A study of the determinants of release probability in hippocampal synapses

The release of neurotransmitter at a synapse is a stochastic process, such that the arrival of an action potential triggers vesicle fusion with a lim ited probability (pr). Although pr is a fundamental parameter in denning synaptic efficacy, it is not uniform across all synapses, and the mechanisms by which a given synapse sets its basal release probability are unknown. This study employed FM-dye imaging, paired whole-cell recordings and se rial ultrastructural analysis with 3D reconstruction to address this question. Optical measurements of pr at single synapses were made in small networks of cultured hippocampal neurons, and suggest a new model of pr regulation ' whereby release probability is set locally by the dendrite through a nega tive feedback mechanism. In synaptically connected pairs of neurons, a high resolution spatial analysis reveals that neighbouring synapses on the same dendritic branch show very similar release probabilities, even though the connection overall has a broad distribution of pr. Moreover, pr is negatively correlated with the number of synapses made between the axon and the den dritic branch. Increasing network activity elicits a homeostatic decrease in pr that is dependent on dendritic depolarization, and imposing a spatially uniform input to the dendrite significantly reduces the variability in pr. Fur thermore, manipulating the activity of a single dendritic branch leads to a spatially selective decrease in pr. These results indicate that local dendritic activity is the major determinant of basal release probability, and theoreti cal simulations suggest that this retrograde regulation provides a means to maintain synchronously activated synapses in their operational range

The critical earthquake concept applied to mine rockbursts with time-to-failure analysis

We report new tests of the critical earthquake concepts performed on rockbursts in deep South African mines. We extend the concept of an optimal time and space correlation region and test it on the eight main shocks of our catalog provided by ISSI. In a first test, we use the simplest signature of criticality in terms of a power law time-to-failure formula. Notwithstanding the fact that the search for the optimal correlation size is performed with this simple power law, we find evidence both for accelerated seismicity and for the presence of logperiodic behavior with a prefered scaling factor close to 2. We then propose a new algorithm based on a space and time smoothing procedure, which is also intended to account for the finite range and time mechanical interactions between events. This new algorithm provides a much more robust and efficient construction of the optimal correlation region, which allows us the use of the logperiodic formula directly in the search process. In this preliminary work, we have only tested the new algorithm on the largest event on the catalog. The result is of remarkable good quality with a dramatic improvement in accuracy and robustness. This confirms the potential importance of logperiodic signals. Our study opens the road for an efficient implemention of a systematic testing procedure of real-time predictions.Comment: 22 pages, 32 figure

Deciphering the genome structure and paleohistory of _Theobroma cacao_

We sequenced and assembled the genome of _Theobroma cacao_, an economically important tropical fruit tree crop that is the source of chocolate. The assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of them anchored on the 10 _T. cacao_ chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example flavonoid-related genes. It also provides a major source of candidate genes for _T. cacao_ disease resistance and quality improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten _T. cacao_ chromosomes were shaped from an ancestor through eleven chromosome fusions. The _T. cacao_ genome can be considered as a simple living relic of higher plant evolution

Evidence for the return of subducted continental crust

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 684-687, doi:10.1038/nature06048.Substantial quantities of terrigenous sediments are known to enter the mantle at subduction zones, but little is known about their fate in the mantle. Subducted sediment may be entrained in buoyantly upwelling plumes and returned to the earth’s surface at hotspots, but the proportion of recycled sediment in the mantle is small and clear examples of recycled sediment in hotspot lavas are rare. We report here remarkably enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures (up to 0.720830 and 0.512285, respectively) in Samoan lavas from three dredge locations on the underwater flanks of Savai’i island, Western Samoa. The submarine Savai’i lavas represent the most extreme 87Sr/86Sr isotope compositions reported for ocean island basalts (OIBs) to date. The data are consistent with the presence of a recycled sediment component (with a composition similar to upper continental crust, or UCC) in the Samoan mantle. Trace element data show similar affinities with UCC—including exceptionally low Ce/Pb and Nb/U ratios—that complement the enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures. The geochemical evidence from the new Samoan lavas radically redefines the composition of the EM2 (enriched mantle 2) mantle endmember, and points to the presence of an ancient recycled UCC component in the Samoan plume

An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Hints of Universality from Inflection Point Inflation

This work aims to understand how cosmic inflation embeds into larger models of particle physics and string theory. Our work operates within a weakened version of the Landscape paradigm, wherein it is assumed that the set of possible Lagrangians is vast enough to admit the notion of a generic model. By focusing on slow-roll inflation, we examine the roles of both the scalar potential and the space of couplings which determine its precise form. In particular, we focus on the structural properties of the scalar potential, and find a surprising result: inflection point inflation emerges as an important —and under certain assumptions, dominant — possibility in the context of generic scalar potentials. We begin by a systematic coarse graining over the set of possible inflection point inflation models using V.I. Arnold’s ADE classification of singularities. Similar to du Val’s pioneering work on surface singularities, these determine structural classes for inflection point inflation which depened on a distinct number of control parameters. We consider both single and multifield inflation, and show how the various structural classes embed within each other. We also show how such control parameters influence the larger physical models in to which inflation is embedded. These techniques are then applied to both MSSM inflation and KKLT-type models of string cosmology. In the former case, we find that the scale of inflation can be entirely encoded within the super- potential of supersymmetric quantum field theories. We show how this relieves the fine-tuning required in such models by upwards of twelve orders of magnitude. Moreover, unnatural tuning between SUSY breaking and SUSY preserving sectors is eliminated without the explicit need for any hidden sector dynamics. In the later case, we discuss how structural stability vastly generalizes — and addresses — the Kallosh-Linde problem. Implications for the spectrum of SUSY breaking soft terms are then discussed, with an emphasis on how they may assist in constraining the inflationary scalar potential. We then pivot to a general discussion of the FLRW-scalar phase space, and show how inflection points induce caustics — or dynamical fixed points — amongst the space of possible trajectories. These fixed points are then used to argue that for uninformative priors on the space of couplings, the likelihood of inflection point inflation scales with the inverse cube of the number of e-foldings. We point out the geometric origin for the known ambiguity in the Liouville measure, and demonstrate of inflection point inflation ameliorates this problem. Finally we investigate the effect of the fixed point structure on the spectrum of density perturbations. We show how an anomaly in the Cosmic Mircowave Background data — low power at large scales — can be explained as a by product of the fixed point dynamics

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples