Biology subjects

Stephenson, R.

Publications and source records attributed to Stephenson, R..

4 recordsLinked to original sources

bioRxiv2025

Sleep and wakefulness in rats: probabilities of state transitions and state-to-state serial correlations in relation to circadian and ultradian phases

Sleep and wakefulness were recorded from undisturbed male rats (n = 10) for 7 days in a 12:12 h light-dark cycle. Data were partitioned by circadian and ultradian phase before quantification of within-state transition probabilities and between-state serial correlations. Within each joint circadian-ultradian phase, short-term statistical patterns were identified, with quantitative variation between phases. Statistical "signatures" of sleep-wake pattern include positive serial correlations between durations of contiguous states, and between state bouts and inter-bout intervals. There was no correlation between wake bout duration and subsequent sleep episode duration, contradicting an oft-cited assumption of the sleep homeostasis hypothesis. The data confirm a positive correlation between the duration of rapid eye movement (REM) sleep and duration of the subsequent inter-REM interval, which is traditionally interpreted as evidence for a short-term REM homeostat. The present study concludes that the REM homeostat hypothesis is underdetermined. It is suggested that this serial correlation and other sleep-wake patterns can be explained by an alternative non-homeostatic mechanism; transition probability prevailing at the end of a state episode is carried over to the beginning of the next state ("inter-state transition momentum"). The plausibility of this hypothesis was supported by preliminary simulations using a 2nd-order 3-state semi-Markov model. HighlightsO_LIWake-related transition probabilities underly circadian and ultradian rhythms. C_LIO_LIStatistical signatures of short-term patterns of sleep-wake state were identified in all circadian and ultradian phases. C_LIO_LITransition probabilities varied with time in state. C_LIO_LIState transition probabilities were influenced by duration and identity of prior state. C_LIO_LISleep homeostasis hypotheses were not supported. C_LIO_LIA hypothesis of state-spanning transition momentum is proposed. C_LI

animal behavior and cognition↗

bioRxiv2025

Combinatorial phosphorylation on CTD of RNA polymerase II selectively controls transcription and export of protein-coding mRNAs

C-terminal domain (CTD) of RNA polymerase II is crucial for recruiting transcription regulators via specific post-translational modifications (PTM), especially phosphorylation. The hypothesis of combination of PTMs, or CTD code, that can allow precise and dynamic recruitment of transcription machinery is highly attractive, yet the experimental evidence to support this hypothesis has been scarce. Here, despite lacking specific antibodies for combinatorial CTD phosphorylation, we developed an innovative approach that detects double phosphorylation patterns on the CTD in a whole-genomic fashion by leveraging the antibody masking effect with selectively removing the flanking interference. Using this method, we detected pT4pS5 double phosphosites occurring exclusively during the transcription of protein-coding genes. Furthermore, we showed that pT4pS5 marks recruit the Transcription and Export complex (TREX), which specifically facilitates mRNA processing and nucleocytoplasmic export of protein-coding mRNAs. The recruitment of TREX by pT4pS5 phosphosites is particularly important for the processing of lengthy neurogenesis-related genes. Our results provide experimental support for the notion that CTD coding system can function combinatorially and in a gene-specific manner, which encodes an exact information about the transcription of specific gene clusters. This method can be broadly applied to map all combinatorial PTM patterns on RNA polymerase II, paving the way for a deeper understanding of gene-specific transcription regulation at the molecular level.

molecular biology↗

bioRxiv2024

The role of ultradian rhythms in post-deprivationrebounds and diurnal rhythms of sleep and wakefulness in rats

The temporal organization of ultradian rhythms in sleep and wakefulness during post-sleep deprivation (TSD) rebound were investigated in 15 rats under contant bright light (LL). Following baseline recordings, rats were subjected to TSD using gentle manual stimulation. Post-TSD rebounds in cumulative wakefulness (WAKE), rapid eye movement sleep (REM) and non-REM sleep (NREM) were analyzed in WAKE-dominant ({upsilon}w) and sleep-dominant ({upsilon}s) ultradian phases. Rebounds in WAKE and NREM were present only when data were analyzed on a full ultradian cycle basis, and were absent in {upsilon}s and {upsilon}w phases alone. These rebounds were approximately 50% complete and not proportional to TSD excess/deficit. Rebounds in REM were present in full ultradian cycles and partially expressed in {upsilon}s but absent in {upsilon}w. REM rebounds fully compensated for REM deficit. Rebounds were mediated mainly by a reduction in the duration of the {upsilon}w ultradian phase, and by decreased probability of arousal in the {upsilon}s ultradian phase. These mechanisms were also found to partially mediate diurnal rhythms in 10 rats under a 12:12 h LD cycle. This study implicates an ultradian timing mechanism in the control of post-TSD rebounds and suggests that rebounds in all three states are mainly mediated by post-TSD adjustments in WAKE-promoting mechanisms. Ultradian rhythms should be taken into account to avoid errors in data analysis. HighlightsO_LISleep-wake state exhibits circadian rhythms and ultradian rhythms. C_LIO_LIThese rhythms interact with rebounds after sleep deprivation. C_LIO_LICircadian amplitude and sleep rebound are partially mediated by ultradian timing. C_LIO_LIArousal-related processes control these sleep-wake patterns in both states. C_LIO_LIMeasuring ultradian rhythms is necessary for accurate analysis of data. C_LI

animal behavior and cognition↗

bioRxiv2018

The Heterotaxy Gene, CCDC11, is Essential for Cytokinesis and Cell-Cell Adhesion Via RhoA Regulation

Mutations in CCDC11 have been identified in multiple patients with heterotaxy (Htx), a disorder of left-right (LR) patterning of the internal organs. In Xenopus, depletion of Ccdc11 causes defects in LR patterning, recapitulating the patient phenotype. Upon Ccdc11 depletion, normally monociliated cells of the Left-Right Organizer (LRO) exhibit multiple cilia per cell. Unexpectedly, we found that Ccdc11 is necessary for successful cytokinesis, and the multiciliation observed in Ccdc11-depleted cells was due to failed cytokinesis. Furthermore, CCDC11 depletion alters cell-cell adhesion with reduction in junctional localization of adhesion molecules. The small GTPase RhoA is critical for cytokinesis and cell-cell adhesion. Because the CCDC11 depletion phenotypes are reminiscent of RhoA loss of function, we investigated a possible connection to regulation of RhoA signaling. We demonstrate that CCDC11 is localized to the cytokinetic contractile ring overlapping with RhoA during cytokinesis and regulates total RhoA protein levels. Our results suggest that CCDC11 connects cytokinesis and LR patterning via RhoA regulation, providing a potential mechanism for heterotaxy disease pathogenesis.

cell biology↗