Differential efficiency of the endocytic machinery in tonic and phasic synapses

Efficient synaptic vesicle membrane recycling is one of the key factors required to sustain neurotransmission. We investigated potential differences in the compensatory endocytic machineries in two glutamatergic synapses with phasic and tonic patterns of activity in the lamprey spinal cord. Post-embedding immunocytochemistry demonstrated that proteins involved in synaptic vesicle recycling, including dynamin, intersectin, and synapsin, occur at higher levels (labeling per vesicle) in tonic dorsal column synapses than in phasic reticulospinal synapses. Synaptic vesicle protein 2 occurred at similar levels in the two types of synapse. After challenging the synapses with high potassium stimulation for 30 min the vesicle pool in the tonic synapse was maintained at a normal level, while that in the phasic synapse was partly depleted along with expansion of the plasma membrane and accumulation of clathrin-coated intermediates at the periactive zone. Thus, our results indicate that an increased efficiency of the endocytic machinery in a synapse may be one of the factors underlying the ability to sustain neurotransmission at high rates.

Nuclear and mitochondrial control of the apoptosis machinery regulates neural stem cell fate

Tese de doutoramento, Farmácia (Bioquímica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Promoting Portuguese exports to Germany: An export promotion plan for the machinery & equipment sector

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Systematic analysis of protein complexes involved in the human RNA polymerase II machinery

La transcription, la maturation d’ARN, et le remodelage de la chromatine sont tous des processus centraux dans l'interprétation de l'information contenue dans l’ADN. Bien que beaucoup de complexes de protéines formant la machinerie cellulaire de transcription aient été étudiés, plusieurs restent encore à identifier et caractériser. En utilisant une approche protéomique, notre laboratoire a purifié plusieurs composantes de la machinerie de transcription de l’ARNPII humaine par double chromatographie d’affinité "TAP". Cette procédure permet l'isolement de complexes protéiques comme ils existent vraisemblablement in vivo dans les cellules mammifères, et l'identification de partenaires d'interactions par spectrométrie de masse. Les interactions protéiques qui sont validées bioinformatiquement, sont choisies et utilisées pour cartographier un réseau connectant plusieurs composantes de la machinerie transcriptionnelle. En appliquant cette procédure, notre laboratoire a identifié, pour la première fois, un groupe de protéines, qui interagit physiquement et fonctionnellement avec l’ARNPII humaine. Les propriétés de ces protéines suggèrent un rôle dans l'assemblage de complexes à plusieurs sous-unités, comme les protéines d'échafaudage et chaperonnes. L'objectif de mon projet était de continuer la caractérisation du réseau de complexes protéiques impliquant les facteurs de transcription. Huit nouveaux partenaires de l’ARNPII (PIH1D1, GPN3, WDR92, PFDN2, KIAA0406, PDRG1, CCT4 et CCT5) ont été purifiés par la méthode TAP, et la spectrométrie de masse a permis d’identifier de nouvelles interactions. Au cours des années, l’analyse par notre laboratoire des mécanismes de la transcription a contribué à apporter de nouvelles connaissances et à mieux comprendre son fonctionnement. Cette connaissance est essentielle au développement de médicaments qui cibleront les mécanismes de la transcription.

Studies On Some Boring And Fouling Crustaceans

The present work comprises studies on the salinity tolerance and respiratory metabolism of a mood-boring sphaeromid, Sphaeroma annandalei, Stabbing and two free living,foulers of the family Cirolanidae, Cirolana fluviatilis Stabbing and C. uilleyi Stabbing. Except for the systematic accounts and general observations by Pillai (1961) and the preliminary studies on the salinity tolerance and respiration of C. fluviatilis by Nagabhushanam and Gopalakrishnamurthy (1965, 1965a) very little is known about these isopods From Indian waters. Studies by John (1968) on the habits, structure, and development of Sphaeroma terebrans and by Cheriyan (1973) on the eoéphysiology of the same are the recent major contributions on this interesting group of animals. 5. annandalei is closely related to S. terebrans and has been reported to occur on timber along with the latter (Pillai, 1951). s. gggandalei is a serious pest attacking wood along the Kerala coast, but detailed works on this species have not been undertaken so Far

Unveiling the components of the signaling pathway between endosomes and the phagocytic uptake machinery in Dictyostelium discoideum

The soil amoebae Dictyostelium discoideum take up particles from their environment in order to obtain nutrition. The particle transits through the cell within a phagosome that fuses with organelles of different molecular compositions, undergoing a gradual degradation by different sets of hydrolytic enzymes. Griffiths’ concept of “phagosome individuality” predicts signaling from phagosomes into the cytoplasm, which might regulate many aspects of cell physiology. The finding that Dictyostelium cells depleted of the lysozyme AlyA or over-expressing the esterase Gp70 exhibit increased uptake of food particles, led to the postulation of a signaling cascade between endocytic compartments and the cytoskeletal uptake machinery at the plasma membrane. Assuming that Gp70 acts downstream of AlyA, gene-expression profiling of both mutants revealed different and overlapping sets of misregulated genes that might participate in this signaling cascade. Based on these results, we analyzed the effects of the artificial misregulation of six candidate genes by over-expression or negative genetic interference, in order to reconstruct at least part of the signaling pathway. SSB420 and SSL793 were chosen as candidates for the first signaling step, as they were up-regulated in AlyA-null cells and remained unaltered in the Gp70 over-expressing cells. The over-expression of SSB420 enhanced phagocytosis and raised the expression levels of Gp70, supporting its involvement in the signaling pathway between AlyA and Gp70 as a positive regulator of phagocytosis. However, this was not the case of cells over-expressing SSL793, as this mutation had no effects on phagocytosis. For the signaling downstream of Gp70, we studied four commonly misregulated genes in AlyA-depleted and Gp70 over-expressing cells. The expression levels of SLB350, SSB389 and TipD were lower in both mutants and therefore these were assumed as possible candidates for the negative regulation of phagocytosis. Cells depleted of SLB350 exhibited an increased phagocytic activity and no effect on Gp70 expression, proving its participation in the signaling pathway downstream of Gp70. Unlike SLB350, the disruption of the genes coding for SSB389 and TipD had no effects on particle uptake, excluding them from the pathway. The fourth candidate was Yipf1, the only gene that was commonly up-regulated in both mutants. Yet, the artificial over-expression of this protein had no effects on phagocytosis, so this candidate is also not included in the signaling pathway. Furthermore, localizing the products of the candidate genes within the cell helped unveiling several cellular organelles that receive signals from the phagosome and transduce them towards the uptake machinery.

