Summary Mutations in the X-linked MECP2, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome (RTT) and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia, and encephalopathy with early lethality. RTT is characterized by apparently normal early development followed by regression, motor abnormalities, seizures, and features of autism, especially stereotyped behaviors. The mechanisms mediating these striking features are poorly understood. Here we show that mice lacking Mecp2 from γ-amino-butyric-acid-(GABA)-ergic neurons recapitulate numerous RTT and autistic features, including repetitive behaviors. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of RTT. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size consistent with presynaptic reduction in glutamic acid decarboxylase-1 and -2 levels and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal GABAergic neuronal function and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.

Congo River water was filtered and then irradiated for 57 d in a solar simulator, resulting in extensive photodegradation of dissolved organic matter (DOM). Whole‐water (i.e., unfractionated) DOM was analyzed pre‐ and post‐irradiation using ultrahigh resolution Fourier transform ion cyclotron mass spectrometry (FT‐ICR MS), revealing the following three pools of DOM classified based upon their photoreactivity: (1) photo‐resistant, (2) photo‐labile, and (3) photo‐produced. Photo‐resistant DOM was heterogeneous, with most molecular classes represented, although only a small number of aromatics and no condensed aromatics were identified. The photoproduced pool was dominated by aliphatic compounds, although it included a small number of aromatics, including condensed aromatics. Aromatic compounds were the most photoreactive, with > 90% being lost upon irradiation. Photochemistry also resulted in a significant drop in the number of molecules identified and a decrease in their structural diversity. The FT‐ICR MS signatures of two classes of refractory organic matter, black carbon and carboxylic‐rich alicyclic molecules (CRAM), were present in the sample prior to irradiation, indicating that the Congo River could be a significant exporter of recalcitrant DOM to the ocean. All black carbon‐like molecules identified in the initial sample were lost during irradiation. Molecular signatures consistent with CRAM were also highly photo‐labile, demonstrating that environmental solar irradiation levels are capable of removing these refractory compounds from aquatic systems. Irradiation also shifted the molecular signature of terrestrial DOM toward that of marine DOM, thereby complicating the task of tracking terrestrial DOM in the ocean.

Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, suggesting that proper SHANK3 dosage is critical for normal brain function. SHANK3 overexpression per se has not been established as a cause of human disorders, however, because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modeling a human SHANK3 duplication exhibit manic-like behavior and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings suggest SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype, we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate, but not lithium, rescues the manic-like behavior of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile.