Host matrix metalloproteinases in cerebral malaria: new kids on the block against bloodbrain barrier integrity?

Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM

Education as a tool to reduce the water footprint of young people

Introduction: Due to the global changes, fresh water became scarce in many geographical realities. In this domain, education can play a significant role, contributing to the sustainable water management. Objectives: Estimate the Water Footprint (WF) of young people, including their direct and indirect water uses. Develop an educational application that aims to exemplify measures which lead to water conservation in their daily activities. Methods: Two questionnaires. The first one was formulated in order to estimate the average WF of a young person, and the second one to establish the basis of the educational application. Samples included 82 students in the 12 – 15 age range. Results: The average WF of a student is 3223±830 L/day. The total indirect water use is over 10 times higher than direct use. Food accounts for the major part (84.4 %) of young person’s WF, and in the second place of indirect uses is clothing-related WF (6.4 %). Among analysed food groups, meat has the largest contribution (39.6 %) to the total personal WF. For both genders, high direct water use (264 L/day) is due in large part to long showers. Conclusions: Young people consume too much fresh water, what suggests the need to improve their behaviour in terms of eating habits, clothing and shower duration.info:eu-repo/semantics/publishedVersio

Neural Networks and Connectivity among Brain Regions

As is widely understood, brain functioning depends on the interaction among several neural populations, which are linked via complex connectivity circuits and work together (in antagonistic or synergistic ways) to exchange information, synchronize their activity, adapt plastically to external stimuli or internal requirements, and more generally to participate in solving multifaceted cognitive tasks [...]

Investigating Power and Limitations of Ensemble Motif Finders Using Metapredictor CE3

Ensemble methods represent a relatively new approach to motif discovery that combines the results returned by "third-party" finders with the aim of achieving a better accuracy than that obtained by the single tools. Besides the choice of the external finders, another crucial element for the success of an ensemble method is the particular strategy adopted to combine the finders' results, a.k.a. learning function. Results appeared in the literature seem to suggest that ensemble methods can provide noticeable improvements over the quality of the most popular tools available for motif discovery. With the goal of better understanding potentials and limitations of ensemble methods, we developed a general software architecture whose major feature is the flexibility with respect to the crucial aspects of ensemble methods mentioned above. The architecture provides facilities for the easy addition of virtually any third-party tool for motif discovery whose code is publicly available, and for the definition of new learning functions. We present a prototype implementation of our architecture, called CE3 (Customizable and Easily Extensible Ensemble). Using CE3, and available ensemble methods, we performed experiments with three well-known datasets. The results presented here are varied. On the one hand, they confirm that ensemble methods cannot be just considered as the universal remedy for "in-silico" motif discovery. On the other hand, we found some encouraging regularities that may help to find a general set up for CE3 (and other ensemble methods as well) able to guarantee substantial improvements over single finders in a systematic way

Mining extraction in the ocean depths: a baseline to understand and reduce acoustic impact on biodiversity

