a scoring function for RNA structure prediction. Here, we analyze in detail the performance of the method, we underline strengths and shortcomings, and we discuss the results with respect to state-of-the-art techniques. These observations provide a starting point for improving current methodologies, thus paving the way to the advances of more accurate approaches for RNA 3D structure prediction

Natural convection heat transfer from a ribbed vertical plate: Effect of rib size, pitch, and truncation

Buoyancy-induced flows over ribbed vertical surfaces involve complex thermal and dynamic interactions between the mainstream and the surface texture, yielding contrasting effects on the heat transfer performance of the heated plate; proper analysis of the overall effect on the heat transfer rate is essential for efficient operation and optimization purposes. The present work pursues an insight into the different factors controlling this problem. Natural convection heat transfer from a vertical plate of 0.5 m height, regularly roughened with wooden transverse square ribs, is experimentally investigated. The surface temperature of the baseplate is varied so that a range of the plate Rayleigh number (Ra) from 3.4 × 108 to 4.9 × 108 is covered. The density of the roughness pattern and the rib pitch-to-height ratio (P/e) are varied by changing the number of ribs attached to the surface (from 10 to 40 rib rows) and using three different square cross-sections (of side lengths 2, 3, or 5 mm). The experimental work relies on the schlieren optical technique, through which the thermal boundary layer is visualized and the Nusselt number distribution is acquired. Analysis of the results reveals that enhancement of the local Nusselt number, relative to a corresponding smooth surface, may be attained only at the central part of the inter-rib region; this occurs exclusively for relatively large values of P/e. At a later stage, the effectiveness of rib truncation in enhancing the heat transfer from the baseplate is explored. Three staggered arrangements are considered, by varying the number of rib segments per row, and heat transfer enhancement, sensitive to the number of rib segments per row, is found. This paper also provides insight into the role of thermal-field disturbances close to turbulent transition, and sheds light on the potential of truncated ribs to amplify such perturbations

Effect of coordinating solvents on the structure of Cu(II)-4,4'-bipyridine coordination polymers

Solvent can play a crucial role in the synthesis of coordination polymers (CPs). Here, this study reports how the coordinating solvent approach (CSA) can be used as an effective tool to control the nature of the final CP. This study exploited the system Cu(II)-4,4 '-bipyridine coupled to different coordinating solvents, such as DMA, DMF and DMSO. This allowed the isolation and structurally characterization of four new CPs: three 2D layered networks and one 1D chain. Moreover, it was evidenced that even adventitious water can play the role of the coordinating solvent in the final CP

A NEW SHORT VERSION OF INTERNET GAMING DISORDER-20: AN EXPLORATORY STRUCTURAL EQUATION MODELING

Objective: The purpose of this paper was to contribute to the psychometric properties and dimensionality of the IGD-20. Method: An online survey was completed by 392 Italian online gamers (Mage = 29.2, SD = 11.3; 45.2% males). A battery of self-report questionnaires was administered to assess internet gaming disorder, internet addiction, loneliness, anxiety, depression, stress, social-interaction anxiety, self-esteem, and perceived social support. To test the factor structure of IGD-20, both traditional (i.e., EFA and CFA) and innovative (i.e., ESEM) techniques were applied. Convergent, concurrent, discriminant, and criterion-related validity were evaluated. Results: Our study revealed the outperforming 3-factor ESEM model (χ2=39.951, p = 0.0021; RMSEA = 0.056, 90% C.I. [0.032 - 0.079]; CFI = 0.986; TLI = 0.965; and SRMR = 0.017; ω = .76, .77, and .79, respectively) as a new short version (IGD- 10SV) for the IGD-20. The validity of the IGD-10SV was supported by significant associations with theoretically related measures. Conclusions: The current findings support the adoption of the analytic ESEM approach for complex multidimensional measures and the use of the IGD-10SV for the assessment of internet gaming disorder

