The genome of the domesticated apple (Malus × domestica Borkh.).

We report a high-quality draft genome sequence of the domesticated apple (Malus × domestica). We show that a relatively recent (>50 million years ago) genome-wide duplication (GWD) has resulted in the transition from nine ancestral chromosomes to 17 chromosomes in the Pyreae. Traces of older GWDs partly support the monophyly of the ancestral paleohexaploidy of eudicots.

Development of a novel cross-linking strategy for fast and accurate identification of cross-linked peptides of protein complexes.

Knowledge of elaborate structures of protein complexes is fundamental for understanding their functions and regulations. Although cross-linking coupled with mass spectrometry (MS) has been presented as a feasible strategy for structural elucidation of large multisubunit protein complexes, this method has proven challenging because of technical difficulties in unambiguous identification of cross-linked peptides and determination of cross-linked sites by MS analysis. In this work, we developed a novel cross-linking strategy using a newly designed MS-cleavable cross-linker, disuccinimidyl sulfoxide (DSSO).

Prepatellar bursitis due to Brucella abortus: case report and analysis of the local immune response.

A case of prepatellar bursitis in a man with chronic brucellosis is presented. Brucella abortus biotype 1 was isolated from the abundant yellowish fluid obtained from the bursa. Clinical and epidemiological data did not suggest a direct inoculation of the agent in the bursa.

Hashing algorithms and data structures for rapid searches of fingerprint vectors.

In many large chemoinformatics database systems, molecules are represented by long binary fingerprint vectors whose components record the presence or absence of particular functional groups or combinatorial features. To speed up database searches, we propose to add to each fingerprint a short signature integer vector of length M. For a given fingerprint, the i component of the signature vector counts the number of 1-bits in the fingerprint that fall on components congruent to i modulo M.

When is chemical similarity significant? The statistical distribution of chemical similarity scores and its extreme values.

As repositories of chemical molecules continue to expand and become more open, it becomes increasingly important to develop tools to search them efficiently and assess the statistical significance of chemical similarity scores. Here, we develop a general framework for understanding, modeling, predicting, and approximating the distribution of chemical similarity scores and its extreme values in large databases. The framework can be applied to different chemical representations and similarity measures but is demonstrated here using the most common binary fingerprints with the Tanimoto similarity measure.

Direct and monocyte-induced innate immune response of human lung epithelial cells to Brucella abortus infection.

Although Brucella frequently infects humans through inhalation, its interaction with pulmonary cells has been overlooked. We examined whether human lung epithelial cells produce proinflammatory mediators in response to Brucella infection. Infection with smooth or rough strains of Brucella abortus induced the secretion of IL-8 and GM-CSF by the bronchial epithelial cell lines Calu-6 and 16HBE14o-, but not by the alveolar epithelial cell line A549.

Large scale immune profiling of infected humans and goats reveals differential recognition of Brucella melitensis antigens.

Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B.

Brucella-infected hepatocytes mediate potentially tissue-damaging immune responses.

Background & Aims: Hepatic involvement is frequent in human brucellosis. While different histopathological lesions have been reported in these patients, the underlying cellular and molecular mechanisms have not been addressed.

Methods: This study assessed whether Brucella abortus can infect a human hepatoma cell line and induce a proinflammatory response in these cells.

A CROC stronger than ROC: measuring, visualizing and optimizing early retrieval.

Motivation: The performance of classifiers is often assessed using Receiver Operating Characteristic ROC [or (AC) accumulation curve or enrichment curve] curves and the corresponding areas under the curves (AUCs). However, in many fundamental problems ranging from information retrieval to drug discovery, only the very top of the ranked list of predictions is of any interest and ROCs and AUCs are not very useful. New metrics, visualizations and optimization tools are needed to address this 'early retrieval' problem.

Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia.

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C.

A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray.

Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria, the targets of protective Abs and the basis of their inefficient acquisition are unknown. Addressing these knowledge gaps could accelerate malaria vaccine development.

Computational and single-molecule force studies of a macro domain protein reveal a key molecular determinant for mechanical stability.

Resolving molecular determinants of mechanical stability of proteins is crucial in the rational design of advanced biomaterials for use in biomedical and nanotechnological applications. Here we present an interdisciplinary study combining bioinformatics screening, steered molecular dynamics simulations, protein engineering, and single-molecule force spectroscopy that explores the mechanical properties of a macro domain protein with mixed alpha + beta topology. The unique architecture is defined by a single seven-stranded beta-sheet in the core of the protein flanked by five alpha-helices.

Of bits and wows: A Bayesian theory of surprise with applications to attention.

The amount of information contained in a piece of data can be measured by the effect this data has on its observer. Fundamentally, this effect is to transform the observer's prior beliefs into posterior beliefs, according to Bayes theorem. Thus the amount of information can be measured in a natural way by the distance (relative entropy) between the prior and posterior distributions of the observer over the available space of hypotheses.

Identification of immunodominant antigens of Chlamydia trachomatis using proteome microarrays.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen in the world. In order to control this infection there is an urgent need to formulate a vaccine. Identification of protective antigens is required to implement a subunit vaccine.

High performance mode adapters based on segmented SPE:LiNbO3 waveguides.

