The zinc finger transcription factor PLAGL2 enhances stem cell fate and activates expression of ASCL2 in intestinal epithelial cells

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A single transcription factor is sufficient to induce and maintain secretory cell architecture

We hypothesized that basic helix–loop–helix (bHLH) MIST1 (BHLHA15) is a “scaling factor” that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules. Mist1 induced a cohort of genes regulated by MIST1 in multiple organs but did not affect PC function. MIST1 bound CATATG/CAGCTG E boxes in the first intron of genes that regulate autophagosome/lysosomal degradation, mitochondrial trafficking, and amino acid metabolism. Similar alterations in cell architecture and gene expression were also caused by ectopically inducing MIST1 in vivo in hepatocytes. Thus, MIST1 is a scaling factor necessary and sufficient by itself to induce and maintain secretory cell architecture. Our results indicate that, whereas mature cell types in each organ may have unique developmental origins, cells performing similar physiological functions throughout the body share similar transcription factor-mediated architectural “blueprints.

Conjugated polymer-fullerene blend with strong optical limiting in the near-infrared

© 2009 Optical Society of AmericaThe definitive version of this paper is available at: http://dx.doi.org/10.1364/OE.17.022062DOI: 10.1364/OE.17.022062Optical-quality, melt processable thick films of a conjugated polymer blend containing poly(2-methoxy-5-(2-ethyl-hexyloxy)-(phenylene vinylene)) (MEH-PPV), a ₆₀ derivative (PCBM) and a plasticizer (1,2-di-iso-octylphthalate) have been developed and their nonlinear absorption and optical limiting properties have been investigated. These blend materials exhibited strong optical limiting characteristics in the near infrared region (750-900 nm), with broad temporal dynamic range spanning femtosecond to nanosecond pulse widths. The dispersion of the optical limiting figure-of-merit of the MEH-PPV:PCBM:DOP blend shows a peak near the wavelength of the MEH-PPV cation, indicating an important role of one-photon and two-photon induced charge transfer in the nonlinear absorption response

Multi-Frequency Electrocochleography and Electrode Scan to Identify Electrode Insertion Trauma during Cochlear Implantation

Intraoperative electrocochleography (ECOG) is performed using a single low-frequency acoustic stimulus (e.g., 500 Hz) to monitor cochlear microphonics (CM) during cochlear implant (CI) electrode insertion. A decrease in CM amplitude is commonly associated with cochlear trauma and is used to guide electrode placement. However, advancement of the recording electrode beyond the sites of CM generation can also lead to a decrease in CM amplitude and is sometimes interpreted as cochlear trauma, resulting in unnecessary electrode manipulation and increased risk of cochlear trauma during CI electrode placement. In the present study, multi-frequency ECOG was used to monitor CM during CI electrode placement. The intraoperative CM tracings were compared with electrode scan measurements, where CM was measured for each of the intracochlear electrodes. Comparison between the peak CM amplitude measured during electrode placement and electrode scan measurements was used to differentiate between different mechanisms for decrease in CM amplitude during CI electrode insertion. Analysis of the data shows that both multi-frequency electrocochleography and electrode scan could potentially be used to differentiate between different mechanisms for decreasing CM amplitude and providing appropriate feedback to the surgeon during CI electrode placement

Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings

BackgroundTo date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits.ObjectivesThis trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD.DesignA randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg).Methods and analysisThis single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale – Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible.EthicsWritten informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623).DiscussionThis study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms.Clinical trial registration: ClinicalTrials.gov, identifier NCT05370911