Use of reliable density maps is crucial for rapid and successful crystal structure determination. Here, the averaged kick (AK) map approach is investigated, its application is generalized and it is compared with other map-calculation methods. AK maps are the sum of a series of kick maps, where each kick map is calculated from atomic coordinates modified by random shifts. As such, they are a numerical analogue of maximum-likelihood maps. AK maps can be unweighted or maximum-likelihood ( A ) weighted. Analysis shows that they are comparable and correspond better to the final model than A and simulated-annealing maps. The AK maps were challenged by a difficult structure-validation case, in which they were able to clarify the problematic region in the density without the need for model rebuilding. The conclusion is that AK maps can be useful throughout the entire progress of crystal structure determination, offering the possibility of improved map interpretation.

The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/.

The dynamics and diversity of human gut microbiota that can remarkably influence the wellbeing and health of the host are constantly changing through the host’s lifetime in response to various factors. The aim of the present study was to determine a set of parameters that could have a major impact on classifying subjects into a single cluster regarding gut bacteria composition. Therefore, a set of demographical, environmental, and clinical data of healthy adults aged 25–50 years (117 female and 83 men) was collected. Fecal microbiota composition was characterized using Illumina MiSeq 16S rRNA gene amplicon sequencing. Hierarchical clustering was performed to analyze the microbiota data set, and a supervised machine learning model (SVM; Support Vector Machines) was applied for classification. Seventy variables from collected data were included in machine learning analysis. The agglomerative clustering algorithm suggested the presence of four distinct community types of most abundant bacterial phyla. Each cluster harbored a statistically significant different proportion of bacterial phyla. Regarding prediction, the most important features classifying subjects into clusters were measures of obesity (waist to hip ratio, BMI, and visceral fat index), total body water, blood pressure, energy intake, total fat, olive oil intake, total fiber intake, and water intake. In conclusion, the SVM model was shown as a valuable tool to classify healthy individuals based on their gut microbiota composition.

The refinement of a molecular model is a computational procedure by which the atomic model is fitted to the diffraction data. The commonly used target in the refinement of macromolecular structures is the maximum-likelihood (ML) function, which relies on the assessment of model errors. The current ML functions rely on cross-validation. They utilize phase-error estimates that are calculated from a small fraction of diffraction data, called the test set, that are not used to fit the model. An approach has been developed that uses the work set to calculate the phase-error estimates in the ML refinement from simulating the model errors via the random displacement of atomic coordinates. It is called ML free-kick refinement as it uses the ML formulation of the target function and is based on the idea of freeing the model from the model bias imposed by the chemical energy restraints used in refinement. This approach for the calculation of error estimates is superior to the cross-validation approach: it reduces the phase error and increases the accuracy of molecular models, is more robust, provides clearer maps and may use a smaller portion of data for the test set for the calculation of R free or may leave it out completely.

Particulate matter (PM) is a major component of urban air pollution and hasand also in chronic obstructive pulmonary diseases (COPD) has been observed in developed countries over the last 3 decades (11,12,13,14,15,16). The adverse effect of PM on respiratory health has a quantifiable impact, not only on the morbidity but also on the mortality of respiratory diseases (17, 18). On the other hand the possible association between cardiovascular diseases (CVD) and exposure to airborne PM has only recently been addressed. As reviewed in several papers (19,20,21), exposure to PM as a result of outdoor air pollution has become a recognized risk factor for adverse cardiovascular events including cardiovascular mortality, cardiac arrhythmia, myocardial infarction (MI), myocardial ischemia, and heart failure (22,23,24,25). Additionally, the mortality in cities with high levels of air pollution exceeds that observed in relatively cleaner cities by 15-20 %. Even in the EU, the average life expectancy is 8.6 months lower due to exposure to PM produced by human activities (5,26). In the present review, the components of air pollution are presented and the effect of PM exposure on the cardiovascular and respiratory system is analysed. THE COMPONENTS OF AIR POLLUTIONPM is a major component of urban air pollution and has a major effect on human health, nature and atmosphere. PM10 means PM that passes through a size-selective inlet with a 50 % efficiency cut-off at 10 µm aerodynamic diameter (27). Likewise PM2.5 means particles that pass through a size-selective inlet with a 50 % efficiency cut-off at 2.5 μm aerodynamic diameter. The limit value for the annual average concentration for PM10 is 40 µg/m 3 . The limit value for 24 h averages, which may be exceeded 35 times per year, is 50 μg/m 3 for PM10. For air quality monitoring purposes, PM10 measurements are most widely used at present. EU Member states were also obliged to gather information on the concentrations of fine PM2.5 particles. The target value of 25 µg/m 3 for PM2.5 entered into force on 01/01/2010 and the limit value enters into force on 01/01/2015 (28). The World Health Organization (WHO) recommended limits for the concentration of PM10 is 20 µg/m 3 and 10 µg/m 3 for PM2.5 (29). 2

Validation of three-dimensional structures is at the core of structural determination methods. The local validation criteria, such as deviations from ideal bond length and bonding angles, Ramachandran plot outliers and clashing contacts, are a standard part of structure analysis before structure deposition, whereas the global and regional packing may not yet have been addressed. In the last two decades, three-dimensional models of macromolecules such as proteins have been successfully described by a network of nodes and edges. Amino acid residues as nodes and close contact between the residues as edges have been used to explore basic network properties, to study protein folding and stability and to predict catalytic sites. Using complex network analysis, we introduced common network parameters to distinguish between correct and incorrect three-dimensional protein structures. The analysis showed that correct structures have a higher average node degree, higher graph energy, and lower shortest path length than their incorrect counterparts. Thus, correct protein models are more densely intra-connected, and in turn, the transfer of information between nodes/amino acids is more efficient. Moreover, protein graph spectra were used to investigate model bias in protein structure.

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