Enlarged ventricles in the cerebrum of loop-tail mice

Résumé Les souris hétérozygotes appartenant à la mutation «loop-tail» (Lp) présentent une hydrocéphalie interne du télencéphale. Jusqu'ici, cette anomalie ainsi que les torsions de la queue et l'oscillation de la tête qui l'accompagnent n'avaient pas été étudiés en détail. Nous avons constaté que par suite de l'élargissement des ventricules encéphaliques, les structures cérébrales qui les entourent sont réduites, déformées ou déplacées. Ces aberrations neuro-anatomiques jettent de la lumière sur les perturbations du comportement observées chez ces mutants.     

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration.     

Vascular normalization in Rgs5-deficient tumours promotes immune destruction

The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.     

LNA-mediated microRNA silencing in non-human primates

microRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg(-1) LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.     

Observations on the centromere area of human chromosomes

Zusammenfassung Das dem Centromer der menschlichen Chromosomen (ebenfalls bei andern Arten) anliegende Gebiet erscheint hell, klar und rund. Dies wurde in einigen Zellen bei fast jedem Centromer, bei andern Zellen nur selten oder überhaupt nicht beobachtet. Eine ähnliche Erscheinung trat auch in Form von Streifen auf, die sich manchmal vom Centromer aus zu anliegenden Chromosomen erstreckten oder sich ins Cytoplasma ausbreiteten. Die mögliche Deutung dieser Beobachtung wurde besprochen.

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This project was supported in part by Public Health Service Career Development Award No. K3-CA-19, 745 from the National Cancer Institute, Research Grant No. GM 11078 from the General Medical Science Branch, and the John A. Hartford Foundation.     

Shock effects on the growth of radish seedlings: the effect of the pressure duration

Résumé Des semis de radis furent soumis à la pression produite par un choc atmosphérique. La pression engendrée par une pulsation augmentant rapidement durait de 0, 1 à 14 sec. La durée de la pression servit de critère pour évaluer les effets des niveaux élevés du choc atmosphérique.