Fetal MRI-Based Body and Adiposity Quantification for Small for Gestational Age Perinatal Risk Stratification.

BACKGROUND: Small for gestational age (SGA) fetuses are at risk for perinatal adverse outcomes. Fetal body composition reflects the fetal nutrition status and hold promise as potential prognostic indicator. MRI quantification of fetal anthropometrics may enhance SGA risk stratification. HYPOTHESIS: Smaller, leaner fetuses are malnourished and will experience unfavorable outcomes. STUDY TYPE: Prospective. POPULATION: 40 SGA fetuses, 26 (61.9%) females: 10/40 (25%) had obstetric interventions due to non-reassuring fetal status (NRFS), and 17/40 (42.5%) experienced adverse neonatal events (CANO). Participants underwent MRI between gestational ages 30 + 2 and 37 + 2. FIELD STRENGTH/SEQUENCE: 3-T, True Fast Imaging with Steady State Free Precession (TruFISP) and T1 -weighted two-point Dixon (T1 W Dixon) sequences. ASSESSMENT: Total body volume (TBV), fat signal fraction (FSF), and the fat-to-body volumes ratio (FBVR) were extracted from TruFISP and T1 W Dixon images, and computed from automatic fetal body and subcutaneous fat segmentations by deep learning. Subjects were followed until hospital discharge, and obstetric interventions and neonatal adverse events were recorded. STATISTICAL TESTS: Univariate and multivariate logistic regressions for the association between TBV, FBVR, and FSF and interventions for NRFS and CANO. Fisher's exact test was used to measure the association between sonographic FGR criteria and perinatal outcomes. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. A P-value <0.05 was considered statistically significant. RESULTS: FBVR (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.2-0.76) and FSF (OR 0.95, CI 0.91-0.99) were linked with NRFS interventions. Furthermore, TBV (OR 0.69, CI 0.56-0.86) and FSF (OR 0.96, CI 0.93-0.99) were linked to CANO. The FBVR sensitivity/specificity for obstetric interventions was 85.7%/87.5%, and the TBV sensitivity/specificity for CANO was 82.35%/86.4%. The sonographic criteria sensitivity/specificity for obstetric interventions was 100%/33.3% and insignificant for CANO (P = 0.145). DATA CONCLUSION: Reduced TBV and FBVR may be associated with higher rates of obstetric interventions for NRFS and CANO. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Glial cells expressing visual cycle genes are vital for photoreceptor survival in the zebrafish pineal gland.

Photoreceptors in the vertebrate eye are dependent on the retinal pigmented epithelium for a variety of functions including retinal re-isomerization and waste disposal. The light-sensitive pineal gland of fish, birds, and amphibians is evolutionarily related to the eye but lacks a pigmented epithelium. Thus, it is unclear how these functions are performed. Here, we ask whether a subpopulation of zebrafish pineal cells, which express glial markers and visual cycle genes, is involved in maintaining photoreceptors. Selective ablation of these cells leads to a loss of pineal photoreceptors. Moreover, these cells internalize exorhodopsin that is secreted by pineal rod-like photoreceptors, and in turn release CD63-positive extracellular vesicles (EVs) that are taken up by pdgfrb-positive phagocytic cells in the forebrain meninges. These results identify a subpopulation of glial cells that is critical for pineal photoreceptor survival and indicate the existence of cells in the forebrain meninges that receive EVs released by these pineal cells and potentially function in waste disposal.

A Zebrafish Model for a Rare Genetic Disease Reveals a Conserved Role for FBXL3 in the Circadian Clock System.

The circadian clock, which drives a wide range of bodily rhythms in synchrony with the day-night cycle, is based on a molecular oscillator that ticks with a period of approximately 24 h. Timed proteasomal degradation of clock components is central to the fine-tuning of the oscillator's period. FBXL3 is a protein that functions as a substrate-recognition factor in the E3 ubiquitin ligase complex, and was originally shown in mice to mediate degradation of CRY proteins and thus contribute to the mammalian circadian clock mechanism. By exome sequencing, we have identified a FBXL3 mutation in patients with syndromic developmental delay accompanied by morphological abnormalities and intellectual disability, albeit with a normal sleep pattern. We have investigated the function of FBXL3 in the zebrafish, an excellent model to study both vertebrate development and circadian clock function and, like humans, a diurnal species. Loss of fbxl3a function in zebrafish led to disruption of circadian rhythms of promoter activity and mRNA expression as well as locomotor activity and sleep-wake cycles. However, unlike humans, no morphological effects were evident. These findings point to an evolutionary conserved role for FBXL3 in the circadian clock system across vertebrates and to the acquisition of developmental roles in humans.

Period 2: A Regulator of Multiple Tissue-Specific Circadian Functions.

The zebrafish represents a powerful model for exploring how light regulates the circadian clock due to the direct light sensitivity of its peripheral clocks, a property that is retained even in organ cultures as well as zebrafish-derived cell lines. Light-inducible expression of the per2 clock gene has been predicted to play a vital function in relaying light information to the core circadian clock mechanism in many organisms, including zebrafish. To directly test the contribution of per2 to circadian clock function in zebrafish, we have generated a loss-of-function per2 gene mutation. Our results reveal a tissue-specific role for the per2 gene in maintaining rhythmic expression of circadian clock genes, as well as clock-controlled genes, and an impact on the rhythmic behavior of intact zebrafish larvae. Furthermore, we demonstrate that disruption of the per2 gene impacts on the circadian regulation of the cell cycle in vivo. Based on these results, we hypothesize that in addition to serving as a central element of the light input pathway to the circadian clock, per2 acts as circadian regulator of tissue-specific physiological functions in zebrafish.

Vertical exploration and dimensional modularity in mice.

Exploration is a central component of animal behaviour studied extensively in rodents. Previous tests of free exploration limited vertical movement to rearing and jumping. Here, we attach a wire mesh to the arena wall, allowing vertical exploration. This provides an opportunity to study the morphogenesis of behaviour along the vertical dimension, and examine the context in which it is performed. In the current set-up, the mice first use the doorway as a point reference for establishing a borderline linear path along the circumference of the arena floor, and then use this path as a linear reference for performing horizontal forays towards the centre (incursions) and vertical forays on the wire mesh (ascents). Vertical movement starts with rearing on the wall, and commences with straight vertical ascents that increase in extent and complexity. The mice first reach the top of the wall, then mill about within circumscribed horizontal sections, and then progress horizontally for increasingly longer distances on the upper edge of the wire mesh. Examination of the sequence of borderline segments, incursions and ascents reveals dimensional modularity: an initial series (bout) of borderline segments precedes alternating bouts of incursions and bouts of ascents, thus exhibiting sustained attention to each dimension separately. The exhibited separate growth in extent and in complexity of movement and the sustained attention to each of the three dimensions disclose the mice's modular perception of this environment and validate all three as natural kinds.