Tesis por compendio[ES] A lo largo de la historia, el hombre ha explotado los recursos minerales de la tierra para su supervivencia y desarrollo tecnológico sin un equilibrio con su regeneración. Dado el crecimiento de la población mundial y la reducción de recursos, el hombre comenzó a buscar nuevos depósitos que se encontraron en la década de 1960 en las profundidades de los océanos. Con estos, la humanidad empezò a pensar en extraer los minerales de estos depósitos y esto llevò al nacimiento de Deep Sea Mining (DSM). Las consecuencias de las actividades mineras en las profundidades del mar no se conocen realmente y los efectos pueden ser diferentes: contaminación acústica, contaminación lumínica, contaminación química, destrucción del hábitat, fragmentación del hábitat y pérdida de especies que son la base de muchos sistemas vitales. El impacto acústico de estas actividades puede tener importantes consecuencias en las especies marinas, aunque este es el tema más ignorado. El propósito de este proyecto de doctorado fue proporcionar una comprensión básica de los posibles impactos acústicos del DSM en la biodiversidad antes de que comiencen estas actividades. Para hacer esto, el proyecto de doctorado se organizó en varios pasos. Primero, durante un experimento indoor, se analizaron las respuestas bioquímicas en invertebrados sometidos a estrés acústico, Arbacia lixula y Mytilus galloprovincialis. Los resultados demostraron efectos significativos en la actividad de citotoxicidad, expresión de heat shock protein (HSPs) y actividades enzimáticas (esterasas, fosfatasas alcalinas, peroxidasas) en el líquido celomático de los erizos de mar sometidos a estrés acústico. También se observaron efectos significativos en el nivel de glucosa, la citotoxicidad y las actividades enzimáticas (esterasa, fosfatasa alcalina, peroxidasa) de la glándula digestiva del mejillón. En segundo lugar, se analizaron las respuestas bioquímicas de vertebrados e invertebrados sometidos in-situ a la emisión de watergun: Chromis chromis, Holothuria tubulosa y Arbacia lixula. Se encontraron efectos significativos sobre los niveles de cortisol en peces y las actividades enzimáticas (esterasas, fosfatasas alcalinas, peroxidasas y superoxide dismutasas) en membrana peristomial de erizo de mar. Además, las respuestas bioquímicas enzimáticas analizadas en los fluidos celómicos de los equinodermos fue significativa solo por A. lixula y solo en la activade peroxidasica. Tercero se estudiaron los cambios de comportamiento en las condiciones experimentales en juveniles de Sparus aurata sometidos a 4 frecuencias de emisión acústica diferentes. Este experimento demostró que solo las bajas frecuencias tuvieron efectos en todas las respuestas comportamental: altura de natación, motilidad y dispersión del grupo. Sobre la base de los datos de comportamiento obtenidos in vivo en peces jóvenes, se creó un modelo numérico para predecir los impactos de diferentes frecuencias de emisión acústica. Utilizando los resultados obtenidos y la bibliografía científica, se propuso un primer estándar técnico que es útil para la minería.[CA] A lo llarc de l'historia, l'home ha explotat els recursos minerals de la terra per a la seua supervivencia i desenroll tecnologic sense un equilibri en la seua regeneracio. Donat el creiximent de la poblacio mundial i la reduccio de recursos, l'home escomençà a buscar nous deposits que se trobaren en la decada de 1960 en les fondaries dels oceans. En estos, l'humanitat empezò a pensar en extraure els minerals d'estos deposits i aço llevò al naiximent de Deep Sea Mining (DSM). Les conseqüencies de les activitats mineres en les fondaries del mar no se coneixen realment i els efectes poden ser diferents: contaminacio acustica, contaminacio lluminica, contaminacio quimica, destruccio de l'habitat, fragmentacio de l'habitat i perdua d'especies que son la base de molts sistemes vitals. L'impacte acustic d'estes activitats pot tindre importants conseqüencies en les especies marines, encara que este es el tema mes ignorat. El proposit d'este proyecte de doctorat fon proporcionar una comprensio basica dels possibles impactes acustics del DSM en la biodiversidad abans de que escomencen estes activitats. Per a fer aço, el proyecte de doctorat s'organisà en varis passos. Primer, durant un experiment indoor, s'analisaren les respostes bioquimiques en invertebrats somesos a estrés acustic, Arbacia lixula i Mytilus galloprovincialis. Els resultats demostraren efectes significatius en l'activitat de citotoxicidad, expressio d'heat shock protein (HSPS) i activitats enzimáticas (esterasa, fosfatasas alcalina, peroxidasas) en el liquit celomático dels capellanets de mar somesos a estrés acustic. Tambe s'observaren efectes significatius en el nivell de glucosa, la citotoxicidad i les activitats enzimáticas (esterasa, fosfatasa alcalina, peroxidasas) de la glandula digestiva de la clochina. En segon lloc, s'analisaren les respostes bioquimiques de vertebrats i invertebrats somesos in-situ a l'emissio de watergun: Chromis chromis, Holothuria tubulosa i Arbacia lixula. se trobaren efectes significatius sobre els nivells de cortisol en peixos i les activitats enzimáticas (esterasas, fosfatasas