1,283 research outputs found
An automatic method for assessing structural importance of amino acid positions
Background: A great deal is known about the qualitative aspects of the sequence-structure relationship, for example that buried residues are usually more conserved between structurally similar homologues, but no attempts have been made to quantitate the relationship between evolutionary conservation at a sequence position and change to global tertiary structure. In this paper we demonstrate that the Spearman correlation between sequence and structural change is suitable for this purpose.
Results:
Buried residues, bends, cysteines, prolines and leucines were significantly more likely to occupy positions highly correlated with structural change than expected by chance. Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.
Conclusion:
The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines. A PERL script which implements the method is provided
Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data
Background:
Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins.
Results:
In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed.
Conclusions:
Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function
185 CAN WE PREDICT RESPONDERS TO LATERAL WEDGE INSOLES IN PATIENTS WITH MEDIAL KNEE OSTEOARTHRITIS?
Unary Pushdown Automata and Straight-Line Programs
We consider decision problems for deterministic pushdown automata over a
unary alphabet (udpda, for short). Udpda are a simple computation model that
accept exactly the unary regular languages, but can be exponentially more
succinct than finite-state automata. We complete the complexity landscape for
udpda by showing that emptiness (and thus universality) is P-hard, equivalence
and compressed membership problems are P-complete, and inclusion is
coNP-complete. Our upper bounds are based on a translation theorem between
udpda and straight-line programs over the binary alphabet (SLPs). We show that
the characteristic sequence of any udpda can be represented as a pair of
SLPs---one for the prefix, one for the lasso---that have size linear in the
size of the udpda and can be computed in polynomial time. Hence, decision
problems on udpda are reduced to decision problems on SLPs. Conversely, any SLP
can be converted in logarithmic space into a udpda, and this forms the basis
for our lower bound proofs. We show coNP-hardness of the ordered matching
problem for SLPs, from which we derive coNP-hardness for inclusion. In
addition, we complete the complexity landscape for unary nondeterministic
pushdown automata by showing that the universality problem is -hard, using a new class of integer expressions. Our techniques have
applications beyond udpda. We show that our results imply -completeness for a natural fragment of Presburger arithmetic and coNP lower
bounds for compressed matching problems with one-character wildcards
ISPIDER Central: an integrated database web-server for proteomics
Despite the growing volumes of proteomic data, integration of the underlying results remains problematic owing to differences in formats, data captured, protein accessions and services available from the individual repositories. To address this, we present the ISPIDER Central Proteomic Database search (http://www.ispider.manchester.ac.uk/cgi-bin/ProteomicSearch.pl), an integration service offering novel search capabilities over leading, mature, proteomic repositories including PRoteomics IDEntifications database (PRIDE), PepSeeker, PeptideAtlas and the Global Proteome Machine. It enables users to search for proteins and peptides that have been characterised in mass spectrometry-based proteomics experiments from different groups, stored in different databases, and view the collated results with specialist viewers/clients. In order to overcome limitations imposed by the great variability in protein accessions used by individual laboratories, the European Bioinformatics Institute's Protein Identifier Cross-Reference (PICR) service is used to resolve accessions from different sequence repositories. Custom-built clients allow users to view peptide/protein identifications in different contexts from multiple experiments and repositories, as well as integration with the Dasty2 client supporting any annotations available from Distributed Annotation System servers. Further information on the protein hits may also be added via external web services able to take a protein as input. This web server offers the first truly integrated access to proteomics repositories and provides a unique service to biologists interested in mass spectrometry-based proteomics
Spillover of a tobamovirus from the Australian indigenous flora to invasive weeds
The tobamovirus yellow tailflower mild mottle virus (YTMMV) was previously reported in wild plants of Anthocercis species (family Solanaceae) and other solanaceous indigenous species growing in natural habitats in Western Australia. Here, we undertook a survey of two introduced solanaceous weeds, namely Solanum nigrum (black nightshade) and Physalis peruviana (cape gooseberry) in the Perth metropolitan area and surrounds to determine if YTMMV has spread naturally to these species. At a remnant natural bushland site where both solanaceous weeds and indigenous Anthocercis hosts grew adjacent to one another, a proportion of S. nigrum and P. peruviana plants were asymptomatically-infected with YTMMV, confirming spillover had occurred. Populations of S. nigrum also grow as weeds in parts of the city isolated from remnant bushland and indigenous sources of YTMMV, and some of these populations were also infected with YTMMV. Fruit was harvested from virus-infected wild S. nigrum plants and the seed germinated under controlled conditions. Up to 80% of resultant seedlings derived from infected parent plants were infected with YTMMV, confirming that the virus is vertically-transmitted in S. nigrum, and therefore infection appears to be self-sustaining in this species. This is the first report of spillover of YTMMV to exotic weeds, and of vertical transmission of this tobamovirus. We discuss the roles of vertical and horizontal transmission in this spillover event, and its implications for biosecurity
Hyperbolic phase and squeeze-parameter estimation
We define a new representation, the hyperbolic phase representation, which enables optimal estimation of a squeeze parameter in the sense of quantum estimation theory. We compare the signal-to-noise ratio for such measurements, with conventional measurement based on photon counting and homodyne detection. The signal-to-noise ratio for hyperbolic phase measurements is shown to increase quadratically with the squeezing parameter for fixed input power
Electromagnetic transitions of the helium atom in superstrong magnetic fields
We investigate the electromagnetic transition probabilities for the helium
atom embedded in a superstrong magnetic field taking into account the finite
nuclear mass. We address the regime \gamma=100-10000 a.u. studying several
excited states for each symmetry, i.e. for the magnetic quantum numbers
0,-1,-2,-3, positive and negative z parity and singlet and triplet symmetry.
The oscillator strengths as a function of the magnetic field, and in particular
the influence of the finite nuclear mass on the oscillator strengths are shown
and analyzed.Comment: 10 pages, 8 figure
Complementary approaches to understanding the plant circadian clock
Circadian clocks are oscillatory genetic networks that help organisms adapt
to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri
is the simplest plant clock discovered so far. Its many advantages as an
experimental system facilitate the testing of computational predictions.
We present a model of the Ostreococcus clock in the stochastic process
algebra Bio-PEPA and exploit its mapping to different analysis techniques, such
as ordinary differential equations, stochastic simulation algorithms and
model-checking. The small number of molecules reported for this system tests
the limits of the continuous approximation underlying differential equations.
We investigate the difference between continuous-deterministic and
discrete-stochastic approaches. Stochastic simulation and model-checking allow
us to formulate new hypotheses on the system behaviour, such as the presence of
self-sustained oscillations in single cells under constant light conditions.
We investigate how to model the timing of dawn and dusk in the context of
model-checking, which we use to compute how the probability distributions of
key biochemical species change over time. These show that the relative
variation in expression level is smallest at the time of peak expression,
making peak time an optimal experimental phase marker. Building on these
analyses, we use approaches from evolutionary systems biology to investigate
how changes in the rate of mRNA degradation impacts the phase of a key protein
likely to affect fitness. We explore how robust this circadian clock is towards
such potential mutational changes in its underlying biochemistry. Our work
shows that multiple approaches lead to a more complete understanding of the
clock
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