Produção de nanopartículas contendo peptídeos bioativos de microalgas

A produção de peptídeos bioativos de distintas fontes de proteínas vem ganhando espaço na produção científica e tecnológica, despertando interesse do setor empresarial. Paralelamente a isso, devido à elevada concentração de proteínas na biomassa das microalgas Spirulina e Chlorella, estas apresentam grande potencial para a extração de biocompostos com alto valor agregado, como biopeptídeos de microalgas. As proteínas são uma importante fonte de peptídeos bioativos, mas estes não estão ativos na proteína precursora e devem ser liberados para que apresentem efeitos fisiológicos desejados. Essa liberação pode ser feita através de hidrólise enzimática a partir de proteases, sendo um dos métodos mais utilizados para a produção destes biocompostos. Dentro deste contexto, vários estudos vêm mostrando o uso da tecnologia por secagem em spray dryer para a obtenção de nanopartículas que contenham compostos bioativos, sendo, essa técnica, amplamente utilizada para transformar líquidos em pós, podendo ser aplicada em materiais sensíveis à temperatura. Este estudo teve como objetivo obter peptídeos bioativos através da reação enzimática, tendo como substrato a biomassa de Spirulina sp. LEB 18 e Chlorella pyrenoidosa e, na sequência, obter nanopartículas contendo os biopeptídeos. Primeiramente, foram testadas as 3 proteases comerciais (Protemax 580 L, Protemax N 200 e pepsina) para a produção de hidrolisados proteicos de microalgas, para isso foram realizados 3 delineamentos compostos centrais para cada microalga em estudo (Chlorella e Spirulina). Os delineamentos utilizados foram do tipo 23 com três repetições no ponto central, variando-se a concentração de enzima (5 a 10 U.mL-1), a concentração de substrato (5 a 10 %) e o tempo de reação (60 a 240 min). Após, realizou-se 2 delineamentos compostos rotacionais do tipo 22 com pontos centrais, um para cada microalga, utilizando-se para a hidrólise a enzima Protemax 580L (5 U.mL-1) variando-se a concentração de substrato e tempo de reação, para todos ensaios estudou-se a solubilidade, capacidade de retenção de água, atividade antioxidante e digestibilidade. Foi selecionado um ensaio para cada microalga, levando em conta os melhores resultados. Então nova hidrólise enzimática foi realizada sendo o sistema reacional composto pela enzima Protemax 580 L (5 U.mL-1) e pela biomassa de Spirulina sp. LEB 18 ou Chlorella pyrenoidosa (4% de proteína) durante tempo de 200 min. Os hidrolisados foram purificados por filtração a vácuo com membranas millipores de diferentes tamanhos (0,45; 0,2 e 0,1 µm) e por colunas com membrana vertical Amicon® Ultra 0.5 (3K e 10K), sendo que após cada etapa, foi realizado teste de atividade antioxidante pelos métodos de poder redutor, DPPH e ABTS, a fim de verificar a permanência da atividade antioxidante. Utilizou-se nano spray dryer Büchi modelo B 90 para a secagem das amostras, sendo o tamanho das partículas obtidas analisados por microscopia eletrônica de varredura (MEV). Por fim, conclui-se que a biomassa de microalgas pode ser utilizada como fonte de produção de peptídeos bioativos com elevada atividade antioxidante e que dentre as microalgas estudadas, Spirulina sp. LEB 18 apresentou melhores resultados, em todas as análises realizadas, quando comparada com Chlorella pyrenoidosa. Esse estudo, também visou utilizar a nanobiotecnologia para obtenção de nanoparículas contendo os biopeptídeos, para tal, utilizou-se o nano Buchi Spray Dryer B-90, o qual gerou partículas nanométricas de 14 a 18 nm para o hidrolisado de Spirulina e de 72 a 108 nm para o hidrolisado de Chlorella.

