Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

Making the case: Health Equity Audit

A briefing aiming to provide guidance to the NHS and local government on undertaking HEA. Aims to increase understanding of the impact of social, economic and environmental influences on health and health inequalities, and to promote effective action.

New insights in carbohydrate-deficient transferrin analysis with capillary electrophoresis-mass spectrometry

Capillary zone electrophoresis (CZE) with UV detection has been widely used for the determination of carbohydrate-deficient transferrin (CDT), an indirect marker of the chronic alcohol consumption (≥60-80g/day). A commercially available method (CEofix? CDT kit), containing a bilayer anionic coating, allows for the analysis of CDT with a high resolution between transferrin (Tf) glycoforms with reduced protein adsorption onto the capillary wall. Although widely used in routine analysis, this procedure presents some limitations in terms of selectivity and sensitivity which may be overcome with mass spectrometry (MS). However, the available method is not MS-compatible due to the non-volatile coating as well as the phosphate and borate buffers present in the background electrolyte (BGE). This study firstly consisted in developing MS-compatible separation conditions, i.e., coating and BGE compositions. Numerous cationic, neutral, and anionic coatings were evaluated in combination with BGEs covering a broad range of pH values. A bilayer coating composed of a cationic layer of 10% polybrene (m/v) and an anionic layer of 10% dextran sulfate (m/v) combined with a BGE composed of 20mM ammonium acetate at pH 8.5 provided the best results in terms of glycoforms' resolution, efficiency, adsorption reduction, migration times' repeatability, and coating stability. The method was then transferred to CZE-MS after investigations of the electrospray ionization (ESI) source, equipped with a sheath-flow interface, and the time-of-flight (TOF/MS) parameters. A successful MS detection of tetrasialo-Tf was obtained during infusion, while the experiments highlighted the challenges and issues encountered with intact glycoprotein analysis by CZE-ESI-MS.

Cluster recognition in spatial-temporal sequences: The case of forest fires

Forest fire sequences can be modelled as a stochastic point process where events are characterized by their spatial locations and occurrence in time. Cluster analysis permits the detection of the space/time pattern distribution of forest fires. These analyses are useful to assist fire-managers in identifying risk areas, implementing preventive measures and conducting strategies for an efficient distribution of the firefighting resources. This paper aims to identify hot spots in forest fire sequences by means of the space-time scan statistics permutation model (STSSP) and a geographical information system (GIS) for data and results visualization. The scan statistical methodology uses a scanning window, which moves across space and time, detecting local excesses of events in specific areas over a certain period of time. Finally, the statistical significance of each cluster is evaluated through Monte Carlo hypothesis testing. The case study is the forest fires registered by the Forest Service in Canton Ticino (Switzerland) from 1969 to 2008. This dataset consists of geo-referenced single events including the location of the ignition points and additional information. The data were aggregated into three sub-periods (considering important preventive legal dispositions) and two main ignition-causes (lightning and anthropogenic causes). Results revealed that forest fire events in Ticino are mainly clustered in the southern region where most of the population is settled. Our analysis uncovered local hot spots arising from extemporaneous arson activities. Results regarding the naturally-caused fires (lightning fires) disclosed two clusters detected in the northern mountainous area.

Forest fires cluster detection with space-time scan statistics

Forest fires are defined as uncontrolled fires often occurring in wildland areas, but that can also affect houses or agricultural resources. Causes are both natural (e.g.,lightning phenomena) and anthropogenic (human negligence or arsons).Major environmental factors influencing the fire ignition and propagation are climate and vegetation. Wildfires are most common and severe during drought period and on windy days. Moreover, under water-stress conditions, which occur after a long hot and dry period, the vegetation is more vulnerable to fire. These conditions are common in the United State and Canada, where forest fires represent a big problem. We focused our analysis on the state of Florida, for which a big dataset on forest fires detection is readily available. USDA Forest Service Remote Sensing Application Center, in collaboration with NASA-Goddard Space Flight Center and the University of Maryland, has compiled daily MODIS Thermal Anomalies (fires and biomass burning images) produced by NASA using a contextual algorithm that exploits the strong emission of mid-infrared radiation from fires. Fire classes were converted in GIS format: daily MODIS fire detections are provided as the centroids of the 1 kilometer pixels and compiled into daily Arc/INFO point coverage.

The Role of AtPHO1 in the Guard Cell Movements of Arabidopsis thaliana

In plants, stomatal opening and closing are driven by ion fluxes that cause changes in guard cell turgor and volume, a process that is in turn regulated by complex environ¬mental and hormonal signals such as light and the phytohormone abscisic acid (ABA). With this study, we present genetic evidence that stomatal movements in response to ABA are influenced by PHOl expression in guard cells of Arabidopsis thaliana. PHOl is a phosphate exporter involved in phosphate loading into the root xylem ves¬sels and, as a result, the phol mutant is characterized by low shoot phosphate lev¬els. In leaves, PHOl was found expressed at higher level in guard cells, and was quickly up-regulated following treatment with ABA. The phol mutant was unaffected in ROS production following ABA treatment, and in stomatal movements in response to different light cues, high extracellular calcium, auxin, and fusicoccin. However, stomatal movements in response to ABA treatment were severely impaired, both in terms of induction of closure and inhibition of opening. Stomatal movements in re¬sponse to hydrogen peroxide and reduced CO2 was altered as well. Micro-grafting a phol shoot scion onto wild-type root stock resulted in plants with normal shoot growth and Pi content, but failed to restore normal stomatal response to ABA treat-ment, showing that the impairment was not a simple pleiotropic consequence of phos¬phate deficiency. PHOl knockdown using RNAi specifically in guard cells of wild-type plants caused a reduced stomatal response to ABA. In agreement, specific expression of PHOl in guard cells of phol plants complemented the mutant guard cell phenotype and re-established ABA sensitivity, although full functional complementation was co- dependent on shoot Pi sufficiency. Down-regulation of PHOl in guard cells did not alter the expression of ABA marker genes, indicating that PHOl does not affect the ABA signal transduction cascade at the transcriptional level. Together, these data reveal an important role for phosphate and PHOl action in the stomatal response to ABA. Résumé L'ouverture et la fermeture des stomates des plantes sont des mouvements contrôlés par des flux d'ions causant des fluctuations de la turgescence des cellules de garde. Ce procédé est en retour régulé par des signaux environnementaux et hormonaux complexes, comme la lumière et l'hormone végétale acide abscissique (ABA). Nous présentons ici des preuves génétiques montrant que les mouvements stomatiques en réponse à l'ABA sont influencés par l'expression de PHOl dans les cellules de garde d'Arabidopsis thaliana. PHOl est un exporteur de phosphate, impliqué dans l'efflux de phosphate des cellules corticales racinaires vers les vaisseaux de xylème. En con¬séquence, le mutant phol est caractérisé par de faibles niveaux de phosphate dans les parties aériennes. Dans les feuilles, PHOl est exprimé préférentiellement dans les cellules de garde, comparé au mésophylle, et est rapidement induit par le traitement à l'ABA. Le mutant phol n'est pas affecté dans la perception de l'ABA, dans la pro¬duction de ROS en réponse à l'ABA, et dans la réponse des stomates aux traitements de lumière, à l'auxine, à la fusiccocine, et la forte concentration extracellulaire de cal¬cium. En revanche, les mouvements de stomates en réponse aux traitements à l'ABA sont fortement affectés, dans l'induction de la fermeture des stomates comme dans l'inhibition de leur ouverture. De plus, les mouvements de stomates en réponse au péroxyde d'hydrogène et à la diminution du CO2 sont aussi compromis. La création de micro-greffes composées d'une partie aérienne phol greffés sur un système racinaire sauvage génère des plantes avec une croissance et une teneur en phosphate normale, mais ne permet pas de restaurer la réponse des stomates à l'ABA, ce qui démontre que le défaut de réponse à l'ABA n'est pas une simple conséquence pléiotropique de la carence en phosphate. La répression par RNAi de l'expression de PHOl dans les stomates de plantes sauvages provoque une réduction de la réponse des stomates à l'ABA, mais n'affecte pas la réponse de gènes marqueurs à l'ABA, ce qui suggère que PHOl n'agit pas au niveau transcriptionnel. Parallèlement, l'expression de PHOl dans les cellules de gardes de mutants phol complémente le phénotype stomatique mutant et rétablit la réponse à l'ABA, bien que la totale complémentation nécessite l'apport normal de phosphate aux parties aériennes. Ensemble, ces résultats révè¬lent l'influence importante de PHOl et du phosphate dans la réponse des stomates à l'ABA.