Data-Driven Text Generation using Neural Networks & Provenance is Complicated and Boring — Is there a solution?

Title: Data-Driven Text Generation using Neural Networks Speaker: Pavlos Vougiouklis, University of Southampton Abstract: Recent work on neural networks shows their great potential at tackling a wide variety of Natural Language Processing (NLP) tasks. This talk will focus on the Natural Language Generation (NLG) problem and, more specifically, on the extend to which neural network language models could be employed for context-sensitive and data-driven text generation. In addition, a neural network architecture for response generation in social media along with the training methods that enable it to capture contextual information and effectively participate in public conversations will be discussed. Speaker Bio: Pavlos Vougiouklis obtained his 5-year Diploma in Electrical and Computer Engineering from the Aristotle University of Thessaloniki in 2013. He was awarded an MSc degree in Software Engineering from the University of Southampton in 2014. In 2015, he joined the Web and Internet Science (WAIS) research group of the University of Southampton and he is currently working towards the acquisition of his PhD degree in the field of Neural Network Approaches for Natural Language Processing. Title: Provenance is Complicated and Boring — Is there a solution? Speaker: Darren Richardson, University of Southampton Abstract: Paper trails, auditing, and accountability — arguably not the sexiest terms in computer science. But then you discover that you've possibly been eating horse-meat, and the importance of provenance becomes almost palpable. Having accepted that we should be creating provenance-enabled systems, the challenge of then communicating that provenance to casual users is not trivial: users should not have to have a detailed working knowledge of your system, and they certainly shouldn't be expected to understand the data model. So how, then, do you give users an insight into the provenance, without having to build a bespoke system for each and every different provenance installation? Speaker Bio: Darren is a final year Computer Science PhD student. He completed his undergraduate degree in Electronic Engineering at Southampton in 2012.

Targeting the cell cycle machinery for the treatment of cardiovascular disease

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

Reprogramming the cell cycle machinery to treat cardiovascular disease

Coronary artery disease is one of the most common heart pathologies. Restriction of blood flow to the heart by atherosclerotic lesions, leading to angina pectoris and myocardial infarction, damages the heart, resulting in impaired cardiac function. Damaged myocardium is replaced by scar tissue since surviving cardiomyocytes are unable to proliferate to replace lost heart tissue. Although narrowing of the coronary arteries can be treated successfully using coronary revascularisation procedures, re-occlusion of the treated vessels remains a significant clinical problem. Cell cycle control mechanisms are key in both the impaired cardiac repair by surviving cardiomyocytes and re-narrowing of treated vessels by maladaptive proliferation of vascular smooth muscle cells. Strategies targeting the cell cycle machinery in the heart and vasculature offer promise both for the improvement of cardiac repair following MI and the prevention of restenosis and bypass graft failure following revascularisation procedures.

Multivariable cluster analysis for high-speed industrial machinery

The overall operation and internal complexity of a particular production machinery can be depicted in terms of clusters of multidimensional points which describe the process states, the value in each point dimension representing a measured variable from the machinery. The paper describes a new cluster analysis technique for use with manufacturing processes, to illustrate how machine behaviour can be categorised and how regions of good and poor machine behaviour can be identified. The cluster algorithm presented is the novel mean-tracking algorithm, capable of locating N-dimensional clusters in a large data space in which a considerable amount of noise is present. Implementation of the algorithm on a real-world high-speed machinery application is described, with clusters being formed from machinery data to indicate machinery error regions and error-free regions. This analysis is seen to provide a promising step ahead in the field of multivariable control of manufacturing systems.

Money enhances memory consolidation – but only for boring material

Money’s ability to enhance memory has received increased attention in recent research. However, previous studies have not directly addressed the time-dependent nature of monetary effects on memory, which are suggested to exist by research in cognitive neuroscience, and the possible detrimental effects of monetary rewards on learning interesting material, as indicated by studies in motivational psychology. By utilizing a trivia question paradigm, the current study incorporated these perspectives and examined the effect of monetary rewards on immediate and delayed memory performance for answers to uninteresting and interesting questions. Results showed that monetary rewards promote memory performance only after a delay. In addition, the memory enhancement effect of monetary rewards was only observed for uninteresting questions. These results are consistent with both the hippocampus-dependent memory consolidation model of reward learning and previous findings documenting the ineffectiveness of monetary rewards on tasks that have intrinsic value.