Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted Contribution to Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

The aqueous extract of yerba mate, a South American tea beverage made from Ilex paraguariensis leaves, has demonstrated bactericidal and inhibitory activity against bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two unique fractions of yerba mate aqueous extract revealed 8 identifiable small molecules in those fractions with antimicrobial activity. For a more comprehensive analysis, a data analysis pipeline was assembled to prioritize compounds for antimicrobial testing against both MRSA and methicillin-sensitive S.aureus using forty-two unique fractions of the tea extract that were generated in duplicate, assayed for activity, and analyzed with GC-MS. As validation of our automated analysis, we checked our predicted active compounds for activity in literature references and used authentic standards to test for antimicrobial activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity against MRSA at low concentrations in our bioassays. In addition, quinic acid and quercetin were identified using random forests analysis and 5-hydroxy pipecolic acid was identified using linear discriminant analysis. We also generated a ranked list of unidentified compounds that may contribute to the antimicrobial activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an automated analysis that resulted in a ranked list of compounds that likely contribute to the antimicrobial activity of aqueous yerba mate extract against MRSA

A predictive model for secondary RNA structure using graph theory and a neural network

Background: Determining the secondary structure of RNA from the primary structure is a challenging computational problem. A number of algorithms have been developed to predict the secondary structure from the primary structure. It is agreed that there is still room for improvement in each of these approaches. In this work we build a predictive model for secondary RNA structure using a graph-theoretic tree representation of secondary RNA structure. We model the bonding of two RNA secondary structures to form a larger secondary structure with a graph operation we call merge. We consider all combinatorial possibilities using all possible tree inputs, both those that are RNA-like in structure and those that are not. The resulting data from each tree merge operation is represented by a vector. We use these vectors as input values for a neural network and train the network to recognize a tree as RNA-like or not, based on the merge data vector. The network estimates the probability of a tree being RNA-like.Results: The network correctly assigned a high probability of RNA-likeness to trees previously identified as RNA-like and a low probability of RNA-likeness to those classified as not RNA-like. We then used the neural network to predict the RNA-likeness of the unclassified trees.Conclusions: There are a number of secondary RNA structure prediction algorithms available online. These programs are based on finding the secondary structure with the lowest total free energy. In this work, we create a predictive tool for secondary RNA structures using graph-theoretic values as input for a neural network. The use of a graph operation to theoretically describe the bonding of secondary RNA is novel and is an entirely different approach to the prediction of secondary RNA structures. Our method correctly predicted trees to be RNA-like or not RNA-like for all known cases. In addition, our results convey a measure of likelihood that a tree is RNA-like or not RNA-like. Given that the majority of secondary RNA folding algorithms return more than one possible outcome, our method provides a means of determining the best or most likely structures among all of the possible outcomes

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin.

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients

Evolving, dynamic clustering of spatio/spectro-temporal data in 3D spiking neural network models and a case study on EEG data

Clustering is a fundamental data processing technique. While clustering of static (vector based) data and of fixed window size time series have been well explored, dynamic clustering of spatiotemporal data has been little researched if at all. Especially when patterns of changes (events) in the data across space and time have to be captured and understood. The paper presents novel methods for clustering of spatiotemporal data using the NeuCube spiking neural network (SNN) architecture. Clusters of spatiotemporal data were created and modified on-line in a continuous, incremental way, where spatiotemporal relationships of changes in variables are incrementally learned in a 3D SNN model and the model connectivity and spiking activity are incrementally clustered. Two clustering methods were proposed for SNN, one performed during unsupervised and one—during supervised learning models. Before submitted to the models, the data is encoded as spike trains, a spike representing a change in the variable value (an event). During the unsupervised learning, the cluster centres were predefined by the spatial locations of the input data variables in a 3D SNN model. Then clusters are evolving during the learning, i.e. they are adapted continuously over time reflecting the dynamics of the changes in the data. In the supervised learning, clusters represent the dynamic sequence of neuron spiking activities in a trained SNN model, specific for a particular class of data or for an individual instance. We illustrate the proposed clustering method on a real case study of spatiotemporal EEG data, recorded from three groups of subjects during a cognitive task. The clusters were referred back to the brain data for a better understanding of the data and the processes that generated it. The cluster analysis allowed to discover and understand differences on temporal sequences and spatial involvement of brain regions in response to a cognitive task

Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer

The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n=case 192, controls 96)], breast cancer patients [ABC (n=case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2–5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI

Effect of ultrapure lipopolysaccharides derived from diverse bacterial species on the modulation of platelet activation

Platelets are small circulating blood cells that play essential roles in the maintenance of haemostasis via blood clotting. However, they also play critical roles in the regulation of innate immune responses. Inflammatory receptors, specifically Toll-like receptor (TLR)-4, have been reported to modify platelet reactivity. A plethora of studies have reported controversial functions of TLR4 in the modulation of platelet function using various chemotypes and preparations of its ligand, lipopolysaccharide (LPS). The method of preparation of LPS may explain these discrepancies however this is not fully understood. Hence, to determine the impact of LPS on platelet activation, we used ultrapure preparations of LPS from Escherichia coli (LPSEC), Salmonella minnesota (LPSSM), and Rhodobacter sphaeroides (LPSRS) and examined their actions under diverse experimental conditions in human platelets. LPSEC did not affect platelet activation markers such as inside-out signalling to integrin IIb3 or P-selectin exposure upon agonist-induced activation in platelet-rich plasma or whole blood whereas LPSSM and LPSRS inhibited platelet activation under specific conditions at supraphysiological concentrations. Overall, our data demonstrate that platelet activation is not largely influenced by any of the ultrapure LPS chemotypes used in this study on their own except under certain conditions