Globalização económica e fragmentação geopolítica : a caminho de um mundo de equilíbrios instáveis e temporários?

Este texto explora a ideia de que a evolução mundial nos próximos anos vai ser marcada pela interacção complexa entre, por um lado as tensões associadas à Globalização da Economia Mundial, e por outro as Incertezas em torno da Fragmentação Geopolítica Mundial. Começa por identificar os grandes processos envolvidos na primeira "força motriz" - uma ampliação e "regionalização" da Economia Mundial; uma dinâmica de Globalização económica; uma competição acesa entre "Modelos de Capitalísmo"; uma mutação tecnológica abrangente, que modifica as estruturas económicas e a posição relativa das economias; e por último uma regulação económica global que procura responder à acumulação de tensões geradas pela interacção dos processos anteriores. Seguidamente identifica alguns processos chave que organizam a segunda" força motriz", como sejam o avanço da democratização, decorrendo em paralelo com a sobreposição de crises profundas em diversos Estados; um processo de fragmentação e "regionalização" em termos geopolíticos e de segurança; uma alteração na relação de forças entre potências, que está ainda numa fase inconclusiva; uma mutação tecnológica militar que pode influenciar decisivamente essa alteração; e a manifestação de dificuldades na regulação estratégica e geopolítica mundial, pela interacção dos processos anteriores e no contexto da ultrapassagem dos mecanismos de regulação típicos da guerra fria. Por último o texto ilustra algumas das interacções que se podem estabelecer entre as dinâmicas das duas "forças motrizes" sem explorar em profundidade o tema

Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice.

International audienceDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, caused by an absence of dystrophin, inevitably leading to death. Although muscle lesions are well characterized, blood vessel alterations that may have a major impact on muscle regeneration remain poorly understood. Our aim was to elucidate alterations of the vascular network organization, taking advantage of Flk1(GFP/+) crossed with mdx mice (model for human DMD where all blood vessels express green fluorescent protein) and functional repercussions using in vivo nuclear magnetic resonance, combining arterial spin-labeling imaging of perfusion, and (31)P-spectroscopy of phosphocreatine kinetics. For the first time, our study focused on old (12-month-old) mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD, in comparison to young-adult (3-month-old) mdx mice displaying only mild muscle lesions with no fibrosis. By using an original approach combining a specific animal model, state-of-the-art histology/morphometry techniques, and functional nuclear magnetic resonance, we demonstrated that the microvascular system is almost normal in young-adult in contrast to old mdx mice, displaying marked microvessel alterations, and the functional repercussions on muscle perfusion and bioenergetics after a hypoxic stress vary depending on stage of pathology. This original approach clarifies disease evolution and paves the way for setting up new diagnostic markers or therapeutic strategies

Exploring the protective role of GDF5 against skeletal muscle disuse atrophy

International audienceSkeletal muscle is a high plastic tissue able to change its mass upon different stimuli accordingly with environmental changes. Its adaptability depends on many factors and is based on complex mechanisms. Among the process that could alter muscle mass homeostasis, disuse and inactivity induce strong muscle mass and function decrease, having heavy impact on life quality and requiring long time to recover. Growth Differentiation Factor 5 (GDF5) is a crucial player in muscle homeostasis, shown to counteract both denervation- and age-related muscle wasting by limiting the activation of catabolic signals. However, its effects on disuse atrophy following muscle immobilization has to be investigated. In order to establish a potential therapeutic tool having a wide relevance, ranging from disease to microgravity exposure (space flight), we evaluated the consequences of GDF5 overexpression after 10 days of immobilization and 3 weeks of release of hind limb mouse muscles. We observed that local GDF5 overexpression in posterior limbs improved muscle mass loss during immobilization. However, three weeks after release, muscle mass and function were not affected by GDF5 overexpression. We aim to better characterize the effect of GDF5 treatment on several morphological and functional parameters of skeletal muscle upon immobilization/release. In addition, we will assess its eventual benefits at shorter time points after release, in order to establish if GDF5-based treatment could be proposed to shorten the time-window needed for optimal muscle recovery after disuse.In parallel, a study of microgravity exposure was carried on a muscle cell line. We showed that, in the absence of gravity, myotube formation was inhibited, suggesting that this condition could impact cytoskeleton and fusion capability. We will establish if GDF5 treatment might be beneficial for myoblast fusion and myotube morphology during microgravity exposure. In conclusion, our preliminary results suggest that a treatment based on GDF5 could have a therapeutic potential to ameliorate the pathophysiology of muscle during disuse condition to be applied also to space flight and microgravity exposure

Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity

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The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA

International audienceRap1 is an essential DNA-binding factor from the yeast Saccharomyces cerevisiae involved in transcription and telomere maintenance. Its binding to DNA targets Rap1 at particular loci, and may optimize its ability to form functional macromolecular assemblies. It is a modular protein, rich in large potentially unfolded regions, and comprising BRCT, Myb and RCT well-structured domains. Here, we present the architectures of Rap1 and a Rap1/DNA complex, built through a step-by-step integration of small angle X-ray scattering, X-ray crystallography and nuclear magnetic resonance data. Our results reveal Rap1 structural adjustment upon DNA binding that involves a specific orientation of the C-terminal (RCT) domain with regard to the DNA binding domain (DBD). Crystal structure of DBD in complex with a long DNA identifies an essential wrapping loop, which constrains the orientation of the RCT and affects Rap1 affinity to DNA. Based on our structural information, we propose a model for Rap1 assembly at telomere

The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA.

International audienceRap1 is an essential DNA-binding factor from the yeast Saccharomyces cerevisiae involved in transcription and telomere maintenance. Its binding to DNA targets Rap1 at particular loci, and may optimize its ability to form functional macromolecular assemblies. It is a modular protein, rich in large potentially unfolded regions, and comprising BRCT, Myb and RCT well-structured domains. Here, we present the architectures of Rap1 and a Rap1/DNA complex, built through a step-by-step integration of small angle X-ray scattering, X-ray crystallography and nuclear magnetic resonance data. Our results reveal Rap1 structural adjustment upon DNA binding that involves a specific orientation of the C-terminal (RCT) domain with regard to the DNA binding domain (DBD). Crystal structure of DBD in complex with a long DNA identifies an essential wrapping loop, which constrains the orientation of the RCT and affects Rap1 affinity to DNA. Based on our structural information, we propose a model for Rap1 assembly at telomere

Intermuscular fat in dystrophic mice.

<p>MRI of the four mouse strains (lower leg), showing intermuscular fat but no visible fat infiltration in the muscles in the three dystrophic strains. The arrows indicate the presence of fat between the muscles, as bright areas in the non fat-supressed images (NFS) and dark areas in the images with fat suppression (FS). The arrowheads indicate hyperintense areas present in the images with and without FS, which are therefore not related to fat infiltration. TE = 52.5 ms, TR = 1800 ms.</p

Texture analysis differentiates the four mouse strains.

<p>Two views of the same plot showing the clustering of mice groups after texture analysis from lower leg MRI. 1: wild-type, 2: <i>mdx/Large^myd</i>, 3: <i>Large^myd</i>, 4: <i>mdx</i> mice. MDF: Most Discriminant Features.</p

Muscle T2 for <i>mdx/Large^myd, Large^myd, mdx</i> and wild-type mice.

<p>Muscle T2 in milliseconds for the four mouse strains evaluated. *: Muscle T2 different from wild-type mice; #: muscle T2 different from <i>mdx</i> mice.</p

MRI versus histological analysis.

<p>MRI (A-D; TE = 40 ms, TR = 1500 ms) and histological images (H&E, magnification X12: E-H; magnification X200: I-L) of the left lower leg from <i>mdx/Large</i>^<i>myd</i> (A, E, I), Large^myd (B, F, J), <i>mdx</i> (C, G, K) and wild-type mice (D, H, L). The regions highlighted in the MRI (first row) and in the whole lower leg histological image (second row) are presented in a higher magnification in the third row. Different histological processes could be related to the hyperintensities regions in the MRI, such as clusters of degenerating cells (I), regenerating and adipose cells cells (K), and regions with mixed dystrophic characteristics (J).</p