Linear stability, transient energy growth and the role of viscosity stratification in compressible plane Couette flow

Linear stability and the non-modal transient energy growth in compressible plane Couette flow are investigated for two prototype mean flows: (a) the {\it uniform shear} flow with constant viscosity, and (b) the {\it non-uniform shear} flow with {\it stratified} viscosity. Both mean flows are linearly unstable for a range of supersonic Mach numbers ($M$). For a given $M$, the critical Reynolds number ($Re$) is significantly smaller for the uniform shear flow than its non-uniform shear counterpart. An analysis of perturbation energy reveals that the instability is primarily caused by an excess transfer of energy from mean-flow to perturbations. It is shown that the energy-transfer from mean-flow occurs close to the moving top-wall for ``mode I'' instability, whereas it occurs in the bulk of the flow domain for ``mode II''. For the non-modal analysis, it is shown that the maximum amplification of perturbation energy, $G_{\max}$, is significantly larger for the uniform shear case compared to its non-uniform counterpart. For $\alpha=0$, the linear stability operator can be partitioned into ${\cal L}\sim \bar{\cal L} + Re^2{\cal L}_p$, and the $Re$-dependent operator ${\cal L}_p$ is shown to have a negligibly small contribution to perturbation energy which is responsible for the validity of the well-known quadratic-scaling law in uniform shear flow: $G(t/{\it Re}) \sim {\it Re}^2$. A reduced inviscid model has been shown to capture all salient features of transient energy growth of full viscous problem. For both modal and non-modal instability, it is shown that the {\it viscosity-stratification} of the underlying mean flow would lead to a delayed transition in compressible Couette flow

Fitting Corrections to an RNA Force Field Using Experimental Data

Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude

Parasitic infection in the scyphozoan Rhizostoma pulmo (Macri, 1778)

: Very little information is reported for parasites of cnidarians, therefore, the present work aimed to investigate parasitic infections in one of the most widespread jellyfish in the Mediterranean Sea, Rhizostoma pulmo. The goals were to determine prevalence and intensity of parasites in R. pulmo, identify the species involved through morphological and molecular analysis, test whether infection parameters differ in different body parts and in relation to jellyfish size. 58 individuals were collected, 100% of them infected with digenean metacercariae. Intensity varied between 18.7 ± 6.7 per individual in 0-2 cm diameter jellyfish up to 505 ± 50.6 in 14 cm ones. Morphological and molecular analyses suggest that the metacercariae belonged to the family Lepocreadiidae and could be possibly assigned to the genus Clavogalea. Prevalence values of 100% suggest that R. pulmo is an important intermediate host in the life cycle of lepocreadiids in the region. Our findings also support the hypothesis that R. pulmo is an important part in the diet of teleost fish, which are reported as definitive hosts of lepocreadiids, since trophic transmission is necessary for these parasites to complete their life cycles. Parasitological data may therefore be useful to investigate fish-jellyfish predation, integrating traditional methods such as gut contents analysis

Ferroelectric order driven Eu3+ photoluminescence in BaZrxTi1−xO3 perovskite

The ability to tune and enhance the properties of luminescent materials is essential for enlarging their application potential. Recently, the modulation of the photoluminescence emission of lanthanide-doped ferroelectric perovskites by applying an electric field has been reported. Herein, we show that the ferroelectric order and, more generally the polar order, has a direct effect on the photoluminescence of Eu3+ in the model BaZrxTi1-xO3 perovskite even in the absence of an external field. The dipole arrangement evolves with increasing xfrom long-range ferroelectric order to short-range order typical of relaxors until the non-polar paraelectric BaZrO3 is achieved. The cooperative polar interactions existing in the lattice (x < 1) promote the off-center displacement of the Eu3+ ion determining a change of the lanthanide site symmetry and, consequently, an abrupt variation of the photoluminescence emission with temperature. Each type of polar order is characterized by a distinct photoluminescence behaviour