alcalines, peroxidasas y superoxide dimutases) en peristomes de capellanet de mar. Ademes, les respostes bioquimiques enzimáticas analisades en els decorreguts celómicos dels equinoderms fon significativa nomes per A. lixula i nomes en l'activade peroxidasica. Tercer s'estudiaren els canvis de comportament en les condicions experimentals en jovenils de Sparus aurata somesos a 4 freqüencies d'emissio acustica diferents. Este experiment demostrà que nomes les baixes freqüencies tingueren efectes en totes les respostes comportamental: alçada de natacio, motilidad i escampada del grup. Sobre la base de les senyes de comportament obtinguts in vivo en peixos jovens, se creó un model numeric per a predecir els impactes de diferents freqüencies d'emissio acustica. Utilisant els resultats obtinguts i la bibliografia cientifica, se propongue un primer estandart tecnic que es util per a la mineria.[EN] Throughout history, man has exploited the earth's mineral resources for its survival and for technological development without regard for their regeneration. Given the growth of the world population and given the fall in resources, man started looking for new deposits, which were found in 1960s in the ocean depths. Humankind then began to consider extracting minerals from these deposits and this gave origin to Deep Sea Mining (DSM). The consequences of mining activities in the deep sea are not entirely known and the effects can be varied: noise pollution, light pollution, chemical pollution, habitat destruction, habitat fragmentation and the loss of species which we consider the basis of many life systems. The acoustic impact of these activities could have significant consequences on marine species; nevertheless, this has been the most overlooked issue to date. The aim of this PhD project was to provide baseline knowledge of possible acoustic impacts of DSM on biodiversity before mining begins. In order to do this, the PhD project was organised into 3 different stages. First, during an indoor experiment, the biochemical responses of invertebrates Arbacia lixula and Mytilus galloprovincialis subjected to acoustic stress were analysed. The results showed significant changes in cytotoxicity activity, expression of heat shock proteins (HSPs), and enzyme activities (esterases, alkaline phosphatases, peroxidases) in the coelomic fluid of sea urchins subjected to acoustic stress. Significant effects were also observed in glucose levels, cytotoxicity and enzyme activities (esterase, alkaline phosphatase, peroxidase) in the digestive gland of the mussel. Second, the biochemical responses of vertebrates and invertebrates subjected in-situ to watergun emission were analysed: Chromis chromis, Holothuria tubulosa and Arbacia lixula. Significant effects on fish cortisol levels and on enzyme activities in sea urchin peristomes were found. Furthermore, the enzyme biochemical responses analysed in the coelomic fluids of echinoderms showed significant effects only in A. lixula sea urchin and only in peroxidase activity. Third, behavioural changes in experimental conditions were studied in juveniles of Sparus aurata subjected to 4 different acoustic emission frequencies. This experiment showed that only low frequencies had effects on all the behavioural responses analysed: swimming height, motility and dispersion of the group. Based on behavioural data obtained in vivo on juvenile fish, a numerical model was created to predict the impacts of different acoustic emission frequencies. Using the results obtained and literature, a first technical standard useful for mining activities was drawn up.The study of the Section 3.3 was supported by grants from MIUR (Ministry of Education, University and Research), Fondo Finalizzato alla Ricerca di Ateneo (FFR, 2018-2021) to M.V. and by the CNR research project: IMPLEMENTATION OF THE SOS CONVENTION - Offshore Platforms & Impacts between MATTM and CNR-DTA, (Capo Granitola, Campobello di Mazara) Work Package E: Indepth technical and scientific evaluation of the effects on marine ecosystems of airgun technologies and the effects of a watergun The study of the Section 3.4 study was conducted in the framework of the PhD program in Mediterranean Biodiversity XXXII cycle (International) of the University of Palermo. I. Perez-Arjona, M. Bou-Cabo and V. Espinosa acknowledge the financial support of the European Comission -project 11.0661/2018794607/SUB/ENV.C2. Risk-based Approaches to Good Environmental Status (RAGES). The other founding supports come from PhD Innovative with Industrial Characterization PON 2014-2020 and the projects CAIMAR Joint Laboratory Italy-Argentina (Laboratori Congiunti Bilaterali Internazionali of the Italian National Reseach Council, 2017-2019) and BOSS – Study of bioacoustics and applications for the sustainable exploitation of marine resources (Projects of major importance in the Scientific and Technological Collaboration Executive Programmes, funded by the Italian Ministry of Foreign Affairs and International Cooperation).Mauro, M. (2020). Mining extraction in the ocean depths: a baseline to understand and reduce acoustic impact on biodiversity [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/144131TESISCompendi

