2,706 research outputs found
From principal component to direct coupling analysis of coevolution in proteins: Low-eigenvalue modes are needed for structure prediction
Various approaches have explored the covariation of residues in
multiple-sequence alignments of homologous proteins to extract functional and
structural information. Among those are principal component analysis (PCA),
which identifies the most correlated groups of residues, and direct coupling
analysis (DCA), a global inference method based on the maximum entropy
principle, which aims at predicting residue-residue contacts. In this paper,
inspired by the statistical physics of disordered systems, we introduce the
Hopfield-Potts model to naturally interpolate between these two approaches. The
Hopfield-Potts model allows us to identify relevant 'patterns' of residues from
the knowledge of the eigenmodes and eigenvalues of the residue-residue
correlation matrix. We show how the computation of such statistical patterns
makes it possible to accurately predict residue-residue contacts with a much
smaller number of parameters than DCA. This dimensional reduction allows us to
avoid overfitting and to extract contact information from multiple-sequence
alignments of reduced size. In addition, we show that low-eigenvalue
correlation modes, discarded by PCA, are important to recover structural
information: the corresponding patterns are highly localized, that is, they are
concentrated in few sites, which we find to be in close contact in the
three-dimensional protein fold.Comment: Supporting information can be downloaded from:
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.100317
Photoswitchable catalysis by a nanozyme mediated by a lightsensitive cofactor
The activity of a gold nanoparticle-based
catalyst can be reversibly up- and down-regulated by light.
Light is used to switch a small molecule between cis- and
trans-isomers, which inhibits the catalytic activity of the
nanoparticles to different extent. The system is functional
in aqueous buffer, which paves the way for integrating the
system in biological networks
Inverse Statistical Physics of Protein Sequences: A Key Issues Review
In the course of evolution, proteins undergo important changes in their amino
acid sequences, while their three-dimensional folded structure and their
biological function remain remarkably conserved. Thanks to modern sequencing
techniques, sequence data accumulate at unprecedented pace. This provides large
sets of so-called homologous, i.e.~evolutionarily related protein sequences, to
which methods of inverse statistical physics can be applied. Using sequence
data as the basis for the inference of Boltzmann distributions from samples of
microscopic configurations or observables, it is possible to extract
information about evolutionary constraints and thus protein function and
structure. Here we give an overview over some biologically important questions,
and how statistical-mechanics inspired modeling approaches can help to answer
them. Finally, we discuss some open questions, which we expect to be addressed
over the next years.Comment: 18 pages, 7 figure
Beltanelliformis brunsae Menner in Keller et al., 1974: an undoubted Ediacaran fossil from Neoproterozoic of Dobrogea (Romania)
International audienceEdiacaran fossils are now largely known in different parts of the world. However, some countries are poorly documented on these remains of a still enigmatic life. Thus, rare fossils from the Neoproterozoic Histria Formation of central Dobrogea (Romania) have been reported. Two specimens with discoid imprints are described here in detail and assigned to the typical Ediacaran species Beltanelliformis brunsae Menner in Keller et al., 1974. This paleontological development confirms both the large geographical distribution of this species and the Ediacaran age of the Histria Formation. KEY WORDS Flat discoid imprints, Ediacaran biota, Precambrian, Dobrogea, Romania. RĂSUMĂLes fossiles Ă©diacariens sont maintenant largement connus Ă travers le monde. Cepednant, certaines rĂ©gions restent peu documentĂ©es sur ces restes, tĂ©moignages dâune vie qui apparaĂźt encore aujourdâhui assez Ă©nigmatique. Ainsi, seuls de rares fossiles provenant de la Formation Histria du NĂ©oprotĂ©rozoĂŻque de Dobrogea centrale (Roumanie) avaient Ă©tĂ© signalĂ©s. Deux Ă©chantillons portant des impressions discoĂŻdes sont ici dĂ©crits en dĂ©tail et attribuĂ©s Ă lâespĂšce typiquement Ă©diacarienne Beltanelliformis brunsae Menner in Keller et al., 1974. Cette identification permet de confirmer la large rĂ©partition de cette espĂšce et lâĂąge Ă©diacarien de la Formation Histria
Free-Riding in Pharmaceutical Price Regulation: Theory and Evidence
