Progress in understanding the vertebrate segmentation clock
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Vernier microcombs for integrated optical atomic clocks
Kerr microcombs have drawn substantial interest as mass-manufacturable, compact alternatives to bulk frequency combs. This could enable the deployment of many comb-reliant applications previously confined to laboratories. Particularly enticing is the prospect of microcombs performing optical frequency division in compact optical atomic clocks. Unfortunately, it is difficult to meet the self-referencing requirement of microcombs in these systems owing to the approximately terahertz repetition rates typically required for octave-spanning comb generation. In addition, it is challenging to spectrally engineer a microcomb system to align a comb mode with an atomic clock transition with a sufficient signal-to-noise ratio. Here we adopt a Vernier dual-microcomb scheme for optical frequency division of a stabilized ultranarrow-linewidth continuous-wave laser at 871 nm to an ~235 MHz output frequency. This scheme enables shifting an ultrahigh-frequency (~100 GHz) carrier-envelope offset beat down to frequencies where detection is possible and simultaneously placing a comb line close to the 871 nm laser—tuned so that, if frequency doubled, it would fall close to the clock transition in 171Yb+. Our dual-comb system can potentially combine with an integrated ion trap towards future chip-scale optical atomic clocks.
Cellpose3: one-click image restoration for improved cellular segmentation
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The circadian clock in enamel development
Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes. The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli. Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown. Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms. Teeth enamel is formed by enamel-forming cells known as ameloblasts, which are regulated and orchestrated by the circadian clock during amelogenesis. This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis. Several physiological processes are involved, including gene expression, cell morphology, metabolic changes, matrix deposition, ion transportation, and mineralization. Next, the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed. Circadian rhythm disruption can directly lead to Enamel Hypoplasia, which might also be a potential causative mechanism of amelogenesis imperfecta. Finally, future research trajectory in this field is extrapolated. It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.
DeltaC and DeltaD ligands play different roles in the segmentation clock dynamics
The vertebrate segmentation clock drives periodic somite segmentation during embryonic development. Her1 and Her7 clock proteins generate oscillatory expression of their own genes as well as that of deltaC in zebrafish. In turn, DeltaC and DeltaD ligands activate Notch signaling, which then activates transcription of clock genes in neighboring cells. While DeltaC and DeltaD proteins form homo- and heterodimers, only DeltaC-containing oscillatory dimers were expected to be functional. To investigate the contributions of DeltaC and DeltaD proteins on the transcription of her1 and her7 segmentation clock genes, we counted their transcripts by performing single molecule fluorescent in situ hybridization imaging in different genetic backgrounds of zebrafish embryos. Surprisingly, we found that DeltaD homodimers are also functional. We further found that Notch signaling promotes transcription of both deltaC and deltaD genes, thereby creating a previously unnoticed positive feedback loop. Our computational model highlighted the intriguing differential roles of DeltaC and DeltaD dimers on the clock synchronization and transcript numbers, respectively. We anticipate that a mechanistic understanding of the Notch signaling pathway will not only shed light on the mechanism driving robust somite segmentation but also inspire similar quantitative studies in other tissues and organs.
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