Avoiding transcription factor competition at promoter level increases the chances of obtaining oscillations

Background: The ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. Nevertheless, the progress in these directions has been substantial. Results: It has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features. Conclusions: In comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.

Protein delivery for retinal diseases: from basic considerations to clinical applications.

Because the eye is protected by ocular barriers but is also easily accessible, direct intravitreous injections of therapeutic proteins allow for specific and targeted treatment of retinal diseases. Low doses of proteins are required in this confined environment and a long time of residency in the vitreous is expected, making the eye the ideal organ for local proteic therapies. Monthly intravitreous injection of Ranibizumab, an anti-VEGF Fab has become the standard of care for patients presenting wet AMD. It has brought the proof of concept that administering proteins into the physiologically low proteic concentration vitreous can be performed safely. Other antibodies, Fab, peptides and growth factors have been shown to exert beneficial effects on animal models when administered within the therapeutic and safe window. To extend the use of such biomolecules in the ophthalmology practice, optimization of treatment regimens and efficacy is required. Basic knowledge remains to be increased on how different proteins/peptides penetrate into the eye and the ocular tissues, distribute in the vitreous, penetrate into the retinal layers and/or cells, are eliminated from the eye or metabolized. This should serve as a basis for designing novel drug delivery systems. The later should be non-or minimally invasive and should allow for a controlled, scalable and sustained release of the therapeutic proteins in the ocular media. This paper reviews the actual knowledge regarding protein delivery for eye diseases and describes novel non-viral gene therapy technologies particularly adapted for this purpose.

Constraints on the late thermotectonic evolution of the Western Alps - Evidence for episodic rapid uplift

Forty-two new apatite and zircon fission track ages are presented for samples from the Western Alps in southern Switzerland, northern Italy, and southeastern France. Measured ages plotted against assumed closure temperatures yield cooling patterns for the final cooling, uplift, and exhumation of the Western Alps. Similar fission track zircon ages in the Penninic Gran Paradiso massif, Dent Blanche nappe, Sesia-Lanzo Zone, and Ivrea Zone indicate cooling of all four units to approximately 225-degrees-C by 33 Ma. Differences in apatite ages reveal differential cooling of the four blocks between 33 Ma and the present. In the Sesia-Lanzo Zone, similarity of apatite ages regardless of elevation, together with near-volcanic confined fission track length patterns suggest rapid cooling and uplift at approximately 25 Ma compared with slow cooling of other Western Alps units around 12 Ma. Uplift is thus not continuous but episodic, often over a short time interval beyond the resolution of other methods. Such episodes of uplift, as revealed here in the Sesia-Lanzo Zone, may be the rule rather than the exception.

Testing for local adaptation in brown trout using reciprocal transplants.

ABSTRACT: BACKGROUND: Local adaptation can drive the divergence of populations but identification of the traits under selection remains a major challenge in evolutionary biology. Reciprocal transplant experiments are ideal tests of local adaptation, yet rarely used for higher vertebrates because of the mobility and potential invasiveness of non-native organisms. Here, we reciprocally transplanted 2500 brown trout (Salmo trutta) embryos from five populations to investigate local adaptation in early life history traits. Embryos were bred in a full-factorial design and raised in natural riverbeds until emergence. Customized egg capsules were used to simulate the natural redd environment and allowed tracking the fate of every individual until retrieval. We predicted that 1) within sites, native populations would outperform non-natives, and 2) across sites, populations would show higher performance at 'home' compared to 'away' sites. RESULTS: There was no evidence for local adaptation but we found large differences in survival and hatching rates between sites, indicative of considerable variation in habitat quality. Survival was generally high across all populations (55% +/- 3%), but ranged from 4% to 89% between sites. Average hatching rate was 25% +/- 3% across populations ranging from 0% to 62% between sites. CONCLUSION: This study provides rare empirical data on variation in early life history traits in a population network of a salmonid, and large-scale breeding and transplantation experiments like ours provide powerful tests for local adaptation. Despite the recently reported genetic and morphological differences between the populations in our study area, local adaptation at the embryo level is small, non-existent, or confined to ecological conditions that our experiment could not capture.