Postnatal depression in Central Vietnam

Postnatal depression (PND) is a significant global health issue, which not only impacts maternal wellbeing, but also infant development and family structures. Mental health disorders represent approximately 14% of global burden of disease and disability, including low and middle-income countries (LMIC), and PND has direct relevance to the Millennium Development Goals of reducing child mortality, improving maternal health, and creating global partnerships (United Nations, 2012; Guiseppe, Becker & Farmer, 2011). Emerging evidence suggests that PND in LMIC is similar to, or higher than in high-income countries (HIC), however, less than 10% of LMIC have prevalence data available (Fisher, Cabral de Mello, & Izutsu 2009; Lund et al., 2011). Whilst a small number of studies on maternal mental disorders have been published in Vietnam, only one specifically focuses on PND in a hospital-based sample. Also, community based mental health studies and information on mental health in rural areas of Vietnam is still scarce. The purpose of this study was to determine the prevalence of PND, and its associated social determinants in postnatal women in Thua Thien Hue Province, Central Vietnam. In order to identify social determinants relevant to the Central Vietnamese context, two qualitative studies and one community survey were undertaken. Associations between maternal mental health and infant health outcomes were also explored. The study was comprised of three phases. Firstly, iterative, qualitative interviews with Vietnamese health professionals (n = 17) and postpartum women (n = 15) were conducted and analysed using Kleinman's theory of explanatory models to identify narratives surrounding PND in the Vietnamese context (Kleinman, 1978). Secondly, a participatory concept mapping exercise was undertaken with two groups of health professionals (n = 12) to explore perceived risk and protective factors for postnatal mental health. Qualitative phases of the research elucidated narratives surrounding maternal mental health in the Vietnamese context such as son preference, use of traditional medicines, and the popularity of confinement practices such as having one to three months of complete rest. The qualitative research also revealed the construct of depression was not widely recognised. Rather, postpartum changes in mood were conceptualised as a loss of 'vital strength' following childbirth or 'disappointment'. Most women managed postpartum changes in mood within the family although some sought help from traditional medicine practitioners or biomedical doctors. Thirdly, a cross-sectional study of twelve randomly selected communes (six urban, six rural) in Thua Thien Hue Province was then conducted. Overall, 465 women with infants between 4 weeks and six months old participated, and 431 questionnaires were analysed. Women from urban (n = 216) and rural (n = 215) areas participated. All eligible women completed a structured interview about their health, basic demographics, and social circumstances. Maternal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) as a continuous variable. Multivariate generalised linear regression was conducted using PASW Statistics version 18.0 (2009). When using the conventional EPDS threshold for probable depression (EPDS score ~ 13) 18.1% (n = 78) of women were depressed (Gibson, McKenzie-McHarg, Shakespeare, Price & Gray, 2009). Interestingly, 20.4% of urban women (n = 44) had EPDS scores~ 13, which was a higher proportion than rural women, where 15.8% (n = 34) had EPDS scores ~ 13, although this difference was not statistically significant: t(429) = -0.689, p = 0.491. Whilst qualitative narratives identified infant gender and family composition, and traditional confinement practices as relevant to postnatal mood, these were not statistically significant in multivariate analysis. Rather, poverty, food security, being frightened of your husband or family members, experiences of intimate partner violence and breastfeeding difficulties had strong statistical associations. PND was also associated with having an infant with diarrhoea in the past two weeks, but not infant malnutrition or acute respiratory infections. This study is the first to explore maternal mental health in Central Vietnam, and provides further evidence that PND is a universally experienced phenomenon. The independent social risk factors of depressive symptoms identified such as poverty, food insecurity, experiences of violence and powerlessness, and relationship adversity points to women in a context of social suffering which is relevant throughout the world (Kleinman, Das & Lock, 1997). The culturally specific risk factors explored such as infant gender were not statistically significant when included in a multivariable model. However, they feature prominently in qualitative narratives surrounding PND in Vietnam, both in this study and previous literature. It appears that whilst infant gender may not be associated with PND per se, the reactions of close relatives to the gender of the baby can adversely affect maternal wellbeing. This study used a community based participatory research approach (CBPR) (Israel.2005). This approach encourages the knowledge produced to be used for public health interventions and workforce training in the community in which the research was conducted, and such work has commenced. These results suggest that packages of interventions for LMIC devised to address maternal mental health and infant wellbeing could be applied in Central Vietnam. Such interventions could include training lay workers to follow up postpartum women, and incorporating mental health screening and referral into primary maternal and child health care (Pate! et al., 2011; Rahman, Malik, Sikander & Roberts, 2008). Addressing the underlying social determinants of PND through poverty reduction and violence elimination programs is also recommended.

