At Odds Over INCO: The International Nickel Company of Canada and New Caledonian Politics in the 1960s

In the 1960s, the International Nickel Company of Canada (INCO) sought to preserve its dominance of the global nickel industry by securing access to New Caledonia’s abundant reserves of nickel ore. In attempting to do so, however, INCO became embroiled in an acrimonious political dispute between New Caledonian autonomists, who wanted to diversify the territory’s economic activities and secure greater self-government from French rule, and the government of France, which considered INCO a threat to French sovereignty over New Caledonia and France’s interests in the Pacific. In obstructing INCO’s ability to operate in New Caledonia throughout the 1960s, however, the French government inadvertently galvanized the territory’s nationalists and increased their demands for autonomy from France.Au cours des années 1960, l’International Nickel Company of Canada (INCO), cherchant à assurer sa prépondérance sur le marché mondial du nickel, a voulu obtenir l’accès aux abondantes réserves de ce minerai en Nouvelle-Calédonie. Par la même occasion, cependant, INCO s’est trouvée mêlée à un acrimonieux conflit politique entre les autonomistes néo-calédoniens intéressés à diversifier les activités économiques du territoire et à accroître l’autonomie gouvernementale, d’une part, et le gouvernement français qui voyait l’arrivée de la société comme une menace envers sa souveraineté en Nouvelle-Calédonie et les intérêts de la France dans le Pacifique, d’autre part. En s’opposant à la liberté de mouvement d’INCO en Nouvelle-Calédonie tout au long des années 1960, le gouvernement français s’est toutefois trouvé à galvaniser involontairement les nationalistes et leurs demandes d’autonomie de la France

Tempered Sympathy: Canada’s Reaction to the Independence Movement in Algeria, 1954-1962

This article examines the reaction of the Canadian government to the Algerian war for independence from France from 1954 to 1962. It reveals that, while sympathetic to the ambitions of colonial peoples to determine their own national destinies, the Canadian government often judged colonial issues after the Second World War by the impact they had on the North Atlantic Treaty Organisation, Canadian security interests and the Cold War. Given that the Algerian war threatened France's ability and willingness to contribute to NATO during this period the Canadian government felt compelled to support France's efforts to retain its North African colony both politically and militarily. Canadian officials wanted France's participation in NATO and were unwilling to antagonise France by opposing its Algerian policies. In this instance national security interests were of a higher priority for the Canadian government than support for the principle of national self-determination for colonial peoples.Le présent article examine la réaction du gouvernement canadien face à la guerre d'Algérie menée contre la France de 1954 à 1962 et au terme de laquelle l'Algérie parvenait à l'indépendance. Après la Deuxième Guerre mondiale en effet, malgré la sympathie que lui inspiraient les ambitions des peuples coloniaux à prendre en main leur destin national, le gouvernement du Canada considérait souvent les questions coloniales en fonction de leurs répercussions sur l'Organisation du Traité de l'Atlantique Nord, sur la sécurité du pays et sur la guerre froide. Or, en raison de cette guerre d'Algérie, la France risquait, au cours de cette période, de ne pas pouvoir et de ne pas vouloir contribuer à l'OTAN. C'est pourquoi le Canada s'est alors senti obligé de soutenir la France dans ses efforts visant à conserver sa colonie d'Afrique du Nord, tant sur le plan politique que militaire. Les dirigeants canadiens, qui tenaient à ce que la France participe à l'OTAN, se sont donc refusés à s'opposer à la politique française en matière algérienne. Dans les circonstances, la sécurité nationale comptait davantage pour le gouvernement que le principe de l'autodétermination des peuples coloniaux

Post-hatching parental care behaviour and hormonal status in a precocial bird

In birds, the link between parental care behaviour and prolactin release during incubation persists after hatching in altricial birds, but has never been precisely studied during the whole rearing period in precocial species, such as ducks. The present study aims to understand how changes in parental care after hatching are related to circulating prolactin levels in mallard hens rearing ducklings. Blood was sampled in hens over at least 13 post-hatching weeks and the behaviour of the hens and the ducklings was recorded daily until fledging. Contacts between hens and the ducklings, leadership of the ducklings and gathering of them steadily decreased over post-hatching time. Conversely, resting, preening and agonistic behaviour of hens towards ducklings increased. Plasma prolactin concentrations remained at high levels after hatching and then fell after week 6 when body mass and structural size of the young were close to those of the hen. Parental care behaviour declined linearly with brood age, showed a disruption of the hen-brood bond at week 6 post-hatching and was related to prolactin concentration according to a sigmoid function. Our results suggest that a definite threshold in circulating prolactin is necessary to promote and/or to maintain post-hatching parental care in ducks