Neuroretinitis: review of the literature and new observations.

Neuroretinitis (NR) is an inflammatory disorder characterized by optic disc edema and subsequent formation of a macular star figure. The underlying pathophysiology involves increased permeability of disc vasculature, but the etiology is not fully defined. In some cases, NR is probably due to an infectious process involving the disc; in others, a postviral or autoimmune mechanism is more likely. Cases can be divided into those in which a specific infectious agent has been identified, those considered idiopathic, and those with recurrent attacks. Some reports have not distinguished among these subgroups, and it is unclear if their clinical features vary. We reviewed the literature and our own patients looking particularly at features that might better distinguish these subtypes. Features common to all 3 groups included age, absence of pain, and fundus appearance. Preceding systemic symptoms were more common in patients with cat scratch disease (CSD) and uncommon in those with recurrence. The pattern and magnitude of visual field loss differed, more commonly confined to the central field in CSD cases and more severe in recurrent cases. Recovery of visual acuity and field was less substantial in recurrent cases even after the initial episode. MRI was usually normal in all 3 groups. Enhancement confined to the optic disc was found in all 3 groups, but enhancement of the retrobulbar optic nerve was seen only in recurrent cases. Findings that are strongly suggestive of CSD include very young age, preceding systemic symptoms, and poor visual acuity but with a small or absent relative afferent pupil defect (RAPD). In contrast, the following are suggestive of idiopathic NR with a high risk of recurrence: absence of systemic symptoms, visual field defect outside the central field, preserved visual acuity with a large RAPD, and poor recovery of vision. Decisions regarding evaluation and treatment should be made with these features in mind.

Besondere Haarstrukturen der Soricidae (Mammalia, Insectivora) und ihre taxonomische Deutung

The following study should clear up the structures of the H-shaped profile found in the hairs of some shrews and show if it has a taxonomic signification. Therefore we studied the concerned hair structures by scanning electron microscopy in 8 genera. The special hair-shape, which is confined to the terminal segment of guard hairs, is found in the species of the following genera:Sorex, Neomys, Blarina andCryptotis, all members of the subfamily Soricinae. All the examined members of the subfamily Crocidurinae, i.e.Crocidura, Praesorex, Suncus andSylvisorex show a simple hair shape. The H-shaped hair characterizes the Soricinae as a monophyletic unity. Yet, the morphological criteria of hair complete the osteological criteria of Repenning (1967) an plead for the validitiy of the often refuted subfamilies.

Organisational Values as "Attractors of Chaos": An Emerging Cultural Change to Manage Organisational Complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.

Value and prices in Russian economic thought (1890-1920)

The subject "Value and prices in Russian economic thought (1890--1920)" should evoke several names and debates in the reader's mind. For a long time, Western scholars have been aware that the Russian economists Tugan-Baranovsky and Bortkiewicz were active participants to the Marxian transformation problem, that the mathematical models of Dmitriev prefigured forthcoming neoricardian based models, and that many Russian economists were either supporting the Marxian labour theory of value or being revisionists. Moreover, these ideas were preparing the ground for Soviet planning. Russian scholars additionally knew that this period was the time of introduction of marginalism in Russia, and that, during this period, economists were active in thinking the relation of ethics with economic theory. All these issues are well covered in the existing literature. But there is a big gap that this dissertation intends to fill. The existing literature handles these pieces separately, although they are part of a single, more general, history. All these issues (the labour theory of value, marginalism, the Marxian transformation problem, planning, ethics, mathematical economics) were part of what this dissertation calls here "The Russian synthesis". The Russian synthesis (in the singular) designates here all the attempts at synthesis between classical political economy and marginalism, between labour theory of value and marginal utility, and between value and prices that occurred in Russian economic thought between 1890 and 1920, and that embraces the whole set of issues evoked above. This dissertation has the ambition of being the first comprehensive history of that Russian synthesis. In this, this contribution is unique. It has always surprised the author of the present dissertation that such a book has not yet been written. Several good reasons, both in terms of scarce availability of sources and of ideological restrictions, may accounted for a reasonable delay of several decades. But it is now urgent to remedy the situation before the protagonists of the Russian synthesis are definitely classified under the wrong labels in the pantheon of economic thought. To accomplish this task, it has seldom be sufficient to gather together the various existing studies on aspects of this story. It as been necessary to return to the primary sources in the Russian language. The most important part of the primary literature has never been translated, and in the last years only some of them have been republished in Russian. Therefore, most translations from the Russian have been made by the author of the present dissertation. The secondary literature has been surveyed in the languages that are familiar (Russian, English and French) or almost familiar (German) to the present author, and which are hopefully the most pertinent to the present investigation. Besides, and in order to increase the acquaintance with the text, which was the objective of all this, some archival sources were used. The analysis consists of careful chronological studies of the authors' writings and their evolution in their historical and intellectual context. As a consequence, the dissertation brings new authors to the foreground - Shaposhnikov and Yurovsky - who were traditionally confined to the substitutes' bench, because they only superficially touched the domains quoted above. In the Russian synthesis however, they played an important part of the story. As a side effect, some authors that used to play in the foreground - Dmitriev and Bortkiewicz - are relegated to the background, but are not forgotten. Besides, the dissertation refreshes the views on authors already known, such as Ziber and, especially, Tugan-Baranovsky. The ultimate objective of this dissertation is to change the opinion that one could have on "value and prices in Russian economic thought", by setting the Russian synthesis at the centre of the debates.

Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage.

OBJECTIVES: In vitro mechanical injury of articular cartilage is useful to identify events associated with development of post-traumatic osteoarthritis (OA). To date, many in vitro injury models have used animal cartilage despite the greater clinical relevance of human cartilage. We aimed to characterize a new in vitro injury model using elderly human femoral head cartilage and compare its behavior to that of an existing model with adult bovine humeral head cartilage. DESIGN: Mechanical properties of human and bovine cartilage disks were characterized by elastic modulus and hydraulic permeability in radially confined axial compression, and by Young's modulus, Poisson's ratio, and direction-dependent radial strain in unconfined compression. Biochemical composition was assessed in terms of tissue water, solid, and glycosaminoglycan (GAG) contents. Responses to mechanical injury were assessed by observation of macroscopic superficial tissue cracks and histological measurements of cell viability following single injurious ramp loads at 7 or 70%/s strain rate to 3 or 14 MPa peak stress. RESULTS: Confined compression moduli and Young's moduli were greater in elderly human femoral cartilage vs adult bovine humeral cartilage whereas hydraulic permeability was less. Radial deformations of axially compressed explant disks were more anisotropic (direction-dependent) for the human cartilage. In both cartilage sources, tissue cracking and associated cell death during injurious loading was common for 14 MPa peak stress at both strain rates. CONCLUSION: Despite differences in mechanical properties, acute damage induced by injurious loading was similar in both elderly human femoral cartilage and adult bovine humeral cartilage, supporting the clinical relevance of animal-based cartilage injury models. However, inherent structural differences such as cell density may influence subsequent cell-mediated responses to injurious loading and affect the development of OA.

Organisational values as "attractors of chaos": An emerging cultural change to manage organisational complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.

The adequacy of artificial oviposition substrates for laboratory rearing of Piezodorus guildinii (Westwood) (Heteroptera, Pentatomidae)

Studies in the laboratory tested the suitability of synthetic wool string, cotton string, cheesecloth, and commercial cotton ball as artificial oviposition substrates for the small green stink bug, Piezodorus guildinii (Westwood) (Heteroptera, Pentatomidae). In confined cages, 54% of total egg masses was laid on synthetic wool string, 31% on cotton string, and only 15% on cheesecloth. In an additional test, the best substrate selected, synthetic wool string, received 92% of egg masses compared to 8% on the commonly used substrate, cotton ball. Synthetic wool string received the most egg masses of any size, in particular those in the range 11-20 eggs/mass. Because the eggs of P. guildinii are laid in two parallel double rows, the egg masses fit the wool string perfectly.

