1,056 research outputs found
The PETfold and PETcofold web servers for intra- and intermolecular structures of multiple RNA sequences
The function of non-coding RNA genes largely depends on their secondary structure and the interaction with other molecules. Thus, an accurate prediction of secondary structure and RNA–RNA interaction is essential for the understanding of biological roles and pathways associated with a specific RNA gene. We present web servers to analyze multiple RNA sequences for common RNA structure and for RNA interaction sites. The web servers are based on the recent PET (Probabilistic Evolutionary and Thermodynamic) models PETfold and PETcofold, but add user friendly features ranging from a graphical layer to interactive usage of the predictors. Additionally, the web servers provide direct access to annotated RNA alignments, such as the Rfam 10.0 database and multiple alignments of 16 vertebrate genomes with human. The web servers are freely available at: http://rth.dk/resources/petfold
DotAligner:Identification and clustering of RNA structure motifs
Abstract The diversity of processed transcripts in eukaryotic genomes poses a challenge for the classification of their biological functions. Sparse sequence conservation in non-coding sequences and the unreliable nature of RNA structure predictions further exacerbate this conundrum. Here, we describe a computational method, DotAligner, for the unsupervised discovery and classification of homologous RNA structure motifs from a set of sequences of interest. Our approach outperforms comparable algorithms at clustering known RNA structure families, both in speed and accuracy. It identifies clusters of known and novel structure motifs from ENCODE immunoprecipitation data for 44 RNA-binding proteins
Cardiac cell modelling: Observations from the heart of the cardiac physiome project
In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field
Mapping QGP properties in Pb--Pb and Xe--Xe collisions at the LHC
A phenomenological analysis of the experimental measurements of transverse
momentum spectra of identified charged hadrons and strange hyperons in \PbPb
and \XeXe collisions at the LHC is presented. The analysis is based on the
relativistic fluid dynamics description implemented in the numerically
efficient \fluidum approach. Building on our previous work, we separate in our
treatment the chemical and kinetic freeze-out, and incorporate the partial
chemical equilibrium to describe the late stages of the collision evolution.
This analysis makes use of Bayesian inference to determine key parameters of
the QGP evolution and its properties including the shear and bulk viscosity to
entropy ratios, the initialisation time, the initial entropy density, and the
freeze-out temperatures. The physics parameters and their posterior
probabilities are extracted using a global search in multidimensional space
with modern machine learning tools, such as ensembles of neural networks. We
employ our newly developed fast framework to assess systematic uncertainties in
the extracted model parameters by systematically varying key components of our
analysis.Comment: 17 pages, 7 figure
Root cortex development is fine-tuned by the interplay of MIGs, SCL3 and DELLAs during arbuscular mycorrhizal symbiosis
Root development is a crucial process that determines the ability of plants to acquire nutrients, adapt to the substrate and withstand changing environmental conditions. Root plasticity is controlled by a plethora of transcriptional regulators that allow, in contrast to tissue development in animals, post-embryonic changes that give rise to new tissue and specialized cells.
One of these changes is the accommodation in the cortex of hyperbranched hyphae of symbiotic arbuscular mycorrhizal (AM) fungi, called arbuscules. Arbuscule-containing cells undergo massive reprogramming to coordinate developmental changes with transport processes.
Here we describe a novel negative regulator of arbuscule development, MIG3. MIG3 induces and interacts with SCL3, both of which modulate the activity of the central regulator DELLA, restraining cortical cell growth. As in a tug-of-war, MIG3-SCL3 antagonizes the function of the complex MIG1-DELLA, which promotes the cell expansion required for arbuscule development, adjusting cell size during the dynamic processes of the arbuscule life cycle.
Our results in the legume plant Medicago truncatula advance the knowledge of root development in dicot plants, showing the existence of additional regulatory elements not present in Arabidopsis that fine-tune the activity of conserved central modules
Thin film evolution equations from (evaporating) dewetting liquid layers to epitaxial growth
In the present contribution we review basic mathematical results for three
physical systems involving self-organising solid or liquid films at solid
surfaces. The films may undergo a structuring process by dewetting,
evaporation/condensation or epitaxial growth, respectively. We highlight
similarities and differences of the three systems based on the observation that
in certain limits all of them may be described using models of similar form,
i.e., time evolution equations for the film thickness profile. Those equations
represent gradient dynamics characterized by mobility functions and an
underlying energy functional.
