Force-induced misfolding in RNA

RNA folding is a kinetic process governed by the competition of a large number of structures stabilized by the transient formation of base pairs that may induce complex folding pathways and the formation of misfolded structures. Despite of its importance in modern biophysics, the current understanding of RNA folding kinetics is limited by the complex interplay between the weak base-pair interactions that stabilize the native structure and the disordering effect of thermal forces. The possibility of mechanically pulling individual molecules offers a new perspective to understand the folding of nucleic acids. Here we investigate the folding and misfolding mechanism in RNA secondary structures pulled by mechanical forces. We introduce a model based on the identification of the minimal set of structures that reproduce the patterns of force-extension curves obtained in single molecule experiments. The model requires only two fitting parameters: the attempt frequency at the level of individual base pairs and a parameter associated to a free energy correction that accounts for the configurational entropy of an exponentially large number of neglected secondary structures. We apply the model to interpret results recently obtained in pulling experiments in the three-helix junction S15 RNA molecule (RNAS15). We show that RNAS15 undergoes force-induced misfolding where force favors the formation of a stable non-native hairpin. The model reproduces the pattern of unfolding and refolding force-extension curves, the distribution of breakage forces and the misfolding probability obtained in the experiments.Comment: 28 pages, 11 figure

Unifying thermodynamic and kinetic descriptions of single-molecule processes: RNA unfolding under tension

We use mesoscopic non-equilibrium thermodynamics theory to describe RNA unfolding under tension. The theory introduces reaction coordinates, characterizing a continuum of states for each bond in the molecule. The unfolding considered is so slow that one can assume local equilibrium in the space of the reaction coordinates. In the quasi-stationary limit of high sequential barriers, our theory yields the master equation of a recently proposed sequential-step model. Non-linear switching kinetics is found between open and closed states. Our theory unifies the thermodynamic and kinetic descriptions and offers a systematic procedure to characterize the dynamics of the unfolding processComment: 13 pages, 3 figure

TRACE ELEMENTS IN SHEEP AND GOATS REPRODUCTION: A REVIEW

The reproduction of small ruminants like goats and sheep managed under extensive range grazing conditions can be affected by nutrients availability and especially by the mineral content of the forages resources on the rangeland. It has been particularly demonstrated that trace elements can have equally, beneficial or detrimental effects, depending on its balance, on reproductive functions in small ruminants. Trace elements as copper, molybdenum, selenium and zinc play key role on the metabolism of carbohydrates, proteins and lipids; however, the mode of action by which these elements affect reproduction in sheep and goats are not completely understood, due to the complexity in the mode of action of the metallobiomolecules and the neuro-hormonal relationship. In this way, their absence or presence of these minerals in several organs, fluids, or tissues of the reproductive tract have allowed obtaining information on the metabolism and the role of these elements on reproduction in sheep and goats. On this regard, the objective of this document is to review the relationships and effects of some trace elements, on reproductive events in sheep and goats

Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding

Ribosome is a molecular machine that polymerizes a protein where the sequence of the amino acid residues, the monomers of the protein, is dictated by the sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that serves as the template. The ribosome is a molecular motor that utilizes the template mRNA strand also as the track. Thus, in each step the ribosome moves forward by one codon and, simultaneously, elongates the protein by one amino acid. We present a theoretical model that captures most of the main steps in the mechano-chemical cycle of a ribosome. The stochastic movement of the ribosome consists of an alternating sequence of pause and translocation; the sum of the durations of a pause and the following translocation is the time of dwell of the ribosome at the corresponding codon. We derive the analytical expression for the distribution of the dwell times of a ribosome in our model. Whereever experimental data are available, our theoretical predictions are consistent with those results. We suggest appropriate experiments to test the new predictions of our model, particularly, the effects of the quality control mechanism of the ribosome and that of their crowding on the mRNA track.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at DOI:10.1088/1478-3975/8/2/02600