Utility of assessing nerve morphology in central cornea versus whorl area for diagnosing diabetic peripheral neuropathy

Purpose To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. Methods A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. Results CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P < 0.001). There was a weak but significant linear relationship for CNFLcenter and CNFLwhorl versus NDS (P < 0.001); however, the corneal location x NDS interaction was not statistically significant (P = 0.17). The area under the receiver operating characteristic curve was similar for CNFLcenter and CNFLwhorl (0.76 and 0.77, respectively, P = 0.98). The sensitivity and specificity of the cutoff points were 0.9 and 0.5 for CNFLcenter and 0.8 and 0.6 for CNFLwhorl. Conclusions Small nerve fiber pathology is comparable at the central and whorl anatomical sites of the cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

Developmental-like responses in injured mature central neurons

Traumatic insults to the central nervous system are frequently followed by profound and irreversible neuronal loss as well as the inability of the damaged neurons to regenerate. One of the major therapeutic challenges is to increase the amount of surviving neurons after trauma. Thus it is crucial to understand how injury affects neuronal responses and which conditions are optimal for survival to prevent neuronal loss. During development neuronal survival is thought to be dependent on the competition for the availability of survival-promoting molecules called neurotrophic factors. Much less is known on the survival mechanisms of mature neurons under traumatic conditions. Increasing amount of evidence points towards the possibility that after injury neuronal responses might aquire some developmental characteristics. One of the important examples is the change in the responses to the neurotransmitter GABA: it is inhibitory in the intact mature neurons, but can induce excitation during development and after trauma. An important step in the maturation of GABAergic transmission in the CNS is the developmental shift in the action of GABAA receptor from depolarization in immature neurons to hyperpolarization in mature neurons. GABAA-mediated responses are tightly linked to the homeostasis of the chloride anion (Cl-), which in neurons is mainly regulated by Na+-K+-2Cl- cotransporter NKCC1 and K+-Cl- cotransporter KCC2. Trauma-induced functional downregulation of KCC2 promotes a shift from hyperpolarizing GABAA-mediated responses to depolarizing. Other important consequences of neuronal trauma are the emergence of dependency of central neurons on brain-derived neuro¬trophic factor (BDNF) for survival, as well as the upregulation of neurotrophin receptor p75NTR. Our aim was to answer the question whether these post-traumatic events are interrelated, and whether the regulation of BDNF and KCC2 expression is different under traumatic conditions and in intact neurons. To study responses of injured mature central neurons, we used an in vitro and in vivo axotomy models. For in vitro studies, we lesioned organotypic hippocampal slices between CA3 and CA1 regions, which resulted in selective axotomy of the CA3 neurons and denervation of the CA1 neurons. Some experiments were repeated in vivo by lesioning the neurons of the corticospinal tract at the internal capsule level, or by lesioning spinal motoneurons at the ventral root. We show that intact mature neurons do not require BDNF for survival, whereas in axotomized neurons apoptosis is induced upon BDNF deprivation. We further show that post-traumatic dependency on BDNF is mediated by injury-induced upregulation of p75NTR. Post-traumatic increase in p75NTR is induced by GABAA-mediated depolarization, consequent opening of voltage-gated Ca2+ channels, and the activation of Rho kinase ROCK. Thus, post-traumatic KCC2 downregulation leads to the dependency on BDNF through the induction of p75NTR upregulation. Neurons that survive after axotomy over longer period of time lose BDNF dependency and regain normal KCC2 levels. This phenomenon is promoted by BDNF itself, since after axotomy contrary to normal conditions KCC2 is upregulated by BDNF. The developmentally important thyroid hormone thyroxin regulates BDNF expression during development. We show that in mature intact neurons thyroxin downregulates BDNF, whereas after axotomy thyroxin upregulates BDNF. The elevation of BDNF expression by thyroxin promoted survival of injured neurons. In addition, thyroxin also enhanced axonal regeneration and promoted the regaining of normal levels of KCC2. Thus we show that this hormone acts at several levels on the axotomy-initiated chain of events described in the present work, and could be a potential therapeutic agent for the injured neurons. We have also characterized a previously unknown downregulatory interaction between thyroxin and KCC2 in intact neurons. In conclusion, we identified several important interactions at the neurotrophin-protein and hormone-neurotrophin level that acquire immature-like characteristics after axotomy and elucidated an important part of the mechanism by which axotomy leads to the requirement of BDNF trophic support. Based on these findings, we propose a new potential therapeutic strategy where developmentally crucial agents could be used to enhance survival and regeneration of axotomized mature central neurons.

