A heterozygous variant in the human cardiac miR-133 gene, MIR133A2, alters miRNA duplex processing and strand abundance

BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Sequential cleavage of miRNA precursors results in a ~22 nucleotide duplex of which one strand, the mature miRNA, is typically loaded into the RNA-induced silencing complex (RISC) while the passenger strand is degraded. Very little is known about how genetic variation might affect miRNA biogenesis and function. RESULTS We re-sequenced the MIR1-1, MIR1-2, MIR133A1, MIR133A2, and MIR133B genes, that encode the cardiac-enriched miRNAs, miR-1 and miR-133, in 120 individuals with familial atrial fibrillation and identified 10 variants, including a novel 79T > C MIR133A2 substitution. This variant lies within the duplex at the 3' end of the mature strand, miR-133a-3p, and is predicted to prevent base-pairing and weaken thermostability at this site, favoring incorporation of the passenger strand, miR-133a-5p, into RISC. Genomic DNA fragments containing miR-133a-2 precursor sequences with 79T and 79C alleles were transfected into HeLa cells. On Northern blotting the 79T allele showed strong expression of miR-133a-3p with weak expression of miR-133a-5p. In contrast, the 79C allele had no effect on miR-133a-3p but there was a significant increase (mean 3.6-fold) in miR-133a-5p levels. Deep sequencing of small RNA libraries prepared from normal human and murine atria confirmed that nearly all the mature miR-133a was comprised of miR-133a-3p and that levels of miR-133a-5p were very low. A number of isomiRs with variations at 5' and 3' ends were identified for both miR-133a-3p and miR-133a-5p, with 2 predominant miR-133a-3p isomiRs and one predominant miR-133a-5p isomiR. Bioinformatics analyses indicate that the major miR-133a-3p and 5p isomiRs have numerous predicted target mRNAs, only a few of which are in common. CONCLUSIONS Multiple miR-133a isomiRs with potential different mRNA target profiles are present in the atrium in humans and mice. We identified a human 79T > C MIR133A2 variant that alters miRNA processing and results in accumulation of the miR-133a-5p strand that is usually degraded

Relative Forage Yield of Intercropped Lucerne (\u3ci\u3eMedicago sativa\u3c/i\u3e L.) And Winter Forage Cereals

In tropical regions of the world intercropping is mainly associated with the production of maize for grain, while in temperate areas it is associated with the efficient production of forage. There is increasing interest in the development of cereal - legume intercropping in some temperate regions (reviewed by Mason & Pritchard, 1987). The aim of this study was to compare the relative forage yield of intercropped lucerne and cereal

General relativity and cosmology derived from principle of maximum power or force

The field equations of general relativity are shown to derive from the existence of a limit force or of a limit power in nature. The limits have the value of c^4/4G and c^5/4G. The proof makes use of a result by Jacobson. All known experimental data is consistent with the limits. Applied to the universe, the limits predict its darkness at night and the observed scale factor. Some experimental tests of the limits are proposed. The main counter-arguments and paradoxes are discussed, such as the transformation under boosts, the force felt at a black hole horizon, the mountain problem, and the contrast to scalar--tensor theories of gravitation. The resolution of the paradoxes also clarifies why the maximum force and the maximum power have remained hidden for so long. The derivation of the field equations shows that the maximum force or power plays the same role for general relativity as the maximum speed plays for special relativity.Comment: 24 pages, 1 figure, LaTeX, published versio

Hypothesis of path integral duality: Applications to QED

We use the modified propagator for quantum field based on a ``principle of path integral duality" proposed earlier in a paper by Padmanabhan to investigate several results in QED. This procedure modifies the Feynman propagator by the introduction of a fundamental length scale. We use this modified propagator for the Dirac particles to evaluate the first order radiative corrections in QED. We find that the extra factor of the modified propagator acts like a regulator at the Planck scales thereby removing the divergences that otherwise appear in the conventional radiative correction calculations of QED. We find that:(i) all the three renormalisation factors $Z_1$, $Z_2$, and $Z_3$ pick up finite corrections and (ii) the modified propagator breaks the gauge invariance at a very small level of ${\mathcal{O}}(10^{-45})$. The implications of this result to generation of the primordial seed magnetic fields are discussed.Comment: 15 pages, LaTeX2e (uses ijmpd.sty); To appear in IJMP-D; References adde

Scattering of Gravitational Waves by the Weak Gravitational Fields of Lens Objects

We consider the scattering of the gravitational waves by the weak gravitational fields of lens objects. We obtain the scattered gravitational waveform by treating the gravitational potential of the lens to first order, i.e. using the Born approximation. We find that the effect of scattering on the waveform is roughly given by the Schwarzschild radius of the lens divided by the wavelength of gravitational wave for a compact lens object. If the lenses are smoothly distributed, the effect of scattering is of the order of the convergence field $\kappa$ along the line of sight to the source. In the short wavelength limit, the amplitude is magnified by $1+\kappa$, which is consistent with the result in weak gravitational lensing.Comment: 4 pages, 2 figures, A&A Letters, in press, minor changes, references adde

Tillage Systems in the Establishment of Pastures in Argentinian Subhumid Area

The effect of three tillage systems on the number of plants produced and forage production of a pasture the first year of establishment was assessed in this experiment. The components of the pasture were alfalfa (Medicago sativa L.), tall fescue (Festuca arundinacea Shreb), orchard grass (Dactilys glomerata L), and prairie grass (Bromus unioloides). Treatments were three tillage systems: conventional tillage (CT), reduced tillage (RT), and direct sowing (DS). Sowing was performed with (NI) and without fertilizers (N0) in each treatment. A split-plot experimental design with two repetitions was used, with tillage being the main factor and the fertilization levels the secondary one. Results were subjected to ANOVA while means were compared by the Duncan Test Counts. These were conducted 90 days after sowing to determine the number of emerged alfalfa and grass seedlings. In November, before starting direct grazing, hand cut samples were taken to determine total biomass and also biomass production of each component of the pasture. Total stand plant and grass stand, was significantly affected (P \u3c 0.05) by the tillage factor. Forage production of both alfalfa and grass, and total production was higher with conventional tillage (CT) and differed significantly (P \u3c 0.05) from direct sowing (DS). The fertilizing effect and its interaction with the tillage factor was not statistically significant (P \u3c 0.05) for any of the components measured. Results indicate that direct sowing seems to condition grass plant stand and forage production of each of the pasture components in the year of establishment

Gravitational coupling to two-particle bound states and momentum conservation in deep inelastic scattering

The momentum conservation sum rule for deep inelastic scattering (DIS) from composite particles is investigated using the general theory of relativity. For two 1+1 dimensional examples, it shown that covariant theories automatically satisy the DIS momentum conservation sum rule provided the bound state is covariantilly normalized. Therefore, in these cases the two DIS sum rules for baryon conservation and momentum conservation are equivalent

Bohmian Quantum Gravity in the Linear Field Approximation

In this paper we have applied Bohmian quantum theory to the linear field approximation of gravity and present a self--consistent quantum gravity theory in the linear field approximation. The theory is then applied to some specific problems, the Newtonian limit, and the static spherically symmetric solution. Some observable effects of the theory are investigated

Photons and Gravitons as Goldstone Bosons, and the Cosmological Constant

We reexamine a scenario in which photons and gravitons arise as Goldstone bosons associated with the spontaneous breaking of Lorentz invariance. We study the emergence of Lorentz invariant low energy physics in an effective field theory framework, with non-Lorentz invariant effects arising from radiative corrections and higher order interactions. Spontaneous breaking of the Lorentz group also leads to additional exotic but weakly coupled Goldstone bosons, whose dispersion relations we compute. The usual cosmological constant problem is absent in this context: being a Goldstone boson, the graviton can never develop a potential, and the existence of a flat spacetime solution to the field equations is guaranteed.Comment: 21 pages, harvma