Student biocuration projects as a learning environment

BACKGROUND: Bioinformatics is becoming an essential tool for the majority of biological and biomedical researchers. Although bioinformatics data is exploited by academic and industrial researchers, limited focus is on teaching this area to undergraduates, postgraduates and senior scientists. Many scientists are developing their own expertise without formal training and often without appreciating the source of the data they are reliant upon. Some universities do provide courses on a variety of bioinformatics resources and tools, a few also provide biocuration projects, during which students submit data to annotation resources. METHODS: To assess the usefulness and enjoyability of annotation projects a survey was sent to University College London (UCL) students who have undertaken Gene Ontology biocuration projects. RESULTS: Analysis of survey responses suggest that these projects provide students with an opportunity not only to learn about bioinformatics resources but also to improve their literature analysis, presentation and writing skills. CONCLUSIONS: Biocuration student projects provide valuable annotations as well as enabling students to develop a variety of skills relevant to their future careers. It is also hoped that, as future scientists, these students will critically assess their own manuscripts and ensure that these are written with the biocurators of the future in mind

An Overrepresentation of High Frequencies in the Mouse Inferior Colliculus Supports the Processing of Ultrasonic Vocalizations

Mice are of paramount importance in biomedical research and their vocalizations are a subject of interest for researchers across a wide range of health-related disciplines due to their increasingly important value as a phenotyping tool in models of neural, speech and language disorders. However, the mechanisms underlying the auditory processing of vocalizations in mice are not well understood. The mouse audiogram shows a peak in sensitivity at frequencies between 15-25 kHz, but weaker sensitivity for the higher ultrasonic frequencies at which they typically vocalize. To investigate the auditory processing of vocalizations in mice, we measured evoked potential, single-unit, and multi-unit responses to tones and vocalizations at three different stages along the auditory pathway: the auditory nerve and the cochlear nucleus in the periphery, and the inferior colliculus in the midbrain. Auditory brainstem response measurements suggested stronger responses in the midbrain relative to the periphery for frequencies higher than 32 kHz. This result was confirmed by single- and multi-unit recordings showing that high ultrasonic frequency tones and vocalizations elicited responses from only a small fraction of cells in the periphery, while a much larger fraction of cells responded in the inferior colliculus. These results suggest that the processing of communication calls in mice is supported by a specialization of the auditory system for high frequencies that emerges at central stations of the auditory pathway

Purification, characterization and application of laccase from Trametes versicolor for colour and phenolic removal of olive mill wastewater in the presence of 1- hydroxybenzotriazole

Laccase forms (L1 and L2) from Trametes versicolor CCT 4521 showed a molecular mass of 66 kDa and optimum temperature around 40oC. The optimum pH (4.0 and 5.0) and Km (28.6 and 5 ìM) values usingsyringaldazine as substrate were found for L1 and L2, respectively. The enzymes were able to oxidize several compounds and were strongly inhibited by sodium azide, L-cysteine and dithiothreitol. The 75%of the N-terminal sequences were identical in both forms and similarities around 40 - 60% of laccases from wood-degrading fungi were observed. The use of 1-hydroxybenzotriazole as a mediator increased the compounds oxidized by laccases in olive mill wastewater

Decoding negative affect personality trait from patterns of brain activation to threat stimuli

INTRODUCTION: Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. METHODS: fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. RESULTS: The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). CONCLUSION: These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts

Quasinormal modes of massive charged flavor branes

We present an analysis and classification of vector and scalar fluctuations in a D3/D7 brane setup at finite termperature and baryon density. The system is dual to an N=2 supersymmetric Yang-Mills theory with SU(N_c) gauge group and N_f hypermultiplets in the fundamental representation in the quenched approximation. We improve significantly over previous results on the quasinormal mode spectrum of D7 branes and stress their novel physical interpretation. Amongst our findings is a new purely imaginary scalar mode that becomes tachyonic at sufficiently low temperature and baryon density. We establish the existence of a critical density above which the scalar mode stays in the stable regime for all temperatures. In the vector sector we study the crossover from the hydrodynamic to the quasiparticle regime and find that it moves to shorter wavelengths for lower temperatures. At zero baryon density the quasinormal modes move toward distinct discrete attractor frequencies that depend on the momentum as we increase the temperature. At finite baryon density, however, the trajectories show a turning behavior such that for low temperature the quasinormal mode spectrum approaches the spectrum of the supersymmetric zero temperature normal modes. We interpret this as resolution of the singular quasinormal mode spectrum that appears at the limiting D7 brane embedding at vanishing baryon density.Comment: 56 pages, 40 figure

MartiTracks: A Geometrical Approach for Identifying Geographical Patterns of Distribution

Panbiogeography represents an evolutionary approach to biogeography, using rational cost-efficient methods to reduce initial complexity to locality data, and depict general distribution patterns. However, few quantitative, and automated panbiogeographic methods exist. In this study, we propose a new algorithm, within a quantitative, geometrical framework, to perform panbiogeographical analyses as an alternative to more traditional methods. The algorithm first calculates a minimum spanning tree, an individual track for each species in a panbiogeographic context. Then the spatial congruence among segments of the minimum spanning trees is calculated using five congruence parameters, producing a general distribution pattern. In addition, the algorithm removes the ambiguity, and subjectivity often present in a manual panbiogeographic analysis. Results from two empirical examples using 61 species of the genus Bomarea (2340 records), and 1031 genera of both plants and animals (100118 records) distributed across the Northern Andes, demonstrated that a geometrical approach to panbiogeography is a feasible quantitative method to determine general distribution patterns for taxa, reducing complexity, and the time needed for managing large data sets

What Does Brain Response to Neutral Faces Tell Us about Major Depression? Evidence from Machine Learning and fMRI

Introduction: A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. Methods: Two independent depressed samples: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Results: Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Conclusions: Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients. © 2013 Oliveira et al

Demethylation of the Coding Region Triggers the Activation of the Human Testis-Specific PDHA2 Gene in Somatic Tissues

Human PDHA2 is a testis-specific gene that codes for the E1α subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the −122 to −6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal promoter region and the consequent increase in PDHA2 mRNA levels. Bisulfite sequencing analysis revealed that DAC treatment induced a significant demethylation of the CpG island II (nucleotides +197 to +460) in PDHA2 coding region, while the promoter region remained highly methylated. Taken together with our previous results that show an in vivo correlation between PDHA2 expression and the demethylation of the CpG island II in testis germ cells, the present results show that internal methylation of the PDHA2 gene plays a part in its repression in somatic cells. In conclusion, our data support the novel finding that methylation of the PDHA2 coding region can inhibit gene transcription. This represents a key mechanism for absence of PDHA2 expression in somatic cells and a target for PDC therapy

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.The work was supported by the Amazonia Fitomedicamentos (FITO05/2012) Ltda. and Barretos Cancer Hospital, all from Brazil