Fibronectin III 13-14 Domains Induce Joint Damage via Toll-Like Receptor 4 Activation and Synergize with Interleukin-1 and Tumour Necrosis Factor

Cartilage loss is a feature of chronic arthritis. It results from degradation of the extracellular matrix which is composed predominantly of aggrecan and type II collagen. Extracellular matrix degradation is mediated by aggrecanases and matrix metalloproteinases (MMPs). Recently, a number of endogenous matrix molecules, including fibronectin (FN), have been implicated in mediating cartilage degradation. We were interested in studying the C-terminal heparin-binding region of FN since it mediates aggrecan and type II collagen breakdown in cartilage, but the specific FN domains responsible for proteolytic enzyme activity and their receptors in cartilage are unknown. In this study, the ability of recombinant FN domains to induce cartilage breakdown was tested. We found that the FN III 13-14 domains in the C-terminal heparin-binding region of FN are potent inducers of aggrecanase activity in articular cartilage. In murine studies, the FN III 13-14-induced aggrecanase activity was inhibited in Toll-like receptor 4 (TLR4) knockout mice but not wild-type mice. FN III 13-14 domains also synergized with the known catabolic cytokines interleukin-1α and tumour necrosis factor and induced secretion of MMP-1, MMP-3, gp38 and serum amyloid-like protein A in chondrocytes. Our studies provide a mechanistic link between the innate immune receptor TLR4 and sterile arthritis induced by the FN III 13-14 domains of the endogenous matrix molecule FN

The FALCON concept: multi-object adaptive optics and atmospheric tomography for integral field spectroscopy. Principles and performances on an 8 meter telescope

Integral field spectrographs are major instruments to study the mechanisms involved in the formation and the evolution of early galaxies. When combined with multi-object spectroscopy, those spectrographs can behave as machines used to derive physical parameters of galaxies during their formation process. Up to now, there is only one available spectrograph with multiple integral field units, e.g. FLAMES/GIRAFFE on the VLT. However, current ground based instruments suffer from a degradation of their spatial resolution due to atmospheric turbulence. In this article we describe the performance of FALCON, an original concept of a new generation multi-object integral field spectrograph with adaptive optics for the ESO Very Large Telescope. The goal of FALCON is to combine high angular resolution (0.25 arcsec) and high spectral resolution (R > 5000) in J and H bands over a wide field of view (10x10 arcmin2) in the VLT Nasmyth focal plane. However, instead of correcting the whole field, FALCON will use multi-object adaptive optics (MOAO) to perform locally on each scientific target the adaptive optics correction. This requires then to use atmospheric tomography in order to use suitable natural guide stars for wavefront sensing. We will show that merging MOAO and atmospheric tomography allows us to determine the internal kinematics of distant galaxies up to z=2 with a sky coverage of 50%, even for objects observed near the galactic pole. The application of such a concept to Extremely Large Telescopes seems therefore to be a very promising way to study galaxy evolution from z = 1 to redshifts as high as z = 7.Comment: Monthly Notices of the Royal Astronomical Society, accepte

Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions

GGGGCC repeat expansions of C9orf72 represent the most common genetic variant of amyotrophic lateral sclerosis and frontotemporal degeneration, but the mechanism of pathogenesis is unclear. Recent reports have suggested that the transcribed repeat might form toxic RNA foci that sequester various RNA processing proteins. Consensus as to the identity of the binding partners is missing and whole neuronal proteome investigation is needed. Using RNA fluorescence in situ hybridization we first identified nuclear and cytoplasmic RNA foci in peripheral and central nervous system biosamples from patients with amyotrophic lateral sclerosis with a repeat expansion of C9orf72 (C9orf72 + ), but not from those patients without a repeat expansion of C9orf72 (C9orf72) or control subjects. Moreover, in the cases examined, the distribution of foci-positive neurons correlated with the clinical phenotype (t-test P5 0.05). As expected, RNA foci are ablated by RNase treatment. Interestingly, we identified foci in fibroblasts from an asymptomatic C9orf72 + carrier. We next performed pulldown assays, with GGGGCC5, in conjunction with mass spectrometry analysis, to identify candidate binding partners of the GGGGCC repeat expansion. Proteins containing RNA recognition motifs and involved in splicing, messenger RNA nuclear export and/or translation were significantly enriched. Immunohistochemistry in central nervous system tissue from C9orf72 + patients with amyotrophic lateral sclerosis demonstrated co-localization of RNA foci with SRSF2, hnRNP H1/F, ALYREF and hnRNP A1 in cerebellar granule cells and with SRSF2, hnRNP H1/F and ALYREF in motor neurons, the primary target of pathology in amyotrophic lateral sclerosis. Direct binding of proteins to GGGGCC repeat RNA was confirmed in vitro by ultraviolet-crosslinking assays. Co-localization was only detected in a small proportion of RNA foci, suggesting dynamic sequestration rather than irreversible binding. Additional immunohistochemistry demonstrated that neurons with and without RNA foci were equally likely to show nuclear depletion of TDP-43 (2 P = 0.75) or poly-GA dipeptide repeat protein inclusions (2 P = 0.46). Our findings suggest two non-exclusive pathogenic mechanisms: (i) functional depletion of RNA-processing proteins resulting in disruption of messenger RNA splicing; and (ii) licensing of expanded C9orf72 pre-messenger RNA for nuclear export by inappropriate association with messenger RNA export adaptor protein(s) leading to cytoplasmic repeat associated non-ATG translation and formation of potentially toxic dipeptide repeat protein.

Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy

GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others have proposed that RNA transcribed from the repeat sequence is toxic via sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG-repeat (antisense) molecules are detectable by fluorescence in situ hybridisation as RNA foci, but their relative expression pattern within the CNS and contribution to disease has not been determined. Blinded examination of CNS biosamples from ALS patients with a repeat expansion of C9ORF72 showed that antisense foci are present at a significantly higher frequency in cerebellar Purkinje neurons and motor neurons, whereas sense foci are present at a significantly higher frequency in cerebellar granule neurons. Consistent with this, inclusions containing sense or antisense derived dipeptide repeat proteins were present at significantly higher frequency in cerebellar granule neurons or motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies showed that sense and antisense RNA molecules share similar interactions with SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest that, although sense and antisense RNA molecules might be expected to be equally toxic via their shared protein binding partners, distinct patterns of expression in various CNS neuronal populations could lead to relative differences in their contribution to the pathogenesis of neuronal injury. Moreover in motor neurons, which are the primary target of pathology in ALS, the presence of antisense foci (χ2, p 2, p = 0.75) correlated with mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This has implications for translational approaches to C9ORF72 disease, and furthermore interacting RNA-processing factors and transcriptional activators responsible for antisense versus sense transcription might represent novel therapeutic targets

The Spectrum of C9orf72-mediated Neurodegeneration and Amyotrophic Lateral Sclerosis

The discovery that a hexanucleotide repeat expansion in C9orf72 is the most numerous genetic variant of both amyotrophic lateral sclerosis and frontotemporal dementia has opened a rapidly growing field, which may provide long hoped for advances in the understanding and treatment of these devastating diseases. In this review we describe the various phenotypes, clinical and pathological, associated with expansion of C9orf72, which go beyond amyotrophic lateral sclerosis and frontotemporal dementia to include neurodegeneration more broadly. Next we take a step back and summarize the current understanding of the C9orf72 expansion and its protein products at a molecular level. Three mechanisms are prominent: toxicity mediated directly by RNA transcribed from the repeat; toxicity mediated by dipeptide repeat proteins translated from the repeat sequence; and haploinsufficiency resulting from reduced transcription of the C9orf72 exonic sequence. A series of exciting advances have recently described how dipeptide repeat proteins might interfere with the normal role of the nucleolus in maturation of RNA binding proteins and in production of ribosomes. Importantly, these mechanisms are unlikely to be mutually exclusive. We draw attention to the fact that clinical and pathological similarities to other genetic variants without a repeat expansion must not be overlooked in ascribing a pathogenic mechanism to C9orf72-disease. Finally, with a view to impact on patient care, we discuss current practice with respect to genetic screening in patients with and without a family history of disease, and the most promising developments towards therapy that have been reported to date