Molecular determinants of vesicular storage and release of the gliotransmitter D-serine from cortical astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of 'gliotransmitters' such as glutamate, ATP or D-serine. A calcium-dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. Over the last years, we have been studying the molecular determinants governing D-serine release from glia using different approaches. Using a novel bioassay for D-serine, we have been able to show that D-serine release occurs mainly through a calcium- and SNARE proteindependent mechanism just supporting the idea that this amino acid is released by exocytosis from glia. We next have pursued our exploration by confocal imaging and tracking of the exocytotic routes for Dserine- mediated gliotransmission and have shown that D-serine releasable pools are confined to synaptobrevin2/cellubrevin-bearing vesicles. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2- positive vesicles from rat cortical astrocytes in culture while preserving their content in gliotransmitters. The purified organelles are clear round shape vesicles of excellent purity with homogeneous size (40 nm) as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles like synaptic vesicle protein 2 (SV2) and the proton pump H?-ATPase. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electrophoresis coupled to laser-induced fluorescence detection. The purified vesicles contain large amount of D-serine. We also detect peaks corresponding to unidentified compounds that may correspond to others amino acids. Postembedding immunogold labelling of the rat neocortex further revealed the expression of D-serine in astrocytes processes contacting excitatory synapses. Finally, we have examined the uptake properties for Dserine and glutamate inside the isolated glial vesicles. Our results provide significant support for the existence of an uptake system for D-serine in secretory glial vesicles and for the storage of chemical substances like D-serine and glutamate. 11th International Congress on Amino Acids, Peptides and Proteins 763 123

Estudo de caso: o uso da língua portuguesa por jovens provindos de outros países no domínio privado, público e educativo

