Epithelial Organization: The Gut and Beyond.

Epithelial cells are essential to the survival and homeostasis of complex organisms. These cells cover the surfaces of all mucosae, the skin, and other compartmentalized structures essential to physiological function. In addition to maintenance of barriers that separate internal and external compartments, epithelia display a variety of organ-specific differentiated functions. Function is reflected in overall epithelial structure and organization, shape of individual cells, and proteins expressed by these cells. More than one epithelial cell type is often present within a single organ and, in many cases, individual cells differentiate to change their functional behaviors as part of normal development or in response to extracellular stimuli. This article discusses the diversity of epithelial structure and function in general terms and explores representative tissues in greater depth to highlight organ specific functions and their contributions to physiology and disease. © 2017 American Physiological Society. Compr Physiol 7:1497-1518, 2017.

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture.

Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1-occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation.

Implementing Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) Education in a Pediatric Residency Curriculum.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care for adolescents as well as adults. In an effort to promote universal SBIRT, the Substance Abuse and Mental Health Services Administration awarded funding to residency programs to develop and implement SBIRT education and training. Our project focused on creating scientifically based, developmentally appropriate strategies and teaching materials for the adolescent age range. This paper describes curriculum development and implementation and presents evaluation data. METHODS: Pediatric and child psychiatry residents were trained. The training consisted of 4 activities: (1) case-based teaching modules, (2) role-play of motivational interviewing and brief interventions, (3) mock interviews with trained adolescents, and (4) supervised "hands-on" screening and brief interventions. Main outcome measures included trainee satisfaction, and SBIRT knowledge, perceived self-efficacy, and self- and observer report of use of the SBIRT algorithm. RESULTS: Among 150 total participants completing the SBIRT training modules, nearly all (92.3%) were satisfied/very satisfied with the training modules. Knowledge accuracy immediately post training was high, but declined significantly by the end of the first residency year, with little change across subsequent years of residency. Confidence ratings also declined over time. Use of the SBIRT algorithm during the Adolescent Medicine rotation was high according to trainee self- and faculty observer report. CONCLUSIONS: We found evidence of training satisfaction, increased confidence in talking to adolescents about substance use, and widespread use of recommended practices immediately following training. Use of a highly structured algorithm to guide practice, and simple, highly structured brief interventions was a successful training approach, as residents self-reported accurate use of the SBIRT algorithm immediately after training. Knowledge and self-confidence declined over time. It is possible that "booster" sessions and ongoing opportunities to review materials could help residents retain knowledge and skills.

NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2.

Brain function is shaped by postnatal experience and vulnerable to disruption of Methyl-CpG-binding protein, Mecp2, in multiple neurodevelopmental disorders. How Mecp2 contributes to the experience-dependent refinement of specific cortical circuits and their impairment remains unknown. We analyzed vision in gene-targeted mice and observed an initial normal development in the absence of Mecp2. Visual acuity then rapidly regressed after postnatal day P35-40 and cortical circuits largely fell silent by P55-60. Enhanced inhibitory gating and an excess of parvalbumin-positive, perisomatic input preceded the loss of vision. Both cortical function and inhibitory hyperconnectivity were strikingly rescued independent of Mecp2 by early sensory deprivation or genetic deletion of the excitatory NMDA receptor subunit, NR2A. Thus, vision is a sensitive biomarker of progressive cortical dysfunction and may guide novel, circuit-based therapies for Mecp2 deficiency.