Defective synapse maturation and enhanced synaptic plasticity in Shank2(-/-) mice

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with a strong genetic aetiology. Since mutations in human SHANK genes have been found in patients with autism, genetic mouse models are employed for a mechanistic understanding of ASDs and the development of therapeutic strategies. In sharp contrast to all studies so far on the function of SHANK proteins, we observe enhanced synaptic plasticity in Shank2(-/-) mice, under various conditions in vitro and in vivo. Reproducing and extending previous results, we here present a plausible mechanistic explanation for the mutants' increased capacity for long-term potentiation (LTP) by describing a synaptic maturation deficit in Shank2(-/-) mice

The key position: influence of staple location on constrained peptide conformation and binding

First published online 29 Sep 2016Constrained α-helical peptides are showing potential as biological probes and therapeutic agents that target protein-protein interactions. However, the factors that determine the optimal constraint locations are still largely unknown. Using the β-integrin/talin protein interaction as a model system, we examine the effect of constraint location on helical conformation, as well as binding affinity, using circular dichroism and NMR spectroscopy. Stapling increased the overall helical content of each integrin-based peptide tested. However, NMR analysis revealed that different regions within the peptide are stabilised, depending on constraint location, and that these differences correlate with the changes observed in talin binding mode and affinity. In addition, we show that examination of the atomic structure of the parent peptide provides insight into the appropriate placement of helical constraints.Kelly L. Keeling, Okki Cho, Denis B. Scanlon, Grant W. Booker, Andrew D. Abell and Kate L. Wegene

QuickXsort: Efficient Sorting with n log n - 1.399n +o(n) Comparisons on Average

In this paper we generalize the idea of QuickHeapsort leading to the notion of QuickXsort. Given some external sorting algorithm X, QuickXsort yields an internal sorting algorithm if X satisfies certain natural conditions. With QuickWeakHeapsort and QuickMergesort we present two examples for the QuickXsort-construction. Both are efficient algorithms that incur approximately n log n - 1.26n +o(n) comparisons on the average. A worst case of n log n + O(n) comparisons can be achieved without significantly affecting the average case. Furthermore, we describe an implementation of MergeInsertion for small n. Taking MergeInsertion as a base case for QuickMergesort, we establish a worst-case efficient sorting algorithm calling for n log n - 1.3999n + o(n) comparisons on average. QuickMergesort with constant size base cases shows the best performance on practical inputs: when sorting integers it is slower by only 15% to STL-Introsort

Defective synapse maturation and enhanced synaptic plasticity in Shank2 Δex7(-/-) mice

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with a strong genetic etiology. Since mutations in human SHANK genes have been found in patients with autism, genetic mouse models are used for a mechanistic understanding of ASDs and the development of therapeutic strategies. SHANKs are scaffold proteins in the postsynaptic density of mammalian excitatory synapses with proposed functions in synaptogenesis, regulation of dendritic spine morphology, and instruction of structural synaptic plasticity. In contrast to all studies so far on the function of SHANK proteins, we have previously observed enhanced synaptic plasticity in Shank2 Δex7(-/-) mice. In a series of experiments, we now reproduce these results, further explore the synaptic phenotype, and directly compare our model to the independently generated Shank2 Δex6-7(-/-) mice. Minimal stimulation experiments reveal that Shank2 Δex7(-/-) mice possess an excessive fraction of silent (i.e., α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, short, AMPA receptor lacking) synapses. The synaptic maturation deficit emerges during the third postnatal week and constitutes a plausible mechanistic explanation for the mutants' increased capacity for long-term potentiation, both in vivo and in vitro. A direct comparison with Shank2 Δex6-7(-/-) mice adds weight to the hypothesis that both mouse models show a different set of synaptic phenotypes, possibly due to differences in their genetic background. These findings add to the diversity of synaptic phenotypes in neurodevelopmental disorders and further support the supposed existence of "modifier genes" in the expression and inheritance of ASDs

3D Two-Photon Microprinting of Nanoporous Architectures

A photoresist system for 3D two‐photon microprinting is presented, which enables the printing of inherently nanoporous structures with mean pore sizes around 50 nm by means of self‐organization on the nanoscale. A phase separation between polymerizable and chemically inert photoresist components leads to the formation of 3D co‐continuous structures. Subsequent washing‐out of the unpolymerized phase reveals the porous polymer structures. To characterize the volume properties of the printed structures, scanning electron microscopy images are recorded from ultramicrotome sections. In addition, the light‐scattering properties of the 3D‐printed material are analyzed. By adjusting the printing parameters, the porosity can be controlled during 3D printing. As an application example, a functioning miniaturized Ulbricht light‐collection sphere is 3D printed and tested

Processing Succinct Matrices and Vectors

We study the complexity of algorithmic problems for matrices that are represented by multi-terminal decision diagrams (MTDD). These are a variant of ordered decision diagrams, where the terminal nodes are labeled with arbitrary elements of a semiring (instead of 0 and 1). A simple example shows that the product of two MTDD-represented matrices cannot be represented by an MTDD of polynomial size. To overcome this deficiency, we extended MTDDs to MTDD_+ by allowing componentwise symbolic addition of variables (of the same dimension) in rules. It is shown that accessing an entry, equality checking, matrix multiplication, and other basic matrix operations can be solved in polynomial time for MTDD_+-represented matrices. On the other hand, testing whether the determinant of a MTDD-represented matrix vanishes PSPACE$-complete, and the same problem is NP-complete for MTDD_+-represented diagonal matrices. Computing a specific entry in a product of MTDD-represented matrices is #P-complete.Comment: An extended abstract of this paper will appear in the Proceedings of CSR 201

The beginnings of geography teaching and research in the University of Glasgow: the impact of J.W. Gregory

J.W. Gregory arrived in Glasgow from Melbourne in 1904 to take up the post of foundation Professor of Geology in the University of Glasgow. Soon after his arrival in Glasgow he began to push for the setting up of teaching in Geography in Glasgow, which came to pass in 1909 with the appointment of a Lecturer in Geography. This lecturer was based in the Department of Geology in the University's East Quad. Gregory's active promotion of Geography in the University was matched by his extensive writing in the area, in textbooks, journal articles and popular books. His prodigious output across a wide range of subject areas is variably accepted today, with much of his geomorphological work being judged as misguided to varying degrees. His 'social science' publications - in the areas of race, migration, colonisation and economic development of Africa and Australia - espouse a viewpoint that is unacceptable in the twenty-first century. Nonetheless, that viewpoint sits squarely within the social and economic traditions of Gregory's era, and he was clearly a key 'Establishment' figure in natural and social sciences research in the first half of the twentieth century. The establishment of Geography in the University of Glasgow remains enduring testimony of J.W. Gregory's energy, dedication and foresight