A afluência de imigrantes a Portugal, nas últimas três décadas transformou radicalmente todo o tecido social português, caracterizando-se hoje pela sua heterogeneidade. Até ao início da década de 90 do século XX, os fluxos migratórios provinham essencialmente dos Países de Língua Oficial Portuguesa, com maior incidência de Cabo Verde, Brasil e Angola. É nessa década que se registam movimentos bastante significativos de imigrantes provenientes da Europa Central e Oriental, principalmente da Ucrânia, Rússia, Roménia e Moldávia, assim como da Ásia, destacando-se os naturais da China, Índia, Paquistão e das antigas repúblicas soviéticas. De acordo com a análise apresentada pelo Instituto Nacional de Estatística em Dezembro de 2006, residiam de forma legal em Portugal 329 898 cidadãos de nacionalidade estrangeira, sendo as maiores comunidades de Cabo Verde (57 349), Brasil (41 728) e Angola (28 854). A sociedade portuguesa do século XXI, distancia-se cada vez mais do conceito de monolinguismo, tal como se evidencia no Projecto Gulbenkian “Diversidade Linguística na Escola Portuguesa”, que, segundo o estudo feito, onze por cento dos alunos residentes na área da Grande Lisboa nasceram fora de Portugal e têm como línguas maternas cinquenta e oito idiomas. É urgente uma intervenção diferente no que corresponde a esta nova realidade linguística em Portugal e sobretudo no que concerne à integração do “outro”, reconhecendo e respeitando as várias línguas maternas e culturas, como também a sua preservação a fim de possibilitar o desenvolvimento íntegro e harmonioso da identidade. A heterogeneidade da actual sociedade portuguesa impõe um olhar atento para com esta nova realidade no país, sobretudo em muitas das escolas onde a par do uso da língua portuguesa outras línguas são também usadas como forma de comunicação entre os mesmos pares, situação esta perfeitamente desajustada da realidade escolar madeirense Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 10 de inícios da década de 90 do século XX, à excepção dos alunos provenientes da Venezuela, os denominados luso-descendentes. A escola mudara, tudo se alterara, havia que tentar perceber o que estava a ocorrer, um novo Mundo “invadira” as turmas, prontas a aprender, a saber, a descobrir. Era preciso preencher o silêncio expectante. Aprender uma nova língua, a portuguesa, decorrente da obrigatoriedade implícita de tratar-se da língua oficial, obrigava a repensar o ensino, a continuamente desvendar novos caminhos possibilitadores de encontro entre a língua materna e a segunda, de reencontro com a identidade linguística e cultural que não se quer perdidas, só tornado possível na diferença. A par de uma escola que se apresentava de forma diferente, cuja intervenção teria de ser oposta à de então, uma vez que a aprendizagem do português era feita como língua segunda (L2), muitas foram e são as inquietações, um turbilhão de interrogações decorriam deste contacto constante de uma língua que se diz minha, fonte de partilha com outros jovens. O uso da língua portuguesa confinar-se-á unicamente à escola com os professores e colegas ou despoletará curiosidades, vontades, interesses, motivados por objectivos confinados ao percurso e à história humana? Muitas são as interrogações que ocorrem, muitos são também os momentos de sabedoria mútua de línguas e países a desvendar num contínuo ininterrupto e é essa constante procura que determina a busca de respostas. Entre muitas interrogações uma afigurava-se de forma latente, quiçá fonte de resposta para outras interrogações inerentes à língua portuguesa como língua segunda. A sua utilização por parte dos alunos de outras nacionalidades nos domínios privado, público e educativo engloba domínios diversos capazes de informar acerca do uso dessa mesma língua. Importa no entanto reforçar que estes alunos constituem um grupo heterogéneo sob diversos pontos de vista: etário, linguístico e cultural. Do ponto de vista linguístico a população que tem o português como língua segunda abrange alunos falantes de diferentes línguas maternas, umas mais próximas, outras mais afastadas do português, propiciando diferentes graus de transferência de conhecimentos linguísticos e de experiências comunicativas, como também em diferentes estádios de aquisição e que fora da escola o usam em maior ou menor número de contextos e com um grau de frequência desigual. Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 11 Dispõem também de diferentes capacidades individuais para discriminar, segmentar e produzir sequências linguísticas. Já do ponto de vista cultural apresentam diferentes hábitos de aprendizagem, bem como diferentes representações e expectativas face à escola. Todos estes factores determinarão ritmos de progressão distintos no que respeita à aprendizagem do português como língua segunda. As oportunidades de aprendizagem e de uso que cada indivíduo tem ao longo da vida, determinantes no processo de aquisição, desenvolvimento e aprendizagem de uma língua, variam bastante de indivíduo para indivíduo. Os alunos podem viver num mesmo contexto no entanto razões variadíssimas determinarão diferentes oportunidades de aprendizagem e de uso. Viver-se num contexto de imersão não é suficiente para que todos tenham o mesmo grau de exposição a material linguístico rico e variado da L2. Essas oportunidades também se relacionam com a distância linguística entre língua primeira (L1) e a língua segunda, quanto mais afastadas são as duas línguas mais os falantes da L2 se refugiam na sua língua materna, assim como também se associam aos hábitos culturais da comunidade e da família.

Estudo de caso : o uso da língua portuguesa por jovens provindos de outros países no domínio privado, público e educativo

