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.

scholarly journals Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

2017 ◽  
Vol 32 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Emily A. Slat ◽  
Jasmin Sponagel ◽  
Luciano Marpegan ◽  
Tatiana Simon ◽  
Najla Kfoury ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Growth Inhibition ◽  
Clock Gene ◽  
Daily Rhythms ◽  
The Core ◽  
Circadian Time ◽  
Damage Response ◽  
Human And Mouse ◽  
Core Clock Gene

The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.

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

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabf1930
Author(s):  
Sandipan Ray ◽  
Utham K. Valekunja ◽  
Alessandra Stangherlin ◽  
Steven A. Howell ◽  
Ambrosius P. Snijders ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Skin Fibroblast ◽  
Clock Gene ◽  
Mouse Skin ◽  
Fibroblast Cells ◽  
The Core ◽  
Core Clock Gene

Ness-Cohn et al. claim that our observations of transcriptional circadian rhythms in the absence of the core clock gene Bmal1 in mouse skin fibroblast cells are supported by inadequate evidence. They claim that they were unable to reproduce some of the original findings with their reanalysis. We disagree with their analyses and outlook.

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.

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

scholarly journals Circadian rhythms in Neurospora crassa: Dynamics of the clock component frequency visualized using a fluorescent reporter

2010 ◽  
Vol 47 (4) ◽  
pp. 332-341 ◽  
Author(s):  
Ernestina Castro-Longoria ◽  
Michael Ferry ◽  
Salomón Bartnicki-Garcia ◽  
Jeff Hasty ◽  
Stuart Brody
Keyword(s):  
Circadian Rhythms ◽  
Neurospora Crassa ◽  
Fluorescent Reporter ◽  
Clock Component

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.

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