When plants produce not enough or at all: metabolic engineering of flavonoids in microbial hosts

As a result of the discovery that flavonoids are directly or indirectly connected to health, flavonoid metabolism and its fascinating molecules that are natural products in plants, have attracted the attention of both the industry and researchers involved in plant science, nutrition, bio/chemistry, chemical bioengineering, pharmacy, medicine, etc. Subsequently, in the past few years, flavonoids became a top story in the pharmaceutical industry, which is continually seeking novel ways to produce safe and efficient drugs. Microbial cell cultures can act as workhorse bio-factories by offering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a selective flavonoid. Furthermore, metabolic engineering methodology is used to reinforce what nature does best by correcting the inadequacies and dead-ends of a metabolic pathway. Combinatorial biosynthesis techniques led to the discovery of novel ways of producing natural and even unnatural plant flavonoids, while, in addition, metabolic engineering provided the industry with the opportunity to invest in synthetic biology in order to overcome the currently existing restricted diversification and productivity issues in synthetic chemistry protocols. In this review, is presented an update on the rationalized approaches to the production of natural or unnatural flavonoids through biotechnology, analyzing the significance of combinatorial biosynthesis of agricultural/pharmaceutical compounds produced in heterologous organisms. Also mentioned are strategies and achievements that have so far thrived in the area of synthetic biology, with an emphasis on metabolic engineering targeting the cellular optimization of microorganisms and plants that produce flavonoids, while stressing the advances in flux dynamic control and optimization. Finally, the involvement of the rapidly increasing numbers of assembled genomes that contribute to the gene- or pathway-mining in order to identify the gene(s) responsible for producing species-specific secondary metabolites is also considered herein.National Strategic Reference Framework. THALES-TEI CRETE, MIS 380210 Progra

The effect of progesterone on the anesthetic and analgesic requirements for ovariohysterectomy in the dog

Η παρούσα μελέτη διερεύνησε την επίδραση της συγκέντρωσης της προγεστερόνης, είτε ενδογενούς κατά τον ωοθηκικό κύκλο και την κυοφορία, είτε εξωγενούς, καθώς και του ενεργού μεταβολίτη της αλλοπρεγνανολόνη, στις απαιτήσεις σε αναισθητικά και αναλγητικά φάρμακα και στην ένταση του μετεγχειρητικού πόνου για τη διεξαγωγή ωοθηκυστερεκτομής στον σκύλο. Περιελήφθησαν 150 υγιείς, θηλυκοί σκύλοι, οι οποίο προσκομίστηκαν στην Κλινική Ζώων Συντροφιάς του ΑΠΘ για ωοθηκυστερεκτομή και οι οποίοι κατανεμήθηκαν σε 6 ομάδες με βάση το στάδιο του ωοθηκικού κύκλου και την ενδεχόμενη ορμονική αγωγή που έλαβαν. Συγκεκριμένα, σχηματίστηκαν 6 ομάδες από ζώα στο στάδιο του ανοίστρου (ομάδα Α), ζώα σε άνοιστρο που έλαβαν προγεστερόνη ενδομυϊκώς (Απ), ζώα στο στάδιο του διοίστρου (Δ), ζώα σε δίοιστρο που έλαβαν υποδορίως αγλεπριστόνη (Δα), ζώα σε δίοιστρο που έλαβαν κάψουλες τριλοστάνης (Δτ) και ζώα σε κυοφορία 28-42 ημερών (Ε). Σε κάθε ζώο καταγράφηκαν οι απαιτήσεις σε προποφόλη για εγκατάσταση της γενικής αναισθησίας, οι απαιτήσεις σε ισοφλουράνιο για διατήρηση, οι απαιτήσεις σε επιπλέον αναλγητικά φάρμακα είτε διεγχειρητικά είτε μετεγχειρητικά και έγιναν μετεγχειρητικές εκτιμήσεις πόνου. Επίσης έγιναν αιμοληψίες σε συγκεκριμένες χρονικές στιγμές για ορμονολογικές αναλύσεις. Μετά τη στατιστική επεξεργασία των αποτελεσμάτων δε βρέθηκε στατιστικώς σημαντική διαφορά στις απαιτήσεις σε αναισθητικά ή σε αναλγητικά φάρμακα μεταξύ των ομάδων, ούτε στατιστικώς σημαντική συσχέτιση μεταξύ των απαιτήσεων αυτών και των συγκεντρώσεων στο αίμα της προγεστερόνης ή της αλλοπρεγνανολόνης, εκτός από 2 συσχετίσεις εντός συγκεκριμένων ομάδων. Συμπεραίνεται ότι οι συγκεντρώσεις προγεστερόνης ή αλλοπρεγνανολόνης στο αίμα δεν επηρεάζουν τις απαιτήσεις σε αναισθητικά ή αναλγητικά φάρμακα για τη διεξαγωγή ωοθηκυστερεκτομής στο σκύλο ή ότι ενδεχόμενη τέτοια επιρροή επικαλύπτεται από τη χορήγηση προαναισθητικής αγωγής και αναλγητικών φαρμάκων.The objective of the current study was to investigate the effect of serum progesterone concentration, either endogenous, during the ovarian cycle and pregnancy, or exogenous, when administered during anestrus, and of its active metabolite allopregnanolone, on anesthetic and analgesic requirements, as well as post-operative pain intensity, for the performance of ovariohysterectomy in dogs. One hundred and fifty healthy female dogs, which were admitted to our clinic for elective ovariohysterectomy, were included in the present study. They were allocated to 6 groups according to the stage of the ovarian cycle and the corresponding serum progesterone co ncentration. The six groups consisted of dogs in anestrus (group A), in anestrus which received intramuscular progesterone injections prior to surgery (group Ap), dogs in diestrus (group D), in diestrus which received subcutaneous aglepristone injections prior to surgery (group Da), in diestrus which received oral trilostane prior to surgery (group Dt) and dogs in pregnancy of duration of 28-42 days (group P). Serum progesterone concentrations were measured in all dogs before and after any hormonal treatment and serum allopregnanolone concentrations were measured in selected dogs from all groups. The required dose of propofol for induction of anesthesia and the required isoflurane concentration for maintenance of anesthesia and the need for intraoperative fentanyl administration and extra postoperative pethidine analgesia were recorded. After statistical analysis, there were no significant differences between groups, regarding their anesthetic or analgesic requirements, that could be attributed to serum progesterone and/or allopregnanolone concentration. However, moderate correlations within certain groups were noted. Serum progesterone or allopregnanolone concentrations do not seem to have an effect on anesthetic and analgesic requirements for ovariohysterectomy in the dog or any potential effect is weak enough to be masked by the action of anesthetic premedication and/or analgesic and/or anaesthetic drugs used

Towards Emotion Recognition: A Persistent Entropy Application

Emotion recognition and classification is a very active area of research. In this paper, we present a first approach to emotion classification using persistent entropy and support vector machines. A topology-based model is applied to obtain a single real number from each raw signal. These data are used as input of a support vector machine to classify signals into 8 different emotions (calm, happy, sad, angry, fearful, disgust and surprised)

Speaker-independent emotion recognition exploiting a psychologically-inspired binary cascade classification schema

In this paper, a psychologically-inspired binary cascade classification schema is proposed for speech emotion recognition. Performance is enhanced because commonly confused pairs of emotions are distinguishable from one another. Extracted features are related to statistics of pitch, formants, and energy contours, as well as spectrum, cepstrum, perceptual and temporal features, autocorrelation, MPEG-7 descriptors, Fujisakis model parameters, voice quality, jitter, and shimmer. Selected features are fed as input to K nearest neighborhood classifier and to support vector machines. Two kernels are tested for the latter: Linear and Gaussian radial basis function. The recently proposed speaker-independent experimental protocol is tested on the Berlin emotional speech database for each gender separately. The best emotion recognition accuracy, achieved by support vector machines with linear kernel, equals 87.7%, outperforming state-of-the-art approaches. Statistical analysis is first carried out with respect to the classifiers error rates and then to evaluate the information expressed by the classifiers confusion matrices. © Springer Science+Business Media, LLC 2011

Cross validation of bi-modal health-related stress assessment

This study explores the feasibility of objective and ubiquitous stress assessment. 25 post-traumatic stress disorder patients participated in a controlled storytelling (ST) study and an ecologically valid reliving (RL) study. The two studies were meant to represent an early and a late therapy session, and each consisted of a "happy" and a "stress triggering" part. Two instruments were chosen to assess the stress level of the patients at various point in time during therapy: (i) speech, used as an objective and ubiquitous stress indicator and (ii) the subjective unit of distress (SUD), a clinically validated Likert scale. In total, 13 statistical parameters were derived from each of five speech features: amplitude, zero-crossings, power, high-frequency power, and pitch. To model the emotional state of the patients, 28 parameters were selected from this set by means of a linear regression model and, subsequently, compressed into 11 principal components. The SUD and speech model were cross-validated, using 3 machine learning algorithms. Between 90% (2 SUD levels) and 39% (10 SUD levels) correct classification was achieved. The two sessions could be discriminated in 89% (for ST) and 77% (for RL) of the cases. This report fills a gap between laboratory and clinical studies, and its results emphasize the usefulness of Computer Aided Diagnostics (CAD) for mental health care

Affective Man-Machine Interface: Unveiling human emotions through biosignals

As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological processes, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals

A serious games platform for cognitive rehabilitation with preliminary evaluation

In recent years Serious Games have evolved substantially, solving problems in diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a relevant role. Traditional cognitive therapies are often considered repetitive and discouraging for patients and Serious Games can be used to create more dynamic rehabilitation processes, holding patients' attention throughout the process and motivating them during their road to recovery. This paper reviews Serious Games and user interfaces in rehabilitation area and details a Serious Games platform for Cognitive Rehabilitation that includes a set of features such as: natural and multimodal user interfaces and social features (competition, collaboration, and handicapping) which can contribute to augment the motivation of patients during the rehabilitation process. The web platform was tested with healthy subjects. Results of this preliminary evaluation show the motivation and the interest of the participants by playing the games.- This work has been supported by FCT - Fundacao para a Ciencia e Tecnologia in the scope of the projects: PEst-UID/CEC/00319/2015 and PEst-UID/CEC/00027/2015. The authors would like to thank also all the volunteers that participated in the study