Spatio-temporal landscape modelling for natural hazard vulnerability analysis in select watersheds of Central Western Ghats

Natural hazards such as landslides are triggered by numerous factors such as ground movements, rock falls, slope failure, debris flows, slope instability, etc. Changes in slope stability happen due to human intervention, anthropogenic activities, change in soil structure, loss or absence of vegetation (changes in land cover), etc. Loss of vegetation happens when the forest is fragmented due to anthropogenic activities. Hence land cover mapping with forest fragmentation can provide vital information for visualising the regions that require immediate attention from slope stability aspects. The main objective of this paper is to understand the rate of change in forest landscape from 1973 to 2004 through multi-sensor remote sensing data analysis. The forest fragmentation index presented here is based on temporal land use information and forest fragmentation model, in which the forest pixels are classified as patch, transitional, edge, perforated, and interior, that give a measure of forest continuity. The analysis carried out for five prominent watersheds of Uttara Kannada district– Aganashini, Bedthi, Kali, Sharavathi and Venkatpura revealed that interior forest is continuously decreasing while patch, transitional, edge and perforated forest show increasing trend. The effect of forest fragmentation on landslide occurrence was visualised by overlaying the landslide occurrence points on classified image and forest fragmentation map. The increasing patch and transitional forest on hill slopes are the areas prone to landslides, evident from the field verification, indicating that deforestation is a major triggering factor for landslides. This emphasises the need for immediate conservation measures for sustainable management of the landscape. Quantifying and describing land use - land cover change and fragmentation is crucial for assessing the effect of land management policies and environmental protection decisions.

Digital image analysis around isotropic points for photoelastic pattern recognition

Fringe tracking and fringe order assignment have become the central topics of current research in digital photoelasticity. Isotropic points (IPs) appearing in low fringe order zones are often either overlooked or entirely missed in conventional as well as digital photoelasticity. We aim to highlight image processing for characterizing IPs in an isochromatic fringe field. By resorting to a global analytical solution of a circular disk, sensitivity of IPs to small changes in far-field loading on the disk is highlighted. A local theory supplements the global closed-form solutions of three-, four-, and six-point loading configurations of circular disk. The local theoretical concepts developed in this paper are demonstrated through digital image analysis of isochromatics in circular disks subjected to three-and four-point loads. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

Preliminary guide to the identification of the early life history stages of Gerreid fishes of the Western Central Atlantic

The family Gerreidae contains four genera and 13 species that occur in the western central North Atlantic. Adult gerreids are small to medium size fishes that are abundant in coastal waters, bays, and estuaries in tropical and warm temperate regions and sometimes occur in freshwaters. They are generally associate~ with grassy or open bottoms, but not with reefs. Gerreids are silvery fishes, with deeply forked tails, and extremely protrusible mouth that points downward when protracted. They apparently feed on bottom-dwelling organisms and at least one species (Eucinostomus gula) shows a distinct transition, during the juvenile period, from a planktivore (exclusively copepods) to a carnivore that includes a diet of almost solely polychaetes (Carr & Adams, 1973; Robins and Ray, 1987; Murdy et al., 1997). (PDF contains 10 pages)

