DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats

Drug‐reinforced excessive operant responding is one fundamental feature of long-lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction. Includes Supplemental informatio

Development and Validation of an RNA-Seq-Based Prognostic Signature in Neuroblastoma

Objective: The stratification of neuroblastoma (NBL) prognosis remains difficult. RNA-based signatures might be able to predict prognosis, but independent cross-platform validation is still rare. Methods: RNA-Seq-based profiles from NBL patients were acquired and then analyzed. The RNA-Seq prognostic index (RPI) and the clinically adjusted RPI (RCPI) were successively established in the training cohort (TARGET-NBL) and then verified in the validation cohort (GSE62564). Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Functional enrichment analysis of the genes was conducted using bioinformatics methods. Results: In the training cohort, 10 gene pairs were eventually integrated into the RPI. In both cohorts, the high-risk group had poor overall survival (OS) (P < 0.001 and P < 0.001, respectively) and favorable event-free survival (EFS) (P = 0.00032 and P = 0.06, respectively). ROC curve analysis also showed that the RPI predicted OS (60 month AUC values of 0.718 and 0.593, respectively) and EFS (60 month AUC values of 0.627 and 0.852, respectively) well in both the training and validation cohorts. Clinicopathological indicators associated with prognosis in the univariate and multivariate regression analyses were identified and added to the RPI to form the RCPI. The RCPI was also used to divide populations into different risk groups, and the high-risk group had poor OS (P < 0.001 and P < 0.001, respectively) and EFS (P < 0.05 and P < 0.05, respectively). Finally, the RCPI had higher accuracy than the RPI for the prediction of OS (60 month AUC values of 0.730 and 0.852, respectively) and EFS (60 month AUC values of 0.663 and 0.763, respectively) in both the training and validation cohorts. Moreover, these differentially expressed genes may be involved in certain NBL-related events. Conclusions: The RCPI could reliably categorize NBL patients based on different risks of death

Critical review on unraveling uncultivable pesticide degraders via stable isotope probing (SIP)

Uncultivable microorganisms account for over 99% of all species on earth, playing essential roles in ecological processes such as carbon/nitrogen cycle and chemical mineralization. Their functions remain unclear in ecosystems and natural habitats, requiring cutting-edge biotechnologies for a deeper understanding. Stable isotope probing (SIP) incorporates isotope-labeled elements, e.g. 13 C, 18 O or 15 N, into the cellular components of active microorganisms, serving as a powerful tool to link phylogenetic identities to their ecological functions in situ. Pesticides raise increasing attention for their persistence in the environment, leading to severe damage and risks to the ecosystem and human health. Cultivation and metagenomics help to identify either cultivable pesticide degraders or potential pesticide metabolisms within microbial communities, from various environmental media including the soil, groundwater, activated sludge, plant rhizosphere, etc. However, the application of SIP in characterizing pesticide degraders is limited, leaving considerable space in understanding the natural pesticide mineralization process. In this review, we try to comprehensively summarize the fundamental principles, successful cases and technical protocols of SIP in unraveling functional-yet-uncultivable pesticide degraders, by raising its shining lights and shadows. Particularly, this study provides deeper insights into various feasible isotope-labeled substrates in SIP studies, including pesticides, pesticide metabolites, and similar compounds. Coupled with other techniques, such as next-generation sequencing, nanoscale secondary ion mass spectrometry (NanoSIMS), single cell genomics, magnetic-nanoparticle-mediated isolation (MMI) and compound-specific isotope analysis (CSIA), SIP will significantly broaden our understanding of pesticide biodegradation process in situ

Generation and Characterization of Novel Human IRAS Monoclonal Antibodies

Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine. A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS), has been cloned from human hippocampus. We reported that IRAS mediated agmatine-induced inhibition of opioid dependence in morphine-dependent cells. To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa) through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa). Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation. Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry. These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions

Xanthogranulomatous Cystitis Arising from the Posterior Wall of the Bladder

Xanthogranulomatous cystitis is a rare, benign chronic inflammatory disease of unknown etiology. Herein we report a case of a 41-year-old man who presented with painless hematuria and a bladder mass on imaging studies

The three-dimensionality of the hiPSC-CM spheroid contributes to the variability of the field potential

