Automated functional classification of experimental and predicted protein structures

BACKGROUND: Proteins that are similar in sequence or structure may perform different functions in nature. In such cases, function cannot be inferred from sequence or structural similarity. RESULTS: We analyzed experimental structures belonging to the Structural Classification of Proteins (SCOP) database and showed that about half of them belong to multi-functional fold families for which protein similarity alone is not adequate to assign function. We also analyzed predicted structures from the LiveBench and the PDB-CAFASP experiments and showed that accurate homology-based functional assignments cannot be achieved approximately one third of the time, when the protein is a member of a multi-functional fold family. We then conducted extended performance evaluation and comparisons on both experimental and predicted structures using our Functional Signatures from Structural Alignments (FSSA) algorithm that we previously developed to handle the problem of classifying proteins belonging to multi-functional fold families. CONCLUSION: The results indicate that the FSSA algorithm has better accuracy when compared to homology-based approaches for functional classification of both experimental and predicted protein structures, in part due to its use of local, as opposed to global, information for classifying function. The FSSA algorithm has also been implemented as a webserver and is available at

Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. RESULTS: There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. CONCLUSION: These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement

Excitability of the Motor Cortex Ipsilateral to the Moving Body Side Depends on Spatio-Temporal Task Complexity and Hemispheric Specialization

Unilateral movements are mainly controlled by the contralateral hemisphere, even though the primary motor cortex ipsilateral (M1ipsi) to the moving body side can undergo task-related changes of activity as well. Here we used transcranial magnetic stimulation (TMS) to investigate whether representations of the wrist flexor (FCR) and extensor (ECR) in M1ipsi would be modulated when unilateral rhythmical wrist movements were executed in isolation or in the context of a simple or difficult hand-foot coordination pattern, and whether this modulation would differ for the left versus right hemisphere. We found that M1ipsi facilitation of the resting ECR and FCR mirrored the activation of the moving wrist such that facilitation was higher when the homologous muscle was activated during the cyclical movement. We showed that this ipsilateral facilitation increased significantly when the wrist movements were performed in the context of demanding hand-foot coordination tasks whereas foot movements alone influenced the hand representation of M1ipsi only slightly. Our data revealed a clear hemispheric asymmetry such that MEP responses were significantly larger when elicited in the left M1ipsi than in the right. In experiment 2, we tested whether the modulations of M1ipsi facilitation, caused by performing different coordination tasks with the left versus right body sides, could be explained by changes in short intracortical inhibition (SICI). We found that SICI was increasingly reduced for a complex coordination pattern as compared to rest, but only in the right M1ipsi. We argue that our results might reflect the stronger involvement of the left versus right hemisphere in performing demanding motor tasks

Transitions at CpG Dinucleotides, Geographic Clustering of TP53 Mutations and Food Availability Patterns in Colorectal Cancer

Colorectal cancer is mainly attributed to diet, but the role exerted by foods remains unclear because involved factors are extremely complex. Geography substantially impacts on foods. Correlations between international variation in colorectal cancer-associated mutation patterns and food availabilities could highlight the influence of foods on colorectal mutagenesis. mutations from 12 countries/geographic areas. For food availabilities, we relied on data extracted from the Food Balance Sheets of the Food and Agriculture Organization of the United Nations. Dendrograms for mutation sites, mutation types and food patterns were constructed through Ward's hierarchical clustering algorithm and their stability was assessed evaluating silhouette values. Feature selection used entropy-based measures for similarity between clusterings, combined with principal component analysis by exhaustive and heuristic approaches. hotspots. Pearson's correlation scores, computed between the principal components of the datamatrices for mutation types, food availability and mutation sites, demonstrated statistically significant correlations between transitions at CpGs and both mutation sites and availabilities of meat, milk, sweeteners and animal fats, the energy-dense foods at the basis of “Western” diets. This is best explainable by differential exposure to nitrosative DNA damage due to foods that promote metabolic stress and chronic inflammation

Present and future evolution of advanced breast cancer therapy

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents

Enzymatic oligomerization and polymerization of arylamines: state of the art and perspectives

The literature concerning the oxidative oligomerization and polymerization of various arylamines, e.g., aniline, substituted anilines, aminonaphthalene and its derivatives, catalyzed by oxidoreductases, such as laccases and peroxidases, in aqueous, organic, and mixed aqueous organic monophasic or biphasic media, is reviewed. An overview of template-free as well as template-assisted enzymatic syntheses of oligomers and polymers of arylamines is given. Special attention is paid to mechanistic aspects of these biocatalytic processes. Because of the nontoxicity of oxidoreductases and their high catalytic efficiency, as well as high selectivity of enzymatic oligomerizations/polymerizations under mild conditions-using mainly water as a solvent and often resulting in minimal byproduct formation-enzymatic oligomerizations and polymerizations of arylamines are environmentally friendly and significantly contribute to a "green'' chemistry of conducting and redox-active oligomers and polymers. Current and potential future applications of enzymatic polymerization processes and enzymatically synthesized oligo/polyarylamines are discussed

Quantitative evaluation for brain CT/MRI coregistration based on maximization of mutual information in patients with focal epilepsy investigated with subdural electrodes

Patients with drug-resistant focal epilepsy may require intracranial investigations with subdural electrodes. These must be correctly localized with respect to the brain cortical surface and require appropriate monitoring. For this purpose, coregistration techniques, which fuse preimplantation 3D magnetic resonance imaging scans with postimplantation computed tomography scans, have been implemented. In order to reduce localization errors due to the fusion process, we used a coregistration method based on the maximization of mutual information (MI) in 11 patients with extratemporal epilepsy who were invasively investigated. Our registration method is based on three processing steps: rigid-body transformation for coregistration, computation of MI as a similarity measure and the use of the Downhill Simplex optimization method. After consistency analysis, the shift of the registration method reached 0.14F0.27 mm in translation and 0.03F0.148 in rotation, and the accuracies assessed on voxels of skull surface and voxels of the center of the brain volume were 1.42F0.61 and 1.15F0.53 mm, respectively. The accuracy of the fusion process reached submillimeter range, and results were considered reliable for surgical planning in all studied patients