scholarly journals Response to Comment on “Circadian rhythms in the absence of the clock gene Bmal1”

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabf1941
Author(s):  
Sandipan Ray ◽  
Utham K. Valekunja ◽  
Alessandra Stangherlin ◽  
Steven A. Howell ◽  
Ambrosius P. Snijders ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Clock Gene ◽  
Statistical Significance ◽  
Statistical Measures ◽  
Statistical Algorithm ◽  
Low Amplitude ◽  
Lines Of Evidence

Abruzzi et al. argue that transcriptome oscillations found in our study in the absence of Bmal1 are of low amplitude, statistical significance, and consistency. However, their conclusions rely solely on a different statistical algorithm than we used. We provide statistical measures and additional analyses showing that our original analyses and observations are accurate. Further, we highlight independent lines of evidence indicating Bmal1-independent 24-hour molecular oscillations.

scholarly journals Comment on “Circadian rhythms in the absence of the clock gene Bmal1”

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabe9230 ◽  
Author(s):  
Elan Ness-Cohn ◽  
Ravi Allada ◽  
Rosemary Braun
Keyword(s):  
Circadian Rhythms ◽  
Clock Gene ◽  
Insufficient Evidence ◽  
The Core ◽  
Clock Component ◽  
Mouse Tissues ◽  
Associated Data

Ray et al. (Reports, 14 February 2020, p. 800) report apparent transcriptional circadian rhythms in mouse tissues lacking the core clock component BMAL1. To better understand these surprising results, we reanalyzed the associated data. We were unable to reproduce the original findings, nor could we identify reliably cycling genes. We conclude that there is insufficient evidence to support circadian transcriptional rhythms in the absence of Bmal1.

RNA Interference of the Clock Gene period Disrupts Circadian Rhythms in the Cricket Gryllus bimaculatus

2008 ◽  
Vol 23 (4) ◽  
pp. 308-318 ◽  
Author(s):  
Yoshiyuki Moriyama ◽  
Tomoaki Sakamoto ◽  
Svetlana G. Karpova ◽  
Akira Matsumoto ◽  
Sumihare Noji ◽  
...  
Keyword(s):  
Rna Interference ◽  
Circadian Rhythms ◽  
Clock Gene ◽  
Gryllus Bimaculatus

Abstract P466: Circadian Rhythm Disruptions in a Novel Diabetic db/db-mPer2 Luc Mouse Model

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Tianfei Hou ◽  
Wen Su ◽  
Ming C Gong ◽  
Zhenheng Guo
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythms ◽  
Real Time ◽  
Clock Gene ◽  
Ex Vivo ◽  
Phase Advance ◽  
Luciferase Reporter ◽  
High Time Resolution ◽  
Peripheral Tissues

Db/db mouse, which lacks functional leptin receptor, is an extensively used model of obesity and type 2 diabetes. We and others have demonstrated that db/db mouse has disruptions in circadian rhythms of behavior, physiology and some clock genes. However, systemic investigations of the alterations in clock gene oscillations in multiple systems with high time resolution in this model are impeded by the impractical demand for large number of animals. To overcome this limitation, we cross bred the db/db mouse with mPer2 Luc mouse in which the clock gene Period2 is fused with a luciferase reporter thus allow real-time monitoring of the clock gene Per2 oscillations. The generated db/db-mPer2 Luc mice had the typical diabetic mellitus including obesity, hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance. In addition, the db/db-mPer2 Luc mice also exhibited disruptions in circadian rhythms in behavior (locomotor activity), physiology (blood pressure) and metabolism (respiratory exchange ratio and energy expenditure). Using the LumiCycle system, we monitored in real-time of the Per2 oscillations in both the SCN central clock and multiple peripheral tissues ex vivo . The results showed no difference in the phase of the central SCN Per2 oscillation. However, the peripheral tissues that related to metabolism, such as liver and white adipose clocks, displayed 3.28±0.86 and 4.64±1.06 hours of phase advance respectively. Aorta, mesentery artery and kidney, organs play important role in blood pressure homeostasis, showed 0.99±0.37, and 2.12±0.4, and 2.21±0.5 hours phase advance respectively. Interestingly, no difference was observed in the lung and adrenal gland. We then investigated the Per2 oscillation in vivo by using the IVIS imaging system. Consistent with the ex vivo results, the liver Per2 oscillation were phase advanced in vivo. Our findings demonstrated that clock gene Per2 oscillations were disrupted in multiple peripheral tissues but not in central SCN. Moreover, the extent of phase advance in peripheral tissue varies largely. Our results suggest dyssynchrony of the clock oscillations among various peripheral systems likely contribute to the multiple disruptions in physiology and metabolism in diabetic db/db mice.

scholarly journals Phase-dependent resetting of the adrenal clock by ACTH in vitro

2014 ◽  
Vol 306 (6) ◽  
pp. R387-R393 ◽  
Author(s):  
J. Marina Yoder ◽  
Megan Brandeland ◽  
William C. Engeland
Keyword(s):  
Circadian Rhythms ◽  
Molecular Clock ◽  
Clock Gene ◽  
External Environment ◽  
Phase Delay ◽  
Melanocyte Stimulating Hormone ◽  
Circadian Time ◽  
Acth Receptor ◽  
Acth Fragments

