Predicting Transcription Factor Specificity with All-Atom Models

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites, rather than an ab initio approach. Here, we examine the possibility of using structure-based energy calculations that require no knowledge of bound sites but rather start with the structure of a protein-DNA complex. We study the PurR E. coli TF, and explore to which extent atomistic models of protein-DNA complexes can be used to distinguish between cognate and non-cognate DNA sites. Particular emphasis is placed on systematic evaluation of this approach by comparing its performance with bioinformatic methods, by testing it against random decoys and sites of homologous TFs. We also examine a set of experimental mutations in both DNA and the protein. Using our explicit estimates of energy, we show that the specificity for PurR is dominated by direct protein-DNA interactions, and weakly influenced by bending of DNA.Comment: 26 pages, 3 figure

Present and LGM permafrost from climate simulations : contribution of statistical downscaling

We quantify the agreement between permafrost distributions from PMIP2 (Paleoclimate Modeling Intercomparison Project) climate models and permafrost data. We evaluate the ability of several climate models to represent permafrost and assess the variability between their results. <br><br> Studying a heterogeneous variable such as permafrost implies conducting analysis at a smaller spatial scale compared with climate models resolution. Our approach consists of applying statistical downscaling methods (SDMs) on large- or regional-scale atmospheric variables provided by climate models, leading to local-scale permafrost modelling. Among the SDMs, we first choose a transfer function approach based on Generalized Additive Models (GAMs) to produce high-resolution climatology of air temperature at the surface. Then we define permafrost distribution over Eurasia by air temperature conditions. In a first validation step on present climate (CTRL period), this method shows some limitations with non-systematic improvements in comparison with the large-scale fields. <br><br> So, we develop an alternative method of statistical downscaling based on a Multinomial Logistic GAM (ML-GAM), which directly predicts the occurrence probabilities of local-scale permafrost. The obtained permafrost distributions appear in a better agreement with CTRL data. In average for the nine PMIP2 models, we measure a global agreement with CTRL permafrost data that is better when using ML-GAM than when applying the GAM method with air temperature conditions. In both cases, the provided local information reduces the variability between climate models results. This also confirms that a simple relationship between permafrost and the air temperature only is not always sufficient to represent local-scale permafrost. <br><br> Finally, we apply each method on a very different climate, the Last Glacial Maximum (LGM) time period, in order to quantify the ability of climate models to represent LGM permafrost. The prediction of the SDMs (GAM and ML-GAM) is not significantly in better agreement with LGM permafrost data than large-scale fields. At the LGM, both methods do not reduce the variability between climate models results. We show that LGM permafrost distribution from climate models strongly depends on large-scale air temperature at the surface. LGM simulations from climate models lead to larger differences with LGM data than in the CTRL period. These differences reduce the contribution of downscaling

Lithium bis­(2-methyl­lactato)borate monohydrate

The title compound {systematic name: poly[[aqua­lithium]-μ-3,3,8,8-tetra­methyl-1,4,6,9-tetra­oxa-5λ4-borataspiro­[4.4]nonane-2,7-dione]}, [Li(C8H12BO6)(H2O)]n (LiBMLB), forms a 12-membered macrocycle, which lies across a crystallographic inversion center. The lithium cations are pseudo-tetra­hedrally coordinated by three methyl­lactate ligands and a water mol­ecule. The asymmetric units couple across crystallographic inversion centers, forming the 12-membered macrocycles. These macrocycles, in turn, cross-link through the Li+ cations, forming an infinite polymeric structure in two dimensions parallel to (101)

Carbon superatom thin films

Assembling clusters on surfaces has emerged as a novel way to grow thin films with targeted properties. In particular, it has been proposed from experimental findings that fullerenes deposited on surfaces could give rise to thin films retaining the bonding properties of the incident clusters. However the microscopic structure of such films is still unclear. By performing quantum molecular dynamics simulations, we show that C_28 fullerenes can be deposited on a surface to form a thin film of nearly defect free molecules, which act as carbon superatoms. Our findings help clarify the structure of disordered small fullerene films and also support the recently proposed hyperdiamond model for solid C_28.Comment: 13 pages, RevTeX, 2 figures available as black and white PostScript files; color PostScript and/or gif files available upon reques

Modeling the dynamics of glacial cycles

This article is concerned with the dynamics of glacial cycles observed in the geological record of the Pleistocene Epoch. It focuses on a conceptual model proposed by Maasch and Saltzman [J. Geophys. Res.,95, D2 (1990), pp. 1955-1963], which is based on physical arguments and emphasizes the role of atmospheric CO2 in the generation and persistence of periodic orbits (limit cycles). The model consists of three ordinary differential equations with four parameters for the anomalies of the total global ice mass, the atmospheric CO2 concentration, and the volume of the North Atlantic Deep Water (NADW). In this article, it is shown that a simplified two-dimensional symmetric version displays many of the essential features of the full model, including equilibrium states, limit cycles, their basic bifurcations, and a Bogdanov-Takens point that serves as an organizing center for the local and global dynamics. Also, symmetry breaking splits the Bogdanov-Takens point into two, with different local dynamics in their neighborhoods

Dissection of quantitative and durable leaf rust resistance in Swiss winter wheat reveals a major resistance QTL in the Lr34 chromosomal region

The Swiss winter bread wheat cv. ‘Forno' has a highly effective, durable and quantitative leaf rust (Puccinia triticina Eriks.) resistance which is associated with leaf tip necrosis (LTN). We studied 240 single seed descent lines of an ‘Arina×Forno' F5:7 population to identify and map quantitative trait loci (QTLs) for leaf rust resistance and LTN. Percentage of infected leaf area (%) and the response to infection (RI) were evaluated in seven field trials and were transformed to the area under the disease progress curves (AUDPC). Using composite interval mapping and LOD>4.4, we identified eight chromosomal regions specifically associated with resistance. The largest and most consistent leaf rust resistance locus was identified on the short arm of chromosome 7D (32.6% of variance explained for AUDPC_% and 42.6% for AUDPC_RI) together with the major QTL for LTN (R 2=55.6%) in the same chromosomal region as Lr34 (Xgwm295). A second major leaf rust resistance QTL (R 2=28% and 31.5%, respectively) was located on chromosome arm 1BS close to Xgwm604 and was not associated with LTN. Additional minor QTLs for LTN (2DL, 3DL, 4BS and 5AL) and leaf rust resistance were identified. These latter QTLs might correspond to the leaf rust resistance genes Lr2 or Lr22 (2DS) and Lr14a (7BL