SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism

Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies

Reinventing foreign aid for inclusive and sustainable development: a survey

This survey essay reviews over 200 papers in arguing that in order to achieve sustainable and inclusive development, foreign aid should not orient developing countries towards industrialisation in the perspective of Kuznets but in the view of Piketty. Abandoning the former’s view that inequality will fall with progress in industrialisation and placing more emphasis on inequality in foreign aid policy will lead to more sustainable development outcomes. Inter alia: mitigate short-term poverty; address concerns of burgeoning population growth; train recipient governments on inclusive development; fight corruption and mismanagement and; avoid the shortfalls of celebrated Kuznets’ conjectures. We discuss how the essay addresses post-2015 development challenges and provide foreign aid policy instruments with which discussed objectives can be achieved. In summary, the essay provides useful policy measures to avoid past pitfalls. ‘Output may be growing, and yet the mass of the people may be becoming poorer’ (Lewis, 1955). ‘Lewis led all developing countries to water, proverbially speaking, some African countries have so far chosen not to drink’ (Amavilah, 2014). Piketty (2014) has led all developing countries to the stream again and a challenging policy syndrome of our time is how foreign aid can help them to drink

Physics Performance of the EBWE in Its Zero to 100 Mw Operation

The distribution of fuel elements in the EBWR core is described. Spike elements with boron steel strips were provided in the core for burnup allowance. A calibration of the control rod system with Zircaloy followers was made. Void coefficient measurements were made for two different H/sub 3/BO/sub 3/ concentrations. Power runs were made, and reactivity loss vs. power characteristic was obtained. Steam remaining in the core, or carryunder,'' was indicated. Some of the spikes were removed for increasing the power to 80 Mw. Calculations were made of the reactivity loss with coolant void and of the average void vs. reactor power. (D. L.C.

EBWR CORE 1A PHYSICS ANALYSIS

The studies were primarily directed toward selection of the optimum loading for Core lA and a prediction of its properties. Included are analyses of some relevant experiments on Core 1, and prelimlnary modifications of Core 1 to Core lA. The factors which must be considered for the optimum loading determination are discussed. Four different loading pattenrs were investigated, which were considered to span the numerous possibilitles. Adequate cold shutdown was found to be almost unobtainable without the use of boric acid. For this reason, and because the heat transfer and stability limitations are severe, greater weight was given to heat transfer as opposed to control requirements. The use of boron-stainless steel poison strips fastened to the sides of the spike elements is considered insofar as in improving the loading from either the heat transfer or control standpoint. The relatlve advantages and disadvantages of the use of stainless steel fuel followers as opposed to Zircaloy followers are discussed. (B.O.G.

An objective climatology of tropical plumes

The first global objective climatology of tropical plumes (TPs), obtained from a novel algorithm based on gridded 10.8-μmbrightness temperatures T, is presented for 1983-2006. TPs are defined as continuous cloud bands (>2000 km) crossing 15°Nor 15°S with T anomalies of less than220 K and a lifetime of at least 3 h. A minimum length-to-width ratio of 3 filters out elongated features. Numbers of identified TPs are sensitive to the chosen thresholds but not their geographical distribution and seasonal cycle. TPs are an important indicator of tropical-extratropical interactions with impacts on radiation and moisture. TP occurrence during boreal winter is largely confined to oceanic regions with main maxima over the South Pacific and South Atlantic as well as the eastern North Atlantic and Pacific Oceans. The geographical distribution during boreal summer is similar, but with lower frequencies, except for monsoon-influenced regions. Interannual variations over the Indo-Pacific region are strongly related to El Niño. TPs often develop downstream of extratropical upper-level troughs propagating into low latitudes, particularly over the wintertime eastern North Pacific and North Atlantic, but also in regions where mean upper-level easterlies do not generally favor equatorward Rossby wave propagation. Synoptic-scale variations in the quasi-permanent cloud bands associated with the South Pacific and South Atlantic convergence zones frequently produce TP-like anomalies, which are climatologically associated with downstream upper-level troughs. Some regions also feature TPs associated with mesoscale tropical disturbances. The new TP algorithm will serve as a basis for more in-depth studies in the future

20-MW D₂O-moderated experimental boiling water reactor design studies /

"Operated by the University of Chicago under Contract W-31-109-eng-38."At head of title: Argonne National Laboratory."February 1957."Includes bibliographical references and abstract.Mode of access: Internet