Population-level changes to promote cardiovascular health.

BACKGROUND: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. DESIGN AND METHODS: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). RESULTS: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. CONCLUSION: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.

Importância da Gestão de Créditos na gestão da Tesouraria das Empresas

A gestão de Crédito é um tema que vem chamando a atenção dos administradores, já que é considerado um instrumento de gestão muito importante no processo competitivo e para o equilíbrio das empresas. O estudo em causa tem como objectivo principal analisar a importância e os impactos da Gestão de Crédito na Tesouraria das empresas, através de um estudo de caso da empresa Electra, SA. Os resultados do estudo mostram que os problemas de tesouraria podem ser de natureza estrutural e conjuntural. A gestão de tesouraria de curto prazo é o mais importante instrumento de gestão financeira que avalia e controla a actividade corrente das empresas, permitindo em tempo oportuno a tomada de decisões, perspectivando uma gestão eficiente, o equilíbrio financeiro e a eficácia organizacional. O tema em estudo pretende realçar a importância que a gestão de créditos tem na gestão da tesouraria de curto prazo, já que este tem como principal função para além da gestão do realizável (créditos), a gestão do disponível, do stock, das dívidas a terceiros a curto prazo. Uma boa gestão de crédito (realizável) permite de uma forma directa ganhos de eficiência a nível da gestão do disponível, na gestão dos stocks e de forma indirecta influencia as decisões a nível da gestão das dívidas a terceiros de curto prazo. Credit management is a subject that has been growing in the administrator’s attention, as it’s considered to be a somewhat important management tool on the competitive process as well as on the company’s balance. The present case study on Electra S.A, aims for the importance and impact analysis of Credit Management on the company’s cashier. The study results demonstrate that the cashier issues can be structure and conjuncture related. The short term cashier management is the most important financial management tool, which assesses and controls the company’s current activity, enabling timely decision making process, foreseeing an efficient management, the financial equilibrium and the organization efficiency. This paper’s main goal is to enhance the credit management importance on the short term cashier management, as the latter’s main goal, apart from the credit management is to administer the availability, the stock and short term third party debts. A good credit management enables a direct efficiency improvement at the availability management level, on the stock management and indirectly influences the decisions taken at the short term third party debt management level.

Padrões de Distribuição da Flora Exótica em Cabo Verde: o Papel dos Factores Antrópicos e Ecológicos

Dada a relevância a nível global do impacto da introdução de espécies exóticas, e tendo sido identificada uma grande escassez de estudos nesta área de investigação em Cabo Verde, pretendeu-se com este estudo actualizar a lista dos taxa exóticos naturalizados deste arquipélago, fornecendo dados sobre a sua distribuição, caracterização taxonómica e principais grupos funcionais. Com o objectivo de averiguar quais são os factores que influenciam os padrões de distribuição da flora exótica nestas ilhas, efectuaram-se correlações de Spearman entre o número de taxa exóticos e várias variáveis ambientais e antrópicas. Sendo conhecida a importância que os factores antrópicos têm na composição e distribuição da flora introduzida, procurou-se ainda perceber se a flora da única ilha desabitada do arquipélago (Santa Luzia) poderá ser indicadora de características invasoras das espécies introduzidas. Os resultados obtidos indicaram um total de 403 taxa exóticos, correspondendo a 55% da flora de Cabo Verde, sendo as Poaceae, Fabaceae e Asteraceae as famílias com maior número de espécies. Verificou-se também que predominam as espécies herbáceas e o tipo biológico mais frequente é o terófito. Além disso, a população rural é o factor que mais fortemente e positivamente correlacionado com os padrões de distribuição da flora exótica em Cabo Verde. Correlações positivas muito significativas foram também encontradas para a área e altitude máxima de cada ilha. A análise da flora exótica da ilha desabitada de Santa Luzia revelou que, embora os taxa exóticos registados nesta ilha estejam presentes em quase todas as outras ilhas, as espécies inventariadas parecem não exibir um comportamento invasor ou de ameaça à flora nativa. Para finalizar, espera-se que os resultados obtidos possam contribuir com informação que fundamente futuras estratégias de conservação da Biodiversidade das ilhas de Cabo Verde.

