Novel treatment strategies for schizophrenia from improved understanding of genetic risk

Recent years have seen significant advances in our understanding of the genetic basis of schizophrenia. In particular, genome-wide approaches have suggested the involvement of many common genetic variants of small effect, together with a few rare variants exerting relatively large effects. While unequivocal identification of the relevant genes has, for the most part, remained elusive, the genes revealed as potential candidates can in many cases be clustered into functionally-related groups which are potentially open to therapeutic intervention. In this review, we summarise this information, focussing on the accumulating evidence that genetic dysfunction at glutamatergic synapses and post-synaptic signalling complexes contributes to the aetiology of the disease. In particular, there is converging support for involvement of post-synaptic JNK pathways in disease aetiology. An expansion of our neurobiological knowledge of the basis of schizophrenia is urgently needed, yet some promising novel pharmacological targets can already be discerned

Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline

Rationale: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. Objective: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Methods: Attentional function in mice haploinsufficient for Map2k7 (Map2k7+/− mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Results: Once stable performance had been achieved, Map2k7+/− mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline—a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia—signs of improvement in attentional performance were detected. Conclusions: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline

Tribological and mechanical properties of graphene nanoplatelet/PEEK composites

Poly(ether ether ketone) (PEEK) is a relevant thermoplastic in industry and in the biomedical sector. In this work, the lubricant capability of graphene nanoplatelets (GNPs) is used for improving the PEEK wear properties. Nanocomposites were prepared by solvent-free melt-blending and injection molding at various compositions between 1 and 10 wt. % of GNPs. The Raman G band shows a progressive increment proportional to the bulk GNP percentage. From calorimetric data, the polymer matrix structure is interpreted in terms of a 3-phase model, in which the crystalline phase fluctuates from 39 to 34% upon GNP addition. Thermal conductivity varies in accordance with the polymer crystallinity. Tensile and flexural tests show a progressive increase in the modulus, as well as a decrease in the fracture strength and the work of fracture. Most important, the composite surface undergoes a substantial improvement in hardness (60%), together with a decrease in the coefficient of friction (-38%) and a great reduction in the wear factor (-83%). Abrasion and fatigue wear mechanisms are predominant at the lowest and highest GNP concentrations respectively. In conclusion, GNPs are used without any chemical functionalization as the filler in PEEK-based materials, improving the surface hardness and the tribological properties

Domain Bubbles of Extra Dimensions

``Dimension bubbles'' of the type previously studied by Blau and Guendelman [S.K. Blau and E.I. Guendelman, Phys. Rev. D40, 1909 (1989)], which effectively enclose a region of 5d spacetime and are surrounded by a region of 4d spacetime, can arise in a 5d theory with a compact extra dimension that is dimensionally reduced to give an effective 4d theory. These bubbles with thin domain walls can be stabilized against total collapse in a rather natural way by a scalar field which, as in the case with ``ordinary'' nontopological solitons, traps light scalar particles inside the bubble.Comment: 13 pages, no figures; to appear in Phys.Rev.

Can a wormhole generate electromagnetic field?

We have considered the possibility of a slowly rotating wormhole surrounded by a cloud of charged particles. Due to slow rotation of the wormhole, the charged particles are dragged thereby producing an electromagnetic field. We have determined the strength of this electromagnetic field and the corresponding flux of radiation.Comment: 9 pages, typos fixe

Gauged Dimension Bubbles

Some of the peculiar electrodynamical effects associated with gauged ``dimension bubbles'' are presented. Such bubbles, which effectively enclose a region of 5d spacetime, can arise from a 5d theory with a compact extra dimension. Bubbles with thin domain walls can be stabilized against total collapse by the entrapment of light charged scalar bosons inside the bubble, extending the idea of a neutral dimension bubble to accommodate the case of a gauged U(1) symmetry. Using a dielectric approach to the 4d dilaton-Maxwell theory, it is seen that the bubble wall is almost totally opaque to photons, leading to a new stabilization mechanism due to trapped photons. Photon dominated bubbles very slowly shrink, resulting in a temperature increase inside the bubble. At some critical temperature, however, these bubbles explode, with a release of radiation.Comment: 14 pages, no figures; to appear in Phys.Rev.

Tribological Behavior and Mechanical Properties of Graphene/PEEK Composites

PEEK has been implemented in various orthopaedic applications due to its many beneficial mechanical, tribological, and radiolucent properties. These properties can be further tailored by introducing fillers into the PEEK matrix. In this work, graphene has been incorporated due to its high mechanical resistance, intrinsic stiffness, and lubricating properties [2]