Análise morfométrica das estruturas maxilo-mandibulares de indivíduos pré-colombianos e contemporâneos da Costa Central do Peru

O objetivo deste trabalho foi avaliar morfometricamente as modificações ocorridas ao longo de 500 anos nas estruturas maxilo-mandibulares de indivíduos da Costa Central do Peru. Foram utilizadas telerradiografias laterais de 30 crânios secos, sem deformidades esqueléticas e em normoclusão, do período Pré-colombiano (grupo Pré-colombiano) e de 30 peruanos nativos contemporâneos, com características esqueléticas e oclusais semelhantes, provenientes da mesma região geográfica (grupo Contemporâneo). Estas telerradiografias foram digitalizadas e 14 pontos cefalométricos foram marcados e utilizados como marcos anatômicos homólogos para a análise morfométrica. O tamanho do centróide, a forma e a alometria foram comparados entre os grupos para a amostra total, para homens e para mulheres, pelos testes de one-way ANOVA, função discriminante e regressão multivariada, respectivamente. As mesmas avaliações foram realizadas para homens e mulheres do mesmo grupo. O tamanho do centróide foi significativamente maior para o grupo Contemporâneo tanto para a amostra total, quanto para homens e mulheres, demonstrando que as estruturas maxilo-mandibulares dos indivíduos contemporâneos é maior do que de seus ancestrais. Quando homens e mulheres foram comparados intra-grupos o tamanho do centróide foi significativamente maior para os homens do grupo Contemporâneo, com a mesma tendência para os homens pré-colombianos, porém sem significância estatística. Observou-se diferenças significativas entre os grupos para a forma das estruturas maxilo-mandibulares indicando que ao longo do tempo houve um deslocamento posterior da região da pré-maxila e um deslocamento considerável para cima e para trás da apófise coronóide, uma abertura do ângulo na região goníaca e um alongamento no sentido vertical da região da sínfise mandibular. Essas mudanças morfológicas foram mais evidentes nas mulheres do que nos homens, parecendo haver maior efeito das tendências seculares nas mulheres. Não houve diferenças morfológicas entre homens e mulheres quando comparados intra-grupos, demonstrando que os resultados observados não foram influenciados pelo dimorfismo sexual. As diferenças de tamanho existentes intra-grupos foram responsáveis por apenas 6% das diferenças de forma, e portanto não há efeito causal do tamanho sobre as diferenças de forma observadas entre os grupos. Pode-se concluir que as diferenças morfológicas das estruturas maxilo-mandibulares encontradas neste estudo sugerem mudanças nas condições ambientais da população da Costa Central do Peru ao longo de 500 anos e podem contribuir para o melhor esclarecimento dos fatores etiológicos das más oclusões.

Finite element analysis of compressor disc heat transfer using the transient conduction method with sparse boundary collocation points

Surface temperature measurements from two discs of a gas turbine compressor rig are used as boundary conditions for the transient conduction solution (inverse heat transfer analysis). The disc geometry is complex, and so the finite element method is used. There are often large radial temperature gradients on the discs, and the equations are therefore solved taking into account the dependence of thermal conductivity on temperature. The solution technique also makes use of a multigrid algorithm to reduce the solution time. This is particularly important since a large amount of data must be analyzed to obtain correlations of the heat transfer. The finite element grid is also used for a network analysis to calculate the radiant heat transfer in the cavity formed between the two compressor discs. The work discussed here proved particularly challenging as the disc temperatures were only measured at four different radial locations. Four methods of surface temperature interpolation are examined, together with their effect on the local heat fluxes. It is found that the choice of interpolation method depends on the available number of data points. Bessel interpolation gives the best results for four data points, whereas cubic splines are preferred when there are considerably more data points. The results from the analysis of the compressor rig data show that the heat transfer near the disc inner radius appears to be influenced by the central throughflow. However, for larger radii, the heat transfer from the discs and peripheral shroud is found to be consistent with that of a buoyancy-induced flow.

Global modes with multiple saddle points

Significant progress has been made towards understanding the global stability of slowly-developing shear flows. The WKBJ theory developed by Patrick Huerre and his co-authors has proved absolutely central, with the result that both the linear and the nonlinear stability of a wide range of flows can now be understood in terms of their local absolute/convective instability properties. In many situations, the local absolute frequency possesses a single dominant saddle point in complex X-space (where X is the slow streamwise coordinate of the base flow), which then acts as a single wavemaker driving the entire global linear dynamics. In this paper we consider the more complicated case in which multiple saddles may act as the wavemaker for different values of some control parameter. We derive a frequency selection criterion in the general case, which is then validated against numerical results for the linearized third-order Ginzburg-Landau equation (which possesses two saddle points). We believe that this theory may be relevant to a number of flows, including the boundary layer on a rotating disk and the eccentric Taylor-Couette-Poiseuille flow. © 2014 Elsevier Masson SAS. All rights reserved.

The Representation of Emotion in Autonomic and Central Nervous System Activity

Phenomenologically, humans effectively label and report feeling distinct emotions, yet the extent to which emotions are represented categorically in nervous system activity is controversial. Theoretical accounts differ in this regard, some positing distinct emotional experiences emerge from a dimensional representation (e.g., along axes of valence and arousal) whereas others propose emotions are natural categories, with dedicated neural bases and associated response profiles. This dissertation aims to empirically assess these theoretical accounts by examining how emotions are represented (either as disjoint categories or as points along continuous dimensions) in autonomic and central nervous system activity by integrating psychophysiological recording and functional neuroimaging with machine-learning based analytical methods. Results demonstrate that experientially, emotional events are well-characterized both along dimensional and categorical frameworks. Measures of central and peripheral responding discriminate among emotion categories, but are largely independent of valence and arousal. These findings suggest dimensional and categorical aspects of emotional experience are driven by separable neural substrates and demonstrate that emotional states can be objectively quantified on the basis of nervous system activity.

Long-period chromospheric oscillations in network bright points

The spatial variation of chromospheric oscillations in network bright points (NBPs) is studied using high-resolution observations in Ca II K3. Light curves and hence power spectra were created by isolating distinct regions of the NBP via a simple intensity thresholding technique. Using this technique, it was possible to identify peaks in the power spectra with particular spatial positions within the NBPs. In particular, long-period waves with periods of 4-15 minutes (1-4 mHz) were found in the central portions of each NBP, indicating that these waves are certainly not acoustic but possibly due to magnetoacoustic or magnetogravity wave modes. We also show that spatially averaged or low spatial resolution power spectra can lead to an inability to detect such long-period waves.

L'économie criminelle de la Camorra et la pratique discursive des différents points de vue dans Gomorra de Roberto Saviano

This thesis will study the Italian literary phenomenon Gomorra, viaggi nell'impero economico e nel sogno di dominio della Camorra. First, the focus will be on the text's hybrid nature and implications and also on its literary and intellectual inspirations (such as Truman Capote, Pier Paolo Pasolini and Leonardo Sciascia). Secondly, we will take a closer look at the structure of the novel's narrative and its literary details, in order to reveal the different processes used by Roberto Saviano to convince the reader. Interwoven in this book's central plot, we will find a main obsession: the need to understand. Lastly, we will discuss the question of the great power treated in this novel, the one of a criminal organisation transformed by the revelations made throughout the story. These revelations will allow us to draw interesting comparisons between organized crime and merchant capitalism. For this part, we will refer to Guy Debord's La société du spectacle, and to Hannah Arendt's work on the question of totalitarianism. All of these elements will allow us to discuss the different perspectives within the narrative's framework, and more precisely, the figure of the narrator/author/character that gives Saviano's novel anthropological qualities, in the form of an ethnofiction (Augé).

