Rapid electroplating of insulators

Electrochemical techniques for depositing metal films and coatings have a long history. Such techniques essentially fall into two categories, with different advantages and disadvantages. The first, and oldest, makes use of spontaneous redox reactions to deposit a metal from solution, and can be used on both insulating and metallic substrates. But the deposition conditions of these processes are difficult to control in situ, in part because of the variety of salts and additives present in the solution. The second approach-electroplating-uses an electric current to reduce metal ions in solution, and offers control over the quantity (and, to some extent, grain size) of deposited metal. But application of this technique has hitherto been restricted to conducting substrates. Here we describe an electroplating technique that permits coating of insulating substrates with metals having controlled grain size, thickness and growth speed. The basis of our approach is the progressive outward growth of the metal from an electrode in contact with the substrate, with the cell geometry chosen so that the electron current providing the reduction passes through the growing deposit. Such an approach would normally form dendritic or powdery deposits, but we identify a range of conditions in which uniform films rapidly form.     

Feedback inhibition controls spike transfer in hybrid thalamic circuits

Sensory information reaches the cerebral cortex through the thalamus, which differentially relays this input depending on the state of arousal. Such 'gating' involves inhibition of the thalamocortical relay neurons by the reticular nucleus of the thalamus, but the underlying mechanisms are poorly understood. We reconstructed the thalamocortical circuit as an artificial and biological hybrid network in vitro. With visual input simulated as retinal cell activity, we show here that when the gain in the thalamic inhibitory feedback loop is greater than a critical value, the circuit tends towards oscillations -- and thus imposes a temporal decorrelation of retinal cell input and thalamic relay output. This results in the functional disconnection of the cortex from the sensory drive, a feature typical of sleep states. Conversely, low gain in the feedback inhibition and the action of noradrenaline, a known modulator of arousal, converge to increase input output correlation in relay neurons. Combining gain control of feedback inhibition and modulation of membrane excitability thus enables thalamic circuits to finely tune the gating of spike transmission from sensory organs to the cortex.     

Interdecadal variation in the extent of South Pacific tropical waters during the Younger Dryas event

During the Younger Dryas event, about 12,000 years ago, the Northern Hemisphere cooled by between 2 and 10 degrees C (refs 1, 2) whereas East Antarctica experienced warming. But the spatial signature of the event in the southern mid-latitudes and tropics is less well known, as records are sparse and inconclusive. Here we present high-resolution analyses of skeletal Sr/Ca and 18O/16O ratios for a giant fossil Diploastrea heliopora coral that was preserved in growth position on the raised reef terraces of Espiritu Santo Island, Vanuatu, in the southwestern tropical Pacific Ocean. Our data indicate that sea surface temperatures in Vanuatu were on average 4.5 +/- 1.3 degrees C cooler during the Younger Dryas event than today, with a significant interdecadal modulation. The amplified annual cycle of sea surface temperatures, relative to today, indicates that cooling was caused by the compression of tropical waters towards the Equator. The positive correlation in our record between the oxygen isotope ratios of sea water and sea surface temperatures suggests that the South Pacific convergence zone, which brings 18O-depleted precipitation to the area today, was not active during the Younger Dryas period.     

Kinetics of decrease and apparent transformation of fluorescence spectra of benzo(a)pyrene absorbed by living cells: case of lymphocytes and macrophages]

A home made microspectrofluorimeter is used in order to follow the decrease of fluorescence intensity of Benzo(a)Pyrene after its absorption by single living cells. The kinetics look to be a first order one; fluorescent metabolite can be detected when peritoneal macrophages of Mice are used but not with human periferic lymphocytes pretreated with mitogens.     

Histofluorescence of catecholamines and visualization of retrograde transported peroxidase in the same tissue section and in the same neuron]

The demonstration of fluorescent catecholamines and horseradish peroxidase (HRP) in the same neuron has been achieved in the Rat in two ways: by submitting vibratome sections to a modified glyoxylic acid fluorescence method followed by the usual procedure to reveal HRP; or by combining the last procedure with the cryostat technique of Chiba et coll. After HRP injection into the striatum or the nucleus accumbens of the Rat, non-fluorescent HRP labelled neurons were observed in the substantia nigra and the ventral tegmental area respectively, in addition to the HRP labelled fluorescent dopaminergic neurons.     

Sequence and structure of D-glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus.

The glyceraldehyde 3-phosphate dehydogenase holoenzyme of Bacillus stearothermophilus possesses precise 222 symmetry: in this respect it differs from the reported structure of the lobster muscle enzyme. Pairs of active sites are linked through a flexible polypeptide loop which probably mediates the structural changes giving rise to cooperative effects. Three additional salt bridges made by each subunit to others would make a major contribution to thermostability of the tetramer.     

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.     

AtSNX1 defines an endosome for auxin-carrier trafficking in Arabidopsis

Polarized cellular distribution of the phytohormone auxin and its carriers is essential for normal plant growth and development. Polar auxin transport is maintained by a network of auxin influx (AUX) and efflux (PIN) carriers. Both auxin transport and PIN protein cycling between the plasma membrane and endosomes require the activity of the endosomal GNOM; however, intracellular routes taken by these carriers remain largely unknown. Here we show that Arabidopsis thaliana SORTING NEXIN 1 (AtSNX1) is involved in the auxin pathway and that PIN2, but not PIN1 or AUX1, is transported through AtSNX1-containing endosomes. We demonstrate that the snx1-null mutant exhibits multiple auxin-related defects and that loss of function of AtSNX1 severely enhances the phenotype of a weak gnom mutant. In root cells, we further show that AtSNX1 localizes to an endosomal compartment distinct from GNOM-containing endosomes, and that PIN2 accumulates in this compartment after treatment with the phosphatidylinositol-3-OH kinase inhibitor wortmannin or after a gravity stimulus. Our data reveal the existence of a novel endosomal compartment involved in PIN2 endocytic sorting and plant development.     

APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy

We report duplication of the APP locus on chromosome 21 in five families with autosomal dominant early-onset Alzheimer disease (ADEOAD) and cerebral amyloid angiopathy (CAA). Among these families, the duplicated segments had a minimal size ranging from 0.58 to 6.37 Mb. Brains from individuals with APP duplication showed abundant parenchymal and vascular deposits of amyloid-beta peptides. Duplication of the APP locus, resulting in accumulation of amyloid-beta peptides, causes ADEOAD with CAA.