The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoids, yet how the clock is synchronized to the external environment is unknown. Using mPER2::Luciferase (mPER2Luc) knockin mice, in which luciferase is rhythmically expressed under the control of the mouse Per2 clock gene, we hypothesized that ACTH transmits entrainment signals to the adrenal. Adrenal explants were administered ACTH at different phases of the mPER2Luc rhythm. Treatment with ACTH 1–39 produced a phase delay that was phase-dependent, with a maximum at circadian time (CT)18; ACTH did not alter the period or amplitude of the rhythm. Forskolin produced a parallel response, suggesting that the phase delay was cAMP-mediated. The response to ACTH was concentration-dependent and peptide-specific. Pulse administration (60 min) of ACTH 1–39 also produced phase delays restricted to late CTs. In contrast to ACTH 1–39, other ACTH fragments, including α-melanocyte-stimulating hormone, which do not activate the melanocortin 2 (MC2/ACTH) receptor, had no effect. The finding that ACTH in vitro phase delays the adrenal mPER2luc rhythm in a monophasic fashion argues for ACTH as a key resetter, but not the sole entrainer, of the adrenal clock.

Analytical and Machine-LearningAnalysis of Hydraulic Fracture-Induced Natural Fracture Slip

SPE Journal ◽  
2021 ◽  
pp. 1-17
Author(s):  
Peidong Zhao ◽  
K. E. Gray
Keyword(s):  
Failure Modes ◽  
Statistical Significance ◽  
Frictional Coefficient ◽  
Natural Fracture ◽  
Hydraulic Fractures ◽  
Well Performance ◽  
Stimulated Reservoir Volume ◽  
Relative Angle ◽  
Statistical Measures ◽  
Net Pressure

Summary Stimulated reservoir volume (SRV) is a prime factor controlling well performance in unconventional shale plays. In general, SRV describes the extent of connected conductive fracture networks within the formation. Being a pre-existing weak interface, natural fractures (NFs) are the preferred failure paths. Therefore, the interaction of hydraulic fractures (HFs) and NFs is fundamental to fracture growth in a formation. Field observations of induced fracture systems have suggested complex failure zones occurring in the vicinity of HFs, which makes characterizing the SRV a significant challenge. Thus, this work uses a broad range of subsurface conditions to investigate the near-tip processes and to rank their influences on HF-NF interaction. In this study, a 2D analytical workflow is presented that delineates the potential slip zone (PSZ) induced by a HF. The explicit description of failure modes in the near-tip region explains possible mechanisms of fracture complexity observed in the field. The parametric analysis shows varying influences of HF-NF relative angle, stress state, net pressure, frictional coefficient, and HF length to the NF slip. This work analytically proves that an NF at a 30 ± 5° relative angle to an HF has the highest potential to be reactivated, which dominantly depends on the frictional coefficient of the interface. The spatial extension of the PSZ normal to the HF converges as the fracture propagates away and exhibits asymmetry depending on the relative angle. Then a machine-learning (ML) model [random forest (RF) regression] is built to replicate the physics-based model and statistically investigate parametric influences on NF slips. The ML model finds statistical significance of the predicting features in the order of relative angle between HF and NF, fracture gradient, frictional coefficient of the NF, overpressure index, stress differential, formation depth, and net pressure. The ML result is compared with sensitivity analysis and provides a new perspective on HF-NF interaction using statistical measures. The importance of formation depth on HF-NF interaction is stressed in both the physics-based and data-driven models, thus providing insight for field development of stacked resource plays. The proposed concept of PSZ can be used to measure and compare the intensity of HF-NF interactions at various geological settings.

scholarly journals Casein Kinase 1 Underlies Temperature Compensation of Circadian Rhythms in Human Red Blood Cells

2019 ◽  
Vol 34 (2) ◽  
pp. 144-153 ◽  
Author(s):  
Andrew D. Beale ◽  
Emily Kruchek ◽  
Stephen J. Kitcatt ◽  
Erin A. Henslee ◽  
Jack S.W. Parry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Temperature Compensation ◽  
Clock Gene ◽  
Cell Types ◽  
Casein Kinase ◽  
Casein Kinase 1 ◽  
Human Red Blood Cells

Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs. As with nucleated cell types, broad-spectrum kinase inhibition with staurosporine lengthened the period of the RBC clock at 37°C, with more specific inhibition of CK1 and CK2 also eliciting robust changes in circadian period. Strikingly, inhibition of CK1 abolished temperature compensation and increased the Q10 for the period of oscillation in RBCs, similar to observations in nucleated cells. This indicates that CK1 activity is essential for circadian rhythms irrespective of the presence or absence of clock gene expression cycles.

scholarly journals Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny

2009 ◽  
Vol 29 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Nariman Ansari ◽  
Manuel Agathagelidis ◽  
Choogon Lee ◽  
Horst-Werner Korf ◽  
Charlotte von Gall
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Clock Gene ◽  
Pars Tuberalis

scholarly journals Comment on “Circadian rhythms in the absence of the clock gene Bmal1”

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabf0922
Author(s):  
Katharine C. Abruzzi ◽  
Cédric Gobet ◽  
Felix Naef ◽  
Michael Rosbash
Keyword(s):  
Circadian Rhythms ◽  
Clock Gene ◽  
Skin Fibroblasts ◽  
Liver Slices ◽  
Free Running

Ray et al. (Reports, 14 February 2020, p. 800) recently claimed temperature-compensated, free-running mRNA oscillations in Bmal1–/– liver slices and skin fibroblasts. We reanalyzed these data and found far fewer reproducible mRNA oscillations in this genotype. We also note errors and potentially inappropriate analyses.

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