Points quantiques : caractérisation et applications en sciences pharmaceutiques

L’imagerie médicale a longtemps été limitée à cause des performances médiocres des fluorophores organiques. Récemment la recherche sur les nanocristaux semi-conducteurs a grandement contribué à l’élargissement de la gamme d’applications de la luminescence dans les domaines de l’imagerie et du diagnostic. Les points quantiques (QDs) sont des nanocristaux de taille similaire aux protéines (2-10 nm) dont la longueur d’onde d’émission dépend de leur taille et de leur composition. Le fait que leur surface peut être fonctionnalisée facilement avec des biomolécules rend leur application particulièrement attrayante dans le milieu biologique. Des QDs de structure « coeur-coquille » ont été synthétisés selon nos besoins en longueur d’onde d’émission. Dans un premier article nous avons modifié la surface des QDs avec des petites molécules bi-fonctionnelles portant des groupes amines, carboxyles ou zwitterions. L’effet de la charge a été analysé sur le mode d’entrée des QDs dans deux types cellulaires. À l’aide d’inhibiteurs pharmacologiques spécifiques à certains modes d’internalisation, nous avons déterminé le mode d’internalisation prédominant. L’endocytose par les radeaux lipidiques représente le mode d’entrée le plus employé pour ces QDs de tailles similaires. D’autres modes participent également, mais à des degrés moindres. Des disparités dans les modes d’entrée ont été observées selon le ligand de surface. Nous avons ensuite analysé l’effet de l’agglomération de différents QDs sur leur internalisation dans des cellules microgliales. La caractérisation des agglomérats dans le milieu de culture cellulaire a été faite par la technique de fractionnement par couplage flux-force (AF4) associé à un détecteur de diffusion de la lumière. En fonction du ligand de surface et de la présence ou non de protéines du sérum, chacun des types de QDs se sont agglomérés de façon différente. À l'aide d’inhibiteur des modes d’internalisation, nous avons corrélé les données de tailles d’agglomérats avec leur mode d’entrée cellulaire. Les cellules microgliales sont les cellules immunitaires du système nerveux central (CNS). Elles répondent aux blessures ou à la présence d’inflammagènes en relâchant des cytokines pro-inflammatoires. Une inflammation non contrôlée du CNS peut conduire à la neurodégénérescence neuronale et est souvent observée dans les cas de maladies chroniques. Nous nous sommes intéressés au développement d’un nanosenseur pour mesurer des biomarqueurs du début de l’inflammation. Les méthodes classiques pour étudier l’inflammation consistent à mesurer le niveau de protéines ou molécules relâchées par les cellules stressées (par exemple monoxyde d’azote, IL-1β). Bien que précises, ces méthodes ne mesurent qu’indirectement l’activité de la caspase-1, responsable de la libération du l’IL-1β. De plus ces méthode ne peuvent pas être utilisées avec des cellules vivantes. Nous avons construit un nanosenseur basé sur le FRET entre un QD et un fluorophore organique reliés entre eux par un peptide qui est spécifiquement clivé par la caspase-1. Pour induire l’inflammation, nous avons utilisé des molécules de lipopolysaccharides (LPS). La molécule de LPS est amphiphile. Dans l’eau le LPS forme des nanoparticules, avec des régions hydrophobes à l’intérieure. Nous avons incorporé des QDs dans ces régions ce qui nous a permis de suivre le cheminement du LPS dans les cellules microgliales. Les LPS-QDs sont internalisés spécifiquement par les récepteurs TLR-4 à la surface des microglies. Le nanosenseur s’est montré fonctionnel dans la détermination de l’activité de la caspase-1 dans cellules microgliales activées par le LPS. Éventuellement, le senseur permettrait d’observer en temps réel l’effet de thérapies ciblant l’inflammation, sur l’activité de la caspase-1.

TLC: los buitres contraatacan (Tema Central)

Este artículo plantea que los TLC se inscriben dentro de una lógica de profundización de la globalización económica y del pensamiento neoliberal, en donde los mercados abiertos, el desmantelamiento del Estado y la reducción del gasto público, entre otras, son las condiciones necesarias para dicha profundización. De acuerdo con el autor los TLC son otra de las estrategias de Estados Unidos frente a la arremetida de los bloques económicos como la Unión Europea y a la lentitud de las negociaciones en la OMC, por lo tanto este tipo de acuerdos solo reedita la misma lógica neo liberal e implica un sometimiento a la geopolítica de Estados Unidos.