Two basic steps of mathematical analysis are used to compare the different
system. First, we discuss the linear stability of homogeneous steady states,
i.e., flat films; and second the systematics of non-trivial steady states,
i.e., drop/hole states for dewetting films and quantum dot states in epitaxial
growth, respectively. Our aim is to illustrate that the underlying solution
structure might be very complex as in the case of epitaxial growth but can be
better understood when comparing to the much simpler results for the dewetting
liquid film. We furthermore show that the numerical continuation techniques
employed can shed some light on this structure in a more convenient way than
time-stepping methods.
Finally we discuss that the usage of the employed general formulation does
not only relate seemingly not related physical systems mathematically, but does
as well allow to discuss model extensions in a more unified way
Am J Hum Genet
Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development
Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C
Growth and differentiation factor 5 (GDF5) plays a central role in bone and cartilage development by regulating the proliferation and differentiation of chondrogenic tissue. GDF5 is synthesized as a preproprotein. The biological function of the proregion comprising 354 residues is undefined. We identified two families with a heterozygosity for the novel missense mutations p.T201P or p.L263P located in the proregion of GDF5. The patients presented with dominant brachydactyly type C characterized by the shortening of skeletal elements in the distal extremities. Both mutations gave rise to decreased biological activity in in vitro analyses. The variants reduced the GDF5-induced activation of SMAD signaling by the GDF5 receptors BMPR1A and BMPR1B. Ectopic expression in micromass cultures yielded relatively low protein levels of the variants and showed diminished chondrogenic activity as compared to wild-type GDF5. Interestingly, stimulation of micromass cells with recombinant human proGDF5(T201P) and proGDF5(L263P) revealed their reduced chondrogenic potential compared to the wild-type protein. Limited proteolysis of the mutant recombinant proproteins resulted in a fragment pattern profoundly different from wild-type proGDF5. Modeling of a part of the GDF5 proregion into the known three-dimensional structure of TGFbeta1 latency-associated peptide revealed that the homologous positions of both mutations are conserved regions that may be important for the folding of the mature protein or the assembly of dimeric protein complexes. We hypothesize that the missense mutations p.T201P and p.L263P interfere with the protein structure and thereby reduce the amount of fully processed, biologically active GDF5, finally causing the clinical loss of function phenotype
Diffusive and ballistic current spin-polarization in magnetron-sputtered L1o-ordered epitaxial FePt
We report on the structural, magnetic, and electron transport properties of a
L1o-ordered epitaxial iron-platinum alloy layer fabricated by
magnetron-sputtering on a MgO(001) substrate. The film studied displayed a long
range chemical order parameter of S~0.90, and hence has a very strong
perpendicular magnetic anisotropy. In the diffusive electron transport regime,
for temperatures ranging from 2 K to 258 K, we found hysteresis in the
magnetoresistance mainly due to electron scattering from magnetic domain walls.
At 2 K, we observed an overall domain wall magnetoresistance of about 0.5 %. By
evaluating the spin current asymmetry alpha = sigma_up / sigma_down, we were
able to estimate the diffusive spin current polarization. At all temperatures
ranging from 2 K to 258 K, we found a diffusive spin current polarization of >
80%. To study the ballistic transport regime, we have performed point-contact
Andreev-reflection measurements at 4.2 K. We obtained a value for the ballistic
current spin polarization of ~42% (which compares very well with that of a
polycrystalline thin film of elemental Fe). We attribute the discrepancy to a
difference in the characteristic scattering times for oppositely spin-polarized
electrons, such scattering times influencing the diffusive but not the
ballistic current spin polarization.Comment: 22 pages, 13 figure
Dewetting of thin polymer films near the glass transition
Dewetting of ultra-thin polymer films near the glass transition exhibits
unexpected front morphologies [G. Reiter, Phys. Rev. Lett., 87, 186101 (2001)].
We present here the first theoretical attempt to understand these features,
focusing on the shear-thinning behaviour of these films. We analyse the profile
of the dewetting film, and characterize the time evolution of the dry region
radius, , and of the rim height, . After a transient time
depending on the initial thickness, grows like while
increases like . Different regimes of growth are
expected, depending on the initial film thickness and experimental time range.Comment: 4 pages, 5 figures Revised version, published in Physical Review
Letters: F. Saulnier, E. Raphael and P.-G. de Gennes, Phys. Rev. Lett. 88,
196101 (2002
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