EFFECT OF SEASON ON SERUM COPPER AND ZINC CONCENTRATIONS IN CROSSBRED GOATS HAVING DIFFERENT REPRODUCTIVE STATUS UNDER SEMIARID RANGELAND CONDITIONS IN SOUTHERN MEXICO STATE

The effect of season (rainy: RS, and dry: DS) and reproductive status on copper (Cu) and zinc (Zn) concentrations in blood serum of crossbred goats (BW= 36.01 ± 1.59 kg) were studied under semiarid rangeland conditions in Southern Mexico State. Blood samples from 80 crossbred goats were taken each season (RS and DS). The goats were clustered into 10 different groups considering their reproductive status. Concentrations of Cu and Zn in serum were assayed using atomic absorption. Data were analyzed using a general linear model procedure for a completely randomized design and differences among means were examined using a Tukey test. Blood serum concentrations of Cu and Zn were affected by reproductive status and season (P<0.001). In relation to the season, Cu and Zn serum levels were lower in RS than DS (P<0.05). Overall, kidded goats had the highest values (P<0.01) for Cu than other animals in both seasons (RS or DS). Anestrous goats had the lowest concentrations (P<0.01) for Zn during RS, while all goats at their second or more kidding, rearing single or twins, showed the highest concentrations of Zn (P<0.001) in this season. Adult goats in Southern Mexico State showed a deficiency of Cu and Zn, especially during RS. As such, mineral supplements should be provided with respect to these elements in feeding systems for goats under semiarid rangeland conditions in order to evaluate their impact on health and reproduction

A refined protocol for calculating air flow rate of naturally ventilated broiler barns based on CO2 mass balance

This study was conducted to evaluate relatively simple protocols for monitoring ventilation rate (VR) in naturally-ventilated barns (NVB). The test protocols were first applied to a mechanically-ventilated broiler barn (MVB), where VR was estimated more accurately and then were used to calculate VR in the NVB. CO2 concentrations were measured with two different sampling schemes: (S1) the average of indoor measurements along the length of the building at two heights of 0.5 m and 1.5 m from the litter floor; and (S2) same as previous but with concentration measurements taken only at 0.5 m from litter. The dynamic metabolic CO2 production rate of the birds was predicted with two different algorithms: (A1) remaining constant throughout the dark and light periods, and (A2) varying with animal activity on an hourly basis. The results demonstrated that the combination of S2 with A1 or A2 yielded the best estimate of building VR in the NVB

Zero Temperature Properties of RNA Secondary Structures

We analyze different microscopic RNA models at zero temperature. We discuss both the most simple model, that suffers a large degeneracy of the ground state, and models in which the degeneracy has been remove, in a more or less severe manner. We calculate low-energy density of states using a coupling perturbing method, where the ground state of a modified Hamiltonian, that repels the original ground state, is determined. We evaluate scaling exponents starting from measurements of overlaps and energy differences. In the case of models without accidental degeneracy of the ground state we are able to clearly establish the existence of a glassy phase with $\theta \simeq 1/3$.Comment: 20 pages including 9 eps figure

Aerodynamics of aero-engine installation

This paper describes current progress in the development of methods to assess aero-engine airframe installation effects. The aerodynamic characteristics of isolated intakes, a typical transonic transport aircraft as well as a combination of a through-flow nacelle and aircraft configuration have been evaluated. The validation task for an isolated engine nacelle is carried out with concern for the accuracy in the assessment of intake performance descriptors such as mass flow capture ratio and drag rise Mach number. The necessary mesh and modelling requirements to simulate the nacelle aerodynamics are determined. Furthermore, the validation of the numerical model for the aircraft is performed as an extension of work that has been carried out under previous drag prediction research programmes. The validation of the aircraft model has been extended to include the geometry with through flow nacelles. Finally, the assessment of the mutual impact of the through flow nacelle and aircraft aerodynamics was performed. The drag and lift coefficient breakdown has been presented in order to identify the component sources of the drag associated with the engine installation. The paper concludes with an assessment of installation drag for through-flow nacelles and the determination of aerodynamic interference between the nacelle and the aircraft