Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit

NpmA, a methyltransferase that confers resistance to aminoglycosides was identified in an Escherichia coli clinical isolate. It belongs to the kanamycin–apramycin methyltransferase (Kam) family and specifically methylates the 16S rRNA at the N1 position of A1408. We determined the structures of apo-NpmA and its complexes with S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.4, 2.7 and 1.68 Å, respectively. We generated a number of NpmA variants with alanine substitutions and studied their ability to bind the cofactor, to methylate A1408 in the 30S subunit, and to confer resistance to kanamycin in vivo. Residues D30, W107 and W197 were found to be essential. We have also analyzed the interactions between NpmA and the 30S subunit by footprinting experiments and computational docking. Helices 24, 42 and 44 were found to be the main NpmA-binding site. Both experimental and theoretical analyses suggest that NpmA flips out the target nucleotide A1408 to carry out the methylation. NpmA is plasmid-encoded and can be transferred between pathogenic bacteria; therefore it poses a threat to the successful use of aminoglycosides in clinical practice. The results presented here will assist in the development of specific NpmA inhibitors that could restore the potential of aminoglycoside antibiotics

A family of dual-activity glycosyltransferasesphosphorylases mediates mannogen turnover and virulence in Leishmania parasites

Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family in Leishmania increased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches

An Algorithm for the Evolutionary-Fuzzy Generation of on-Line Signature Hybrid Descriptors

In biometrics, methods which are able to precisely adapt to the biometric features of users are much sought after. They use various methods of artificial intelligence, in particular methods from the group of soft computing. In this paper, we focus on on-line signature verification. Such signatures are complex objects described not only by the shape but also by the dynamics of the signing process. In standard devices used for signature acquisition (with an LCD touch screen) this dynamics may include pen velocity, but sometimes other types of signals are also available, e.g. pen pressure on the screen surface (e.g. in graphic tablets), the angle between the pen and the screen surface, etc. The precision of the on-line signature dynamics processing has been a motivational springboard for developing methods that use signature partitioning. Partitioning uses a well-known principle of decomposing the problem into smaller ones. In this paper, we propose a new partitioning algorithm that uses capabilities of the algorithms based on populations and fuzzy systems. Evolutionary-fuzzy partitioning eliminates the need to average dynamic waveforms in created partitions because it replaces them. Evolutionary separation of partitions results in a better matching of partitions with reference signatures, eliminates dispro-portions between the number of points describing dynamics in partitions, eliminates the impact of random values, separates partitions related to the signing stage and its dynamics (e.g. high and low velocity of signing, where high and low are imprecise-fuzzy concepts). The operation of the presented algorithm has been tested using the well-known BioSecure DS2 database of real dynamic signatures

Consideration of analogies between magnetic and quantum notices for molecular network

Magnetic properties of spin glass materials [9,13] are close to quantum interpretation in their nature description [17]. Therefore, we can look for possible kinds of analogies in process of defining theoretic and practice conventions, rules and applications of the specific characteristics in elaboration quantum calculation strategies. We have not investigated possibilities to create directly quantum calculation units and practice calculation structures like qubits, registers, gates etc. [4,18], but dealing with spin and quantum definitions and descriptions we can try to involve these notices from different domains. Such a pragmatic approach only intuitively gives chances to create the transition theory and implement it even partially. Obviously, almost all of us have heard about quantum factorization, cryptography or teleportation but it is obtained as a result of exploration casually selected quantum properties and adapting them to mathematic problems. In our approach, we carefully investigate involutions among spin and quantum nature looking at possible implementation in molecular network

Magnetic behaviour of nickel-cyclam complexes in mesoporous silica: EPR investigations