We propose a new mode adapter which allows more efficient launching of the optical power selectively in the fundamental mode of a multimode waveguide. Theoretical and experimental results confirm that such a mode adapter increases the performances in terms of coupling efficiency, coupling tolerances and transmitted power with respect to previously proposed solutions. Proof of principle of device operation is obtained with a simple Coupled Mode Theory model.

No electron left behind: a rule-based expert system to predict chemical reactions and reaction mechanisms.

Predicting the course and major products of arbitrary reactions is a fundamental problem in chemistry, one that chemists must address in a variety of tasks ranging from synthesis design to reaction discovery. Described here is an expert system to predict organic chemical reactions based on a knowledge base of over 1500 manually composed reaction transformation rules. Novel rule extensions are introduced to enable robust predictions and describe detailed reaction mechanisms at the level of electron flows in elementary reaction steps, ensuring that all reactions are properly balanced and atom-mapped.

A Burkholderia pseudomallei protein microarray reveals serodiagnostic and cross-reactive antigens.

Understanding the way in which the immune system responds to infection is central to the development of vaccines and many diagnostics. To provide insight into this area, we fabricated a protein microarray containing 1,205 Burkholderia pseudomallei proteins, probed it with 88 melioidosis patient sera, and identified 170 reactive antigens. This subset of antigens was printed on a smaller array and probed with a collection of 747 individual sera derived from 10 patient groups including melioidosis patients from Northeast Thailand and Singapore, patients with different infections, healthy individuals from the USA, and from endemic and nonendemic regions of Thailand.

An intersection inequality sharper than the tanimoto triangle inequality for efficiently searching large databases.

Bounds on distances or similarity measures can be useful to help search large databases efficiently. Here we consider the case of large databases of small molecules represented by molecular fingerprint vectors with the Tanimoto similarity measure. We derive a new intersection inequality which provides a bound on the Tanimoto similarity between two fingerprint vectors and show that this bound is considerably sharper than the bound associated with the triangle inequality of the Tanimoto distance.

SOLpro: accurate sequence-based prediction of protein solubility.

Motivation: Protein insolubility is a major obstacle for many experimental studies. A sequence-based prediction method able to accurately predict the propensity of a protein to be soluble on overexpression could be used, for instance, to prioritize targets in large-scale proteomics projects and to identify mutations likely to increase the solubility of insoluble proteins.

Results: Here, we first curate a large, non-redundant and balanced training set of more than 17 000 proteins.

Lévy processes and stochastic von Bertalanffy models of growth, with application to fish population analysis.

The study of animal growth is a longstanding crucial topic of theoretical biology. In this paper we introduce a new class of stochastic growth models that enjoy two crucial properties: the growth path of an individual is monotonically increasing and the mean length at time t follows the classic von Bertalanffy model. Besides the theoretical development, the models are also tested against a large set of length-at-age data collected on Atlantic herring (Clupea harengus): the mean lengths and variances of the cohorts were directly estimated by least squares.

Data structures and compression algorithms for genomic sequence data.

Motivation: The continuing exponential accumulation of full genome data, including full diploid human genomes, creates new challenges not only for understanding genomic structure, function and evolution, but also for the storage, navigation and privacy of genomic data. Here, we develop data structures and algorithms for the efficient storage of genomic and other sequence data that may also facilitate querying and protecting the data.

Results: The general idea is to encode only the differences between a genome sequence and a reference sequence, using absolute or relative coordinates for the location of the differences.

Differential composition of culture supernatants from wild-type Brucella abortus and its isogenic virB mutants.

The virB genes coding type IV secretion system are necessary for the intracellular survival and replication of Brucella spp. In this study, extracellular proteins from B. abortus 2308 (wild type, WT) and its isogenic virB10 polar mutant were compared.

Smooth Brucella strains invade and replicate in human lung epithelial cells without inducing cell death.

Inhalation is a common route for Brucella infection. We investigated whether Brucella species can invade and replicate within alveolar(A549) and bronchial (Calu-6 and 16HBE14o-) human epithelial cells. The number of adherent and intracellular bacteria was higher for rough strains (Brucella canis and Brucella abortus RB51) than for smooth strains (B.

Influence relevance voting: an accurate and interpretable virtual high throughput screening method.

Given activity training data from high-throughput screening (HTS) experiments, virtual high-throughput screening (vHTS) methods aim to predict in silico the activity of untested chemicals. We present a novel method, the Influence Relevance Voter (IRV), specifically tailored for the vHTS task. The IRV is a low-parameter neural network which refines a k-nearest neighbor classifier by nonlinearly combining the influences of a chemical's neighbors in the training set.

Genotype-specific regulation of cold-responsive genes in cypress (Cupressus sempervirens L.).

Cold acclimation in plants involves a very complex molecular response, with the regulation of many different genes and metabolic pathways. In this work fifteen cypress (Cupressus sempervirens) genes putatively regulated during cold exposure were isolated and their expression was studied in five cypress genotypes, along 15 days of treatment at 3 degrees C. Treated samples of shoots were collected from four year old cypress seedlings and a subtractive hybridization approach (PCR-Select) was performed after mRNA extraction.