SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and intellectual disability. SHANK3 also plays a key role in the chromosome 22q13.3 microdeletion syndrome (Phelan-McDermid syndrome), which includes ASD and cognitive dysfunction as major clinical features. To evaluate the role of Shank3 in vivo, we disrupted major isoforms of the gene in mice by deleting exons 4-9. Isoform-specific Shank3(e4-9) homozygous mutant mice display abnormal social behaviors, communication patterns, repetitive behaviors and learning and memory. Shank3(e4-9) male mice display more severe impairments than females in motor coordination. Shank3(e4-9) mice have reduced levels of Homer1b/c, GKAP and GluA1 at the PSD, and show attenuated activity-dependent redistribution of GluA1-containing AMPA receptors. Subtle morphological alterations in dendritic spines are also observed. Although synaptic transmission is normal in CA1 hippocampus, long-term potentiation is deficient in Shank3(e4-9) mice. We conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.

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The objective of this research was to characterize the anaerobic biodegradability of major wood products in municipal waste by measuring methane yields, decay rates, the extent of carbohydrate decomposition, carbon storage, and leachate toxicity. Tests were conducted in triplicate 8 L reactors operated to obtain maximum yields. Measured methane yields for red oak, eucalyptus, spruce, radiata pine, plywood (PW), oriented strand board (OSB) from hardwood (HW) and softwood (SW), particleboard (PB) and medium-density fiberboard (MDF) were 32.5, 0, 7.5, 0.5, 6.3, 84.5, 0, 5.6, and 4.6 mL CH(4) dry g(-1), respectively. The red oak, a HW, exhibited greater decomposition than either SW (spruce and radiata), a trend that was also measured for the OSB-HW relative to OSB-SW. However, the eucalyptus (HW) exhibited toxicity. Thus, wood species have unique methane yields that should be considered in the development of national inventories of methane production and carbon storage. The current assumption of uniform biodegradability is not appropriate. The ammonia release from urea formaldehyde as present in PB and MDF could contribute to ammonia in landfill leachate. Using the extent of carbon conversion measured in this research, 0-19.9%, predicted methane production from a wood mixture using the Intergovernmental Panel for Climate Change waste model is only 7.9% of that predicted using the 50% carbon conversion default.

BackgroundIt remains unclear how executive function (EF) is affected in the stage of amnestic mild cognitive impairment (aMCI). Previous studies using different methods to assess EF in patients with aMCI have reached inconsistent conclusions. The aim of the study was to explore the characteristics of EF impairments in patients with aMCI.MethodsWe investigated three core components of EF (i.e., working memory, response inhibition and task switching) based on the theoretical model of EF proposed by Miyake et al. (2000) in 34 aMCI patients and 36 healthy elderly controls using computerized tasks programmed with E-prime (the 2-back task and the keep track task for working memory, the stop-signal task and the Stroop task for response inhibition and the more-odd shifting task for task switching). The overall EF and the three individual EF components were compared between groups. For EF components that were impaired, the extent of impairment was compared using a paired analysis. The aMCI group was further divided into EF-intact and EF-deficit groups according to their performances on the EF tests in clinical neuropsychological assessments. We tested for group differences among the normal controls and the EF-intact and EF-deficit aMCI groups and paid special attention to the comparisons between the EF-intact aMCI group and the control group.ResultsCompared to the control group, overall EF was significantly impaired in patients with aMCI (Wilks’ λ=0.572,P<0.001). Four tasks (the 2-back task, the keep track task, the stop-signal task and the more-odd shifting task) that tapped the three core components of EF displayed group differences that favored the normal controls. The results of the Stroop task revealed no differences in performance between the two groups. The EF-intact aMCI patients also exhibited significantly impaired capabilities in the four tasks compared to the normal controls. There were no significant differences in the extent of impairment between the four affected tasks in the aMCI group, suggesting that the three core EF components were impaired to the same extent.ConclusionsBoth the overall EF and all of the core EF components in the Miyake model of EF (working memory, response inhibition and task switching) were significantly impaired in aMCI patients, regardless of whether they had shown obvious clinical executive dysfunction.

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Recent studies have shown that impairment in executive function (EF) is common in patients with amnestic mild cognitive impairment (aMCI). However, the neuroanatomic basis of executive impairment in patients with aMCI remains unclear. In this study, multiple regression voxel-based morphometry analyses were used to examine the relationship between regional gray matter volumes and EF performance in 50 patients with aMCI and 48 healthy age-matched controls. The core EF components (response inhibition, working memory and task switching, based on the EF model of Miyake et al) were accessed with computerized tasks. Atrophic brain areas related to decreases in the three EF components in patients with aMCI were located in the frontal and temporal cortices. Within the frontal cortex, the brain region related to response inhibition was identified in the right inferior frontal gyrus. Brain regions related to working memory were located in the left anterior cingulate gyrus, left premotor cortex, and right inferior frontal gyrus, and brain regions related to task shifting were distributed in the bilateral frontal cortex. Atrophy in the right inferior frontal gyrus was most closely associated with a decrease in all three EF components in patients with aMCI. Our data, from the perspective of brain morphology, contribute to a better understanding of the role of these brain areas in the neural network of EF.

Clinical data have shown women are more susceptible to depression. This study was performed to identify differentially regulated proteins from hippocampus in chronic unpredicted mild stress (CUMS)-exposed male and female young rats. After 7 weeks of CUMS, depressed male (M-D) and female rats (F-D) and unstressed male (M-C) and female controls (F-C) were studied. By proteomics analysis, 74 differential proteins in F-C/M-C, 79 in F-D/M-D, 77 in F-D/F-C, and 32 in M-D/M-C were found. Further, the synapse-related proteins, cytoskeleton protein tau, and stress-related kinases in hippocampus were assayed by Western blotting. F-C rats were found to have lower levels of metabotropic glutamate receptor 1 (mGluR1) and mGluR2 and higher levels of N-methyl-D-aspartate receptor 2B (NR2B), synapsin1, total tau, and dephosphorylated tau than M-C rats. Both F-D and M-D rats had lower levels of glutamate transporter SLC1α2, mGluR1, and mGluR2, and higher levels of total tau and phosphorylated tau than their controls. Compared with their controls, M-D rats had lower NR1 and higher NR2B, and F-D rats had lower NR2A, NR2B, PSD95, and synapsin1. F-C rats had higher JNK and lower phosphorylation levels of ERK at Thr202/Thr204, JNK at Thr183/Thr185, and GSK-3β at Ser9 than M-C ones. Both M-D and F-D rats had decreased phosphorylation of ERK at Thr202/Thr204 and GSK-3β at Ser9, and increased JNK phosphorylation at Thr183/Thr185 compared with their controls. All these data illustrate the biochemical complexity behind the genders, and may also aid in the development of more accurate treatment strategies for depression.