International audienceElectron paramagnetic resonance (EPR) investigations are carried out on mesoporous silica (SBA15) functionalized by Ni-cyclam complexes (1,4,8,11-tetraazacyclotetradecane groups chelating nickel ions). The magnetic behaviour of nickel-cyclam groups, their mutual interactions and dispersions in the mesoporous silica are compared with respect to the doping rates and the synthesis procedures. The spin–spin interactions and the relaxation processes were clarified from the thermal evolution in the temperature range (4 K, 300 K) of the paramagnetic spin susceptibilities and EPR line widths. Thus, the relaxation mechanisms seem marked by the Jahn–Teller effect on the nickel ions mediated by exchange interactions between nearest spins. Isolated Ni-cyclam molecules are involved in some samples while others show the formation of clusters where phonon-assisted one-dimensional (1D) ferromagnetic ordering occurs below 45 K. The performed experiments point out the efficiency of the EPR technique to probe the degree of functionalization of mesoporous silica by Ni-cyclam molecules and to give valuable feedback to improve the synthesis routes

Consideration of analogies between magnetic and quantum notices for molecular network

Magnetic properties of spin glass materials [9,13] are close to quantum interpretation in their nature description [17]. Therefore, we can look for possible kinds of analogies in process of defining theoretic and practice conventions, rules and applications of the specific characteristics in elaboration quantum calculation strategies. We have not investigated possibilities to create directly quantum calculation units and practice calculation structures like qubits, registers, gates etc. [4,18], but dealing with spin and quantum definitions and descriptions we can try to involve these notices from different domains. Such a pragmatic approach only intuitively gives chances to create the transition theory and implement it even partially. Obviously, almost all of us have heard about quantum factorization, cryptography or teleportation but it is obtained as a result of exploration casually selected quantum properties and adapting them to mathematic problems. In our approach, we carefully investigate involutions among spin and quantum nature looking at possible implementation in molecular network

The Separation of the Mn₁₂ Single-Molecule Magnets onto Spherical Silica Nanoparticles

The Mn12 single-molecule magnets (SMMs) could be attached to the surface of spherical silica for the first time with a high probability. This allowed separation of the individual molecular magnets and direct microscopic observation of the SMMs. We described in detail how to fabricate such a composite material. The synthesis procedure proposed here is simple and efficient. We confirmed the efficiency of the method by transmission electron microscopy (TEM): single-molecule magnets were visible at the surface of a silica substrate. Based on TEM observation, we described how the molecules anchor to the surface of silica (the geometry of the magnetic molecule in regard to the surface of the substrate). The SQUID magnetometry showed that single-molecule magnet behaviour is kept intact after grafting. The attachment of the single-molecule magnets to the surface of silica allows to investigate their properties as separate molecules. This is particularly important in the analysis of magnetic properties such as magnetic states of the separated SMMs, their mutual interactions, and the influence of a silica support

Optimizing distributed data mining applications based on object clustering methods

International audienceThe exponential computational cost involved in traditional data mining methods enforces search for less complex new algorithms. Especially, data mining on Grid is a challenge due to the lack of shared memory in Grid computing, which puts special attention to communication optimization. The aim of the DisDaMin project (Distributed Data Mining), descibed in the paper, is solving data mining problems by using new distributed algorithms intented for execution in Grid environments. The DisDaMin implements intelligent fragmentation of data by clustering methods and asynchronous collaborative processing adjusted to Grid environments. The DG-ADAJ environment provides adaptive control of distributed applications written in Java for Desktop Grid. It constitutes a component-based middleware, which allows for optimized distribution of applications on clusters of Java Virtual Machines, monitoring of application execution and dynamic on-line balancing of processing and communication. The DG-ADAJ system provides a middleware platform for Desktop Grid that could be used as a deployment base for DisDaMin algorithms. In this paper, we propose static object placement optimization algorithms for fragmentation of data in the DisDaMin project. The algorithms use DG-ADAJ's object clustering methods to provide optimized local processing on each node with minimized inter-node communication

Synthesis and optical behaviuor of mesoporous silica functionalized by organometallic molecules

International audienc