Background: Field potential (FP) signals from human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) spheroid which are used for drug safety tests in the preclinical stage are different from action potential (AP) signals and require working knowledge of the multi-electrode array (MEA) system. In this study, we developed in silico three-dimensional (3-D) models of hiPSC-CM spheroids for the simulation of field potential measurement. We compared our model simulation results against in vitro experimental data under the effect of drugs E-4031 and nifedipine.Methods:In silico 3-D models of hiPSC-CM spheroids were constructed in spherical and discoidal shapes. Tetrahedral meshes were generated inside the models, and the propagation of the action potential in the model was obtained by numerically solving the monodomain reaction-diffusion equation. An electrical model of electrode was constructed and FPs were calculated using the extracellular potentials from the AP propagations. The effects of drugs were simulated by matching the simulation results with in vitro experimental data.Results: The simulated FPs from the 3-D models of hiPSC-CM spheroids exhibited highly variable shapes depending on the stimulation and measurement locations. The values of the IC50 of E-4031 and nifedipine calculated by matching the simulated FP durations with in vitro experimental data were in line with the experimentally measured ones reported in the literature.Conclusion: The 3-D in silico models of hiPSC-CM spheroids generated highly variable FPs similar to those observed in in vitro experiments. The in silico model has the potential to complement the interpretation of the FP signals obtained from in vitro experiments

Electronic Structure, Surface Doping, and Optical Response in Epitaxial WSe2 Thin Films

High quality WSe2 films have been grown on bilayer graphene (BLG) with layer-by-layer control of thickness using molecular beam epitaxy (MBE). The combination of angle-resolved photoemission (ARPES), scanning tunneling microscopy/spectroscopy (STM/STS), and optical absorption measurements reveal the atomic and electronic structures evolution and optical response of WSe2/BLG. We observe that a bilayer of WSe2 is a direct bandgap semiconductor, when integrated in a BLG-based heterostructure, thus shifting the direct-indirect band gap crossover to trilayer WSe2. In the monolayer limit, WSe2 shows a spin-splitting of 475 meV in the valence band at the K point, the largest value observed among all the MX2 (M = Mo, W; X = S, Se) materials. The exciton binding energy of monolayer-WSe2/BLG is found to be 0.21 eV, a value that is orders of magnitude larger than that of conventional 3D semiconductors, yet small as compared to other 2D transition metal dichalcogennides (TMDCs) semiconductors. Finally, our finding regarding the overall modification of the electronic structure by an alkali metal surface electron doping opens a route to further control the electronic properties of TMDCs

Similarities and differences among Internet gaming disorder, gambling disorder and alcohol use disorder: A focus on impulsivity and compulsivity

Background and aims: The aim of the present study was to test the impulsivities and compulsivities of behavioral addictions, including Internet gaming disorder (IGD) and gambling disorder (GD), by directly comparing them with alcohol use disorder (AUD) and a healthy control (HC) group. Methods: We enrolled male patients who were diagnosed with IGD, GD or AUD, with 15 patients per group, as well as 15 HCs. Trait impulsivity was measured using the Barratt Impulsiveness Scale version 11 (BIS-11). The stop-signal test (SST) from the Cambridge Neuro-psychological Test Automated Battery (CANTAB) was used to assess the patients’ abilities to inhibit prepotent responses. Compulsivity was measured using the intra–extra dimensional set shift (IED) test from the CANTAB. The Trail Making Test (TMT) was also used in this study. Results: The IGD and AUD groups scored significantly higher on the BIS-11 as a whole than did the HC group (p = 0.001 and p = 0.001, respectively). The IGD and AUD groups also scored significantly higher on the BIS-11 as a whole than did the GD group (p = 0.006 and p = 0.001, respectively). In addition, the GD group made significantly more errors (p = 0.017 and p = 0.022, respectively) and more individuals failed to achieve criterion on the IED test compared with the IGD and HC groups (p = 0.018 and p = 0.017, respectively). Discussion: These findings may aid in the understanding of not only the differences in categorical aspects between individuals with IGD and GD but also in impulsivity–compulsivity dimensional domains. Conclusion: Additional studies are needed to elucidate the neurocognitive characteristics of behavioral addictive disorders in terms of impulsivity and compulsivity