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While ablation of PTP1B in glutamatergic neurons prevented ketamine-induced deficits in memory and sensorimotor gating, it failed to prevent hyperlocomotion (a psychosis-like phenotype). Taken together, these results suggest that PTP1B in glutamatergic neurons mediates ketamine-induced deficits in eCB mobilization, memory and sensorimotor gating whereas PTP1B in other cell types contributes to hyperlocomotion. Our study suggests that the PTP1B inhibitor Trodusquemine may represent a new class of fast-acting antipsychotic drugs to treat schizophrenia-like symptoms.Schizophrenia exhibits up to 80% heritability. A number of genome wide association studies (GWAS) have repeatedly shown common variants in voltage-gated calcium (Cav) channel genes CACNA1C, CACNA1I and CACNA1G have a major contribution to the risk of the disease. More recently, studies using whole exome sequencing have also found that CACNA1B (Cav2.2 N-type) deletions and rare disruptive variants in CACNA1A (Cav2.1 P/Q-type) are associated with schizophrenia. The negative symptoms of schizophrenia include behavioural defects such as impaired memory, sleep and circadian rhythms. It is not known how variants in schizophrenia-associated genes contribute to cognitive and behavioural symptoms, thus hampering the development of treatment for schizophrenia symptoms. In order to address this knowledge gap, we studied behavioural phenotypes in a number of loss of function mutants for the Drosophila ortholog of the Cav2 gene family called cacophony (cac). cac mutants showed several behavioural features including decreauses a number of cognitive and behavioural deficits and underlying reduced neuronal Ca2+ transients, establishing Drosophila as a high-throughput in vivo genetic model to study the Cav channel pathophysiology related to schizophrenia.The treatment outcomes of ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma in the caudate lobe with and without fusion imaging (FI) assistance were evaluated and compared. Twenty-six patients with 28 tumors in the FI group and 8 patients with 8 tumors in the non-FI group were included. Although a higher number of tumors measured >20 mm in the FI group, the technique efficacy and local tumor progression were similar between the 2 groups (P > .99 and P = .45, respectively). FI aided in the detection, guidance, and treatment monitoring of thermal ablation for caudate lobe hepatocellular carcinomas, especially for tumors measuring >20 mm.Transhepatic duodenal stent placement may be a solution when endoscopy fails or when duodenal and biliary stents are needed simultaneously. This approach is usually not considered as an option when the duodenal stent must be deployed across the ampulla of Vater. The authors present a series of 10 patients who underwent a novel transhepatic technique to place a duodenal stent across the ampulla of Vater by establishing a wire scaffold from the liver toward the jejunum and then curving back on itself retrogradely through the duodenal tumor and out the mouth. Technical success was 90% with no associated mortality.Transcranial alternating current stimulation (tACS), applied to two brain sites with different phase lags, has been shown to modulate stimulation-outlasting functional EEG connectivity between the targeted regions. Given the lack of knowledge on mechanisms of tACS aftereffects, it is difficult to further enhance effect sizes and reduce variability in experiments. In this computational study, we tested if spike-timing-dependent plasticity (STDP) can explain stimulation-outlasting connectivity modulation by dual-site tACS and explored the effects of tACS parameter choices. Two populations of spiking neurons were coupled with synapses subject to STDP, and results were validated via a re-analysis of EEG data. P7C3 NAMPT activator Our simulations showed stimulation-outlasting connectivity changes between in- and anti-phase tACS, dependent on both tACS frequency and synaptic conduction delays. Importantly, both a simple network entraining to a wide range of tACS frequencies as well as a more realistic network that spontaneously oscillated at alpha frequency predicted that the largest effects would occur for short conduction delays between the stimulated regions. This finding agreed with experimental EEG connectivity modulation by 10Hz tACS, showing a clear negative correlation of tACS effects with estimated conduction delays between regions. In conclusion, STDP can explain connectivity aftereffects of dual-site tACS. However, not all combinations of tACS frequency and application sites are expected to effectively modulate connectivity via STDP. We therefore suggest using appropriate computational models and/or EEG analysis for planning and interpretation of dual-site tACS studies relying on aftereffects.Polar cod (Boreogadus saida) is a key species in the arctic marine ecosystem vulnerable to effects of pollution, particularly from petroleum related activities. To facilitate studying the effects of those pollutants, we adapted a precision-cut liver slice culture protocol for this species. Using this system on board a research vessel, we studied gene expression in liver slice after exposure to the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP), ethynylestradiol (EE2), and their mixtures, to map their molecular targets and examine possible anti-estrogenic effects of BaP. The exposure experiments were performed with BaP alone (0.1, 1, and 10 μM) or in combination with low concentrations of EE2 (5 nM) to mimic physiological estradiol levels in early vitellogenic female fish. Transcriptome analysis (RNA-seq) was performed after 72 h exposure in culture to map the genes and cellular pathways affected. The results provide a view of global transcriptome responses to BaP and EE2, which resulted in enrichment of many pathways such as the aryl hydrocarbon (Ahr) and estrogen receptor pathways. In the mixture exposure, BaP resulted in anti-estrogenic effects, shown by attenuation of EE2 activated transcription of many estrogen target genes. The results from this ex vivo experiment suggest that pollutants that activate the Ahr pathway such as the PAH compound BaP can result in anti-estrogenic effects that may lead to endocrine disruption in polar cod.
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