Transcription factor CP2-like protein 1 (Tfcp2l1), a naïve pluripotency transcription factor, is expressed in both early embryonic and adult tissues, where it enforces pluripotency of embryonic stem cells (ESCs) and stemness features of cancer cells, respectively. However, the detailed molecular pathways by which Tfcp2l1 is regulated in early embryonic development and cancer cells remain unknown. Here, we identified the pseudophosphatase dual specificity phosphatase 27 (Dusp27), also known as serine/threonine/tyrosine-interacting like-2, as a novel Tfcp2l1-interacting protein through a sterile alpha motif-like domain in the C-terminus of Tfcp2l1 in murine ESCs. The interaction between Dusp27 and Tfcp2l1 was dependent on the cell cycle status and increased during mitosis. Expression of Dusp27 was upregulated during naïve pluripotency and repressed during spontaneous differentiation of murine ESCs. Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

Background: Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). Methods: Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract.Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. Results: Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10−6 , showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. Conclusion Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

A case of persistent Ralstonia mannitolilytica bacteremia in the neonatal intensive care unit prompted source investigation due to its rarity. After an extensive investigation, a contaminated ultrasonic nebulizer was identified as the source, and the infection was controlled by removing the source. This study emphasizes the importance of further investigations, even in single cases of rare pathogens.

Objectives: Restricted and repetitive behaviors (RRBs) are a core symptom in the diagnosis of autism spectrum disorder (ASD). The complexity of behavioral patterns has called for the creation of phenotypically homogeneous subgroups among individuals with ASD.The purpose of this study was 1) to investigate the different types of RRBs and 2) to explore whether subgroups created by RRBs would show unique levels of functioning in toddlers and young children with ASD. Methods: A total of 313 children with ASD, aged 12–42 months were included in the analysis. The Autism Diagnostic Interview-Revised was used to obtain information on the different types of RRBs by grouping 15 items into six categories. The Vineland Adaptive Behaviors Scale, a parent-reported questionnaire, was used to measure adaptive functioning. A portion of the children were analyzed separately for verbal-related RRBs based on their expressive language level. Two-step cluster analysis using RRB groups as features was used to create subgroups. Analysis of covariance while covarying for age and language was performed to explore the clinical characteristics of each cluster group. Results: Sensory-related RRBs were the most prevalent, followed by circumscribed interests, interest in objects, resistance to change, and repetitive body movements. A subset of the children was analyzed separately to explore verbal-related RRBs. Four cluster groups were created based on reported RRBs, with multiple RRBs demonstrating significant delays in adaptive functioning. Conclusion Heterogeneity of RRBs emerges at a young age. The different patterns of RRBs can be used as valuable information to determine developmental trajectories with better implications for treatment approaches.