A afluência de imigrantes a Portugal, nas últimas três décadas transformou radicalmente todo o tecido social português, caracterizando-se hoje pela sua heterogeneidade. Até ao início da década de 90 do século XX, os fluxos migratórios provinham essencialmente dos Países de Língua Oficial Portuguesa, com maior incidência de Cabo Verde, Brasil e Angola. É nessa década que se registam movimentos bastante significativos de imigrantes provenientes da Europa Central e Oriental, principalmente da Ucrânia, Rússia, Roménia e Moldávia, assim como da Ásia, destacando-se os naturais da China, Índia, Paquistão e das antigas repúblicas soviéticas. De acordo com a análise apresentada pelo Instituto Nacional de Estatística em Dezembro de 2006, residiam de forma legal em Portugal 329 898 cidadãos de nacionalidade estrangeira, sendo as maiores comunidades de Cabo Verde (57 349), Brasil (41 728) e Angola (28 854). A sociedade portuguesa do século XXI, distancia-se cada vez mais do conceito de monolinguismo, tal como se evidencia no Projecto Gulbenkian “Diversidade Linguística na Escola Portuguesa”, que, segundo o estudo feito, onze por cento dos alunos residentes na área da Grande Lisboa nasceram fora de Portugal e têm como línguas maternas cinquenta e oito idiomas. É urgente uma intervenção diferente no que corresponde a esta nova realidade linguística em Portugal e sobretudo no que concerne à integração do “outro”, reconhecendo e respeitando as várias línguas maternas e culturas, como também a sua preservação a fim de possibilitar o desenvolvimento íntegro e harmonioso da identidade. A heterogeneidade da actual sociedade portuguesa impõe um olhar atento para com esta nova realidade no país, sobretudo em muitas das escolas onde a par do uso da língua portuguesa outras línguas são também usadas como forma de comunicação entre os mesmos pares, situação esta perfeitamente desajustada da realidade escolar madeirense Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 10 de inícios da década de 90 do século XX, à excepção dos alunos provenientes da Venezuela, os denominados luso-descendentes. A escola mudara, tudo se alterara, havia que tentar perceber o que estava a ocorrer, um novo Mundo “invadira” as turmas, prontas a aprender, a saber, a descobrir. Era preciso preencher o silêncio expectante. Aprender uma nova língua, a portuguesa, decorrente da obrigatoriedade implícita de tratar-se da língua oficial, obrigava a repensar o ensino, a continuamente desvendar novos caminhos possibilitadores de encontro entre a língua materna e a segunda, de reencontro com a identidade linguística e cultural que não se quer perdidas, só tornado possível na diferença. A par de uma escola que se apresentava de forma diferente, cuja intervenção teria de ser oposta à de então, uma vez que a aprendizagem do português era feita como língua segunda (L2), muitas foram e são as inquietações, um turbilhão de interrogações decorriam deste contacto constante de uma língua que se diz minha, fonte de partilha com outros jovens. O uso da língua portuguesa confinar-se-á unicamente à escola com os professores e colegas ou despoletará curiosidades, vontades, interesses, motivados por objectivos confinados ao percurso e à história humana? Muitas são as interrogações que ocorrem, muitos são também os momentos de sabedoria mútua de línguas e países a desvendar num contínuo ininterrupto e é essa constante procura que determina a busca de respostas. Entre muitas interrogações uma afigurava-se de forma latente, quiçá fonte de resposta para outras interrogações inerentes à língua portuguesa como língua segunda. A sua utilização por parte dos alunos de outras nacionalidades nos domínios privado, público e educativo engloba domínios diversos capazes de informar acerca do uso dessa mesma língua. Importa no entanto reforçar que estes alunos constituem um grupo heterogéneo sob diversos pontos de vista: etário, linguístico e cultural. Do ponto de vista linguístico a população que tem o português como língua segunda abrange alunos falantes de diferentes línguas maternas, umas mais próximas, outras mais afastadas do português, propiciando diferentes graus de transferência de conhecimentos linguísticos e de experiências comunicativas, como também em diferentes estádios de aquisição e que fora da escola o usam em maior ou menor número de contextos e com um grau de frequência desigual. Estudo de caso: O uso da Língua Portuguesa por jovens oriundos de outros países nos domínios privado, público e educativo. 11 Dispõem também de diferentes capacidades individuais para discriminar, segmentar e produzir sequências linguísticas. Já do ponto de vista cultural apresentam diferentes hábitos de aprendizagem, bem como diferentes representações e expectativas face à escola. Todos estes factores determinarão ritmos de progressão distintos no que respeita à aprendizagem do português como língua segunda. As oportunidades de aprendizagem e de uso que cada indivíduo tem ao longo da vida, determinantes no processo de aquisição, desenvolvimento e aprendizagem de uma língua, variam bastante de indivíduo para indivíduo. Os alunos podem viver num mesmo contexto no entanto razões variadíssimas determinarão diferentes oportunidades de aprendizagem e de uso. Viver-se num contexto de imersão não é suficiente para que todos tenham o mesmo grau de exposição a material linguístico rico e variado da L2. Essas oportunidades também se relacionam com a distância linguística entre língua primeira (L1) e a língua segunda, quanto mais afastadas são as duas línguas mais os falantes da L2 se refugiam na sua língua materna, assim como também se associam aos hábitos culturais da comunidade e da família.

Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging.

INTRODUCTION: Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. METHODS: Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. RESULTS: In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. CONCLUSION: This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern.