Formation and regulation of excitatory glutamatergic synapses is essential for shaping neural circuits throughout development. In a Drosophila genetic screen for synaptogenesis mutants, we identified ...mind the gap (mtg), which encodes a secreted, extracellular N-glycosaminoglycan-binding protein. MTG is expressed neuronally and detected in the synaptic cleft, and is required to form the specialized transsynaptic matrix that links the presynaptic active zone with the post-synaptic glutamate receptor (GluR) domain. Null mtg embryonic mutant synapses exhibit greatly reduced GluR function, and a corresponding loss of localized GluR domains. All known post-synaptic signaling/scaffold proteins functioning upstream of GluR localization are also grossly reduced or mislocalized in mtg mutants, including the dPix-dPak-Dock cascade and the Dlg/PSD-95 scaffold. Ubiquitous or neuronally targeted mtg RNA interference (RNAi) similarly reduce post-synaptic assembly, whereas post-synaptically targeted RNAi has no effect, indicating that presynaptic MTG induces and maintains the post-synaptic pathways driving GluR domain formation. These findings suggest that MTG is secreted from the presynaptic terminal to shape the extracellular synaptic cleft domain, and that the cleft domain functions to mediate transsynaptic signals required for post-synaptic development.
Helminth infections in children are associated with impaired cognitive development; however, the biological mechanisms for this remain unclear. Using a murine model of gastrointestinal helminth ...infection, we demonstrate that early-life exposure to helminths promotes local and systemic inflammatory responses and transient changes in the gastrointestinal microbiome. Behavioral and cognitive analyses performed 9-months postinfection revealed deficits in spatial recognition memory and an anxiety-like behavioral phenotype in worm-infected mice, which was associated with neuropathology and increased microglial activation within the brain. This study demonstrates a previously unrecognized mechanism through which helminth infections may influence cognitive function, via perturbations in the gut-immune-brain axis.
Abstract The purpose of this article is to provide a framework for developing a sports nutrition education program in a collegiate athletic department. A review of literature on student-athlete ...nutrition behaviors is combined with practical suggestions from personnel who wrote a sports nutrition curriculum at a large Midwestern university. There are 2 primary implications for practice. First, maintaining a written curriculum and conducting periodic evaluation are fundamental aspects of sports nutrition education programs. Second, better documentation of program outcomes is needed to establish best practices in collegiate sports nutrition education and demonstrate the value of full-time sports registered dietitians.
Ischemia–reperfusion (I/R) injury occurs when a tissue is temporarily deprived of blood supply and the return of the blood supply triggers an intense inflammatory response. Pathologically, increased ...complement activity can cause substantial damage to blood vessels, tissues and also facilitate leukocyte activation and recruitment following I/R injury. Herein, previously published studies are reported and critically reviewed.
Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) Complement pathways; (2) The complement system and the inflammatory response; (3) Complement in ischemia–reperfusion injuries; and (4) Therapeutic approaches against complement in I/R injuries.
I/R injury is a common clinical event with the potential to seriously affect, and sometimes kill, the patient and is a potent inducer of complement activation that results in the production of a number of inflammatory mediators. Complement activation leads to the release of biologically active potent inflammatory complement substances including the anaphylatoxins (C3a and C5a) and the cytolytic terminal membrane attack complement complex C5b-9 (MAC). The use of specific complement inhibitors to block complement activation at various levels of the cascade has been shown to prevent or reduce local tissue injury after I/R. Several agents that inhibit all or part of the complement system, such as soluble complement receptor type 1 (sCR1), C1 inhibitor (C1-INH), C5a monoclonal antibodies, a C5a receptor antagonist and soluble CD59 (sCD59) have been shown to reduce I/R injury of various organs. The novel inhibitors of complement products may eventually find wide clinical application because there are no effective drug therapies currently available to treat I/R injuries.
The growth and characterisation of a non-planar phthalocyanine (vanadyl phthalocyanine, VOPc) on a complete monolayer (ML) of a planar phthalocyanine (Iron(
ii
) phthalocyanine, FePc) on an Au(111) ...surface, has been investigated using ultra-high vacuum (UHV) scanning tunnelling microscopy (STM) and low energy electron diffraction (LEED). The surface mesh of the initial FePc monolayer has been determined and shown to correspond to an incommensurate overlayer, not commensurate as previously reported. Ordered islands of VOPc, with (1 × 1) epitaxy, grow on the FePc layer at submonolayer coverages. The individual VOPc molecules occupy sites directly atop the underlying FePc molecules, indicating that significant intermolecular bonding must occur. It is proposed that this interaction implies that the V&z.dbd;O points down into the surface, allowing a Fe-O bond to form. The detailed appearance of the STM images of the VOPc molecules is consistent with previous studies in other VOPc growth studies in which this molecular orientation has been proposed.
A combination of LEED and STM measurements demonstrate epitaxial ordering in bilayers formed from non-planar and planar phthalocyanines.
We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified ...in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.
This prospective study investigated a cohort of 59 scaphoid waist fractures which were treated nonoperatively in a below-elbow plaster cast for 4 weeks and then underwent a Week 4 CT scan to assess ...displacement and progress to union. Forty-three were classed as undisplaced and 37 of these 43 were also classed as ‘united’. All the 37 undisplaced and ‘united’ fractures united with up to 8 weeks’ cast immobilisation, including 26 which were taken out of plaster at 4 weeks and mobilised. We conclude that scaphoid waist fractures which appear to be undisplaced and united on a week 4 CT scan will unite, and may not need to be immobilised in a plaster cast for more than 4 weeks. Such a treatment policy may reduce the period of disability and time off work associated with nonoperative treatment.