Mulheres imigrantes cabo-verdianas nas prisões portuguesas (des) integração, reclusão e projectos de vida

O presente estudo baseia-se em mulheres imigrantes cabo-verdianas nas prisões portuguesas. A informação foi recolhida no Estabelecimento Prisional de Tires e assentou em mulheres condenadas que cumprem pena efetiva de prisão. Quisemos perceber quais os motivos que levaram estas mulheres imigrantes a abandonarem o seu país de origem, se tiveram dificuldades de integração no país que as acolheu e se em resultado desse acolhimento caíram nas malhas da justiça. Pretendíamos também saber se o espaço que se vêm obrigadas a abraçar, resultado do contacto com a justiça, servia para reflexão das suas vidas pregressas e se daí resultavam mais valias para a concretização dos seus projetos de vida. Imaginar o ambiente prisional não é certamente o mesmo que ter contacto com a instituição. A ideia de prisão não passa apenas pelo espaço fechado, mas também pelo local frio, receoso, degradante, onde se aperfeiçoa o crime e onde existe um código de ética por parte de reclusos/as. As prisões são muitas vezes apelidadas de “escolas de crime”. Importa por isso fazer uma abordagem à evolução do sistema prisional português, compreender a sua evolução, as limitações, o avanço feito ao nível da abertura ao exterior e sobretudo a evolução ao nível da humanização. Aquele espaço fechado e altruísta teve o seu fim, e em boa hora o possamos dizer. Fez-se uma abordagem à integração social, aos fatores que intervêm no processo e uma breve sinopse caraterizando a comunidade Cabo-verdiana. Pela metodologia utilizada, concluiu-se que as dificuldades de integração não parecem estar diretamente relacionadas com a prática do crime. As razões económicas e as influências externas foram os dois fatores mais vincados, retirados da análise dos dados. Importa aqui salientar que quadros sociais e económicos fragilizados poderão ser fomentadores de atividades ilícitas.

Calidad del ambiente marino y costero en la Región Áncash, 2012

Entre abril y octubre 2012, se evaluó la línea costera y las bahías Coishco, El Ferrol, Samanco, Tortuga, Casma, Huarmey y Caleta Culebras y los ríos Santa, Lacramarca, Casma, Culebras, Huarmey y Samanco. Se localizaron valores termohalinos propios de Aguas Costeras Frías (ACF) con influencias de vertidos antropogénicos y variaciones locales del proceso de evaporación. En abril el oxígeno disuelto presentó valores >5,00 mg/L en toda el área a excepción de la bahía Coishco (3,72 mg/L); en octubre la concentración más alta estuvo en Samanco (7,51 mg/L) y la más baja en Huarmey (2,53 mg/L), el pH estuvo en relación directa con el oxígeno. En abril y octubre los agentes contaminantes de sólidos suspendidos totales presentaron valores >30,00 mg/L en las bahías Coishco, El Ferrol y Tortuga, superando lo permitido por los Estándares Nacionales de Calidad Ambiental para Agua, categoría 4. En abril y octubre la calidad de agua en la cuenca baja de los ríos Santa, Lacramarca, Casma, Culebras y Huarmey respecto a la concentración de la demanda bioquímica de oxígeno estuvo dentro de los Estándares Nacionales de Calidad Ambiental para Agua, categoría 4.

Identifying the socioeconomic determinants of crime in Spanish provinces

In this paper we study, having as theoretical reference the economic model of crime (Becker, 1968; Ehrlich, 1973), which are the socioeconomic and demographic determinants of crime in Spain paying attention on the role of provincial peculiarities. We estimate a crime equation using a panel dataset of Spanish provinces (NUTS3) for the period 1993 to 1999 employing the GMMsystem estimator. Empirical results suggest that lagged crime rate and clear-up rate are correlated to all typologies of crime rate considered. Property crimes are better explained by socioeconomic variables (GDP per capita, GDP growth rate and percentage of population with high school and university degree), while demographic factors reveal important and significant influences, in particular for crimes against the person. These results are obtained using an instrumental variable approach that takes advantage of the dynamic properties of our dataset to control for both measurement errors in crime data and joint endogeneity of the explanatory variables

Identifying the socioeconomic determinants of crime in Spanish provinces

In this paper we study, having as theoretical reference the economic model of crime (Becker, 1968; Ehrlich, 1973), which are the socioeconomic and demographic determinants of crime in Spain paying attention on the role of provincial peculiarities. We estimate a crime equation using a panel dataset of Spanish provinces (NUTS3) for the period 1993 to 1999 employing the GMMsystem estimator. Empirical results suggest that lagged crime rate and clear-up rate are correlated to all typologies of crime rate considered. Property crimes are better explained by socioeconomic variables (GDP per capita, GDP growth rate and percentage of population with high school and university degree), while demographic factors reveal important and significant influences, in particular for crimes against the person. These results are obtained using an instrumental variable approach that takes advantage of the dynamic properties of our dataset to control for both measurement errors in crime data and joint endogeneity of the explanatory variables

Covalent binding of C3b to monoclonal antibodies selectively up-regulates heavy chain epitope recognition by T cells.

Protein C3 of the complement system is known for its role in the nonspecific immune response. Covalent binding of C3b to antigen upon complement activation also plays a significant role in specific T cell immune response. C3b-antigen complexes can bind to complement receptors on the antigen-presenting cell, and the C3b antigen link (most often an ester link) remains fairly stable inside the cells. In this study, IgG1,kappa and IgG2a,kappa murine monoclonal antibodies (mAb) were used as antigens; covalent complexes between mAb and C3b were produced and purified in vitro from purified proteins; human B cell lines and T cell clones were raised from tumor patients who received mAb injections for cancer therapy or diagnosis. Recognition of epitopes of these mAb by T cell clones when the mAb were processed alone or bound to C3b was compared. IgG or IgG-C3b complexes presented by B cell lines were able to stimulate proliferation of kappa light chain-specific T cell clones at similar concentrations. In contrast, IgG-C3b complex recognition by heavy chain-specific T cell clones required 100-fold less IgG-C3b than uncomplexed IgG. As C3b was shown to be covalently bound only to the IgG heavy chains in the complexes, C3b chaperoning is restricted to only the IgG heavy chain and selectively influences intracellular steps of IgG heavy chain processing. This differential modulation of C3b suggests an early dissociation of IgG heavy and light chains in antigen-presenting cells.

Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae.

The equilibrium of membrane fusion and fission influences the volume and copy number of organelles. Fusion of yeast vacuoles has been well characterized but their fission and the mechanisms determining vacuole size and abundance remain poorly understood. We therefore attempted to systematically characterize factors necessary for vacuole fission. Here, we present results of an in vivo screening for deficiencies in vacuolar fragmentation activity of an ordered collection deletion mutants, representing 4881 non-essential genes of the yeast Saccharomyces cerevisiae. The screen identified 133 mutants with strong defects in vacuole fragmentation. These comprise numerous known fragmentation factors, such as the Fab1p complex, Tor1p, Sit4p and the V-ATPase, thus validating the approach. The screen identified many novel factors promoting vacuole fragmentation. Among those are 22 open reading frames of unknown function and three conspicuous clusters of proteins with known function. The clusters concern the ESCRT machinery, adaptins, and lipases, which influence the production of diacylglycerol and phosphatidic acid. A common feature of these factors of known function is their capacity to change membrane curvature, suggesting that they might promote vacuole fragmentation via this property.