We present a model of the strategic interaction among authorities regulating pharmaceutical prices in different countries and the R&D investment decisions of pharmaceutical firms. Regulatorsâ decisions affect consumer surplus directly, via prices, and indirectly via firmsâ profits and R&D investment policies, which in turn affect patient health. The positive externality of a price increase in one country provides an incentive for other countries to free-ride, and we show how country-level characteristics affect optimal pricing decisions and equilibria. Our theoretical predictions are tested using price data for a set of 70 cancer drugs in 25 OECD countries. We find evidence of behaviour that is consistent with the free-riding hypothesis and which, in line with the theoretical predictions, differs according to country-level characteristics. Countries with comparatively large market shares tend to react to increases in other countriesâ prices by lowering their own prices; in countries with comparatively small market shares, regulatorsâ decisions are consistent with the objective of introducing the product at as low a price as possible. We discuss the policy implications of our results for incentivising global pharmaceutical R&D and the recent proposal to move towards a joint pharmaceutical procurement process at the European level
On the Structure of the Lower Troposphere in the Summertime Stratocumulus Regime of the Northeast Pacific
Data collected in situ as part of the second field study of the Dynamics and Chemistry of Marine Stratocumulus field program are used to evaluate the state of the atmosphere in the region of field operations near 30°N, 120°W during July 2001, as well as its representation by a variety of routinely available data. The routine data include both the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) and NCEPâNCAR reanalyses, forecasts from their respective forecast systems (the Integrated and Global Forecast Systems), the 30-km archive from the International Satellite Cloud Climatology Project (ISCCP), the Quick Scatterometer surface winds, and remotely sensed fields derived from radiances measured by the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI), the Advanced Microwave Sounding Unit, and the Advanced Very High Resolution Radiometer. The analysis shows that outside of the boundary layer the state of the lower troposphere is reasonably represented by the reanalysis and forecast products, with the caveat of a slight warm bias at 850 hPa in the NCEPâNCAR products. Within the planetary boundary layer (PBL) the agreement is not as good: both the boundary layer depth and cloud amount are underpredicted, and the boundary layer temperature correlates poorly with the available data, which may be related to a poor representation of SSTs in this region of persistent cloud cover. ERA-40 also suffers from persistently weak zonal winds within the PBL. Among the satellite records the ISCCP data are found to be especially valuable, evincing skill in both predicting boundary layer depth (from cloud-top temperatures and TMI surface temperatures) and cloud liquid water paths (from cloud optical depths). An analysis of interannual variability (among Julys) based on ERA-40 and the 1983â2001 ISCCP record suggests that thermodynamic quantities show similar interannual and synoptic variability, principally concentrated just above the PBL, while dynamic quantities vary much more on synoptic time scales. Furthermore, the analysis suggests that the correlation between stratocumulus cloud amount and lower-tropospheric stability exhibits considerable spatial structure and is less pronounced than previously thought
Nine-amino-acid transactivation domain: Establishment and prediction utilities
AbstractHere we describe the establishment and prediction utilities for a novel nine-amino-acid transactivation domain, 9aa TAD, that is common to the transactivation domains of a large number of yeast and animal transcription factors. We show that the 9aa TAD motif is required for the function of the transactivation domain of Gal4 and the related transcription factors Oaf1 and Pip2. The 9aa TAD possesses an autonomous transactivation activity in yeast and mammalian cells. Using sequence alignment and experimental data we derived a pattern that can be used for 9aa TAD prediction. The pattern allows the identification of 9aa TAD in other Gal4 family members or unrelated yeast, animal, and viral transcription factors. Thus, the 9aa TAD represents the smallest known denominator for a broad range of transcription factors. The wide occurrence of the 9aa TAD suggests that this domain mediates conserved interactions with general transcriptional cofactors. A computational search for the 9aa TAD is available online from National EMBnet-Node Austria at http://www.at.embnet.org/toolbox/9aatad/
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