CE3: Customizable and Easily Extensible Ensemble Tool for Motif Discovery

Ensemble methods (or simply ensembles) for motif discov- ery represent a relatively new approach to improve the ac- curacy of stand-alone motif finders. The performance of an ensemble is clearly determined by the included finders as well as the strategy to combine the results returned by the latter (the so called learning rule). A potential obstacle to a widespread adoption of ensembles is that the choice of the particular finders included is closed. Although possible in principle, the addition to an ensemble of a new "promising" tool requires knowledge of the internals of the ensemble and usually non trivial programming skills. In this research we propose a general architecture for ensem- bles and a prototype called CE3: Customizable and Easily Extensible Ensemble, which is meant to be extensible and customizable at the level of the two key components mod- ules namely external tools finding and learning rule. In this way the user will be able to essentially "simulate" any ex- isting ensemble, create his/her own ensemble according to his/her preferences on finding tools and learning functions and, finally, keep it up to date when new tools and new ideas for learning functions are proposed in literature. These fea- tures also make CE3 a suitable tool to perform experiments that may lead to a proper configuration of ensembles in the research of novel motifs

Collective locomotion of human cells, woundh healing and their control by extracts and isolated compounds from marine ivertebrates

The collective migration of cells is a complex integrated process that represents a common theme joining morphogenesis, tissue regeneration, and tumor biology. It is known that a remarkable amount of secondary metabolites produced by aquatic invertebrates displays active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of crude extracts or isolated compounds that exert a modulatory effect on collective cell locomotion and/or skin tissue reconstitution and recapitulate the molecular, biochemical, and/or physiological aspects, where available, which are associated to the substances under examination, grouping the producing species according to their taxonomic hierarchy. Taken all of the collected data into account, marine invertebrates emerge as a still poorly-exploited valuable resource of natural products that may significantly improve the process of skin regeneration and restrain tumor cell migration, as documented by in vitro and in vivo studies. Therefore, the identification of the most promising invertebrate-derived extracts/molecules for the utilization as new targets for biomedical translation merits further and more detailed investigations

Direct vs 2-stage approaches to structured motif finding

BACKGROUND: The notion of DNA motif is a mathematical abstraction used to model regions of the DNA (known as Transcription Factor Binding Sites, or TFBSs) that are bound by a given Transcription Factor to regulate gene expression or repression. In turn, DNA structured motifs are a mathematical counterpart that models sets of TFBSs that work in concert in the gene regulations processes of higher eukaryotic organisms. Typically, a structured motif is composed of an ordered set of isolated (or simple) motifs, separated by a variable, but somewhat constrained number of “irrelevant” base-pairs. Discovering structured motifs in a set of DNA sequences is a computationally hard problem that has been addressed by a number of authors using either a direct approach, or via the preliminary identification and successive combination of simple motifs. RESULTS: We describe a computational tool, named SISMA, for the de-novo discovery of structured motifs in a set of DNA sequences. SISMA is an exact, enumerative algorithm, meaning that it finds all the motifs conforming to the specifications. It does so in two stages: first it discovers all the possible component simple motifs, then combines them in a way that respects the given constraints. We developed SISMA mainly with the aim of understanding the potential benefits of such a 2-stage approach w.r.t. direct methods. In fact, no 2-stage software was available for the general problem of structured motif discovery, but only a few tools that solved restricted versions of the problem. We evaluated SISMA against other published tools on a comprehensive benchmark made of both synthetic and real biological datasets. In a significant number of cases, SISMA outperformed the competitors, exhibiting a good performance also in most of the cases in which it was inferior. CONCLUSIONS: A reflection on the results obtained lead us to conclude that a 2-stage approach can be implemented with many advantages over direct approaches. Some of these have to do with greater modularity, ease of parallelization, and the possibility to perform adaptive searches of structured motifs. As another consideration, we noted that most hard instances for SISMA were easy to detect in advance. In these cases one may initially opt for a direct method; or, as a viable alternative in most laboratories, one could run both direct and 2-stage tools in parallel, halting the computations when the first halts