Psychedelics reopen the social reward learning critical period.

Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness1,2. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies3-9. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the 'open state' versus the 'closed state' provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Cocaine-induced locomotor stimulation involves autophagic degradation of the dopamine transporter.

Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. We previously showed that toxic levels of cocaine induce autophagic neuronal cell death. Here, we show that subnanomolar concentrations of cocaine elicit neural autophagy in vitro and in vivo. Autophagy inhibitors reduce the locomotor stimulant effect of cocaine in mice. Cocaine-induced autophagy degrades transporters for dopamine but not serotonin in the nucleus accumbens. Autophagy inhibition impairs cocaine conditioned place preference in mice. Our findings indicate that autophagic degradation of DAT modulates behavioral actions of cocaine.

ZnO Nanocluster-Functionalized Single-Walled Carbon Nanotubes Synthesized by Microwave Irradiation for Highly Sensitive NO2 Detection at Room Temperature.

To improve the NO2-sensing performance of single-walled carbon nanotube (SWCNT)-based sensors, zinc oxide (ZnO) nanoclusters (NCs) were functionalized by a microwave (MW)-assisted synthesis technique. Gas sensors based on pristine SWCNTs and ZnO NC-SWCNT composites synthesized using different weight ratios (ZnO/SWCNTs = 0.5:1, 1:1, 2:1, and 3:1) were fabricated, and their ability to sense various gases at room temperature (25 °C) was investigated. The results showed that the sensing performance of the ZnO NC-SWCNT composite synthesized with a weight ratio of 1:1 (denoted as Z-SWCNTs) was significantly enhanced with respect to NO2 response and selectivity. This enhanced sensing performance is thought to be a result of both the modulation of the conduction channel at the ZnO NC-SWCNT heterointerfaces and the generation of defects (or holes) by MW irradiation that act as active sites for the target gases. The results obtained in this work provide not only a facile method of cofunctionalizing oxide NCs and defects but also a new methodology for improving the sensing capabilities of SWCNT-based gas sensors.

Molecular characterization and phylogenetic analysis of H3N2 human influenza A viruses in Cheongju, South Korea.

To investigate the genetic characteristics of human influenza viruses circulating in Chungbuk province, we tested 510 clinical samples of nasopharyngeal suction from pediatric patients diagnosed with respiratory illness between June 2007 and June 2008. Genetic characterization of the HA genes of H3N2 isolates indicated the relative higher similarity to A/Virginia/04/07 (99.6%) rather than that of A/Wisconsin/67/2005 (98.4%), a Northern Hemisphere 2007-2008 vaccine strain, based on amino acid sequences. We found several altered amino acids at the H3 HA1 antigenic sites compared with the vaccine strain; K140I at site A, K158R at site B, and K173N (H471) or K173Q, and S262N at site E, but there was no antigenic shift among the H3N2 viruses. Interestingly, A/Cheongju/H383/08 and A/Cheongju/H407/08 isolates had single amino acid substitution at D151G on the catalytic site of the N2 NA while A/Cheongju/H412/08 and A/Cheongju/ H398/07 isolates had one amino acid deletion at residue 146. Furthermore, we found that 25% (3 out of 12 isolates) of the H3N2 subtype viruses had the amino acid substitution at position 31 on the M2 protein (Aspartic acid to Asparagine) and confirmed their drug-resistance by biological assays. Taken together, the results of this study demonstrated continuous evolutions of human H3N2 viruses by antigenic drift and also highlighted the need to closely monitor antigenic drug resistance in influenza A viruses to aid in the early detection of potentially pandemic strains, as well as underscore the need for new therapeutics.

Emergence of amantadine-resistant H3N2 avian influenza A virus in South Korea.

We found a relatively high frequency of unique amantadine-resistant H3N2 and H9N2 avian influenza viruses (Val27Ile on M2 protein) isolated from live poultry markets in South Korea and confirmed that a Val27Ile single substitution in the M2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.

[A case of duodenal intramural hematoma treated by percutaneous external drainage].

Complicating intramural hematoma is an interesting, relatively unusual condition. Various etiologic factors have been described, with the most common being blunt trauma, anticoagulant therapy, Henoch-Sch nlein purpura and blood dyscrasias. Most intramural hematomas resolve spontaneously with conservative treatment, and the prognosis is good. However, if the abdominal pain or obstruction does not resolve with medical management over seven to ten days, complications such as infarction or peritonitis may occur, and surgical intervention might be required. We report a case of intramural hematoma of duodenum treated with percutaneous drainage and embolization of bleeding focus which was complicated with acute pancreatitis after anticoagulation treatment in a patient with recurrent history of deep vein thrombosis. In addition, we reviewed reports of intramural hematoma of the duodenum and treatment strategies.